Tesis sobre el tema "Patients recruitment"

The neutrophil is central to the development of COPD. To enter lung, neutrophils must migrate accurately from the circulation to inflamed tissue. It is unclear which migratory stimuli are important and whether COPD neutrophils vary in their migratory behaviour, either to controls or patients with similar lung disease. COPD sputum and plasma samples were collected on 11 occasions over one month. Significant correlations were demonstrated between the inflammatory biomarkers and between inflammatory biomarkers and markers of disease. IL-8 correlated most strongly both with other inflammatory mediators, neutrophil counts and indices of disease. Neutrophils from healthy older subjects migrated with maintained speed but reduced accuracy to IL-8. Differences could not be accounted for by surface receptor expression or shedding, but inhibition of CXCR2 gave young neutrophils and old migratory phenotype, suggesting altered downstream signalling. COPD neutrophils migrated with increased speed and reduced accuracy compared with control groups. They formed less pseudopodia when migrating, and had reduced surface expression of CXCR1 and CXCR2. Inhibitory studies suggested that CXCR2 was the predominant receptor in migration to biological samples. Treating COPD cells with a PI3 Kinase inhibitor differentially altered their migration, reducing speed but increasing accuracy, so that cells now resembled those from controls.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.
OBJECTIVE: To demonstrate the safety of lung recruitment maneuvers in post-operative pediatric cardiac surgical patients. To assess the ability of lung recruitment maneuvers to improve lung function. HYPOTHESIS: We hypothesize that ventilator recruitment strategies be well-­tolerated in cardiac patients, and that they may benefit such patients by improving physiologic variables such as lung function and oxygenation. METHODS: Sixty‐two pediatric post-operative cardiac surgical patients were randomly selected to include in this retrospective chart review. Study subjects were selected from all patients who met inclusion criteria in the year immediately following implementation of a lung recruitment protocol in a local free‐standing pediatric hospital. Physiologic variables before, during, and after lung recruitment were recorded as well as patient demographics, diagnoses, morbidities and mortality. RESULTS: A statistically significant increase in dynamic compliance of the lungs and renal non-invasive regional oximetry was noted immediately after each recruitment maneuver. There was no statistically significant change in blood pressure, heart rate or oxygen saturation during the maneuvers. There was a transient increase in central venous pressure during the maneuvers (average increase < 1 mmHg). Of the 62 patients, there were 7 cases of pneumonia and 5 cases of small pneumothorax, often resolving without intervention. Significance: Demonstrating recruitment maneuvers are safe in pediatric patients with cardiac disease will allow practitioners to confidently utilize them when caring for ventilated patients. Such patients may benefit from potential improvements in lung function and decreased ventilator-associated morbidities.

Formation of atelectasis, defined as reversible collapse of aerated lung, often occurs after induction of anaesthesia with mechanical ventilation. As a consequence, there is a risk for hypoxemia, altered hemodynamics and impaired respiratory system mechanics. In certain situations, the risk for atelectasis formation is increased and its consequences may also be more difficult to manage. Anesthesia for bariatric surgery in morbidly obese patients and surgery requiring one-lung ventilation (OLV) with capnothorax are examples of such situations. In Paper I (30 patients with BMI > 40 kg/m2 scheduled for bariatric surgery) a recruit­ment maneuver followed by positive end-expiratory pressure (PEEP) re­duced the amount of atelectasis and improved oxygenation for a prolonged period of time. PEEP or a recruitment maneuver alone did not reduce the amount of atelectasis. In paper II we investigated whether it is possible to predict respiratory function impairment in morbidly obese patients without pulmonary disease from a preoperative lung function test. Patients with mild signs of airway obstruction (reduced end-expiratory flow) in the preoperative spirometry developed less atelectasis during anaesthesia. In paper III we developed an experimental model of sequential OLV with capnothorax using electrical impedance tomography (EIT) that in real-time detected lung separation and dynamic changes in pulmonary ventilation and perfusion distributions. OLV to the left side caused a decrease in cardiac output, arterial oxygenation and mixed venous saturation. In paper IV we used our model of OLV with capnothorax and applied a CO2-insufflation pressure of 16 cm H2O. We demonstrated that a PEEP level of 12-16 cm H2O is needed for optimal oxygenation and lowest possible driving pressure without compromising hemodynamic variables. Thus, the optimal PEEP was closely related to the level of the capnothorax insufflation pressure. With insufficient PEEP, ventilation/perfusion mismatch in the ventilated lung and redistribution of blood flow to the non-ventilated lung occurred.

Background: Patient recruitment to trials is problematic; many fail to achieve targets, leaving them underpowered and unable to address their hypothesis. Few solutions have been identified in existing literature. This thesis aimed to: identify factors associated with recruitment; and understand clinicians’ experiences of recruiting patients to a primary care based randomised controlled trial (RCT). This was explored using The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) trial as a case study. Methods: Mixed methods were used: a systematic review to identify factors influencing recruitment to primary care based RCTs; quantitative analysis of BAFTA data to identify factors associated with recruitment; and qualitative interviews with General Practitioners involved with BAFTA, to understand their experience of participation. Results: Existing literature demonstrated that influences on recruitment include: study workload; study question; concerns about patients. Recommendations to address these issues are not based on strong empirical evidence. BAFTA identified factors associated with patient recruitment (practice size; GP age; recruitment year); and patterns over time. Interviews identified differences in attitude between high and low recruiters, including risk perception and motivation. Conclusions: This thesis demonstrates how practitioners can influence patient recruitment. Revised recruitment methods need testing in prospective trials.

