Journal articles on the topic '929999 Health not elsewhere classified'

BackgroundThis is an exploratory study of readmission in mood disorder.MethodThe study is naturalistic and employs survival analysis. We identified 821 individuals with ICD–9 diagnoses, drawn from the Tasmanian Mental Health Register.ResultsNo demographic variables influence the time to readmission. Two groups emerge: those with affective psychoses, and those with neurotic depression, brief depressive reaction and depressive disorders not elsewhere classified. The former group demonstrated shorter times to readmission than the latter. There was no support for a unipolar–bipolar distinction.ConclusionsAffective psychoses have a less favourable outcome than expected. There was support for an endogenous-neurotic distinction.

AbstractBuilders of medical informatics applications need controlled medical vocabularies to support their applications and it is to their advantage to use available standards. In order to do so, however, these standards need to address the requirements of their intended users. Overthe past decade, medical informatics researchers have begun to articulate some of these requirements. This paper brings together some of the common themes which have been described, including: vocabulary content, concept orientation, concept permanence, nonsemantic concept identifiers, polyhierarchy, formal definitions, rejection of “not elsewhere classified” terms, multiple granularities, mUltiple consistent views, context representation, graceful evolution, and recognized redundancy. Standards developers are beginning to recognize and address these desiderata and adapt their offerings to meet them.

AbstractManic depression, or bipolar disorder, is a multifaceted illness with an inevitably complex treatment. The current article summarizes the current status of our knowledge and practice concerning its diagnosis and treatment. While the prototypic clinical picture concerns the “classic” bipolar disorder, today mixed episodes with incomplete recovery and significant psychosocial impairment are more frequent. The clinical picture of these mixed episodes is variable, eludes contemporary classification systems, and possibly includes a constellation of mental syndromes currently classified elsewhere. Treatment includes the careful combination of lithium, antiepileptics, atypical antipsychotics, and antidepressants, but not all of the agents in these broad categories are effective for the treatment of bipolar disorder.

SummaryThe family registration records from a village population in a small island of Japan are used to assess the effect of demographic differentiation within a population on genetic measures. When the couples studied are classified by birth cohorts and origins, wives of the couples where one spouse came from elsewhere were older at marriage and had a shorter duration of marriage or registration than wives where both spouses were natives of the village. The mean number of offspring is statistically smaller in the former except for the latest cohort, due mainly to out-migration during the reproductive ages which also resulted in low rates of marriage among the offspring within the village. This leads to a small effective population size and an increased likelihood of genetic drift in the overall population.

This paper outlines a diagnostic entity called ‘Pathological Habit Disorder’ which is suggested for inclusion in the DSM as an Axis II option. Specific areas of concern, either mental (Axis I) or physical (Axis III), would delineate the syndrome. Pathological Habit Disorder (PHD) points to treatment options where the syndrome is wholly or partly habit-driven. Whether the syndrome is habit-driven or not will remain a clinical judgement even though many conditions, previously thought immutable except by medication, are proving accessible to behavioural engineering. In the ICD system, PHD seems to fit in “Special Symptoms or Syndromes not elsewhere Classified”. It is demonstrably useful to have a diagnosis such as PHD and to incorporate it into the body of medical classification, recognizing current practices for dealing with unwelcome or damaging habits.

PurposeThis research aimed to determine the differences and similarities in each pilot project to understand the primary design forms and concepts of sponge city concept (SCC) projects in China. It also aimed to examine ten pilot projects in Shanghai to extrapolate their main characteristics and the processes necessary for implementing SCC projects effectively.Design/methodology/approachA literature review and field survey case study were employed. Data were mostly collected through a field survey in Shanghai, focusing on both the projects and the surrounding environment. Based on these projects' examination, a comparative method was used to determine the characteristics of the ten pilot SCC projects and programs in Shanghai.FindingsSix main types of SCC projects among 30 pilot cities were classified in this research to find differences and similarities among the pilot cities. Four sponge design methods were classified into ten pilot projects. After comparing each project size using the same geographical size, three geometrical types were categorized into both existing and new city areas. SCC project characteristics could be identified by combining four methods and three geometrical types and those of the SCC programs by comparing the change in land-use and the surrounding environment in ten pilot projects.Originality/valueThe results are valuable for implementing SCC projects in China and elsewhere and future research on the impact of SCC projects.

BackgroundGambling disorder is a relatively common psychiatric disorder recently re-classified within the DSM-5 under the category of ‘substance-related and addictive disorders'.AimsTo compare white matter integrity in patients with gambling disorder with healthy controls; to explore relationships between white matter integrity and disease severity in gambling disorder.MethodIn total, 16 participants with treatment-resistant gambling disorder and 15 healthy controls underwent magnetic resonance imaging (MRI). White matter integrity was analysed using tract-based spatial statistics.ResultsGambling disorder was associated with reduced fractional anisotropy in the corpus callosum and superior longitudinal fasciculus. Fractional anisotropy in distributed white matter tracts elsewhere correlated positively with disease severity.ConclusionsReduced corpus callosum fractional anisotropy is suggestive of disorganised/damaged tracts in patients with gambling disorder, and this may represent a trait/vulnerability marker for the disorder. Future research should explore these measures in a larger sample, ideally incorporating a range of imaging markers (for example functional MRI) and enrolling unaffected first-degree relatives of patients.

Due to the high levels of alcohol use, alcohol-attributable mortality and burden of disease, and detrimental drinking patterns, Lithuania implemented a series of alcohol control policies within a relatively short period of time, between 2008 and 2019. Based on their expected impact on alcohol consumption and alcohol-attributable harm, as well as their target population, these policies have been classified using a set of objective criteria and expert opinion. The classification criteria included: positive vs. negative outcomes, mainly immediate vs. delayed outcomes, and general population vs. specific group outcomes. The judgement of the alcohol policy experts converged on the objective criteria, and, as a result, two tiers of intervention were identified: Tier 1—highly effective general population interventions with an anticipated immediate impact; Tier 2—other interventions aimed at the general population. In addition, interventions directed at specific populations were identified. This adaptable methodological approach to alcohol control policy classification is intended to provide guidance and support for the evaluation of alcohol policies elsewhere, to lay the foundation for the critical assessment of the policies to improve health and increase life expectancy, and to reduce crime and violence.

Abstract Background Retention in care is critical for treatment and prevention of HIV. Many HIV care clinics measure retention rate, but data are often incomplete for patients who are classified as lost to follow-up but may be actually in care elsewhere, moved, or died. The Data to Care (D2C) initiative supports data sharing between health departments and HIV providers to confirm patient care status and facilitate reengagement efforts for out of care HIV patients. Methods The University of Chicago Medicine (UCM) provided an electronic list to the Chicago Department of Public Health (CDPH) of adult HIV-positive patients whose retention status was not certain. Retention in care was defined as at least 2 visits >90 days apart within the prior 12 months. CDPH matched this list of patients with data from the Chicago electronic HIV surveillance database. Matches were based on patient name, including alternative spellings and phonetics, and birth date. CDPH also cross-checked patient names with the CDC’s national enhanced HIV-AIDS Reporting System (eHARS) database. CDPH provided UCM with patient current care status, i.e., patient was in care elsewhere (as verified by lab data), moved out of state, or deceased. Results 780 HIV-positive patients received care in the UCM adult HIV clinic from January 1, 2013 to March 31, 2017. Of these, 360 were retained in care as of March 2017. We shared data with CDPH for 492 patients. Of these, 294 (59.8%) were matched, and 168 (34.1%) had a date of last medical care provided. See Table 1 for patient dispositions, before and after data sharing. 24 (13.4%) of patients believed to be lost to follow up according to UCM records were confirmed either transferred care or deceased according to health department data. Conclusion Data sharing between the health department and HIV providers can improve data accuracy regarding retention in care among people living with HIV. Disclosures J. P. Ridgway, Gilead FOCUS: Grant Investigator, Grant recipient; D. Pitrak, Gilead Sciences FOCUS: Grant Investigator, Grant recipient

Background The term Nodding Syndrome (NS) refers to an atypical and severe form of childhood epilepsy characterized by a repetitive head nodding (HN). The disease has been for a long time limited to East Africa, and the cause is still unknown. The objective of this study was to confirm the existence of NS cases in Central African Republic (CAR). Methodology/Principal findings This was a cross-sectional descriptive study in the general population. The identification of NS cases was conducted through a door-to-door survey in a village near Bangui along the Ubangui River. Based on Winkler’s 2008 and the World Health Organization (WHO)’s 2012 classifications, the confirmation of cases was done by a neurologist who also performed the electroencephalograms. No laboratory tests were done during this investigation. Treatment was offered to all patients. A total of 6,175 individuals was surveyed in 799 households. After reviewing the cases, we identified 5 NS cases in girls aged between 8 and 16. The age of onset of the seizures was between 5 and 12 years of age. Two cases were classified as "HN plus" according to Winkler’s 2008 classification. Four NS cases were classified as probable and one as confirmed according to the WHO’s 2012 classification. Three of them presented with developmental delay and cognitive decline, and one had an abnormally low height-for-age z-score. Electroencephalographic abnormalities were found in four patients. Conclusions/Significance Nodding Syndrome cases were described in CAR for the first time. Despite certain peculiarities, these cases are similar to those described elsewhere. Given that only a small part of the affected area was investigated, the study area along the Ubangui River needs to be expanded in order to investigate the association between Onchocerca volvulus and NS and also evaluate the real burden of NS in CAR.

Objectives: To review the literature evaluating outcomes resulting from expansion of the bipolar disorder (BD) diagnostic category. We were particularly interested in identifying high-level evidence for improved clinical outcomes as documented by randomized controlled trials (RCTs) or cohort studies. Methods: The English-language literature was searched using Ovid MEDLINE for studies of BD referenced against the key word spectrum. We used bibliographies and other databases to extend this search when no relevant RCTs or relevant cohort studies were identified. Results: In the MEDLINE searches, abstracts and titles of 86 studies were examined and 48 were found to be related to the topic of bipolar spectrum disorders (BSD). No RCTs or prospective cohort studies evaluating modified diagnostic or therapeutic practices were identified. The literature about the BSD consists mostly of expert opinion emphasizing: various links between bipolar and unipolar mood disorders; a proposal that a greater proportion of the population without a mood disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders should be diagnosed under the BD category; and, proposals that syndromes currently classified elsewhere should be subsumed under the BD category. Conclusions: Our search failed to uncover high-level evidence demonstrating the clinical utility of proposed diagnostic realignments. The widespread acceptance of the expanded spectrum concept appears to be based on interpretation of descriptive epidemiologic data by high-profile experts.

Abstract. Aerosol particles from shipping emissions both cool the climate and cause adverse health effects. The cooling effect is, however, declining because of shipping emission controls aiming to improve air quality. We used an aerosol-climate model ECHAM-HAMMOZ to test whether by altering ship fuel sulfur content, the present-day aerosol-induced cooling effect from shipping could be preserved, while at the same time reducing premature mortality rates related to shipping emissions. We compared the climate and health effects of a present-day shipping emission scenario (ship fuel sulfur content of 2.7%) with (1) a simulation with strict emission controls in the coastal waters (ship fuel sulfur content of 0.1%) and twofold the present-day fuel sulfur content (i.e. 5.4%) elsewhere; and (2) a scenario with global strict shipping emission controls (ship fuel sulfur content of 0.1% in coastal waters and 0.5% elsewhere) roughly corresponding to international agreements to be enforced by the year 2020. Scenario 1 had a slightly stronger aerosol-induced effective radiative forcing (ERF) from shipping than the present-day scenario (−0.43 W m−2 vs. −0.39 W m−2) while reducing premature mortality from shipping by 69% (globally 34 900 deaths avoided per year). Scenario 2 decreased the ERF to −0.06 W m−2 and annual deaths by 96% (globally 48 200 deaths avoided per year) compared to present-day. Our results show that the cooling effect of present-day emissions could be retained with simultaneous notable improvements in air quality, even though the shipping emissions from the open ocean clearly have a significant effect on continental air quality. However, increasing ship fuel sulfur content in the open ocean would violate existing international treaties, could cause detrimental side-effects, and could be classified as geoengineering.

The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915–2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme.

Background In recent years, both suicide and overdose rates have been increasing. Many individuals who struggle with opioid use disorder are prone to suicidal ideation; this may often result in overdose. However, these fatal overdoses are difficult to classify as intentional or unintentional. Intentional overdose is difficult to detect, partially due to the lack of predictors and social stigmas that push individuals away from seeking help. These individuals may instead use web-based means to articulate their concerns. Objective This study aimed to extract posts of suicidality among opioid users on Reddit using machine learning methods. The performance of the models is derivative of the data purity, and the results will help us to better understand the rationale of these users, providing new insights into individuals who are part of the opioid epidemic. Methods Reddit posts between June 2017 and June 2018 were collected from r/suicidewatch, r/depression, a set of opioid-related subreddits, and a control subreddit set. We first classified suicidal versus nonsuicidal languages and then classified users with opioid usage versus those without opioid usage. Several traditional baselines and neural network (NN) text classifiers were trained using subreddit names as the labels and combinations of semantic inputs. We then attempted to extract out-of-sample data belonging to the intersection of suicide ideation and opioid abuse. Amazon Mechanical Turk was used to provide labels for the out-of-sample data. Results Classification results were at least 90% across all models for at least one combination of input; the best classifier was convolutional neural network, which obtained an F1 score of 96.6%. When predicting out-of-sample data for posts containing both suicidal ideation and signs of opioid addiction, NN classifiers produced more false positives and traditional methods produced more false negatives, which is less desirable for predicting suicidal sentiments. Conclusions Opioid abuse is linked to the risk of unintentional overdose and suicide risk. Social media platforms such as Reddit contain metadata that can aid machine learning and provide information at a personal level that cannot be obtained elsewhere. We demonstrate that it is possible to use NNs as a tool to predict an out-of-sample target with a model built from data sets labeled by characteristics we wish to distinguish in the out-of-sample target.

Purpose: To analyze 10-year trends in utilization of visual field tests for adult glaucoma or glaucoma-suspect patients using the Korean Health Insurance Review and Assessment data.Methods: Health claims for the years 2010 to 2019, as recorded via Korea’s Health Insurance Review and Assessment service, were accessed. We identified glaucoma patients using the glaucoma diagnostic codes H40 (glaucoma) and H42 (glaucoma in other diseases classified elsewhere). For verification of the glaucoma diagnosis, information on any antiglaucoma medication prescriptions and ocular surgery history also was obtained. Visual field testing data was isolated using procedural codes E6690 (kinetic perimetry) and E6691 (standard automated perimetry [SAP]) performed in tertiary hospitals. Any changes in visual field test utilization were identified using regression trend analysis.Results: From 2010 to 2019, the total number of SAP procedures performed in tertiary hospitals for either glaucoma or glaucoma-suspect patients increased gradually from 93,459 to 216,433. With regard to kinetic perimetry examinations, the total number decreased gradually from 6,364 to 3,792. The yearly average SAP number per patient showed a slight increase, from 1.168 to 1.248 (ß = 0.008, R2 = 0.669, p = 0.004). Meanwhile, the yearly average number of kinetic perimeter examinations per patient showed a significant decrease, from 1.093 to 0.940 (ß = -0.013, R2 = 0.580, p = 0.010).Conclusions: Between 2010 and 2019, the yearly average number of SAP procedures performed per glaucoma or glaucoma-suspect patient increased in Korea. Meanwhile, the yearly average number of kinetic perimetry examinations per patient significantly decreased.