Randomised Controlled Trials (RCTs) are regarded as a ‘gold standard’ technique to evaluate and compare clinical interventions. Strict ethical criteria dictate the participation of humans in clinical research, based on informed consent, voluntary decision making and putting patients’ interests first. Demand for RCTs in Trauma and Orthopaedics is high, but patient recruitment continues to pose a significant challenge, especially when the treatments being compared are obviously different. Lack of blinding, treatment preference and negative perception of random allocation to interventions are among the obstacles which need to be considered. Based on review and analysis of current knowledge, an attempt is made to develop a new recruitment process that incorporates high ethical standards and provision of the best possible clinical care for an individual patient. By integrating the principle of clinical equipoise, modern technology and statistical concepts, such as subjective probability, the Patient Eligibility Assessment through Clinical Equipoise (PEACE) framework has been introduced. This provides an alternative that could be used in trials where the fixed eligibility criteria approach is likely to fail. It was tested involving 77 real clinical cases from a national multi-centre trauma RCT, which compared contrasting treatments. A new trial recruitment approach aiming to avoid direct contact between a patient and a treating clinician was rolled out in the same trial. The feedback was collected from both the clinicians and the patients involved. Thematic analysis of 23 semi-structured interviews improved understanding of the various factors influencing patients’ decision about trial participation. Further typological analysis provided a valuable insight into the different attitudes that patients adopted when faced with the dilemma. In particular, that many are positive towards research involvement, but not comfortable with randomisation based on fixed eligibility criteria. According to these results, a new model for patient recruitment is suggested, which could be researched and tested in future trials.

The aim of this research is to provide novel approach how to use social media in patient recruitment for clinical trials. This research has been commissioned by a Finland based company Synoste, and is limited to consider the patient recruitment in a medical device start-up with a very limited number of patients. To be able to produce new approach into existing literature, this study has been conducted as a qualitative case study from the perspective of social media agencies and patient recruitment firms. Understanding the factors, such as scarce information about the clinical trials, possible benefits, lack of support by patients and families as well as lack of encouragement to participate by practicing physicians all affect a decision of an individual, whether to participate into a clinical trial or not. Understanding these factors enables to analyze proper social media strategies for patient recruitment. Challenges and benefits of different social media strategies have been discussed in the theoretical part of this study also. Theoretical framework concludes previous literature about the research subject together by focusing on the different aspects of promotion, including channels, content, communication and messages. Theoretical framework created a base for a request for quotation (RFQ), which was used to collect approaches from social media agencies and patient recruitment firms. These companies were selected by searching Finland based marketing companies with a high level of competence about the use of social media. Due to the lack of actual patient recruitment firms in Finland, and to get more comprehensive approach about the overall situation, a few professional patient recruitment firms out of Finland are also included for this study. Empirical analysis follows both abductive and inductive reasoning. The participant companies suggested a wide variation of different strategies for the use of social media in patient recruitment. The right kind of content and advertising, selecting the most suitable channels to reach target group and driving traffic to trial website are important stages when planning the social media strategy for patient recruitment. The main findings of this research indicate that increasing the awareness and targeting, as well as Google advertising can be used as effective methods to recruit patients into clinical trials, when social media is not used as an only strategy for patient recruitment. Due to the fact, that the use of social media misses the establishes practices, there is not a “right way” to use social media in a patient recruitment process.

Introduction and background Recruitment to cancer clinical trials needs to be improved, as does patient understanding about clinical trials, to enable patients to make an informed choice about whether or not to take part. The main reason that clinically eligible patients do not take part in clinical trials is because they refuse; poor understanding of the research has been associated with patient refusal. Audiovisual patient information (AVPI) has been shown to improve knowledge/understanding in various areas of practice but there is limited information about its effect in the cancer clinical trial setting, particularly in relation to recruitment rates. Understanding the research is necessary for informed consent, and it was hypothesised that if patient understanding about clinical trials was increased with AVPI, then this could result in a reduction in the number of patients refusing clinical trials, and therefore provide an ethical approach to improving recruitment. This study aimed to test the impact of an audiovisual patient information intervention on recruitment to randomised cancer clinical trials (refusal rates), patient understanding of the information given, and levels of anxiety. Reasons for patients’ decisions about trial participation were also assessed. Method An AVPI intervention was developed that aimed to address the common misconceptions associated with randomisation and clinical equipoise, as well as improve patient understanding generally of randomised cancer trials, and of other core clinical trial informational requirements, such as voluntariness. Patients were randomised to receive either AVPI in addition to the standard trial-specific written information, or the written information alone. A new questionnaire was developed to assess patient understanding (also referred to as knowledge) in the randomised trial setting and, following testing with patients and research nurses, this was shown to be reliable and valid. Patients completed self-report questionnaires to assess their understanding (new knowledge questionnaire) and anxiety (Spielberger State-Trait Anxiety Inventory), at baseline and after they had made their decision about clinical trial entry, when their perceptions of the intervention, as well as factors contributing to their decision were also determined (this tool incorporated Jenkins and Fallowfield’s (2005) questionnaire which assessed reasons for accepting and declining randomised cancer trials). Results A total of 173 patients with breast cancer (65%), colorectal cancer (32%) and lung cancer (3%) were entered into the main study. The median age was 60 (range 37-92 years). There was no difference in clinical trial recruitment rates between the two groups: 72.1% in the AVPI group and 75.9% in the standard information group. The estimated odds ratio for refusal (intervention/no intervention) was 1.19 (95% ci 0.55-2.58, p=0.661). Knowledge scores increased more in the intervention group compared to the standard group (U= 2029, p=0.0072). The change in anxiety score between the arms was also statistically significant (p=0.011) with anxiety improving in the intervention arm more than in the no-intervention arm. The estimated difference in the median anxiety change score between the groups is –4.6 (95% ci –7.0 to –2.0). Clinical trial entry was not influenced by tumour type, stage of cancer, age, educational qualifications or previous research experience, however, there was a modest association with deprivation status (p=0.046) where more affluent patients were the least likely to consent to a trial. Educational qualifications and stage of cancer were independently associated with knowledge: patients who were better educated had higher levels of knowledge about randomised trials, and patients who had limited stage of cancer had higher baseline knowledge than patients with advanced cancer. Acceptability of the intervention was high with 93% of those who watched it finding it useful, and 42% stating that it made them want to take part in the clinical trial. Personal benefit and altruism were key motivating factors for clinical trial participation, with reasons for refusal being less clear. Discussion and conclusions Although the potential for AVPI to increase clinical trial recruitment rates was highlighted in the literature, in this study, AVPI was not shown to have any effect on refusal rates to randomised cancer trials. However, by improving patient understanding prior to decision making, AVPI was shown to be a useful addition to the consent process for randomised cancer trials. AVPI addresses the fundamental ethical challenges of informed consent by improving patient understanding, and supports the ethical framework integral to Faden and Beauchamp’s (1986) theory of informed consent. The new knowledge questionnaire was shown to be a sensitive and effective instrument for measuring understanding of randomised clinical trials in the cancer setting, although it would benefit from further testing. The AVPI appears to reduce anxiety at the decision making time point and has been shown to be an acceptable medium for patients. This study confirms existing findings from studies assessing factors affecting decision making, with personal benefit and altruism being key motivating factors, and reasons for refusal being less clear. The need for further qualitative work in this area is highlighted to gain a deeper understanding of what is important to patients, in terms of why they refuse clinical trial participation. Implications for practice and further research Several implications for practice have been identified, including using AVPI as part of the standard information package for patients considering randomised cancer trials, and focussing on patient and staff education in this area. The knowledge questionnaire could be introduced to routine practice as a tool to determine patient understanding prior to decision making, allowing clinicians the opportunity to correct any misconceptions prior to consent. Further research focussing on AVPI specific to individual trials would be helpful, to determine if a more customised approach would be of benefit in terms of clinical trial recruitment. The importance of studying other aspects of the consent process such as the interaction between the clinician and the patient, in addition to more detailed exploration of the factors affecting patients’ decisions were highlighted.