BackgroundScant evidence is available regarding the pharmacological management of acute episodes of mental disorders in children and adolescents attending emergency departments (ED). In this regard, we performed a retrospective study with the aim to evaluate the pattern of psychotropic drug use in an ED of a large hospital.MethodsA retrospective chart review of adolescents (13–17 years) visited in the ED of San Paolo University Hospital in Milan for a mental disorder between January and June 2018 was conducted. In particular, information concerning age, gender, type of mental disorder, psychotropic drugs administered in the ED and outcome of the visit were extracted and analysed, using an anonymous patient code.ResultsA total of 1,298 adolescents 13–17 years old were visited during the observation period, 56 (4%) of whom had a diagnosis of mental disorder (35 females and 21 males).The most common disorder was predominant psychomotor disturbance (International Classification of Diseases 9 (ICD9) revision code 308.2; 12 patients), followed by anxiety disorder in conditions classified elsewhere (293.84, 8 patients) and anxiety states (300.0, 7 patients).Ten adolescents were hospitalised, while 16 (29%) received a psychotropic drug in the ED: 14 patients received a benzodiapine (8 delorazepam, 3 lorazepam), and 2 an antipsychotic drug (risperidone+olanzapine; promazine). Five out of 12 adolescents with psychomotor disturbance received a psychotropic drug (3 delorazepam, 1 lorazepam, 1 risperidone+olanzapine).Although no randomized controlled trial has evaluated the safety and effectiveness of benzodiazepines in the paediatric population, delorazepam was identified as the first choice pharmacological treatment for agitation in children and adolescents in a local protocol.ConclusionNearly all children received drugs for which no controlled trials have been performed in the paediatric population and for which the appropriateness is debatable. More evidence is needed to guide the pharmacological management of acute episodes of mental disorders.Disclosure(s)Nothing to disclose

Abstract. Aerosol particles from shipping emissions both cool the climate and cause adverse health effects. The cooling effect is, however, declining because of shipping emission controls aiming to improve air quality. We used an aerosol-climate model ECHAM-HAMMOZ to test whether by altering ship fuel sulfur content, the present-day aerosol-induced cooling effect from shipping could be preserved while at the same time reducing premature mortality rates related to shipping emissions. We compared the climate and health effects of a present-day shipping emission scenario with (1) a simulation with strict emission controls in the coastal waters (ship fuel sulfur content of 0.1%) and twofold ship fuel sulfur content compared to current global average of 2.7% elsewhere; and (2) a scenario with global strict shipping emission controls (ship fuel sulfur content of 0.1% in coastal waters and 0.5% elsewhere) roughly corresponding to international agreements to be enforced by the year 2020. Scenario 1 had a slightly stronger aerosol-induced radiative flux perturbation (RFP) from shipping than the present-day scenario (−0.43 W m−2 vs. −0.39 W m−2) while reducing premature mortality from shipping by 69% (globally 34 900 deaths avoided per year). Scenario 2 decreased the RFP to −0.06 W m−2 and annual deaths by 96% (globally 48 200 deaths avoided per year) compared to present-day. A small difference in radiative effect (global mean of 0.04 W m−2) in the coastal regions between Scenario 1 and the present-day scenario imply that shipping emission regulation in the existing emission control areas should not be removed in hope of climate cooling. Our results show that the cooling effect of present-day emissions could be retained with simultaneous notable improvements in air quality, even though the shipping emissions from the open ocean clearly have a significant effect on continental air quality. However, increasing ship fuel sulfur content in the open ocean would violate existing international treaties, could cause detrimental side-effects, and could be classified as geoengineering.

AbstractObjectiveOver 300 million people rely on desalinated seawater and the numbers are growing. Desalination removes iodine from water and could increase the risk of iodine-deficiency disorders (IDD). The present study assessed the relationship between iodine intake and thyroid function in an area reliant on desalination.DesignA case–control study was performed between March 2012 and March 2014. Thyroid function was rigorously assessed by clinical examination, ultrasound and blood tests, including serum thyroglobulin (Tg) and autoimmune antibodies. Iodine intake and the contribution made by unfiltered tap water were estimated by FFQ. The contribution of drinking-water to iodine intake was modelled using three iodine concentrations: likely, worst-case and best-case scenario.SettingThe setting for the study was a hospital located on the southern Israeli Mediterranean coast.SubjectsAdult volunteers (n102), 21–80 years old, prospectively recruited.ResultsAfter screening, seventy-four participants met the inclusion criteria. Thirty-seven were euthyroid controls. Among those with thyroid dysfunction, twenty-nine were classified with non-autoimmune thyroid disease (NATD) after excluding eight cases with autoimmunity. Seventy per cent of all participants had iodine intake below the Estimated Average Requirement (EAR) of 95 µg/d. Participants with NATD were significantly more likely to have probable IDD with intake below the EAR (OR=5·2; 95 % CI 1·8, 15·2) and abnormal serum Tg>40 ng/ml (OR=5·8; 95 % CI 1·6, 20·8).ConclusionsEvidence of prevalent probable IDD in a population reliant on desalinated seawater supports the urgent need to probe the impact of desalinated water on thyroid health in Israel and elsewhere.

AbstractMalnutrition predicts preterm death, but whether this is valid irrespective of the cause of death is unknown. The aim of the present study was to determine whether malnutrition is associated with cause-specific mortality in older adults. This cohort study was conducted in Sweden and included 1767 individuals aged ≥65 years admitted to hospital in 2008–2009. On the basis of the Mini Nutritional Assessment instrument, nutritional risk was assessed as well nourished (score 24–30), at risk of malnutrition (score 17–23·5) or malnourished (score <17). Cause of death was classified according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, into twenty different causes of death. Data were analysed using Cox proportional hazards regression models. At baseline, 55·1 % were at risk of malnutrition, and 9·4 % of the participants were malnourished. During a median follow-up of 5·1 years, 839 participants (47·5 %) died. The multiple Cox regression model identified significant associations (hazard ratio (HR)) between malnutrition and risk of malnutrition, respectively, and death due to neoplasms (HR 2·43 and 1·32); mental or behavioural disorders (HR 5·73 and 5·44); diseases of the nervous (HR 4·39 and 2·08), circulatory (HR 1·95 and 1·57) or respiratory system (HR 2·19 and 1·49); and symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified (HR 2·23 and 1·43). Malnutrition and risk of malnutrition are associated with increased mortality regardless of the cause of death, which emphasises the need for nutritional screening to identify older adults who may require nutritional support in order to avoid preterm death.

AbstractObjective:To determine whether volumetric measures of the hippocampus, entorhinal cortex, and other cortical measures can differentiate between cognitively normal individuals and subjects with mild cognitive impairment (MCI).Method:Magnetic resonance imaging (MRI) data from 46 cognitively normal subjects and 50 subjects with MCI as part of the Boston University Alzheimer’s Disease Center research registry and the Alzheimer’s Disease Neuroimaging Initiative were used in this cross-sectional study. Cortical, subcortical, and hippocampal subfield volumes were generated from each subject’s MRI data using FreeSurfer v6.0. Nominal logistic regression models containing these variables were used to identify subjects as control or MCI.Results:A model containing regions of interest (superior temporal cortex, caudal anterior cingulate, pars opercularis, subiculum, precentral cortex, caudal middle frontal cortex, rostral middle frontal cortex, pars orbitalis, middle temporal cortex, insula, banks of the superior temporal sulcus, parasubiculum, paracentral lobule) fit the data best (R2= .7310, whole model test chi-square = 97.16,p&lt; .0001).Conclusions:MRI data correctly classified most subjects using measures of selected medial temporal lobe structures in combination with those from other cortical areas, yielding an overall classification accuracy of 93.75%. These findings support the notion that, while volumes of medial temporal lobe regions differ between cognitively normal and MCI subjects, differences that can be used to distinguish between these two populations are present elsewhere in the brain.

AbstractObjectivesTo estimate the dietary intakes of heterocyclic amines (HCAs), to examine the intakes in relation to socio-economics, lifestyle and other dietary factors and to compare the classification of subjects by intake of HCA versus intake of meat and fish.DesignCross-sectional analysis within the Malmö Diet and Cancer (MDC) cohort. Data were obtained from a modified diet history, a structured questionnaire on socio-economics and lifestyle, anthropometric measurements and chemical analysis of HCAs. HCA intake was cross-classified against meat and fish intake. The likelihood of being a high consumer of HCAs was estimated by logistic regression analysis. Dietary intakes were examined across quintiles of HCA intake using analysis of variance.SettingBaseline examinations conducted in 1991–1994 in Malmö, Sweden.SubjectsA sub-sample of 8599 women and 6575 men of the MDC cohort.ResultsThe mean daily HCA intake was 583 ng for women and 821 ng for men. Subjects were ranked differently with respect to HCA intake compared with intake of fried and baked meat and fish (κ = 0.13). High HCA intake was significantly associated with lower age, overweight, sedentary lifestyle and smoking. Intakes of dietary fibre, fruits and fermented milk products were negatively associated with HCA intake, while intakes of selenium, vegetables, potatoes, alcohol (among men) and non-milk-based margarines (among women) were positively associated with HCA intake.ConclusionsThe estimated daily HCA intake of 690 ng is similar to values obtained elsewhere. The present study suggests that lifestyle factors (e.g. smoking, physical activity, fruit and vegetable intakes, and types of milk products and margarines) may confound associations between HCA intake and disease. The poor correlation between HCA intake and intakes of fried meat and fish facilitates an isolation of the health effects of HCAs.

Abstract The risk of radiation effects in children of individuals exposed to ionising radiation remains an ongoing concern for aged veterans of the British nuclear testing programme. The genetic and cytogenetic family trio (GCFT) study is the first study to obtain blood samples from a group of British nuclear test veterans and their families for the purposes of identifying genetic alterations in offspring as a consequence of historical paternal exposure to ionising radiation. In this report, we describe the processes for recruitment and sampling, and provide a general description of the study population recruited. In total, blood samples were received from 91 (49 test and 42 control) families representing veteran servicemen from the army, Royal Air Force and Royal Navy. This translated to an overall response rate of 14% (49/353) for test veterans and 4% (42/992) for control veterans (excluding responders known to be ineligible). Due to the lack of dose information available, test veterans were allocated to a three-point exposure rank. Thirty (61%) test veterans were ranked in the lower group. Nineteen (39%) of the 49 test veterans were classified in the mid (5 veterans; 10%)/high (14 veterans; 29%) exposure ranks and included 12 veterans previously identified as belonging to the special groups or listed in health physics documents. An increased number of test veteran families (20%), compared with control families (5%), self-reported offspring with congenital abnormalities (p = 0.03). Whether this observation in this small group is reflective of the entire UK test veteran cohort or whether it is selection bias requires further work. The cohort described here represent an important and unique family trio grouping whose participation is enabling genetic studies, as part of the GCFT study, to be carried out. The outcomes of these studies will be published elsewhere. ISRCTN Registry: 17461668.

It is proposed that proteins/enzymes be classified into two classes according to their essentiality for immediate survival/reproduction and their function in long-term health: that is, survival proteins versus longevity proteins. As proposed by the triage theory, a modest deficiency of one of the nutrients/cofactors triggers a built-in rationing mechanism that favors the proteins needed for immediate survival and reproduction (survival proteins) while sacrificing those needed to protect against future damage (longevity proteins). Impairment of the function of longevity proteins results in an insidious acceleration of the risk of diseases associated with aging. I also propose that nutrients required for the function of longevity proteins constitute a class of vitamins that are here named “longevity vitamins.” I suggest that many such nutrients play a dual role for both survival and longevity. The evidence for classifying taurine as a conditional vitamin, and the following 10 compounds as putative longevity vitamins, is reviewed: the fungal antioxidant ergothioneine; the bacterial metabolites pyrroloquinoline quinone (PQQ) and queuine; and the plant antioxidant carotenoids lutein, zeaxanthin, lycopene, α- and β-carotene, β-cryptoxanthin, and the marine carotenoid astaxanthin. Because nutrient deficiencies are highly prevalent in the United States (and elsewhere), appropriate supplementation and/or an improved diet could reduce much of the consequent risk of chronic disease and premature aging.

The cost analysis of pain treatment is not a topic often taken up by the health economists community. The subjective dimension and pain assessment by the patient is one of the main determinants of the lack of interest in this topic. Work carried out on this topic currently includes analysis accompanying the process of pharmacotherapy treatment, care provided by medical personnel as well as costs resulting from administrative services. The aim of the work is to present the cost analysis of care for a „pain” patient and to indicate the most optimal financial package of these activities. The study was performed on the basis of financial data of the Clinical Emergency Department of the University Clinical Center in Gdańsk for the last year. We analyzed the cases of patients complaining of pain who received pharmacotherapy. Results The total cost for 2017 amounted to 1.128.668 PLN. The largest amount of money was allocated to the group of patients qualified to the group R: „Symptoms, disease features and abnormal results of clinical trials not classified elsewhere” – 327.313.72 PLN. The symptom of pain is one of the most frequently indicated symptoms among patients who receive medical help at the Clinical Emergency Department of the University Clinical Center in Gdańsk, which should be associated with a greater degree of involvement in analgesic therapy in patients who require it.

Background: Prehospital dyspnoea patients are a frequent group with a high mortality. However, there is limited knowledge about their characteristics. We aimed to investigate causes for dispatched ambulances to patients diagnosed with dyspnoea, and diagnoses given to patients to whom an ambulance was dispatched due to dyspnoea. Method: Retrospective cohort study in the North Denmark region in the period 2012-2015. We included all emergency ambulance patients where the main cause for a dispatched ambulance was “Breathing difficulty”, and all emergency ambulance patients who were diagnosed within the ICD-10 chapter “Diseases of the respiratory system” at hospital. Results: 4933 patients had an ambulance dispatched due to “Breathing difficulty”. Their most frequent diagnoses at hospital were ICD-10 chapter “Diseases of the respiratory system” (49.45%), “Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified” (18.56%), “Diseases of the circulatory system” (9.20%), and “Factors influencing health status and contact with health services” (5.71%). Contrariwise, 5163 emergency ambulance patients received a diagnosis within ICD-10 chapter “Diseases of the respiratory system” at hospital. The most frequent causes for dispatched ambulances to these patients were “Breathing difficulty” (49.45%), “Unclarified problem” (11.16%), and “Chest pain - heart disease” (9.55%). 16.00% of dispatches were without cause. Conclusion: Only half of the patients had both ambulance dispatch and hospital diagnose related to breathing difficulties. The variation and distribution of causes for ambulance dispatch and diagnoses given at hospital, suggests that dyspnoea is a symptom present in many conditions and the patient group is complex.