Bei Patienten mit einem akuten Lungenversagen (ALI oder ARDS) ist der Sauerstoffverbrauch der Lunge (VO2pulm) durch pathophysiologische Prozesse insbesondere die Ausbildung von Atelektasen stark beeinträchtigt. Aufgrund der Annahme, dass eine Steigerung der Anzahl ventilierter Lungenareale zu einer Erhöhung des pulmonalen Sauerstoffverbrauchs führt, haben wir den Einfluss eines definierten Rekrutierungsmanövers (PEEP/PEAK + 10 cmH2O) auf den pulmonalen Sauerstoffverbrauch (VO2pulm), pulmonalen kapillären Blutfluss (PCBF), der den nicht geshunteten Anteil am HZV darstellt, und den transpulmonalen Shunt (Qs/Qt) untersucht. In der vorliegenden Studie wurde der VO2pulm als Differenz zwischen dem Sauerstoffverbrauch des gesamten Körpers, gemessen über die indirekte Kalorimetrie (VO2cal), und dem über das inverse Fick`sche Prinzip errechneten Sauerstoffverbrauch (VO2Fick) bestimmt. Im Rahmen einer klinisch-prospektiven Studie konnten nach Annahme des Studienprotokolls durch die zuständige Ethikkommission 13 beatmete Patienten, welche die Consensus-Kriterien eines ALI oder ARDS erfüllten, eingeschlossen werden. Nach Sicherstellung einer adäquaten Volumensituation und Messung der Ausgangsparameter wurde der PEEP um 10 cmH2O erhöht. Um ein stabiles Atemzugvolumen (VT 6-8 ml/kgKG) und damit gleichbleibende Bedingungen für die alveoläre Ventilation bis auf das von uns durchgeführte Rekrutierungsmanöver zu gewährleisten, wurde zeitgleich der Spitzendruck ebenfalls um 10 cmH2O erhöht. Nach 15 und 60 min wurden die Zieldeterminanten pulmonaler Sauerstoffverbrauch (VO2pulm), PCBF und transpulmonaler Shunt erneut bestimmt. Die Messung der indirekten Kalorimetrie (VO2cal) wurde mit dem Deltatrac TM, MBM 200® durchgeführt, VO2Fick über die Thermodilutionsmethode ermittelt, die partielle CO2-Rückatmungsmethode (David®) zur Bestimmung des PCBF genutzt und der transpulmonale Shunt (Qs/Qt) mittels der Formel nach BERGGREN berechnet. Die statistische Auswertung der Daten erfolgte mittels T-Tests für gepaarte Stichproben. Nach dem Manöver konnte eine signifikante Steigerung des PCBF von 4,44 ± 1,15 l/min auf 5,4 ± 1,68 l/min nach 15 min, respektive 5,12 ± 1,67 l/min nach 60 min nachgewiesen werden (p&lt;0,025). Dieser Anstieg wurde von einer signifikanten Reduktion des transpulmonalen Shunts (Qs/Qt) von 0,24 ± 0,08 auf 0,16 ± 0,07 nach 15 min und 0,16 ± 0,07 nach 60 min begleitet (p&lt;0,005). Diese Veränderungen der pulmonalen Hämodynamik gehen mit statistisch relevanten Verbesserungen der Oxygenierung sowie der Atemmechanik einher. Eine signifikante Steigerung des pulmonalen Sauerstoffverbrauchs konnte für die gesamte Studienpopulation nicht festgestellt werden. In dieser Untersuchung steigt der Sauerstoffverbrauch der Lunge deskriptiv von baseline 10,1 +/- 30,59 ml/min über 11,42 +/- 27,42 ml/min nach 15 min, respektive auf 28,69 +/- 56,75 ml/min nach 60 min an. Die signifikante Steigerung des pulmonal-kapillären Blutflusses und die konsekutive Reduktion des transpulmonalen Shunts schon 15 min nach dem Manöver impliziert einen Anstieg der an der alveolären Ventilation teilnehmenden alveolokapillären Einheiten, was einer Rekrutierung von vorher atelektatischen Lungenabschnitten entspricht. Insbesondere bei ARDS-Patienten und Respondern konnten Rekrutierungs-induzierte Veränderungen detektiert werden, wohingegen die Patienten mit ALI oder Nonresponder keinerlei statistische Unterschiede während der Intervention zeigten. Trotz stattgefundener Wiederbelüftung von Atelektasen konnte ein statistisch relevanter Unterschied bezüglich des pulmonalen Sauerstoffverbrauchs durch das Rekrutierungsmanöver für die gesamte Studienpopulation nicht festgestellt werden.