Background: The prevalence of dementia is generally reported to be higher among Indigenous peoples. Objective: The rates and coding of dementia mortality were compared between Indigenous and non-Indigenous Australians. Methods: De-identified individual records on causes of death for all people aged 40 years or more who died in Australia between 2006 and 2014 (n = 1,233,084) were used. There were 185,237 records with International Classification of Diseases, Tenth Revision, codes for dementia (Alzheimer’s Disease, vascular dementia, or unspecified dementia) as the underlying cause of death or mentioned elsewhere on the death certificate. Death rates were compared using Poisson regression. Logistic regression was used to assess whether dementia was more likely to be classified as ‘unspecified’ type in Indigenous Australians. Results: The rates of death with dementia were 57% higher in Indigenous Australians, compared to non-Indigenous, relative rate (RR) 1.57, 95% confidence interval (CI) (1.48, 1.66), p < 0.0001. This excess of deaths was highest at ages below 75 (RRs > 2, test for interaction p < 0.0001), and among men (test for interaction p < 0.0001). When the underreporting of Indigenous status on the death certificate was taken into account the relative rate increased to 2.17, 95% CI (2.07, 2.29). Indigenous Australians were also more likely to have their dementia coded as ‘unspecified’ on their death certificate (Odds Ratio 1.92, 95% CI (1.66, 2.21), p < 0.0001), compared to the non-Indigenous group. Conclusion: This epidemiological analysis based on population level mortality data demonstrates the higher dementia-related mortality rate for Indigenous Australians especially at younger ages.

Purpose The purpose of this paper is to gather epidemiologicalinformation concerning firesetters with intellectual disabilities (ID) in Denmark to identify the assessment and treatment needs of this population and inform further research in this area. Design/methodology/approach The records held by the Danish Ministry of Justice concerning all firesetters with ID convicted of deliberate firesetting were reviewed for the period January 2001 to December 2010 inclusive. File information was extracted for 83 offenders concerning: demographic and personal characteristics; mental health characteristics; offending behaviour; offence-specific factors; and motives for offending. A sub-group of seven offenders were interviewed to explore some of the themes that emerged from the file review. Findings The majority of study participants were male and were classified as having mild ID and around 50 per cent had additional mental health problems. Many came from disturbed and deprived backgrounds. Two-thirds had set more than one fire and over 60 per cent had convictions for offences other than firesetting. Alcohol was involved in the firesetting behaviour in a significant proportion of cases (25 per cent). The motives for setting fires were – in descending order – communication (of anger, frustration and distress), fire fascination and vandalism. Interviews with participants indicated the important communicative function of firesetting, the difficulties people had in talking about and acknowledging their firesetting behaviour, and lack of access to targeted interventions. Research limitations/implications Interventions for Danish firesetters with ID, as for firesetters with ID elsewhere, need to target the communicative function of this behaviour, along with offenders’ lack of insight and initial reluctance to accept responsibility for their behaviour and associated risks. Adjunctive treatment is required to address the psychiatric comorbidity experienced by many of these offenders, along with the alcohol use/misuse that is associated with many of these offences. Originality/value This is the first study concerning nature and needs of firesetters with ID in Denmark.

This paper investigates the probable nexus between methane (CH4) and air pollutants, a public health hazard in Bangladesh. The hypothesis considers that the concentration of CH4 is dependent on the ten air pollutants found in the five districts in Dhaka Division, a major urban and industrial area in Bangladesh. These pollutants are: Particular matters (PM2.5), Nitrogen dioxide (NO2), Nitrogen oxide (NOx), Aerosol optical thickness (AOT), Sulfur dioxide (SO2), Carbon monoxide (CO), Ozone (O3), Black carbon (BC), Formaldehyde (HCHO) and Dust. The study applies Machine Learning (ML) technique and Geographically Weighted Regression (GWR) Modeling. Temporal CH4 datasets from the Sentinel-5P sensor are classified to estimate the annual CH4 concentration during 2019-2021.Seven supervised classifiers of ML coupled with the GWR model are used to predict the statistical and spatial relationships. CH4 increases gradually during 2018-2021 in Dhaka, Gazipur, and Munshiganj Districts. It relates differently with various air pollutants, e.g., positively with BC, Dust, NO2, PM2.5, O3, and AOT, and negatively with NOx, CO, HCHO, and SO2.This study results that Rational quadratic (RMSE-0.001, MAE-0.001, R2-0.96), Random Forest (RMSE-0.004, MAE-0.003, R2-0.91), and Stepwise regression (RMSE-0.002, MAE-0.002, R2-0.87) are the suitable method in ML. The highest goodness-of-fit (R2) of 82%-96% is found in Dhaka and Narshingdi Districts. The key findings may help formulate the appropriate action plan to mitigate ongoing and future air pollution in Bangladesh. In addition, the methodology of the research may be applicable elsewhere nationally and internationally for air pollution research.

Background: Pleomorphic xanthoastrocytoma (PXA) is a rare form of astrocytic neoplasm most commonly found in children and young adults. This neoplasm, which is classified as a Grade II tumor by the World Health Organization classification of tumors of the central nervous system, carries a relatively favorable outcome. It is usually found supratentorially in cortical regions of the cerebral hemispheres, and as such, presenting symptoms are similar to other supratentorial cortical neoplasms; with seizures being a common initial symptom. Due to the rarity of this type of neoplasm, PXA arising elsewhere in the brain is often not included in the initial differential diagnosis. Case Description: This report presents an extremely rare patient with PXA arising in the suprasellar region who presented with progressive peripheral vision loss. Magnetic resonance imaging of the brain demonstrated a heterogeneous suprasellar mass with cystic and enhancing components initially; the most likely differential diagnosis was craniopharyngioma. The patient underwent endoscopic endonasal resection of the tumor. Microscopically, the tumor was consistent with a glial neoplasm with variable morphology. Based on these findings along with further immunohistochemical workup, the patient was diagnosed with a PXA arising in the suprasellar region. At the 1-year follow-up, the patient remained free of recurrence. Although rare PXA originating in other uncommon locations, such as the spinal cord, cerebellum, the ventricular system, and the pineal region have been previously described. Conclusion: Although rare, PXA should be included in the differential diagnosis for solid-cystic tumors arising in the suprasellar region in young adults.

Background: Adverse drug reactions (ADRs) constitute a major clinical problem in terms of human suffering and increased health care costs. To study the adverse drug reactions reported in a tertiary care hospital and study of causality assessment and severity of adverse drug reaction (ADR) cases reported.Methods: A prospective observational study was conducted as part of pharmacovigilance program over 12months between September 2015 and August 2016. Adverse drug reactions reported from hospital were filled into Suspected ADR - CDSCO forms and submitted to pharmacovigilance unit. Causal relationship was assessed and categorized by Naranjo’s algorithm and WHO - UMC causality scale. The severity of each ADR was assessed using Modified Hartwig and Siegel scale.Results: Total 120 cases were reported over 12 months. Among them, 66% were in males and 55% were in females. The majority of ADRs were due to antimicrobial agents (40.78%) followed by haematinics (12%) and anti-epileptics (10%). Maximum number of patients (30.25%) reported with dermatological manifestations. Highest number of ADRs was reported from the department of medicine (45%). As per Naranjo’s scale, 54% reports were assessed as probable and 46% classified as possible. Majority of cases were mild to moderate in severity.Conclusions: The pattern of ADRs reported in our hospital is similar with the pattern of studies conducted in other hospitals elsewhere. This study provides a database of ADRs due to commonly used drugs in our hospital, which will help clinicians for their optimum and safe use. Hence effective pharmacovigilance is required for the use of these drugs and their safety assessment.

OBJECTIVES/SPECIFIC AIMS: Approximately 50% of people who have been diagnosed with HIV are either not linked to a care provider or not retained in medical care. This has substantial implications for both individual and public health outcomes. On an individual level, being retained in care is necessary for continuous receipt of antiretroviral therapy and sustained viral suppression. The public health implications of poor retention in HIV care are also serious, as it is estimated that people with HIV who are not retained in medical care are responsible for a majority of HIV transmissions, even more than the number of transmissions attributable to those who are HIV infected but undiagnosed. State departments of health routinely collect surveillance data including positive HIV test results, CD4 counts and viral load measures for monitoring trends in HIV infection. A shift in the use of these surveillance measures, guided by the CDC, has brought forth the opportunity to use these data for direct patient services and, more specifically, to direct re-engagement and retention in care efforts. Although the risk factors for poor retention in HIV care have been characterized using information from individual or multiple clinics, this study seeks to incorporate state surveillance data into the retention measures. METHODS/STUDY POPULATION: This retrospective cohort study was performed at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic among patients with at least one attended HIV primary care visit during the calendar year of 2015. Retention during the calendar year of 2016 was then measured as whether or not a patient had 2 or more completed clinic visits which were separated by more than 90 days (in accordance with the Health Resources and Services Administration or HRSA guidelines, a National HIV Quality Indicator). For patients who did not have any primary care visit in 2016, the Alabama Department of Public Health will provide a status of care (out of care, in care elsewhere, died, moved out of state, and cannot locate) based on HIV laboratory results reported from all clinics and labs across the state and/or mortality information. A multinominal regression model of the status of care will be fitted to demographic, clinical, laboratory, and behavioral patient reported outcomes captured during an index visit in 2015. RESULTS/ANTICIPATED RESULTS: Data were recently obtained and is currently being analyzed on 3107 patients included in this study. We anticipate that there will be differences in the factors significantly associated with patients classified as out of care, poorly retained (patients who have only one completed clinic visit), and retained in care by the HRSA measure during calendar year 2016. DISCUSSION/SIGNIFICANCE OF IMPACT: By incorporating state surveillance data into our analysis, we expect to obtain a more precise picture of the risk factors for poor retention among HIV patients. For the first time, we will be able to determine if patients lost to our HIV clinic (~10% annually) are entirely lost to medical care or are seeking care elsewhere as indicated by HIV lab data reported to public health via surveillance. Identified risk factors will then be able to better inform the efforts to proactively improve the efficiency for HIV patient retention and re-engagement, and therefore lead to better individual outcomes for HIV patients and reduce the incidence of new HIV cases.

<b><i>Introduction:</i></b> The underlying pathophysiology of idiopathic REM sleep behavior disorder (iRBD) is not fully understood, although the condition is currently recognized as an early-stage alpha-synuclein disorder. We evaluated the morbidity, mortality, and rate of conversion to a neurodegenerative disorder in a national group of patients. <b><i>Methods:</i></b> All patients in Denmark with a diagnosis of RBD between 2006 and 2013 were identified from the Danish National Patient Registry (NPR) records. We excluded patients who had received a diagnosis of narcolepsy or any of the following neurodegenerative diseases before their diagnosis of RBD: Parkinson’s disease, multiple system atrophy, progressive supranuclear paralysis, Alzheimer’s, and Lewy body dementia. We used randomly chosen controls matched for age, gender, and municipality. <b><i>Results:</i></b> In total, 246 iRBD patients and 982 matched controls were analyzed. The mortality rate was the same in both groups. The morbidity rate was significantly higher in the years before and after an RBD diagnosis, due to a wide variety of disorders in the following major disease groups: mental/behavioral disorders; endocrine/metabolic diseases; diseases of the eye; diseases of the nervous, digestive, musculoskeletal, circulatory, and respiratory systems; abnormal findings not classified elsewhere; external causes; and factors influencing health status. The conversion rate from RBD to a neurodegenerative disease was 13% over the 8 years after a diagnosis of RBD. <b><i>Conclusions:</i></b> A diagnosis of RBD is associated with increased morbidity several years before and after a diagnosis is made. Patients have a higher risk of converting to a neurodegenerative disorder than matched controls. Mortality rates are unchanged.

Introduction: Data on the cause of death form the cornerstone for analyzing the health situation and disease in countries, and they make a major contribution to building evidence for health policies. Aim: The aim of this study was to determine the extent to which diagnoses from the group - Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified (R00-R99), International Classification of Diseases (ICD - Revision X) were used as the main cause of death in Serbia, Croatia, North Macedonia, and Slovenia in the ten-year period, 2007 - 2016. Materials and methods: Methods of descriptive and analytical statistics were used in this research. An analysis of data on the causes of death (R00-R99 ICD - Revision X), by gender, during the ten-year period (2007 - 2016) was performed. Linear regression was also used as an analytical method to analyze the trend. Results: During the ten-year period, in Serbia, the R00-R99 diagnoses were among the five most common groups of diagnoses of death, i.e., in each year they took third place, with a percentage of 4.7%. In the observed period, in the surrounding countries, there was an increase in the death rate in Slovenia, with the highest rate in 2016 (19.9), while in Croatia there was a decrease in the death rate related to the diagnoses from group XVIII ICD - X (R00-R99). In Macedonia, the rate had a linear trend, with a slight decline in 2012 (52.3) and 2013 (58.7). In the observed period, an increase in the death rate of the population of Serbia with an unknown cause of death was observed, with particularly high rates in 2009 and 2016. Comparative analysis has shown that R00-R99 diagnoses are represented more in the mortality statistics of Serbia than in Slovenia and Croatia, and less than in Northern Macedonia. Conclusion: Urgent interventions are needed to improve the quality of mortality statistics and data on the causes of death in the described countries.

Abstract The World Health Organization (WHO) central nervous system (CNS) tumor classification has represented the primary source of diagnosis and grading criteria of brain tumors. Nonetheless, recent advances of studies on their molecular alterations require more rapid update of recommendations for clinical practice. To accomplish this, cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established in 2016 and has published four updates. For adult gliomas, update 1 clarified the use of the term NOS (Not Otherwise Specified) and proposed a new term NEC (Not Elsewhere Classified); update 2 revised clarifications regarding diffuse astrocytoma/anaplastic astrocytoma, IDH-mutant; update 3 proposed molecular criteria for an IDH-wildtype diffuse or anaplastic astrocytic glioma without histological features of glioblastoma, which would behave similarly to a grade IV glioblastoma. Nonetheless, no consensus on pathologic or molecular markers that could be incorporated into a more clinically relevant grading scheme for IDH-mutant gliomas has been reached. The molecular alterations previously studied using relatively large cohorts include CDKN2A/B homozygous deletion, CDK4 amplification, RB1 mutation/homozygous deletion, PIK3CA or PIK3R1 mutations, PDGFRA amplification, NMYC amplification, global hypomethylation, genomic instability and chromosome 14 loss. The proliferative activity, based on the mitotic count or Ki67 indices, and other morphologic features typical of a high grade that might stratify the risk better than the current criteria have also been evaluated. Despite the discordance among the results of previous studies, CDKN2A/2B homozygous deletions have been shown prognostic significance in high-grade IDH-mutant astrocytomas and microvascular proliferation stratifies IDH-mutant gliomas lacking a CDKN2A homozygous deletion, suggesting that the integration of molecular information and traditional histological findings is still essential for achieving maximum risk stratification of adult cases of IDH-mutant diffuse gliomas. The grading scheme for adult IDH-mutant as well as wild-type gliomas should therefore be revised in the next WHO update.

Danish patients calling the Emergency Medical Services (EMS) with unclear problems are assigned a Danish Index for Emergency Care (DI) criteria called ‘unclear problem’. Previous Danish studies found ‘unclear problem’ in 17% and 19% of all emergency calls. In the Emergency Departments, unclear problems identified as non-specific symptoms are well documented. We investigated EMS patients given an ‘unclear problem’ DI-criteria prehospitally, their hospital discharge diagnoses and 1-day and 30-day mortality rates. Population-based observational cohort study investigating 7,935 EMS patients who received the DI-criteria ‘unclear problem’ upon an emergency call and who were brought to hospital in the North Denmark Region during January 1st, 2016 – December 31st, 2018. Outcome variables were; number of emergency ambulances dispatched, ‘unclear problem’ DI-criteria, and vital status (dead or alive) 30 days after hospital contact. We evaluated the association between ICD-10 diagnosis chapters and mortality adjusted for age, gender, and comorbidity. ICD-10 chapters 18: “Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified” and 21: “Factors influencing health status and contact with health services” were defined as ‘non-specific diagnoses’.All ICD-10 chapters were represented in the discharge diagnoses. The majority (40.4%) were non-specific diagnoses. Common discharge diagnoses were circulatory (9.6%), injuries and poisoning (9.4%), and respiratory diseases (6.9%). Overall mortality rates were for 1-day and 30-day 2.3% (n=181) and 7.1% (n=566), respectively. Day 1 mortality rates were highest for circulatory diseases (8.6%), infections (5.4%), and respiratory diseases (4.0%). Mortality on day 30 was 2.6% and 4.1% for non-specific diagnoses, whereas circulatory, respiratory diagnoses and infections exhibted highest mortality rates. Risk of mortality was associated with age and comorbidities and when adjusted for these confounders, mortality rates decreased for all diagnoses. EMS patients assigned ‘unclear problem’ and brought to the hospital received diagnoses from all ICD-10 chapters, the majority with non-specific diagnoses, followed by injuries and poisoning, circulatory and respiratory diseases. The latter two groups exhibited the highest crude mortality rates, decreasing substantially when adjusted for age and comorbidity. Mortality rates among patients with unclear problems were associated with age and comorbidities rather than the unclear emergency medical call and following discharge diagnoses.