La mise au point de nouveaux vaccins reste cruciale, notamment dans le contexte des épidémies dues à des pathogènes émergents et de la lutte contre l’antibiorésistance. Le développement clinique des vaccins prend du temps et coûte cher. Optimiser le recrutement dans ces essais est donc primordial. L’objectif a donc été d’identifier les barrières et motivations à la participation à un essai vaccinal. L’altruisme et l’indemnisation financière ont ainsi été identifiés dans notre revue de la littérature comme facteurs motivants principaux et la peur des effets secondaires et le design de l’étude comme les principaux freins. Nous avons d‘une part étudié l’attitude des praticiens référents face à leur patient qui s’est vu proposer de participer à un essai vaccinal préventif. Ils se révèlent être peu informés quant à la recherche clinique et aimeraient avoir plus d’informations au préalable afin de donner un avis objectif au patient. Nous avons aussi étudié les barrières et motivations des personnes approchées pour participer à un essai vaccinal préventif. Nous avons pu mettre en évidence que l’altruisme était la motivation principale à participer et qu’un avis favorable aux vaccins en général était associé au fait d’accepter de participer à ce type d’essai. De plus, la peur des effets secondaires potentiels s’est révélée être le frein principal à la décision de participer. L’incitation financière, motivation chez les plus jeunes, était un frein à la participation chez les personnes plus âgées. La qualité de l’information donnée au participant potentiel par le médecin est cruciale et renforce l’importance de partager l’information avec le médecin référent du patient
The development of new vaccines remains crucial, particularly in the context of epidemics due to emerging pathogens and the fight against antibiotic resistance. Clinical development of vaccines is time consuming and expensive. Optimizing recruitment in these trials is therefore essential. The objective was therefore to identify the barriers and motivations to participation in a vaccine trial. Altruism and financial incentives were identified in our literature review as the main motivating factors and fear of side effects and study design as the main obstacles. On the one hand, we studied the attitude of primary physicians towards their patients who were offered to participate in a preventive vaccine trial. They are not well informed about clinical research and would like to have more information in advance in order to give an objective opinion to the patient. We also studied the barriers and motivations of people approached to participate in a preventive vaccine trial. We were able to highlight that altruism was the main motivation to participate and that a favorable opinion for vaccines in general was associated with agreeing to participate in this type of trial. In addition, fear of potential side effects was found to be the main reason for the decision to participate. Financial incentives, which are a motivation for younger people, were a barrier to participation among older people. The quality of the information given to the potential participant by the physician is crucial and reinforces the importance of sharing information with the patient's primary physician

Background: There is a great need for effective treatments for mental health problems. Randomised controlled trials are the gold standard for evaluating treatments, however recruitment into trials is challenging, highlighting a clear need for evidence-based recruitment strategies. This thesis aimed to systematically develop a recruitment intervention and evaluate its effectiveness for improving the recruitment of participants into mental health trials. Methods: A mixed-methods approach, adopting the Medical Research Council’s complex interventions framework: 1) a systematic review to identify the evidence base and describe the factors affecting recruitment into depression trials; 2) a qualitative study to understand patients’ decision-making process in declining to enrol in a depression trial; 3) development of a recruitment intervention, using Participatory Design methods; and 4) evaluation of the recruitment intervention, using a randomised controlled trial, embedded in an ongoing mental health trial (the EQUIP trial). The primary outcome was the proportion of participants enrolled in EQUIP. Results: From the systematic review, a conceptual framework of factors influencing the decision to participate was developed, which highlighted that the decision to enrol involves a judgement between risk and reward. Findings suggested that patient and public involvement in research (PPIR) might be advertised to potential participants to reduce such perceived risk. The qualitative study found positive views of trials. Interviewees’ decision making resembled a four-stage process; in each stage they either decided to decline or progressed to the next stage. In Stage 1, those with an established position of declining trials opted out – they are termed ‘prior decliners’. In Stage 2, those who opted out after judging themselves ineligible are termed ‘self-excluders’. In Stage 3, those who decided they did not need the trial therapy and opted out are termed ‘treatment decliners’. In Stage 4, those who opted out after judging that disadvantages outweighed advantages are termed ‘trial decliners’. While ‘prior decliners’ are unlikely to respond to trial recruitment initiatives, the factors leading others to decline are amenable to amelioration as they do not arise from a rejection of trials. We recruited a host mental health trial (EQUIP), and worked with key stakeholders, including mental health service users and carers, to develop an intervention using a leaflet to advertise the nature and function of the PPIR in EQUIP to potential trial participants. 34 community mental health teams were randomised and 8182 patients invited. For the primary outcome, 4% of patients in the PPIR group were enrolled versus 5.3% of the control group. The intervention was not effective for improving recruitment rates (adjusted OR= 0.75, 95% CI= 0.53 to 1.07, p=0.113). Conclusions: This thesis reports the largest ever trial to evaluate the impact of a recruitment intervention. It also reports the largest trial of a PPIR intervention and makes a contribution to the evidence base on trial recruitment as well as to that assessing the impact of PPIR. Two further embedded trials are underway to evaluate the effectiveness of different versions of the recruitment intervention in different trial contexts and patient populations. This will also allow the results to be pooled to generate a more precise estimate of effect; to evaluate the impact of the intervention on trial retention; and to explore patient experiences of receiving the intervention.

Yes
Background: Recruitment of patients with advanced cancer into studies is challenging. Objective: To evaluate recruitment methods in a study of pharmacist-led cancer pain medicines consultations and produce recommendations for future studies. Method: Two methods of recruitment were employed: 1) community-based (general practitioner computer search, identification by general practitioner, community pharmacist or district nurse and hospital outpatient list search), and 2) hospice-based (in and outpatient list search). Patients identified in method 1 were invited by post and in method 2 were invited face-to-face. Information was designed in collaboration with patients and carers. Results: 128 patients were identified (85 from the community and 43 from the hospice), 47 met the inclusion criteria. Twenty-three agreed to take part and 19 completed the study, 17 of whom were already under specialist palliative care. Recruitment rates were 7% for community-based methods and 40% for hospice. The recruitment methods differed in intensity of resource use. Recruitment via letter and a lack of engagement by healthcare professionals were found to be barriers. Facilitators included the researcher having personal involvement in recruitment. Conclusion: The overall recruitment rate was in line with other studies for this patient cohort. Attempts to identify and engage patients through community-based postal contact were less effective than where personal contact with patients was both possible and occurred. Methods were less successful at recruiting patients who were not already engaged with hospice services.
Programme Grants for Applied Research. Grant Number: RP-PG-0610-10114

碩士
長庚大學
護理學研究所
90
Use of mechanical ventilator support through tracheostomy or intubation has been one of extremely important medical intervention to help support life for ICU patients. However, as the result of using current medical intervention for patients with lung collapse during mechanical ventilation is limited, manual hyperinflation helps alveolar recruitment that results in secretion clearance, ventilation improvement, lung collapse prevention, lung collapse re-inflation, dynamic compliance improvement, artery oxygenation improvement and work of breathing reduction according to certain clinic reports from foreign sources. This study seeks to verify success of sputum clearance and ventilation in giving manual hyperinflation to patients suffering from lung collapse who has been using mechanical ventilation for more than one week. The study takes the assumption that through manual hyperinflation to recruit alveolar, it will help patients sputum clearance and ventilation. A controlled, randomized, single blind, experimental design was used. Each patient was assigned a random number upon entering the research project, which allowed randomly allocation to two groups: experimental group and control group. The samples were collected in the ICU of a Medical Center in northern Taiwan and the Chronic Respiratory Treatment Center of the Regional Hospital under the cooperation program. A total of 28 patients joined the study in two groups, i.e., experimental group and control group, 14 patients in each group. Cases from the experimental group were treated with ventilation support and additional manual hyperinflation while cases from the control group were only treated with ventilation support. Patients in experimental group received the manual hyperinflation once of 20 minutes in 3 times per day for 5 days. Outcome measurement was evaluated by noting changes in the patient’s score in dry/wet ratio of sputum, sputum viscosity, tidal volume, maximal respiratory pressure, PaO2/FiO2, upper chest X-ray film, dynamic lung compliance and the index of rapid shallow breathing. Outcome measurements were assessed 3 times for all patients: at the day admitted to this study, the 3rd day, and 6th day. Upon giving the conclusions are as follows: (1)For the sputum clearance, patients from the experiment group indicate significant improvement than those from control group does depending on the time-point in terms of sputum viscosity (p=0.002); while patients from both group indicate no significant variance in dry/wet ratio of sputum; (2)For the ventilation, patients from the experimental group indicate significant improvement than those from control group does depending on the time-point in terms of improved tidal volume (p=0.033), maximal respiratory pressure (p=0.05), PaO2/FiO2 (p=0.016), upper chest X-ray film (p=0.069), the index of rapid shallow breathing (p=0.008); and while patients from both groups indicate no significant variance in terms of dynamic compliance.

BACKGROUND: Hypoplastic Left Heart Syndrome is a congenital birth defect that is defined by underdevelopment of the left heart during pregnancy. This is especially dangerous as the left heart holds the systemic flow of blood- the oxygenated blood. Not enough oxygen throughout the whole body causes cyanosis, which symptoms include bluish discoloration of the skin or mucous membrane due to low oxygen saturation. Single Ventricle Palliation followed by Biventricular Conversion is the most common surgical procedural pathway to correct this defect. The goal is to convert from a single ventricle circulation during single ventricle palliation to biventricular circulation via biventricular conversion, which is the normal heart anatomy. Single Ventricle Pallation consists of three stages: Stage 1 Norwood Procedure, Bidirectional Glenn, and Fontan. Biventricular Conversion can be performed after any of the three stages. In addition, further compromise of the left ventricle includes other factors such as a thickening of fibroblast-like cells on the endocardial layer called endocardial fibroelastosis. Therefore, additional surgical procedures, also known as recruitment procedures, combat these problems. It is critical to find a correlation between a specific procedure and post surgery success in left ventricle growth and function for these patients. OBJECTIVES: Patients with Hypoplastic Left Heart Syndrome at Boston Children’s Hospital have undergone single ventricle palliation with some patients proceeding to biventricular conversion. This study aimed to study the palliation stages individually and recruitment procedures (specifically endocardial fibroelastosis resection) on the effect of left ventricle growth. METHODS: Patients with Hypoplastic Left Heart Syndrome were studied retrospectively (before 2014) and prospectively (after 2014 until December 1, 2018). Single Ventricle Palliation and Biventricular Conversion were analyzed via descriptional analysis with evidence of left ventricular growth measured by left ventricular end diastolic volume and respective z-scores. Z-scores were used to standardize end diastolic volume values across variability in age, weight, and height. RESULTS: A total of 55 patients underwent single ventricle palliation and 39 ended with biventricular circulation via biventricular conversion. Overall, there was a 9.29 ml increase in end diastolic volume between Bidirectional Glenn and Fontan and a 0.795 increase in end diastolic volume z-score between Fontan and Biventricular Conversion. Next, those who did not have recruitment procedures experienced a 135.6%, 48.8%, and 0% growth at Stage 1, Bidirectional Glenn, and Fontan, respectively, before directly proceeding to biventricular conversion. Those with recruitment experienced a 44.5%, 90.4%, and 83.0% growth at Stage 1, Bidirectional Glenn, and Fontan, respectively, before directly proceeding to biventricular conversion. Finally, there was a 50.2% and 62.3% in left ventricular growth at Bidirectional Glenn and Fontan, respectively, after endocardial fibroelastosis resection compared to only a 6.9% growth at Stage 1. CONCLUSION: Bidirectional Glenn was the most effective palliation stage for left ventricular growth. Recruitment in patients at this stage was associated with growth that exceeds those who did not have recruitment. This stage also best demonstrates the ability and success of growing a small ventricle to be adequate for biventricular conversion. Left ventricular growth at Fontan circulation holds promising results that are a point of interest for more studies. Endocardial Fibroelastosis resection is more effective on left ventricular growth at Bidirectional Glenn and Fontan compared to Stage 1.