In this era of startling developments in the medical field there remains a serious worry about the hazardous potential of various by products which if not properly addressed can lead to consequences of immense public concern. Hospitals and other health care facilities generate waste products which are evidently hazardous to all those exposed to its potentially harmful effects. Need for effective legislation ensuring its safe disposal is supposed to be an integral part of any country's health related policy. This issue is of special importance in developing countries like Pakistan which in spite of framing various regulations for safeguarding public health, seem to overlook its actual implementation. The result unfortunately is the price wehave to pay not only in terms of rampant spread of crippling infections but a significant spending of health budget on combating epidemics which could easily have been avoided through effective waste disposal measures in the first place. Waste classified under the heading 'bio-hazardous' includes any infectious or potentially infectious material which can be injurious or harmful to humans and other living organisms. Amongst the many potential sources are the hospitals or other health delivery centres which are ironically supposed to be the centres of infection control and treatment. Whilst working in these setups, health care workers such as doctors, nurses, paramedical staff and sanitation workers are actually the ones most exposed and vulnerable to these challenges. Biomedical waste may broadly be classified into Infectious and toxic waste. Infectious waste includes sharps, blood, body fluids and tissues etcwhile substances such as radioactive material and by-products of certain drugs qualify as toxic waste. Furthermore health institutions also have to cater for general municipal waste such as carton boxes, paper and plastics. The World Health Organisation has its own general classification of hospital waste divided into almost eight categories of which almost 15% (10% infectious and 5% toxic) is estimated to be of a hazardous nature while the remaining 85% is general non hazardous content.1A recent study from Faisalabad, Pakistan has estimated hospital waste generation around 1 to 1.5 kg / bed /day for public sector hospitals in the region,2while figures quoted from neighbouring India are approximately 0.5 to 2 KG / hospital bed /day.3 Elsewhere in the world variable daily hospital waste production has been observed ranging from as low as 0.14 to 0.49 kg /day in Korea4 and 0.26 to 0.89 kg/day in Greece5to as high as 2.1 to 3.83 kg/day in Turkey6 and 0.84 to 5.8 kg/day in Tanzania.7Ill effects of improper management of hospital waste can manifest as nosocomial infections or occupational hazards such as needle stick injuries. Pathogens or spores can be borne either through the oro-faecal or respiratory routes in addition to direct inoculation through contact with infected needles or sharps. Environmental pollution can result from improper burning of toxic material leading to emission of dioxins, particulate matter or furans into the air. The habitat can also be affected by illegal dumping and landfills or washing up of medical waste released into the sea or river. Potential organisms implicated in diseases secondary to mismanagement of hospital waste disposal include salmonella, cholera, shigella, helminths, strep pneumonia, measles, tuberculosis, herpesvirus, anthrax, meningitis, HIV, hepatitis and candida etc. These infections can cause a considerable strain on the overall health and finances of the community or individuals affected. The basic principal of Public health management i.e 'prevention is better than cure' cannot be more stressed in this scenario as compared to any other health challenge. Health facilities must have a clear policy on hazardous waste management. To ensure a safe environment hospitals need to adopt and implement international and local systems of waste disposal. Hospital waste management plan entails policy and procedures addressing waste generation, accumulation, handling, transportation, storage, treatment and disposal. Waste needs to be collected in marked containers usually colour coded and leak proof. Segregation at source is of vital importance. The standard practice in many countries is the Basic Three Bin System ie to segregate the waste into RED bags/ boxes for sharps, YELLOW bags for biological waste and BLUE or BLACK ones for general/ municipal waste. All hospital staff needs to be trained in the concept of putting the right waste in relevant containers/ bags. They need to know that more than anything else this practice is vital for their own safety. The message can be reinforced through appropriate labelling on the bins and having posters with simple delineations to avoid mixing of different waste types. Sharps essentially should be kept in rigid, leak and puncture-resistant containers which are tightly lidded and labelled. Regular training sessions for nurses and cleaning staff can be organised as they are the personnel who are more likely to deal with waste disposition at the level of their respective departments. Next of course is transportation of waste products to the storage or disposal. Sanitary staff and janitors must be aware of the basic concepts of waste handling and should wear protective clothing, masks and gloves etc, besides ensuring regular practice of disinfection and sterilization techniques.8Special trolleys or vehicles exclusively designed and reserved for biomedical waste and operated by trained individuals should be used for transportation to the dumping or treatment site. Biomedical waste treatment whether on site or off site is a specialised entity involving use of chemicals and equipment intended for curtailing the hazardous potential of the material at hand. Thermal treatment via incinerators, not only results in combustion of organic substances but the final product in the form of non-toxicash is only 10 to 15% of the original solid mass of waste material fed to the machine. Dedicated autoclaves and microwaves can also be used for the purpose of disinfection. Chemicals such as bleach, sodium hydroxides, chlorine dioxide and sodiumhypochlorite are also effective disinfectants having specialised indications. Countries around the world have their own regulations for waste management. United Kingdom practices strict observance of Environmental protection act 1990, Waste managementlicensing regulations 1994 and Hazardous waste regulations 2005 making it one of thesafest countries in terms of hazardous waste disposal. Similar regulations specific for each state have been adopted in United States following passage of the Medical Waste tracking act 1988. In Pakistan, every hospital must comply with the Waste Management Rules 2005 (Environment Protection Act 1997), though actual compliance is far from satisfactory. It is high time that the government and responsible community organisations shape up to seriously tackle the issue of bio hazardous waste management through enforcement of effective policies and standard operating procedures for safeguarding the health and lives of the public in general and health workers in particular.

<p class="abstract"><strong><span lang="EN-US">Background: </span></strong>Reliable data on mortality and morbidity among women of reproductive age are scarce in India. The present study is the Rajasthan component of a large multi-centric study on cause of death by verbal autopsy conducted in five states of India. The data pertaining to deaths among women of reproductive age are presented. </p><p class="abstract"><strong><span lang="EN-US">Methods: </span></strong>House-to-house surveys of a representative population from rural and urban areas in six districts of Rajasthan were undertaken by Probability of Proportion to Size (PPS) sampling. Information on death was obtained from the relatives of the deceased and cause of death was assigned using the standardized algorithm prepared for the purpose. International Classification of Diseases - ICD-10 was used to code the assigned cause of death. </p><p class="abstract"><strong><span lang="EN-US">Results: </span></strong>A total of 231 deaths of women of reproductive age were investigated, of which 36 (16%) were maternal deaths while 195 (84%) were non-maternal deaths. Nine out of ten maternal deaths were in rural area.</p><p class="abstract"><strong><span lang="EN-US">Conclusions: </span></strong>Certain infectious and parasitic diseases; pregnancy, childbirth and the puerpurium; injury, poisoning and other consequences of external causes; and symptoms, signs and abnormal clinical and laboratory findings not elsewhere classified were found to be the major killers among the women of reproductive age. A comprehensive approach that includes in addition to reproductive health interventions, interventions addressing underlying illiteracy among women and social reforms needs to be undertaken. </p><p class="keywords"><strong><span lang="EN-US">Keywords: </span></strong>Maternal deaths, Non-maternal deaths, Women of reproductive age, Verbal autopsy</p>

Abstract Background Patients with solid tumors treated at a National Cancer Institute designated cancer center (NCI-CC) have been found to have improved survival when compared to those treated elsewhere. Few population-based studies have evaluated the association between location of care, complications associated with intensive therapy and early mortality (defined here as death ² 60 days from diagnosis) in patients with AML. Methods Using linked data from the California Cancer Registry and Patient Discharge Dataset from 1999 to 2012, we identified patients ³15 years of age diagnosed with AML who received inpatient treatment. Hospitals where patients received their care were classified as either NCI-CC or non-NCI designated facilities (non-NCI-CC). Logistic regression was used to estimate associations between patient characteristics (age, sex, race/ethnicity, year of diagnosis, marital status, neighborhood socioeconomic status, health insurance, and medical comorbidities) and location of care (NCI-CC vs non-NCI-CC facilities), and then to build a propensity score. Inverse probability weighted logistic regression models were used to determine associations between location of care and complications with early mortality. Interactions of complications and location of care with early mortality were also considered. Results are presented as adjusted odds ratios (OR) and 95% confidence intervals (CI). Results Of the 5613 patients with AML identified, 1406 (25%) were treated at an NCI-CC. Compared to patients treated elsewhere, AML patients treated at an NCI-CC were more likely to be <65 years of age, Hispanic (versus non-Hispanic white), live in higher socioeconomic status neighborhoods, have fewer comorbidities and have Medicare or public (versus private) health insurance. Patients treated at NCI-CCs had higher rates of renal failure (21% vs 18%, P=0.03) and lower rates of respiratory failure (11% vs 14%, P=0.002) and sepsis (33% vs 36%, P=0.04) than those treated at non-NCI-CCs. Rates of bleeding, thrombosis, liver failure and cardiac arrest did not differ by location of care. After propensity-score weighting, baseline characteristics were balanced between patients treated at NCI-CCs versus non-NCI-CCs (all standardized mean differences <2.3%). In multivariable, inverse probability weighted models, treatment at an NCI-CC (versus non-NCI-CC) was associated with lower early mortality (OR 0.50, CI 0.42-0.59) (Table). Complications associated with higher early mortality, regardless of treatment location, included: bleeding (OR 1.91, CI 1.54-2.37), liver (OR 3.41, CI 1.91-6.09), renal (OR 2.39, CI 1.97-2.90) and respiratory (OR 6.08, CI 4.88-7.57) failure and cardiac arrest (OR 15.28, CI 8.11-27.78) (Table). The impact of complications on early mortality did not differ by location of care with the exception of respiratory failure (P for interaction=0.001); AML patients with respiratory failure had a higher odds of early mortality when treated at non-NCI-CCs (OR 8.59, CI 6.66-11.07) versus NCI-CCs (OR 4.43, CI 2.68-7.33). Other factors significantly associated with early mortality included younger age, treatment after 2002, non-Hispanic White race/ethnicity (versus African Americans, Hispanics and Asians), single marital status (versus married), residence in low socioeconomic status neighborhoods (versus high) and presence of any comorbidities (versus none). Conclusions In patients with AML, initial treatment at a NCI-CC is associated with 50% reduction in early mortality than treatment at a non-NCI-CC, adjusted for baseline socio-demographic variables, comorbidities and complications within 60 days. Lower early mortality may result from differences in supportive care practices, hospital or provider experience and access to clinical trials at NCI-CCs. Future studies should evaluate the specific differences in care at NCI-CCs to inform strategies to improve early mortality outcomes for all AML patients. Table. Table. Disclosures No relevant conflicts of interest to declare.

Background: The NHSN parameter estimate for predicted number of central-line–associated bloodstream infection (CLABSI) is the same for gastroenterology wards as other specialty wards, such as behavioral health and gerontology. We conducted this study to contribute to the body of knowledge surrounding the risk for hospital-acquired bloodstream infection (HABSI) in patients with and without hepatic failure. The Cleveland Clinic is a 1,200-bed, multispecialty hospital with a solid-organ transplant service. Patients with hepatic failure who do not require critical care are housed on 36-bed unit A. On unit A, 43% of patients are under hepatology or gastroenterology service, although 51% of patients are under general internal medicine. Overall, unit A has a high incidence of HABSI. Methods: Surveillance for HABSI and CLABSI is performed at the Cleveland Clinic per NHSN protocol. All patients with a midnight stay on unit A from January 2019 through September 2021 were dichotomized as having hepatic failure (yes or no) if they ever received the International Classification of Diseases Tenth Revision code for “hepatic failure, not elsewhere classified.” We joined the diagnostic code to patient days and central-line-days databases and summarized the data using Microsoft Excel software. We stratified the number of patients, patient days, device days, infection classification, and hospital length of stay by whether the patient had hepatic failure, and we compared the incidence of HABSI and CLABSI between the 2 groups using OpenEpi version 3.01 software. Results: We identified 72 HABSIs among 4,285 patients who stayed on unit A for 30,910 patient days during the study period. The incidences of HABSI in patients with and without hepatic failure were 39.0 and 13.9 per 10,000 patient days, respectively (P < .001). The incidence of CLABSI was 5.4 and 1.9 per 1,000 line days, respectively (P = .01). Patients with hepatic failure stayed longer (11.5 vs 5.9 days), yet the central-line utilization ratios were not substantially different (0.25 vs 0.24). Enterococcus was the most common pathogen involved in CLABSI in both groups (Table 2). Conclusions: Patients with hepatic failure experienced CLABSI more frequently than patients without hepatic failure, stayed longer in the hospital, and were less likely have HABSI attributed to another primary focus of infection according to NHSN definitions. Although hepatic failure may be among the most severe conditions among patients in a gastroenterology ward, we have demonstrated that these units house a population uniquely susceptible to HABSI and CLABSI.Funding: NoneDisclosures: None