碩士
國立臺灣大學
臨床牙醫學研究所
88
The purpose of this study was to examine the recruitment of masticatory muscles and sternocleidomastoid muscle at different protrusive-retrusive jaw positions under the control of biting forces. Twenty female patients of TMJ arthritis whose overjet and overbite of anterior teeth had found to be changed during the course of treatment were included in this study. Twenty-one normal subjects with similar age, height and weight were selected as control group. A fork-type force transducer was constructed with four bonded strain gauges connected in full bridge, which was then calibrated at different loading positions. It was found that the change of loading positions on the fork end did not lead to statistically significant difference of voltage output (p=0.9998). In the main study, electromyographic(EMG) activities of maximum voluntary clenching were firstly obtained by surface electrodes from both sides of masseter, sternocleidomastoid（SCM）, anterior and posterior temporalis muscles at intercuspal position (ICP) and anterior edge to edge position. Then the subjects were instructed to bite at controlled protrusive-retrusive jaw positions with the force transducer placed in the first molar locations of habitual chewing side. The most retrusive jaw position is defined as ?" position, which then determined protrusive 2 and 4 mm jaw positions. At each jaw positions, biting force levels of 50, 100 and 150N, were conducted with visual analog. Each experimental task consists of 3 seconds continuous biting with 5 repeated trials. The magnitude of force was synchronously recorded with EMG activities of masseter, SCM, anterior and posterior temporalis muscles on both sides. Root mean square of muscle activities was derived for each muscle. The results showed that the arthritic patients revealed lower EMG activities at ICP than the controls whereas no significant difference was found between groups at anterior edge to edge biting position. With GEE model, it was found that muscle activities were positively influenced by bite force magnitude（P＜0.05）in both group. The muscle activities were negatively influenced by protrusive jaw positions only in control group（P＜0.05）, but not significant in patient group. Bite fork position also showed positive influence on ipsilateral muscle activities（P＜0.05）. Besides, muscle recruitment pattern of SCM showed similar tendency as that of masseter muscle during clenching at ICP, while no clear co-activation of masticatory muscles and SCM was found during unilateral bite tasks. Based on these findings, it can be concluded that the most significant factor influenced the muscle activities was the magnitude of bite force；however, masticatory muscles recruitment did not show significant difference at different jaw position in the patient group.

Background e obiettivi L’intolleranza all’esercizio fisico (ES), la sintomatologia e gli effetti extra-polmonari incrementano il rischio di disabilità, bassa qualità della vita (QoL) e sedentarietà nel paziente affetto da Broncopneumopatia Cronica Ostruttiva (BPCO). In riabilitazione respiratoria l’ES è considerato il principale intervento non farmacologico per incrementare la salute e la capacità di esercizio nei pazienti. Sfortunatamente, si rilevano pochi interventi strutturati di attività fisica (AF). Inoltre, un numero elevato di pazienti declina la partecipazione. Le ragioni di abbandono o non partecipazione sono state poco investigate. Inoltre, esiste un considerevole dibatto riguardo l’efficacia dei diversi modelli applicativi di AF nell’incrementare i parametri salute correlati (PSC) dei pazienti BPCO e il loro impatto sul mantenimento a lungo termine di uno stile di vita attivo. Infine, l’AF quotidiana, i PSC, la forza muscolare e la performance motoria dei pazienti BPCO sono intimamente correlati. Sebbene la disfunzione muscoolare sia presente in tutti i pazienti BPCO, è stato osservato che la contrazione eccentrica (ECC) è più elevata nei BPCO rispetto ai soggetti sani (HC). La maggior parte delle ricerche del settore hanno utilizzato parametri isometrici i concentrici (CON), però poco è conosciuto riguardo all’associazione tra forza ECC e alte velocità di contrazione nei pazienti BPCO. Pertanto gli studi proposti vogliono evidenziare le motivazioni e le barriere che riducono il reclutamento e impediscono a pazienti BPCO di acquisire uno stile di vita attivo. Inoltre, si vogliono verificare le modifiche ai PSC ottenute da due modelli di attività fisica adattata (AFA) specifici per BPCO e il loro impatto nell’acquisizione di uno stile di vita attivo. Infine si vogliono investigate le performance muscolari CON ed ECC degli arti inferiori dei pazienti BPCO a diverse velocità di contrazione. Metodi 1° studio: single-centre, multi-practice, parallel-group trial clinico randomizzato. 269 maschi affetti da BPCO males sono stati sottoposti a screening per individuare 132 pazienti elegibili. I 38 soggetti reclutati hanno compilato il questionario EMI-2. 2° studio: trial longitudinale, randomizzato. Sono state effettuate valutazioni ad inizio (T1), dopo 3 mesi (T2), 6 mesi (T3) and a 3 mesi di follow up (T4). La composizione corporea e il contenuto minerale osseo (BMC) tramite DXA, i parametri motori (6MWT, Leg press, leg extension, chest press e biceps curl 1RM, flessibilità del cingolo scapolo-omerale e della schiena, e l’equilibrio), lo stile di vita (IPAQ e registrazione SenseWear PRO-2) e la QoL (questionario MRF-26) sono stati investigati. 3° stadio: studio osservazionale, caso/controllo, cross over. Misure di architettura muscolare, contrazione CON ed ECC del quadricipite a diverse velocità (30deg/sec, 210 deg/sec), stile di vita e PSC di 35 pazienti con BPCO sono state confrontati con quelli rilevati in 25 soggetti sani di controllo (HC). Risultati 1° studio: la principale causa che impedisce la partecipazione è dovuta al non rispetto dei criteri di inclusione (65.53%). La mancanza di interesse (8.94%), di tempo disponibile (6.81%) e la difficoltà a raggiungere le strutture sportive (1.7%) sono le principali ragioni che inducono il paziente ad abbandonare il programma. Il reclutamento dello studio ha un’aderenza molto elevata (25.7%) in confronto alla letteratura di riferimento, confermato anche dal numero esiguo di drop out (10.52%). Bassi livelli iniziali di motivazione intrinseca da parte dei pazienti con BPCO sono stati rilevati (media 81.69pt ±48.08), sebbene miglioramenti statisticamente significativi si osservino solo nel gruppo FC dopo la partecipazione ad interventi di AF dopo 3 mesi (+43.99%, p<0.05) e 6 mesi (+47.42%, p<0.05). A 3 mesi modificano gli item socio/emotivi (p<0.01), di gestione ponderale (p<0.05) e di piacevolezza (p<0.01), riconfermandosi a 6 mesi (socio/emotivi p<0.01, piacevolezza p<0.05). 2° studio: 7 pazienti abbandono il programma nei 9 mesi. A breve termine, il gruppo FC incrementa significativamente i parametri di %BMC (0.112 ±0.029, p<0.01), Biceps curl 1RM (1.9kg ±0.6, p<0.05), Chest press 1RM (8.1kg ±1.7, p<0.001) ed equilibrio (48.5sec ±14.2, p<0.05). Modificazioni significative si rilevano nel gruppo EDU, i.e. grasso corporeo (-736.4g ±240.0, p<0.05), BMI (-0.332 ±0.106, p<0.05), Leg Extension 1RM (7.2kg ±2.4, p<0.05), Chest Press 1RM (6.1kg±1.7, p<0.05) e mobilità della spalla (2.7cm ±0.7, p<0.01). Il gruppo CG modifica i parametri di BMI (-0.588 ±0.157, p<0.01), grasso corporeo (-1086.4g ±365, p<0.05), and massa totale (-1849.8g ±494.1 p<0.01). A lungo termine, FC modifica significativamente %BMC (0.071 ±0.024 p<0.05), Chest Press 1RM (9.8kg ±2.4, p<0.01), equilibrio (57.0sec±13.3, p<0.01), quantità di attività moderata (1024 ±272, p<0.01), tempo totale in attività sedentaria (-3.3 ±0.7, p<0.01) and MRF-26 (-2.3 ±0.7, p<0.05). Il gruppo EDU riduce la percezione di sforzo al 6MWT (-1.37 ±0.41 p<0.05) e il tempo totale in attività sedentaria (-3.6 ±0.7, p=0.000), aumentando l’attività di cammino (618 ±208, p<0.05) e l’MRF-26 (-2.1 ±0.7, p<0.05). Al termine del follow up, il gruppo FC riduce i parametri di %BMC (-0.069 ±0.020 p<0.05), 6MWT (-48.2 ±14.8, p<0.05), Leg Extension 1RM (-9.3 ±2.8, p<0.05), Chest Press 1RM (-11.6 ±2.1, p=0.000), flessibilità del busto (-3.8 ±0.9, p<0.01) ed equilibrio (-21.0 ±7 p<0.05). Il gruppo EDU group riduce i parametri di Leg Press 1RM (-32.6 ±9.1, p<0.05), Leg Extension 1RM (-10+5 ±1.9, p<0.001), Chest Press 1RM (-14.3 ±1.3, p=0.000), flessibilità del cingolo scapolo-omerale (-4.3 ±1.3, p<0.05), tempo totale in attività sedentaria (-3.5 ±0.9, p<0.01) and MRF-26 (-2.9 ±0.8, p<0.05). anche il gruppo CG dimostra riduzioni al Chest Press 1RM (-10.9 ±2.6, p<0.01). Nessuna modificazione è stata osservata con il SenseWear PRO-2. 3° studio: I soggetti del gruppo HC presentano valori più elevati in termini di capacità d’esercizio, i.e. 6MWT (p<0.001) e 1RM alla Leg Press (p<0.05), rispetto ai pazienti BPCO. Solo il torque CON a 30deg/s è più elevato nei soggetti HC rispetto ai BPCO (p<0.05). Nessuna differenza statisticamente significativa è stata rilevata tra i gruppi per i parametri di architettura muscolare, torque CON a 210 deg/sec e nei toque ECC. Differenze significative si evidenziano nel rapporto tra torque ECC e CON (30 deg/sec p<0.001; 210 deg/sec p<0.01). Correlazioni significative sono state osservate tra FEV1 e 6MWT (0.719 p<0.001), 1RM Leg Press (0.449 p<0.001), torque a 30 deg/sec (0.427 p<0.01; 0.280 p<0.05), a 210 deg/sec (0.285 p<0.05; 0.276 p<0.05) and rapporto ECC/CON di torque ad entrambe le velocità (-0.562 p<0.001; -0.292 p<0.05). Le medesime osservazioni sono state rilevate tra FEV1/FVC e i parametri investigati. Conclusioni La principale barriera è rappresentata dai criteri di inclusione. La pratica di reclutamento effettuata da un singolo specialista sembra essere la più efficace. La supervisione dello specialista in AFA e l’aumento della collaborazione tra clinici e specialisti AFA potrebbe incrementare la partecipazione dei pazienti BPCO. Semplici modelli applicativi di AFA possono risultano efficaci ad incrementare sia la motivazione all’ES e sia alcuni dei PSC specifici per BPCO. Questi miglioramenti sembrano essere apportati prevalentemente dai “well rounded program”. Il supporto dello specialista APA risulta necessario per poter mantenere a lungo termine i guadagni ottenuti con l’ES. Invece, i miglioramenti di capacità funzionale non sembrano modificare lo stile di vita. Sebbene i pazienti BPCO siano caratterizzati da basse performance dei PSC, ridotta capacità di contrazione CON e stile di vita inattivo rispetto ai soggetti HC, sembrano preservare la contrazione ECC e il torque nelle contrazioni ad alta velocità. Ulteriori ricerche sembrano essere necessarie.