Abstract Introduction: ELANE neutropenia represents the cause of 25-30% of the cases of congenital neutropenia. Classically, its appears in the literature as in OMIM, under two distinct entities: Severe congenital neutropenia (SCN) and cyclic neutropenia (CyN). The delineation between the 2 entities is the "cyclicity" i.e. the periodic variation of the absolute neutrophils count (ANC), also called a 21-day time clock 1. However, it is extremely difficult to obtain enough sequential complete blood counts (CBC) at the onset of the disease, during an enough length period, while the patient is not experiencing a severe infection or receiving GCSF therapy. The purpose of our study is to analyze the ANC periodicity at the onset of the disease, prior to the initiation of GCSF in a cohort of patients with ELANE neutropenia. Methods : Available data from the patients, with ELANE class 4 and 5 variants, enrolled in the French Severe Chronic Neutropenia Registry, were analysed. The final diagnostic of CyN and SCN was performed considering all the follow up period (median 16.7 years) and based on the presence of recurrent periodic variation of ANC in the absence of GCSF therapy. CyN was defined as multiple documented ANCs &gt;500 cells/mm 3 , with intermittent ANC variation (n=49), while SCN is defined as ANC persistently &lt;500 cells/mm 3 (n=94). In case of irregularity (i.e. not a regular periodic pattern during all the follow up), the classification takes in consideration the majority of the follow up. A comprehensive analysis of the infectious profile is available elsewhere 2. We were focused here on the diagnostic period (roughly the 2 first months since the diagnosis). We have analysed the initial blood count of the patients and cast the patients by categories if at least 4 ANCs can be evaluated. ANC oscillations defined 4 groups: Group 1: oscillation of ANC values above and below 500 ANC/mm 3 for at least 2 cycles lead to consider the patient as Cyclic; Group 2: clear oscillation of ANC values above and below 200 ANC/mm 3 (but ever&lt;500 ANC/mm 3) for at least 2 cycles; Group 3: no oscillation of ANC values whose level are ever below 500 ANC/mm 3; Group 4: Early GCSF treatment. Results : Among the 143 patients enrolled in this study (Table 1), 137 have at least 4 CBC evaluable during the diagnosis period, including 30 who have been treated almost front line after diagnosis of neutropenia by GCSF hampering evaluation of periodicity. Such patients were all initially considered as SCN. Among the 67 finally classified as SCN, 28 (27.38%) showed an oscillation pattern (group 1), 14 (15.48%) showed minor oscillations (group 2), while 25 (30.95%) had a persistent and severe neutropenia (group 3). Among the 40 CyN, 1 have showed minor oscillations (group 2) below 500/mm 3, while 3 had a persistent and severe neutropenia (group 3). Globally, 32 /107 patients were miss- classified at diagnosis compare to the final diagnosis. Additional data shows that many health indicators could not be deducted from the initial classification like the infections rate, the use of GCSF, the death rate, the sequels rate. Conclusions: Periodic variation of ANC despite being the criteria to define the sub type of ELANE neutropenia is difficult to evaluate at the initial presentation of the disease. In addition, cyclicity is not a permanent feature in ELANE neutropenia, some patients being cyclic only for a certain time in their life span. It results a high rate of miss classification if we compare the initial diagnostic period and all the medical history of the patients. Noteworthy, the rate of several severe complications is not so clearly different between diagnosis sub categories. We propose to consider ELANE neutropenia as a unique disease characterized by a clinical spectrum ranging from more severe forms (corresponding to SCN) to milder forms, the latter often characterized at onset by ANC fluctuations. In addition, some intermediate severity forms could be characterized by minor oscillations. References 1 Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat.Genet. 1999;23:433-436. 2 Rotulo GA, Plat G, Beaupain B et al. Recurrent bacterial infections, but not fungal infections, characterise patients with ELANE-related neutropenia: a French Severe Chronic Neutropenia Registry study. Br J Haematol. 2021 doi: 10.1111/bjh.17695 Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background Long-term PI-based treatment is associated with improved outcomes in MM. Nonetheless, prolonged therapy with parenteral PIs (e.g. bortezomib) can be challenging in the real world, with median duration of therapy (DOT) of 4-7 months. Barriers to this long-term approach may include the burden of repeated intravenous/subcutaneous administration, difficulty travelling to/accessing treatment centers (e.g. due to environmental factors, travel restrictions, social/family situations), patient preference for treatment outside of a hospital or clinic setting, comorbidities, and toxicity. The US MM-6 study (NCT03173092) is investigating in-class transition (iCT) from parenteral bortezomib-based induction to all-oral ixazomib-based therapy (ixazomib-lenalidomide-dexamethasone; IRd) in the diverse US community population with the aim of increasing PI-based treatment duration while maintaining quality of life and improving outcomes. We report updated efficacy and safety for the first 101 patients. Methods Transplant-ineligible/delayed-transplant (&gt;24 months) NDMM patients with stable disease or better after 3 cycles of bortezomib-based induction are being enrolled at US community sites (including Veterans Affairs hospitals) to receive IRd (ixazomib 4 mg, days 1, 8, 15; lenalidomide 25 mg, days 1-21; dexamethasone 40 mg, days 1, 8, 15, 22) for up to 39 x 28-day cycles or until progression/toxicity. The primary endpoint is progression-free survival (PFS); key secondary endpoints include rates of partial (PR), very good PR (VGPR), and complete response (CR), and DOT. Results As of June 1 2020, 101 patients had been treated at 21 sites. Median age was 73 years (range 48-90), with 46% aged ≥75 years; 16% and 10% were of African American and Hispanic ethnicity, respectively. Table 1 summarizes the key characteristics of these real-world patients. A total of 95% of patients had ≥1 comorbidity at the start of IRd therapy including renal and urinary disorders (38%), cardiac disorders (29%), peripheral neuropathy (PN; 14%), and diabetes mellitus (13%) (Table 2). With 53 (52%) patients remaining on therapy and enrollment ongoing, mean duration of PI therapy from the start of bortezomib-based induction was 12.4 months, and mean duration of IRd therapy after iCT was 9.2 months (Table 3). Patients have received up to 29.4 months (31 cycles) of IRd to date. The overall response rate (ORR) after bortezomib-based induction was 62% (7% CR, 32% ≥VGPR). After iCT to IRd, the ORR increased to 71%, with the CR and ≥VGPR rates increasing to 29% and 53%, respectively (Figure); of 33 patients with stable disease following bortezomib-based induction, 14 (42%) achieved CR (n=10) or VGPR (n=4) after iCT. With a median follow-up of 12 months and enrollment ongoing, 13 patients had progressed and two had died during PFS analysis. The 12-month PFS rate was 84% (95% CI, 73-91) from the start of bortezomib-based induction and 80% (95% CI, 69-88) from the start of IRd. During IRd treatment to date, 91% of patients have had treatment-emergent adverse events (TEAEs) (54% grade ≥3). Grade 3 TEAEs (≥5% of patients) were diarrhea (8%), pneumonia (7%), and syncope (5%). TEAEs led to study drug modification in 52% of patients and discontinuation in 7% of patients; 37% had serious TEAEs. Diarrhea, nausea, and vomiting occurred in 43%, 23%, and 14% of patients (8%, 2%, 2% grade 3), and led to dose modification in 11%, 5%, and 2%. PN (not elsewhere classified; high-level term) occurred in 32% of patients (2% grade 3) and led to dose modification in 9%. There were three on-study deaths (i.e. occurring &lt;30 days after last dose). Conclusions US MM-6 patients reflect the heterogeneous real-world US MM population; the population for this study includes patients from the community who may not be eligible for traditional clinical trials. These updated data in mostly elderly, comorbid, NDMM patients treated in the community setting demonstrate the feasibility and tolerability of iCT to IRd after 3 cycles of bortezomib-based induction; approximately half of patients remain on treatment, and enrollment is ongoing. iCT to IRd resulted in improved responses, with increased rates of ≥VGPR, and prolonged DOT and may thereby improve outcomes for real-world patients. iCT to an all oral regimen could also prevent treatment interruptions for patients who are unable to or prefer not to travel in the context of travel restrictions or other factors. Disclosures Girnius: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Yimer:TG Therapeutics: Consultancy; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Sanofi: Speakers Bureau; Texas Oncology: Current Employment; BeiGene: Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Celgene, a Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Karyopharm: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Epizyme: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months. Noga:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Manda:AbbVie: Other: Investigator in AbbVie-sponsored clinical trials. Lyons:Texas Oncology/US Oncology: Current Employment; Novartis: Honoraria. Bogard:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Whidden:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Cherepanov:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Lu:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Aiello:Takeda: Honoraria; Travera: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria. Richter:Celgene: Consultancy, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Speakers Bureau; Janssen: Speakers Bureau; Sanofi: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; AstraZeneca: Consultancy; Secura Bio: Consultancy; Bristol Myers Squibb: Consultancy; X4 Pharmaceuticals: Consultancy; Oncopeptides: Consultancy; Antengene: Consultancy. Rifkin:McKesson: Current equity holder in publicly-traded company, Ended employment in the past 24 months, Other: Stock ownership; Takeda, Amgen, Celgene, BMS, Mylan, Coherus BioSciences, Fresenius: Consultancy; AbbVie: Other: Investigator in AbbVie sponsored clinical trials; Takeda, Amgen, BMS (Celgene): Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Real-world evaluation of long-term proteasome inhibition with ixazomib in combination with lenalidomide and dexamethasone for the treatment of newly diagnosed multiple myeloma in non-transplant patients with stable disease after 3 cycles of a bortezomib-based induction.

In this era of startling developments in the medical field there remains a serious worry about the hazardous potential of various by products which if not properly addressed can lead to consequences of immense public concern. Hospitals and other health care facilities generate waste products which are evidently hazardous to all those exposed to its potentially harmful effects. Need for effective legislation ensuring its safe disposal is supposed to be an integral part of any country's health related policy. This issue is of special importance in developing countries like Pakistan which in spite of framing various regulations for safeguarding public health, seem to overlook its actual implementation. The result unfortunately is the price wehave to pay not only in terms of rampant spread of crippling infections but a significant spending of health budget on combating epidemics which could easily have been avoided through effective waste disposal measures in the first place. Waste classified under the heading 'bio-hazardous' includes any infectious or potentially infectious material which can be injurious or harmful to humans and other living organisms. Amongst the many potential sources are the hospitals or other health delivery centres which are ironically supposed to be the centres of infection control and treatment. Whilst working in these setups, health care workers such as doctors, nurses, paramedical staff and sanitation workers are actually the ones most exposed and vulnerable to these challenges. Biomedical waste may broadly be classified into Infectious and toxic waste. Infectious waste includes sharps, blood, body fluids and tissues etcwhile substances such as radioactive material and by-products of certain drugs qualify as toxic waste. Furthermore health institutions also have to cater for general municipal waste such as carton boxes, paper and plastics. The World Health Organisation has its own general classification of hospital waste divided into almost eight categories of which almost 15% (10% infectious and 5% toxic) is estimated to be of a hazardous nature while the remaining 85% is general non hazardous content.1A recent study from Faisalabad, Pakistan has estimated hospital waste generation around 1 to 1.5 kg / bed /day for public sector hospitals in the region,2while figures quoted from neighbouring India are approximately 0.5 to 2 KG / hospital bed /day.3 Elsewhere in the world variable daily hospital waste production has been observed ranging from as low as 0.14 to 0.49 kg /day in Korea4 and 0.26 to 0.89 kg/day in Greece5to as high as 2.1 to 3.83 kg/day in Turkey6 and 0.84 to 5.8 kg/day in Tanzania.7Ill effects of improper management of hospital waste can manifest as nosocomial infections or occupational hazards such as needle stick injuries. Pathogens or spores can be borne either through the oro-faecal or respiratory routes in addition to direct inoculation through contact with infected needles or sharps. Environmental pollution can result from improper burning of toxic material leading to emission of dioxins, particulate matter or furans into the air. The habitat can also be affected by illegal dumping and landfills or washing up of medical waste released into the sea or river. Potential organisms implicated in diseases secondary to mismanagement of hospital waste disposal include salmonella, cholera, shigella, helminths, strep pneumonia, measles, tuberculosis, herpesvirus, anthrax, meningitis, HIV, hepatitis and candida etc. These infections can cause a considerable strain on the overall health and finances of the community or individuals affected. The basic principal of Public health management i.e 'prevention is better than cure' cannot be more stressed in this scenario as compared to any other health challenge. Health facilities must have a clear policy on hazardous waste management. To ensure a safe environment hospitals need to adopt and implement international and local systems of waste disposal. Hospital waste management plan entails policy and procedures addressing waste generation, accumulation, handling, transportation, storage, treatment and disposal. Waste needs to be collected in marked containers usually colour coded and leak proof. Segregation at source is of vital importance. The standard practice in many countries is the Basic Three Bin System ie to segregate the waste into RED bags/ boxes for sharps, YELLOW bags for biological waste and BLUE or BLACK ones for general/ municipal waste. All hospital staff needs to be trained in the concept of putting the right waste in relevant containers/ bags. They need to know that more than anything else this practice is vital for their own safety. The message can be reinforced through appropriate labelling on the bins and having posters with simple delineations to avoid mixing of different waste types. Sharps essentially should be kept in rigid, leak and puncture-resistant containers which are tightly lidded and labelled. Regular training sessions for nurses and cleaning staff can be organised as they are the personnel who are more likely to deal with waste disposition at the level of their respective departments. Next of course is transportation of waste products to the storage or disposal. Sanitary staff and janitors must be aware of the basic concepts of waste handling and should wear protective clothing, masks and gloves etc, besides ensuring regular practice of disinfection and sterilization techniques.8Special trolleys or vehicles exclusively designed and reserved for biomedical waste and operated by trained individuals should be used for transportation to the dumping or treatment site. Biomedical waste treatment whether on site or off site is a specialised entity involving use of chemicals and equipment intended for curtailing the hazardous potential of the material at hand. Thermal treatment via incinerators, not only results in combustion of organic substances but the final product in the form of non-toxicash is only 10 to 15% of the original solid mass of waste material fed to the machine. Dedicated autoclaves and microwaves can also be used for the purpose of disinfection. Chemicals such as bleach, sodium hydroxides, chlorine dioxide and sodiumhypochlorite are also effective disinfectants having specialised indications. Countries around the world have their own regulations for waste management. United Kingdom practices strict observance of Environmental protection act 1990, Waste managementlicensing regulations 1994 and Hazardous waste regulations 2005 making it one of thesafest countries in terms of hazardous waste disposal. Similar regulations specific for each state have been adopted in United States following passage of the Medical Waste tracking act 1988. In Pakistan, every hospital must comply with the Waste Management Rules 2005 (Environment Protection Act 1997), though actual compliance is far from satisfactory. It is high time that the government and responsible community organisations shape up to seriously tackle the issue of bio hazardous waste management through enforcement of effective policies and standard operating procedures for safeguarding the health and lives of the public in general and health workers in particular. Outbreaks, defined as excess cases of a particular disease or illness which outweighs the response capabilities, have the capacity to overwhelm health care facilities and need timely response and attention to details in order to avoid potentially disastrous sequelae . In this day and age when improvement in public health practices have significantly curtailed outbreak of various diseases, certain viral illnesses continue to make headlines. One of the notable vector borne infectious disease affecting significant portions of south east Asia in the early part of twenty first century is 'Dengue fever'. Dreaded as it is by those suffering from the illness, a lot of the hysteria created is secondary to a lack of education and understanding of the nature of the disease and at times a result of disinformation campaign for vested interests by certain political and media sections.'Dengue' in fact is a Spanish word, assumed to have originated from the Swahili phrase -ka dinga peppo -which describes the disease as being caused by evil spirit. 1 Over the course of time it has been called 'breakbone fever', 'bilious vomiting fever', 'break heart fever', 'dandy fever', 'la dengue' and 'Phillipine, Thai and Singapore hemorrhagic fever' Whilst the first reported case referring to dengue fever as a water poison spread by flying insects, exists in the Chinese medical encyclopedia from Jin Dynasty (265-420 AD), the disease is believed to have disseminated from Africa with the spread of the primary vector, aedes egypti, in the 15th to 19th century as a result of globalisation of slave trade 45In 80% of the patients affected by this condition the presentation is rather insidious and at best characterized by mild fever. The classical 'Dengue fever' present in about 5% of the cases is characterized by high temperature, body aches, vomiting and at times a skin rash. The disease may regresses in two to seven days. However inrare instances (<5%) it may develop into more serious conditions such as Dengue hemorrhagic fever whereby the platelet count is significantly reduced leading to bleeding tendencies and may even culminate in a more life threatening presentation i.e Dengue shock syndrome.6To understand the actual dynamics of Dengue epidemic it is important to understand the mode of its spread in affected areas. Aedes mosquito (significantly Aedes Egypti) acts a vector for this disease. Early morning and evening times7 are favoured by these mosquitos to feed on their prey. There is some evidence that the disease may be transmitted via blood products and organ donation. 8 Moreover vertical transmission (mother to child) has also been reported 9Diagnostic investigations include blood antigen detection through NS-I or nucleic acid detection via PCR. IO Cell cultures and specific serology may also be used for confirming the underlying disease. Whilst sporadic and endemic cases are part of routine medical practice and may not raise any alarm bells, outbreaks certainly need mobilization of appropriate resources for effective control. Needless to say 'prevention is better than cure' and should be the primary target of the health authorities in devising strategies for disease control.The WHO recommended 'Integrated Vector control programme', lays stress on social mobilisation and strengthening of public health bodies, coherent response of health and related departments and effective capacity building of relevant personnel and organisations as well as the community at risk. For Aedes Egypti the primary control revolves around eliminating its habitats such as open sources of water. In a local perspective in our city Peshawar, venue of the recent dengue epidemic, it may be seen in the form of incidental reservoirs such as receptacles and tyres dumped in open areas such as roof tops with rain water accumulating in them and provtdjng excellent breeding habitats, Larvicidal and insecticides may be added to more permanent sources such as watertanks and farm lands. There is not much of a role for spraying with organophosphorous agents which is at times resorted to for public consumption. Public education is the key to any effective strategy which must highlight the need for wearing clothing that fully covers the skin, avoiding unnecessary early morning and evening exposure to vector agents, application of insect repellents and use of mosquito nets. It is also important not to panic if affliction with the disease is suspected as in a vast majority of instances it is a self limiting illness without any long term harmful effects and needs simple conservative management like antipyretics and analgesics.An important consideration for responsible authorities in a dengue epidemic is to ensure that maximum management facilities for simple cases are provided at the community level through primary and secondary health care facilities and that the tertiary care hospitals are not inundated with all sort of patients demanding consultation. These later facilities should be reserved for those patients who end up with any complications or more severe manifestation of the disease.Research is underway to develop an ideal vaccine for Dengue fever. In 2016, a vaccine by the name 'Dengvaxia' was marketed in Phillipines and Indonesia. However with development of new serotypes of the virus, its efficacy has been somewhat compromised.As for treatment , there are no specific antiviral drugs. Management is symptomatic revolving mainly around oral and intravenous hydration. Paracetamol (Acetaminophen) is used for fever as compared to NSAIDS such as Ibuprophen infusion as well as blood and platelet transfusion.Data to date shows that slightly more than twenty three thousand people have been diagnosed with dengue over the past three months ie August to October there is a lower risk of bleeding with the former. Those with more severe form of the disease may need Dextran 2017, in Peshawar, Pakistan with around fourteen thousand needing admission and about sixty nine recorded deaths. The mortality is well within the acceptable international standards of less than 1% for the disease. In the backdrop of all the debate surrounding the current epidemic, one can infer that such outbreaks are best addressed with effective planningwell ahead of the time before the disease threatens to spiral out of control. Simple measures such as covering water storage facilities, using larvicidals where practical, use of insect repellents, mosquito nets and avoiding unnecessary exposure can offerthe best protection. Public health messages via print and electronic media can help educate people in affected areas and allay any anxiety building up from a fear of developing life threatening complications. Health department must mobilise all its resources to ensure local management of diagnosed patients with simple dengue fever and facilitate hospital admission only for those suffering from more severe form of the disease. Moreover the media hype into such situations needs to be addressed through constant updates and discouraging any negative politicking on the issue. To sum up Dengue fever is not really an affliction to be dreaded provided it is viewed and managed in the right perspective.

In this era of startling developments in the medical field there remains a serious worry about the hazardous potential of various by products which if not properly addressed can lead to consequences of immense public concern. Hospitals and other health care facilities generate waste products which are evidently hazardous to all those exposed to its potentially harmful effects. Need for effective legislation ensuring its safe disposal is supposed to be an integral part of any country's health related policy. This issue is of special importance in developing countries like Pakistan which in spite of framing various regulations for safeguarding public health, seem to overlook its actual implementation. The result unfortunately is the price wehave to pay not only in terms of rampant spread of crippling infections but a significant spending of health budget on combating epidemics which could easily have been avoided through effective waste disposal measures in the first place. Waste classified under the heading 'bio-hazardous' includes any infectious or potentially infectious material which can be injurious or harmful to humans and other living organisms. Amongst the many potential sources are the hospitals or other health delivery centres which are ironically supposed to be the centres of infection control and treatment. Whilst working in these setups, health care workers such as doctors, nurses, paramedical staff and sanitation workers are actually the ones most exposed and vulnerable to these challenges. Biomedical waste may broadly be classified into Infectious and toxic waste. Infectious waste includes sharps, blood, body fluids and tissues etcwhile substances such as radioactive material and by-products of certain drugs qualify as toxic waste. Furthermore health institutions also have to cater for general municipal waste such as carton boxes, paper and plastics. The World Health Organisation has its own general classification of hospital waste divided into almost eight categories of which almost 15% (10% infectious and 5% toxic) is estimated to be of a hazardous nature while the remaining 85% is general non hazardous content.1A recent study from Faisalabad, Pakistan has estimated hospital waste generation around 1 to 1.5 kg / bed /day for public sector hospitals in the region,2while figures quoted from neighbouring India are approximately 0.5 to 2 KG / hospital bed /day.3 Elsewhere in the world variable daily hospital waste production has been observed ranging from as low as 0.14 to 0.49 kg /day in Korea4 and 0.26 to 0.89 kg/day in Greece5to as high as 2.1 to 3.83 kg/day in Turkey6 and 0.84 to 5.8 kg/day in Tanzania.7Ill effects of improper management of hospital waste can manifest as nosocomial infections or occupational hazards such as needle stick injuries. Pathogens or spores can be borne either through the oro-faecal or respiratory routes in addition to direct inoculation through contact with infected needles or sharps. Environmental pollution can result from improper burning of toxic material leading to emission of dioxins, particulate matter or furans into the air. The habitat can also be affected by illegal dumping and landfills or washing up of medical waste released into the sea or river. Potential organisms implicated in diseases secondary to mismanagement of hospital waste disposal include salmonella, cholera, shigella, helminths, strep pneumonia, measles, tuberculosis, herpesvirus, anthrax, meningitis, HIV, hepatitis and candida etc. These infections can cause a considerable strain on the overall health and finances of the community or individuals affected. The basic principal of Public health management i.e 'prevention is better than cure' cannot be more stressed in this scenario as compared to any other health challenge. Health facilities must have a clear policy on hazardous waste management. To ensure a safe environment hospitals need to adopt and implement international and local systems of waste disposal. Hospital waste management plan entails policy and procedures addressing waste generation, accumulation, handling, transportation, storage, treatment and disposal. Waste needs to be collected in marked containers usually colour coded and leak proof. Segregation at source is of vital importance. The standard practice in many countries is the Basic Three Bin System ie to segregate the waste into RED bags/ boxes for sharps, YELLOW bags for biological waste and BLUE or BLACK ones for general/ municipal waste. All hospital staff needs to be trained in the concept of putting the right waste in relevant containers/ bags. They need to know that more than anything else this practice is vital for their own safety. The message can be reinforced through appropriate labelling on the bins and having posters with simple delineations to avoid mixing of different waste types. Sharps essentially should be kept in rigid, leak and puncture-resistant containers which are tightly lidded and labelled. Regular training sessions for nurses and cleaning staff can be organised as they are the personnel who are more likely to deal with waste disposition at the level of their respective departments. Next of course is transportation of waste products to the storage or disposal. Sanitary staff and janitors must be aware of the basic concepts of waste handling and should wear protective clothing, masks and gloves etc, besides ensuring regular practice of disinfection and sterilization techniques.8Special trolleys or vehicles exclusively designed and reserved for biomedical waste and operated by trained individuals should be used for transportation to the dumping or treatment site. Biomedical waste treatment whether on site or off site is a specialised entity involving use of chemicals and equipment intended for curtailing the hazardous potential of the material at hand. Thermal treatment via incinerators, not only results in combustion of organic substances but the final product in the form of non-toxicash is only 10 to 15% of the original solid mass of waste material fed to the machine. Dedicated autoclaves and microwaves can also be used for the purpose of disinfection. Chemicals such as bleach, sodium hydroxides, chlorine dioxide and sodiumhypochlorite are also effective disinfectants having specialised indications. Countries around the world have their own regulations for waste management. United Kingdom practices strict observance of Environmental protection act 1990, Waste managementlicensing regulations 1994 and Hazardous waste regulations 2005 making it one of thesafest countries in terms of hazardous waste disposal. Similar regulations specific for each state have been adopted in United States following passage of the Medical Waste tracking act 1988. In Pakistan, every hospital must comply with the Waste Management Rules 2005 (Environment Protection Act 1997), though actual compliance is far from satisfactory. It is high time that the government and responsible community organisations shape up to seriously tackle the issue of bio hazardous waste management through enforcement of effective policies and standard operating procedures for safeguarding the health and lives of the public in general and health workers in particular. Outbreaks, defined as excess cases of a particular disease or illness which outweighs the response capabilities, have the capacity to overwhelm health care facilities and need timely response and attention to details in order to avoid potentially disastrous sequelae . In this day and age when improvement in public health practices have significantly curtailed outbreak of various diseases, certain viral illnesses continue to make headlines. One of the notable vector borne infectious disease affecting significant portions of south east Asia in the early part of twenty first century is 'Dengue fever'. Dreaded as it is by those suffering from the illness, a lot of the hysteria created is secondary to a lack of education and understanding of the nature of the disease and at times a result of disinformation campaign for vested interests by certain political and media sections.'Dengue' in fact is a Spanish word, assumed to have originated from the Swahili phrase -ka dinga peppo -which describes the disease as being caused by evil spirit. 1 Over the course of time it has been called 'breakbone fever', 'bilious vomiting fever', 'break heart fever', 'dandy fever', 'la dengue' and 'Phillipine, Thai and Singapore hemorrhagic fever' Whilst the first reported case referring to dengue fever as a water poison spread by flying insects, exists in the Chinese medical encyclopedia from Jin Dynasty (265-420 AD), the disease is believed to have disseminated from Africa with the spread of the primary vector, aedes egypti, in the 15th to 19th century as a result of globalisation of slave trade 45In 80% of the patients affected by this condition the presentation is rather insidious and at best characterized by mild fever. The classical 'Dengue fever' present in about 5% of the cases is characterized by high temperature, body aches, vomiting and at times a skin rash. The disease may regresses in two to seven days. However inrare instances (<5%) it may develop into more serious conditions such as Dengue hemorrhagic fever whereby the platelet count is significantly reduced leading to bleeding tendencies and may even culminate in a more life threatening presentation i.e Dengue shock syndrome.6To understand the actual dynamics of Dengue epidemic it is important to understand the mode of its spread in affected areas. Aedes mosquito (significantly Aedes Egypti) acts a vector for this disease. Early morning and evening times7 are favoured by these mosquitos to feed on their prey. There is some evidence that the disease may be transmitted via blood products and organ donation. 8 Moreover vertical transmission (mother to child) has also been reported 9Diagnostic investigations include blood antigen detection through NS-I or nucleic acid detection via PCR. IO Cell cultures and specific serology may also be used for confirming the underlying disease. Whilst sporadic and endemic cases are part of routine medical practice and may not raise any alarm bells, outbreaks certainly need mobilization of appropriate resources for effective control. Needless to say 'prevention is better than cure' and should be the primary target of the health authorities in devising strategies for disease control.The WHO recommended 'Integrated Vector control programme', lays stress on social mobilisation and strengthening of public health bodies, coherent response of health and related departments and effective capacity building of relevant personnel and organisations as well as the community at risk. For Aedes Egypti the primary control revolves around eliminating its habitats such as open sources of water. In a local perspective in our city Peshawar, venue of the recent dengue epidemic, it may be seen in the form of incidental reservoirs such as receptacles and tyres dumped in open areas such as roof tops with rain water accumulating in them and provtdjng excellent breeding habitats, Larvicidal and insecticides may be added to more permanent sources such as watertanks and farm lands. There is not much of a role for spraying with organophosphorous agents which is at times resorted to for public consumption. Public education is the key to any effective strategy which must highlight the need for wearing clothing that fully covers the skin, avoiding unnecessary early morning and evening exposure to vector agents, application of insect repellents and use of mosquito nets. It is also important not to panic if affliction with the disease is suspected as in a vast majority of instances it is a self limiting illness without any long term harmful effects and needs simple conservative management like antipyretics and analgesics.An important consideration for responsible authorities in a dengue epidemic is to ensure that maximum management facilities for simple cases are provided at the community level through primary and secondary health care facilities and that the tertiary care hospitals are not inundated with all sort of patients demanding consultation. These later facilities should be reserved for those patients who end up with any complications or more severe manifestation of the disease.Research is underway to develop an ideal vaccine for Dengue fever. In 2016, a vaccine by the name 'Dengvaxia' was marketed in Phillipines and Indonesia. However with development of new serotypes of the virus, its efficacy has been somewhat compromised.As for treatment , there are no specific antiviral drugs. Management is symptomatic revolving mainly around oral and intravenous hydration. Paracetamol (Acetaminophen) is used for fever as compared to NSAIDS such as Ibuprophen infusion as well as blood and platelet transfusion.Data to date shows that slightly more than twenty three thousand people have been diagnosed with dengue over the past three months ie August to October there is a lower risk of bleeding with the former. Those with more severe form of the disease may need Dextran 2017, in Peshawar, Pakistan with around fourteen thousand needing admission and about sixty nine recorded deaths. The mortality is well within the acceptable international standards of less than 1% for the disease. In the backdrop of all the debate surrounding the current epidemic, one can infer that such outbreaks are best addressed with effective planningwell ahead of the time before the disease threatens to spiral out of control. Simple measures such as covering water storage facilities, using larvicidals where practical, use of insect repellents, mosquito nets and avoiding unnecessary exposure can offerthe best protection. Public health messages via print and electronic media can help educate people in affected areas and allay any anxiety building up from a fear of developing life threatening complications. Health department must mobilise all its resources to ensure local management of diagnosed patients with simple dengue fever and facilitate hospital admission only for those suffering from more severe form of the disease. Moreover the media hype into such situations needs to be addressed through constant updates and discouraging any negative politicking on the issue. To sum up Dengue fever is not really an affliction to be dreaded provided it is viewed and managed in the right perspective.

Environments containing significant concentration of NaCl such as salt lakes harbor extremophiles microorganisms which have a great biotechnology interest. To explore the diversity of Bacteria in Chott Tinsilt (Algeria), an isolation program was performed. Water samples were collected from the saltern during the pre-salt harvesting phase. This Chott is high in salt (22.47% (w/v). Seven halophiles Bacteria were selected for further characterization. The isolated strains were able to grow optimally in media with 10–25% (w/v) total salts. Molecular identification of the isolates was performed by sequencing the 16S rRNA gene. It showed that these cultured isolates included members belonging to the Halomonas, Staphylococcus, Salinivibrio, Planococcus and Halobacillus genera with less than 98% of similarity with their closest phylogenetic relative. The halophilic bacterial isolates were also characterized for the production of biosurfactant and industrially important enzymes. Most isolates produced hydrolases and biosurfactants at high salt concentration. In fact, this is the first report on bacterial strains (A4 and B4) which were a good biosurfactant and coagulase producer at 20% and 25% ((w/v)) NaCl. In addition, the biosurfactant produced by the strain B4 at high salinity (25%) was also stable at high temperature (30-100°C) and high alkalinity (pH 11).Key word: Salt Lake, Bacteria, biosurfactant, Chott, halophiles, hydrolases, 16S rRNAINTRODUCTIONSaline lakes cover approximately 10% of the Earth’s surface area. The microbial populations of many hypersaline environments have already been studied in different geographical regions such as Great Salt Lake (USA), Dead Sea (Israel), Wadi Natrun Lake (Egypt), Lake Magadi (Kenya), Soda Lake (Antarctica) and Big Soda Lake and Mono Lake (California). Hypersaline regions differ from each other in terms of geographical location, salt concentration and chemical composition, which determine the nature of inhabitant microorganisms (Gupta et al., 2015). Then low taxonomic diversity is common to all these saline environments (Oren et al., 1993). Halophiles are found in nearly all major microbial clades, including prokaryotic (Bacteria and Archaea) and eukaryotic forms (DasSarma and Arora, 2001). They are classified as slight halophiles when they grow optimally at 0.2–0.85 M (2–5%) NaCl, as moderate halophiles when they grow at 0.85–3.4 M (5–20%) NaCl, and as extreme halophiles when they grow at 3.4–5.1 M (20–30%) NaCl. Hyper saline environments are inhabited by extremely halophilic and halotolerant microorganisms such as Halobacillus sp, Halobacterium sp., Haloarcula sp., Salinibacter ruber , Haloferax sp and Bacillus spp. (Solomon and Viswalingam, 2013). There is a tremendous demand for halophilic bacteria due to their biotechnological importance as sources of halophilic enzymes. Enzymes derived from halophiles are endowed with unique structural features and catalytic power to sustain the metabolic and physiological processes under high salt conditions. Some of these enzymes have been reported to be active and stable under more than one extreme condition (Karan and Khare, 2010). Applications are being considered in a range of industries such as food processing, washing, biosynthetic processes and environmental bioremediation. Halophilic proteases are widely used in the detergent and food industries (DasSarma and Arora, 2001). However, esterases and lipases have also been useful in laundry detergents for the removal of oil stains and are widely used as biocatalysts because of their ability to produce pure compounds. Likewise, amylases are used industrially in the first step of the production of high fructose corn syrup (hydrolysis of corn starch). They are also used in the textile industry in the de-sizing process and added to laundry detergents. Furthermore, for the environmental applications, the use of halophiles for bioremediation and biodegradation of various materials from industrial effluents to soil contaminants and accidental spills are being widely explored. In addition to enzymes, halophilic / halotolerants microorganisms living in saline environments, offer another potential applications in various fields of biotechnology like the production of biosurfactant. Biosurfactants are amphiphilic compounds synthesized from plants and microorganisms. They reduce surface tension and interfacial tension between individual molecules at the surface and interface respectively (Akbari et al., 2018). Comparing to the chemical surfactant, biosurfactant are promising alternative molecules due to their low toxicity, high biodegradability, environmental capability, mild production conditions, lower critical micelle concentration, higher selectivity, availability of resources and ability to function in wide ranges of pH, temperature and salinity (Rocha et al., 1992). They are used in various industries which include pharmaceuticals, petroleum, food, detergents, cosmetics, paints, paper products and water treatment (Akbari et al., 2018). The search for biosurfactants in extremophiles is particularly promising since these biomolecules can adapt and be stable in the harsh environments in which they are to be applied in biotechnology.OBJECTIVESEastern Algeria features numerous ecosystems including hypersaline environments, which are an important source of salt for food. The microbial diversity in Chott Tinsilt, a shallow Salt Lake with more than 200g/L salt concentration and a superficies of 2.154 Ha, has never yet been studied. The purpose of this research was to chemically analyse water samples collected from the Chott, isolate novel extremely or moderate halophilic Bacteria, and examine their phenotypic and phylogenetic characteristics with a view to screening for biosurfactants and enzymes of industrial interest.MATERIALS AND METHODSStudy area: The area is at 5 km of the Commune of Souk-Naâmane and 17 km in the South of the town of Aïn-Melila. This area skirts the trunk road 3 serving Constantine and Batna and the railway Constantine-Biskra. It is part the administrative jurisdiction of the Wilaya of Oum El Bouaghi. The Chott belongs to the wetlands of the High Plains of Constantine with a depth varying rather regularly without never exceeding 0.5 meter. Its length extends on 4 km with a width of 2.5 km (figure 1).Water samples and physico-chemical analysis: In February 2013, water samples were collected from various places at the Chott Tinsilt using Global Positioning System (GPS) coordinates of 35°53’14” N lat. and 06°28’44”E long. Samples were collected randomly in sterile polythene bags and transported immediately to the laboratory for isolation of halophilic microorganisms. All samples were treated within 24 h after collection. Temperature, pH and salinity were measured in situ using a multi-parameter probe (Hanna Instruments, Smithfield, RI, USA). The analytical methods used in this study to measure ions concentration (Ca2+, Mg2+, Fe2+, Na+, K+, Cl−, HCO3−, SO42−) were based on 4500-S-2 F standard methods described elsewhere (Association et al., 1920).Isolation of halophilic bacteria from water sample: The media (M1) used in the present study contain (g/L): 2.0 g of KCl, 100.0/200.0 g of NaCl, 1.0 g of MgSO4.7HO2, 3.0 g of Sodium Citrate, 0.36 g of MnCl2, 10.0 g of yeast extract and 15.0 g agar. The pH was adjusted to 8.0. Different dilutions of water samples were added to the above medium and incubated at 30°C during 2–7 days or more depending on growth. Appearance and growth of halophilic bacteria were monitored regularly. The growth was diluted 10 times and plated on complete medium agar (g/L): glucose 10.0; peptone 5.0; yeast extract 5.0; KH2PO4 5.0; agar 30.0; and NaCl 100.0/200.0. Resultant colonies were purified by repeated streaking on complete media agar. The pure cultures were preserved in 20% glycerol vials and stored at −80°C for long-term preservation.Biochemical characterisation of halophilic bacterial isolates: Bacterial isolates were studied for Gram’s reaction, cell morphology and pigmentation. Enzymatic assays (catalase, oxidase, nitrate reductase and urease), and assays for fermentation of lactose and mannitol were done as described by Smibert (1994).Optimization of growth conditions: Temperature, pH, and salt concentration were optimized for the growth of halophilic bacterial isolates. These growth parameters were studied quantitatively by growing the bacterial isolates in M1 medium with shaking at 200 rpm and measuring the cell density at 600 nm after 8 days of incubation. To study the effect of NaCl on the growth, bacterial isolates were inoculated on M1 medium supplemented with different concentration of NaCl: 1%-35% (w/v). The effect of pH on the growth of halophilic bacterial strains was studied by inoculating isolates on above described growth media containing NaCl and adjusted to acidic pH of 5 and 6 by using 1N HCl and alkaline pH of 8, 9, 10, 11 and 12 using 5N NaOH. The effect of temperature was studied by culturing the bacterial isolates in M1 medium at different temperatures of incubation (4°C–55°C).Screening of halophilic bacteria for hydrolytic enzymes: Hydrolase producing bacteria among the isolates were screened by plate assay on starch, tributyrin, gelatin and DNA agar plates respectively for amylase, lipase, protease and DNAse activities. Amylolytic activity of the cultures was screened on starch nutrient agar plates containing g/L: starch 10.0; peptone 5.0; yeast extract 3.0; agar 30.0; NaCl 100.0/250.0. The pH was 7.0. After incubation at 30 ºC for 7 days, the zone of clearance was determined by flooding the plates with iodine solution. The potential amylase producers were selected based on ratio of zone of clearance diameter to colony diameter. Lipase activity of the cultures was screened on tributyrin nutrient agar plates containing 1% (v/v) of tributyrin. Isolates that showed clear zones of tributyrin hydrolysis were identified as lipase producing bacteria. Proteolytic activity of the isolates was similarly screened on gelatin nutrient agar plates containing 10.0 g/L of gelatin. The isolates showing zones of gelatin clearance upon treatment with acidic mercuric chloride were selected and designated as protease producing bacteria. The presence of DNAse activity on plates was determined on DNAse test agar (BBL) containing 10%-25% (w/v) total salt. After incubation for 7days, the plates were flooded with 1N HCl solution. Clear halos around the colonies indicated DNAse activity (Jeffries et al., 1957).Milk clotting activity (coagulase activity) of the isolates was also determined following the procedure described (Berridge, 1952). Skim milk powder was reconstituted in 10 mM aqueous CaCl2 (pH 6.5) to a final concentration of 0.12 kg/L. Enzyme extracts were added at a rate of 0.1 mL per mL of milk. The coagulation point was determined by manual rotating of the test tube periodically, at short time intervals, and checking for visible clot formation.Screening of halophilic bacteria for biosurfactant production. Oil spread Assay: The Petridis base was filled with 50 mL of distilled water. On the water surface, 20μL of diesel and 10μl of culture were added respectively. The culture was introduced at different spots on the diesel, which is coated on the water surface. The occurrence of a clear zone was an indicator of positive result (Morikawa et al., 2000). The diameter of the oil expelling circles was measured by slide caliber (with a degree of accuracy of 0.02 mm).Surface tension and emulsification index (E24): Isolates were cultivated at 30 °C for 7 days on the enrichment medium containing 10-25% NaCl and diesel oil as the sole carbon source. The medium was centrifuged (7000 rpm for 20 min) and the surface tension of the cell-free culture broth was measured with a TS90000 surface tensiometer (Nima, Coventry, England) as a qualitative indicator of biosurfactant production. The culture broth was collected with a Pasteur pipette to remove the non-emulsified hydrocarbons. The emulsifying capacity was evaluated by an emulsification index (E24). The E24 of culture samples was determined by adding 2 mL of diesel oil to the same amount of culture, mixed for 2 min with a vortex, and allowed to stand for 24 h. E24 index is defined as the percentage of height of emulsified layer (mm) divided by the total height of the liquid column (mm).Biosurfactant stability studies : After growth on diesel oil as sole source of carbone, cultures supernatant obtained after centrifugation at 6,000 rpm for 15 min were considered as the source of crude biosurfactant. Its stability was determined by subjecting the culture supernatant to various temperature ranges (30, 40, 50, 60, 70, 80 and 100 °C) for 30 min then cooled to room temperature. Similarly, the effect of different pH (2–11) on the activity of the biosurfactant was tested. The activity of the biosurfactant was investigated by measuring the emulsification index (El-Sersy, 2012).Molecular identification of potential strains. DNA extraction and PCR amplification of 16S rDNA: Total cellular DNA was extracted from strains and purified as described by Sambrook et al. (1989). DNA was purified using Geneclean® Turbo (Q-BIO gene, Carlsbad, CA, USA) before use as a template in polymerase chain reaction (PCR) amplification. For the 16S rDNA gene sequence, the purified DNA was amplified using a universal primer set, forward primer (27f; 5′-AGA GTT TGA TCM TGG CTC AG) and a reverse primer (1492r; 5′-TAC GGY TAC CTT GTT ACG ACT T) (Lane, 1991). Agarose gel electrophoresis confirmed the amplification product as a 1400-bp DNA fragment.16S rDNA sequencing and Phylogenic analysis: Amplicons generated using primer pair 27f-1492r was sequenced using an automatic sequencer system at Macrogene Company (Seoul, Korea). The sequences were compared with those of the NCBI BLAST GenBank nucleotide sequence databases. Phylogenetic trees were constructed by the neighbor-joining method using MEGA version 5.05 software (Tamura et al., 2011). Bootstrap resembling analysis for 1,000 replicates was performed to estimate the confidence of tree topologies.Nucleotide sequence accession numbers: The nucleotide sequences reported in this work have been deposited in the EMBL Nucleotide Sequence Database. The accession numbers are represented in table 5.Statistics: All experiments were conducted in triplicates. Results were evaluated for statistical significance using ANOVA.RESULTSPhysico-chemical parameters of the collected water samples: The physicochemical properties of the collected water samples are reported in table 1. At the time of sampling, the temperature was 10.6°C and pH 7.89. The salinity of the sample, as determined in situ, was 224.70 g/L (22,47% (w/v)). Chemical analysis of water sample indicated that Na +and Cl- were the most abundant ions (table 1). SO4-2 and Mg+2 was present in much smaller amounts compared to Na +and Cl- concentration. Low levels of calcium, potassium and bicarbonate were also detected, often at less than 1 g/L.Characterization of isolates. Morphological and biochemical characteristic feature of halophilic bacterial isolates: Among 52 strains isolated from water of Chott Tinsilt, seven distinct bacteria (A1, A2, A3, A4, B1, B4 and B5) were chosen for further characterization (table 2). The colour of the isolates varied from beige, pale yellow, yellowish and orange. The bacterial isolates A1, A2, A4, B1 and B5 were rod shaped and gram negative (except B5), whereas A3 and B4 were cocci and gram positive. All strains were oxidase and catalase positive except for B1. Nitrate reductase and urease activities were observed in all the bacterial isolates, except B4. All the bacterial isolates were negative for H2S formation. B5 was the only strain positive for mannitol fermentation (table 2).We isolated halophilic bacteria on growth medium with NaCl supplementation at pH 7 and temperature of 30°C. We studied the effect of NaCl, temperature and pH on the growth of bacterial isolates. All the isolates exhibited growth only in the presence of NaCl indicating that these strains are halophilic. The optimum growth of isolates A3 and B1 was observed in the presence of 10% NaCl, whereas it was 15% NaCl for A1, A2 and B5. A4 and B4 showed optimum growth in the presence of 20% and 25% NaCl respectively. A4, B4 and B5 strains can tolerate up to 35% NaCl.The isolate B1 showed growth in medium supplemented with 10% NaCl and pH range of 7–10. The optimum pH for the growth B1 was 9 and they did not show any detectable growth at or below pH 6 (table 2), which indicates the alkaliphilic nature of B1 isolate. The bacterial isolates A1, A2 and A4 exhibited growth in the range of pH 6–10, while A3 and B4 did not show any growth at pH greater than 8. The optimum pH for growth of all strains (except B1) was pH 7.0 (table 2). These results indicate that A1, A2, A3, A4, B4 and B5 are neutrophilic in nature. All the bacterial isolates exhibited optimal growth at 30°C and no detectable growth at 55°C. Also, detectable growth of isolates A1, A2 and A4 was observed at 4°C. However, none of the bacterial strains could grow below 4°C and above 50°C (table 2).Screening of the halophilic enzymes: To characterize the diversity of halophiles able to produce hydrolytic enzymes among the population of microorganisms inhabiting the hypersaline habitats of East Algeria (Chott Tinsilt), a screening was performed. As described in Materials and Methods, samples were plated on solid media containing 10%-25% (w/v) of total salts and different substrates for the detection of amylase, protease, lipase and DNAse activities. However, coagulase activity was determined in liquid medium using milk as substrate (figure 3). Distributions of hydrolytic activity among the isolates are summarized in table 4.From the seven bacterial isolates, four strains A1, A2, A4 and B5 showed combined hydrolytic activities. They were positive for gelatinase, lipase and coagulase. A3 strain showed gelatinase and lipase activities. DNAse activities were detected with A1, A4, B1 and B5 isolates. B4 presented lipase and coagulase activity. Surprisingly, no amylase activity was detected among all the isolates.Screening for biosurfactant producing isolates: Oil spread assay: The results showed that all the strains could produce notable (>4 cm diameter) oil expelling circles (ranging from 4.11 cm to 4.67 cm). The average diameter for strain B5 was 4.67 cm, significantly (P < 0.05) higher than for the other strains.Surface tension and emulsification index (E24): The assimilation of hydrocarbons as the sole sources of carbon by the isolate strains led to the production of biosurfactants indicated by the emulsification index and the lowering of the surface tension of cell-free supernatant. Based on rapid growth on media containing diesel oil as sole carbon source, the seven isolates were tested for biosurfactant production and emulsification activity. The obtained values of the surface tension measurements as well as the emulsification index (E24) are shown in table 3. The highest reduction of surface tension was achieved with B5 and A3 isolates with values of 25.3 mN m−1 and 28.1 mN m−1 respectively. The emulsifying capacity evaluated by the E24 emulsification index was highest in the culture of isolate B4 (78%), B5 (77%) and A3 (76%) as shown in table 3 and figure 2. These emulsions were stable even after 4 months. The bacteria with emulsification indices higher than 50 % and/or reduction in the surface tension (under 30 mN/m) have been defined as potential biosurfactant producers. Based on surface tension and the E24 index results, isolates B5, B4, A3 and A4 are the best candidates for biosurfactant production. It is important to note that, strains B4 and A4 produce biosurfactant in medium containing respectively 25% and 20% (w/v) NaCl.Stability of biosurfactant activities: The applicability of biosurfactants in several biotechnological fields depends on their stability at different environmental conditions (temperatures, pH and NaCl). For this study, the strain B4 appear very interesting (It can produce biosurfactant at 25 % NaCl) and was choosen for futher analysis for biosurfactant stability. The effects of temperature and pH on the biosurfactant production by the strain B4 are shown in figure 4.biosurfactant in medium containing respectively 25% and 20% (w/v) NaCl.Stability of biosurfactant activities: The applicability of biosurfactants in several biotechnological fields depends on their stability at different environmental conditions (temperatures, pH and NaCl). For this study, the strain B4 appear very interesting (It can produce biosurfactant at 25 % NaCl) and was chosen for further analysis for biosurfactant stability. The effects of temperature and pH on the biosurfactant production by the strain B4 are shown in figure 4. The biosurfactant produced by this strain was shown to be thermostable giving an E-24 Index value greater than 78% (figure 4A). Heating of the biosurfactant to 100 °C caused no significant effect on the biosurfactant performance. Therefore, the surface activity of the crude biosurfactant supernatant remained relatively stable to pH changes between pH 6 and 11. At pH 11, the value of E24 showed almost 76% activity, whereas below pH 6 the activity was decreased up to 40% (figure 4A). The decreases of the emulsification activity by decreasing the pH value from basic to an acidic region; may be due to partial precipitation of the biosurfactant. This result indicated that biosurfactant produced by strain B4 show higher stability at alkaline than in acidic conditions.Molecular identification and phylogenies of potential isolates: To identify halophilic bacterial isolates, the 16S rDNA gene was amplified using gene-specific primers. A PCR product of ≈ 1.3 kb was detected in all the seven isolates. The 16S rDNA amplicons of each bacterial isolate was sequenced on both strands using 27F and 1492R primers. The complete nucleotide sequence of 1336,1374, 1377,1313, 1305,1308 and 1273 bp sequences were obtained from A1, A2, A3, A4, B1, B4 and B5 isolates respectively, and subjected to BLAST analysis. The 16S rDNA sequence analysis showed that the isolated strains belong to the genera Halomonas, Staphylococcus, Salinivibrio, Planococcus and Halobacillus as shown in table 5. The halophilic isolates A2 and A4 showed 97% similarity with the Halomonas variabilis strain GSP3 (accession no. AY505527) and the Halomonas sp. M59 (accession no. AM229319), respectively. As for A1, it showed 96% similarity with the Halomonas venusta strain GSP24 (accession no. AY553074). B1 and B4 showed for their part 96% similarity with the Salinivibrio costicola subsp. alcaliphilus strain 18AG DSM4743 (accession no. NR_042255) and the Planococcus citreus (accession no. JX122551), respectively. The bacterial isolate B5 showed 98% sequence similarity with the Halobacillus trueperi (accession no. HG931926), As for A3, it showed only 95% similarity with the Staphylococcus arlettae (accession no. KR047785). The 16S rDNA nucleotide sequences of all the seven halophilic bacterial strains have been submitted to the NCBI GenBank database under the accession number presented in table 5. The phylogenetic association of the isolates is shown in figure 5.DICUSSIONThe physicochemical properties of the collected water samples indicated that this water was relatively neutral (pH 7.89) similar to the Dead Sea and the Great Salt Lake (USA) and in contrast to the more basic lakes such as Lake Wadi Natrun (Egypt) (pH 11) and El Golea Salt Lake (Algeria) (pH 9). The salinity of the sample was 224.70 g/L (22,47% (w/v). This range of salinity (20-30%) for Chott Tinsilt is comparable to a number of well characterized hypersaline ecosystems including both natural and man-made habitats, such as the Great Salt Lake (USA) and solar salterns of Puerto Rico. Thus, Chott Tinsilt is a hypersaline environment, i.e. environments with salt concentrations well above that of seawater. Chemical analysis of water sample indicated that Na +and Cl- were the most abundant ions, as in most hypersaline ecosystems (with some exceptions such as the Dead Sea). These chemical water characteristics were consistent with the previously reported data in other hypersaline ecosystems (DasSarma and Arora, 2001; Oren, 2002; Hacěne et al., 2004). Among 52 strains isolated from this Chott, seven distinct bacteria (A1, A2, A3, A4, B1, B4 and B5) were chosen for phenotypique, genotypique and phylogenetique characterization.The 16S rDNA sequence analysis showed that the isolated strains belong to the genera Halomonas, Staphylococcus, Salinivibrio, Planococcus and Halobacillus. Genera obtained in the present study are commonly occurring in various saline habitats across the globe. Staphylococci have the ability to grow in a wide range of salt concentrations (Graham and Wilkinson, 1992; Morikawa et al., 2009; Roohi et al., 2014). For example, in Pakistan, Staphylococcus strains were isolated from various salt samples during the study conducted by Roohi et al. (2014) and these results agreed with previous reports. Halomonas, halophilic and/or halotolerant Gram-negative bacteria are typically found in saline environments (Kim et al., 2013). The presence of Planococcus and Halobacillus has been reported in studies about hypersaline lakes; like La Sal del Rey (USA) (Phillips et al., 2012) and Great Salt Lake (Spring et al., 1996), respectively. The Salinivibrio costicola was a representative model for studies on osmoregulatory and other physiological mechanisms of moderately halophilic bacteria (Oren, 2006).However, it is interesting to note that all strains shared less than 98.7% identity (the usual species cut-off proposed by Yarza et al. (2014) with their closest phylogenetic relative, suggesting that they could be considered as new species. Phenotypic, genetic and phylogenetic analyses have been suggested for the complete identification of these strains. Theses bacterial strains were tested for the production of industrially important enzymes (Amylase, protease, lipase, DNAse and coagulase). These isolates are good candidates as sources of novel enzymes with biotechnological potential as they can be used in different industrial processes at high salt concentration (up to 25% NaCl for B4). Prominent amylase, lipase, protease and DNAase activities have been reported from different hypersaline environments across the globe; e.g., Spain (Sánchez‐Porro et al., 2003), Iran (Rohban et al., 2009), Tunisia (Baati et al., 2010) and India (Gupta et al., 2016). However, to the best of our knowledge, the coagulase activity has never been detected in extreme halophilic bacteria. Isolation and characterization of crude enzymes (especially coagulase) to investigate their properties and stability are in progress.The finding of novel enzymes with optimal activities at various ranges of salt concentrations is of great importance. Besides being intrinsically stable and active at high salt concentrations, halophilic and halotolerant enzymes offer great opportunities in biotechnological applications, such as environmental bioremediation (marine, oilfiel) and food processing. The bacterial isolates were also characterized for production of biosurfactants by oil-spread assay, measurement of surface tension and emulsification index (E24). There are few reports on biosurfactant producers in hypersaline environments and in recent years, there has been a greater increase in interest and importance in halophilic bacteria for biomolecules (Donio et al., 2013; Sarafin et al., 2014). Halophiles, which have a unique lipid composition, may have an important role to play as surface-active agents. The archae bacterial ether-linked phytanyl membrane lipid of the extremely halophilic bacteria has been shown to have surfactant properties (Post and Collins, 1982). Yakimov et al. (1995) reported the production of biosurfactant by a halotolerant Bacillus licheniformis strain BAS 50 which was able to produce a lipopeptide surfactant when cultured at salinities up to 13% NaCl. From solar salt, Halomonas sp. BS4 and Kocuria marina BS-15 were found to be able to produce biosurfactant when cultured at salinities of 8% and 10% NaCl respectively (Donio et al., 2013; Sarafin et al., 2014). In the present work, strains B4 and A4 produce biosurfactant in medium containing respectively 25% and 20% NaCl. To our knowledge, this is the first report on biosurfactant production by bacteria under such salt concentration. Biosurfactants have a wide variety of industrial and environmental applications (Akbari et al., 2018) but their applicability depends on their stability at different environmental conditions. The strain B4 which can produce biosurfactant at 25% NaCl showed good stability in alkaline pH and at a temperature range of 30°C-100°C. Due to the enormous utilization of biosurfactant in detergent manufacture the choice of alkaline biosurfactant is researched (Elazzazy et al., 2015). On the other hand, the interesting finding was the thermostability of the produced biosurfactant even after heat treatment (100°C for 30 min) which suggests the use of this biosurfactant in industries where heating is of a paramount importance (Khopade et al., 2012). To date, more attention has been focused on biosurfactant producing bacteria under extreme conditions for industrial and commercial usefulness. In fact, the biosurfactant produce by strain B4 have promising usefulness in pharmaceutical, cosmetics and food industries and for bioremediation in marine environment and Microbial enhanced oil recovery (MEOR) where the salinity, temperature and pH are high.CONCLUSIONThis is the first study on the culturable halophilic bacteria community inhabiting Chott Tinsilt in Eastern Algeria. Different genera of halotolerant bacteria with different phylogeneticaly characteristics have been isolated from this Chott. Culturing of bacteria and their molecular analysis provides an opportunity to have a wide range of cultured microorganisms from extreme habitats like hypersaline environments. Enzymes produced by halophilic bacteria show interesting properties like their ability to remain functional in extreme conditions, such as high temperatures, wide range of pH, and high salt concentrations. 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Abstract Objective To evaluate excess mortality in Brazil from January 2020 to April 2021, according to the primary causes of death registered in the Brazilian Mortality Information System (MIS). Methods Cross-sectional study with data extracted from the MIS. Excess deaths were examined by the primary cause of death according to 11 grouped causes. Autoregressive models used mortality data from 2015 to 2019 to predict expected deaths from January 2020 to April 2021. Excess deaths were calculated as the difference between the observed and the expected number of deaths. Results Total excess deaths of 370 055 were observed in the studied period, corresponding to a ratio of observed to expected of 1.14 in 2020 and 1.40 in 2021. Excess deaths were seen in three groups: symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified; other diseases of the respiratory system and coronavirus infection, unspecified site. Conclusions The excess mortality in Brazil in these 16 months was 1.20 times greater than the previous year. The increase in not elsewhere classified causes and causes of death associated to COVID-19 indicate caution about the negative balance for some causes. Furthermore, the inequalities of mortality reporting systems in low- and middle-income countries in relation to underestimation of mortality still need to be addressed.

Abstract Since 2018, the Health System and Policy Monitor (HSPM) network of the European Observatory on Health Systems and Policies has tracked health reform activity in its countries. Top three reforms are identified by national experts yearly and classified across 11 policy clusters. Efforts inform a standardized overview of healthcare development. 337 reforms have been assessed for 31 (mainly EU) countries over 4 years, with clear trends like the converging of PHC and care coordination. Main reform areas were primary/ambulatory care, governance, and hospital care (2018-2019); coordination, governance, and digital health (2020); and care coordination, governance, and insurance coverage/resource generation (2021). For PHC, this suggests a shift from leveraging innovations to support existing delivery mechanisms to transforming PHC. Some PHC reforms in 2018-2019 introduced elements of integrated care, but more focused narrowly on specific levers, e.g., gatekeeping. Early care coordination reforms focused on certain patient groups or care delivery across the system. Separately, PHC and care coordination have long been reform priorities. Since 2020, they are increasingly linked to one another, and to multidisciplinary care. This suggests a recognition that multidisciplinary processes/staffing are key to realizing the promises of PHC-to coordinate the care of patients and ensure comprehensive and continuous care over time for most health needs. This vision is underpinned by the UN SDGs and COVID-19, which highlighted the need for health systems to be set up for and with the resources to respond to crises while maintaining core functions. The overview of HSPM health reforms identifies reform trends and opportunities for cross-country learning. More research is needed for policymakers to benefit fully from reform experiences abroad. Case studies with in-depth analysis of reform design and implementation processes can help inspire or support future health reforms elsewhere.

Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is a provisional entity in the 2017 Revision of the World Health Organization Classification. This indolent entity, which is frequently discovered incidentally, is currently classified under the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI), an aggressive lymphoma with poor survival. Several authors have proposed that it be classified separately since, in contrast to DLBCL-CI, transformation to aggressive lymphoma has rarely been reported and this entity has distinct clinical and histological features. We describe a rare case of a 62-year-old male with FA-DLBCL associated with atrial myxoma, which was incidentally discovered. In contrast to typically described immunophenotypic features of this entity, that is, activated B-cell phenotype (ABC) and Epstein-Barr virus (EBV) positivity, our case showed germinal center B-cell (GCB) phenotype and was EBV negative. Clinical staging revealed no evidence of lymphoma elsewhere in the body, and the patient did not receive adjuvant chemotherapy after surgical excision and remains in remission. This case illustrates that occasionally FA-DLBCL can show GCB phenotype, as opposed to the typical ABC phenotype. Moreover, we propose that the definition of the entity be expanded to include EBV-negative cases.

The World Health Organization defines a zoonosis as any infection naturally transmissible from vertebrate animals to humans. The pandemic of Coronavirus disease (COVID-19) caused by SARS-CoV-2 has been classified as a zoonotic disease, however, no animal reservoir has yet been found, so this classification is premature. We propose that COVID-19 should instead be classified an “emerging infectious disease (EID) of probable animal origin.” To explore if COVID-19 infection fits our proposed re-categorization vs. the contemporary definitions of zoonoses, we reviewed current evidence of infection origin and transmission routes of SARS-CoV-2 virus and described this in the context of known zoonoses, EIDs and “spill-over” events. Although the initial one hundred COVID-19 patients were presumably exposed to the virus at a seafood Market in China, and despite the fact that 33 of 585 swab samples collected from surfaces and cages in the market tested positive for SARS-CoV-2, no virus was isolated directly from animals and no animal reservoir was detected. Elsewhere, SARS-CoV-2 has been detected in animals including domesticated cats, dogs, and ferrets, as well as captive-managed mink, lions, tigers, deer, and mice confirming zooanthroponosis. Other than circumstantial evidence of zoonotic cases in mink farms in the Netherlands, no cases of natural transmission from wild or domesticated animals have been confirmed. More than 40 million human COVID-19 infections reported appear to be exclusively through human-human transmission. SARS-CoV-2 virus and COVID-19 do not meet the WHO definition of zoonoses. We suggest SARS-CoV-2 should be re-classified as an EID of probable animal origin.