Background and aims Exercise intolerance, symptoms and extra-pulmonary effects may increase patients disabilities, affecting quality of life (QoL) and reducing maintenance of an active lifestyle. Exercise training (ExT) is considered the most effective non-pharmacological intervention to improve COPD patients health and exercise capacity. Unfortunately, there are few available health-care structured programs of physical activity (PA) and a considerable proportion of eligible patients decline participation or drop out. Reasons for decline and drop-out from ExT programs have seldom been investigated. Moreover, a considerable debate continues about what kind of model of PA and ExT intervention is more effective to improve COPD patients’ health related parameters (HRQL), and to maintain long-term active lifestyle. Finally, evidences support notions that daily physical activity (DPA), HRQL, muscle strength and performance are likely intimately interlinked. Although, muscle wasting is common in COPD patients across all disease stages, it has been observed that eccentric contraction (ECC) results greater compared to healthy control subjects. Majority of COPD leg muscle function’s research has used isometric or concentric (CON) quadriceps torque, but there is lack of knowledge about associa¬tion between ECC muscle strength and fast-velocity muscle contractions in COPD patients. Therefore, we would to outline motivation and barriers which reduced COPD patients recruitment in ExT program and hindered an active lifestyle acquisition. Secondly, it would be verify short and long-term modifications of several HRQL provided by two different and easily applied-field models of adapted fitness activity (APA) for COPD patients to evaluate long-term active-lifestyle maintenance. Finally, we would to investigate COPD patients lower limb strength performances as a function of contraction modalities and velocities comparing with healthy control (HC). Methods Fist study: single-centre, multi-practice, randomized, parallel-group clinical trial. 269 COPD males were screened to establish 132 eligible patients. 38 recruited COPD patients were administrated by EMI-2 questionnaire. Recruitment steps were recorded in order to assess patients’ motivation of decline or drop out. Second study: longitudinal randomized controlled trial, in which baseline (T1), 3 months (T2), 6 months (T3) and 3 months of follow up (T4) evaluations were performed. Body composition and bone mass content, i.e. BMC (DXA scanner), functional health-related (6MWT, Leg press, leg extension, chest press and biceps curl 1RM, shoulder and lower back flexibility and balance), lifestyle (IPAQ questionnaire and SenseWear PRO-2 assessment) and quality of life (MRF-26 questionnaire) parameters were administrated. 38 COPD patients were randomized and assigned to one of the three evaluation groups: Fitness Center based group (FC=13), Educational PA group (EDU=12) and Control group (CG=13). Third study: case/control research, cross over and observational trial. Architectural muscle measurements, CON and ECC quadriceps contractions at different velocities (30deg/sec, 210 deg/sec), lifestyle and health-related parameters of COPD patients (N=35) and HC (N=25) subjects were recorded. Results First study: major cause of not-participation was mismatched inclusion criteria (65.53%). No-interest in exercise training (8.94%), lack of available time (6.81%) and inability to access at the PA structures (1.7%) were most commonly cited reasons to drop out. Recruitment showed higher adherence (25.7%) compared to literature, also confirmed by lower number of drop out (10.52%). Low score of intrinsic motivation towards PA were recorded (mean 81.69pt ±48.08) and significant improvements in EMI-2 were observed after 3 months (+43.99%, p<0.05) and 6 months of ExT (+47.42%, p<0.05) by FC group. Significant increases in Socio/Emotional (p<0.01), Weight management (p<0.05) and Enjoyment items (p<0.01) were recorded after 3 months. Socio/Emotional aspects (p<0.01) and Enjoyment items (p<0.05) improved after 6 months. Second study: 7 patients dropped out. At short term, FC group shows significant improvement in %BMC (0.112 ±0.029, p<0.01), Biceps curl 1RM (1.9kg ±0.6, p<0.05), Chest press 1RM (8.1kg ±1.7, p<0.001) and Balance test (48.5sec ±14.2, p<0.05). EDU group shows significant modification in Fat (-736.4g ±240.0, p<0.05), BMI (-0.332 ±0.106, p<0.05), Leg Extension 1RM (7.2kg ±2.4, p<0.05), Chest Press 1RM (6.1kg±1.7, p<0.05) and Shoulder flexibility (2.7cm ±0.7, p<0.01). The CG group shows significant differences in BMI (-0.588 ±0.157, p<0.01), Fat (-1086.4g ±365, p<0.05), and Total Body Mass (-1849.8g ±494.1 p<0.01). At long-term, FC modified significantly %BMC (0.071 ±0.024 p<0.05), Chest Press 1RM (9.8kg ±2.4, p<0.01), Balance (57.0sec±13.3, p<0.01), IPAQ moderate activity (1024 ±272, p<0.01), IPAQ sedentary hours (-3.3 ±0.7, p<0.01) and MRF-26 (-2.3 ±0.7, p<0.05). EDU group recorded modifications in 6MWT Borg scale (-1.37 ±0.41 p<0.05), IPAQ walking activity (618 ±208, p<0.05), IPAQ sedentary hours (-3.6 ±0.7, p=0.000) and MRF-26 (-2.1 ±0.7, p<0.05). CG group did not shows significant differences. At follow up, FC shows significant changes in %BMC (-0.069 ±0.020 p<0.05), 6MWD (-48.2 ±14.8, p<0.05), Leg Extension 1RM (-9.3 ±2.8, p<0.05), Chest Press 1RM (-11.6 ±2.1, p=0.000), Sit & Reach (-3.8 ±0.9, p<0.01), Balance (-21.0 ±7 p<0.05). EDU group shows significant modification in 6MWT Borg score (-1.36 ±0.41 p<0.05), Leg Press 1RM (-32.6 ±9.1, p<0.05), Leg Extension 1RM (-10+5 ±1.9, p<0.001), Chest Press 1RM (-14.3 ±1.3, p=0.000), Back Scratch (-4.3 ±1.3, p<0.05), IPAQ sedentary hours (-3.5 ±0.9, p<0.01) and MRF-26 (-2.9 ±0.8, p<0.05). CG group shows significant difference in Chest Press 1RM (-10.9 ±2.6, p<0.01). No significant modification were observed in SenseWear PRO-2 administration. Third study: HC subjects were significantly different in exercise capacity, i.e. 6MWT (p<0.001) and 1RM Leg Press (p<0.05), than COPD patients. Only CON 30deg/s peak torque was significantly higher in HC compared to COPD (p<0.05). No differences in muscle architecture, fast CON and/or e ECC torque were observed between groups. Significant differences were found between groups in ECC/CON torque ratio (30 deg/sec p<0.001; 210 deg/sec p<0.01). Finally, significant correlations were found between FEV1 and 6MWT (0.719 p<0.001), 1RM Leg Press (0.449 p<0.001), peak torque contraction at 30 deg/sec (0.427 p<0.01; 0.280 p<0.05), at 210 deg/sec (0.285 p<0.05; 0.276 p<0.05) and ECC/CON peak torque ratio at both velocities (-0.562 p<0.001; -0.292 p<0.05). Same results were observed between FEV1/FVC and parameters assessed. Conclusions Recruit COPD patients becomes very challenging. Cause of not-participation was related to mismatched inclusion criteria. Great effort practice of recruitment, managed by only one person, seems to be more effective. Supervision of ExT specialist and incresed level of liaison between specialist physicians and healthcare professionals could be useful to increase participation. An easily applied-field models of COPD specific APA training could be efficient in order to improve some of COPD-specific HRQL. These improvements seem to be better provide by a “well rounded” APA program. APA exercise specialist support is necessary to maintain long-term significant health’s gains. Whereas, improvement in functional exercise capacity does not automatically turn into a more active lifestyle. COPD patients are characterized by lower health related parameters and lifestyle. Also COPD performed lower CON contraction compared to HC. COPD preserved ECC contractions and fast concentric torque. We hypothesize that COPD males develop a favorable profile to minimize strength loss likely due to neural-muscular modification. Further studies are aimed.

Recent attention has focused on the performance of sample selection techniques employed in clinical research. In studies having a specified, yet arbitrary, target population, one objective of recruiting is to limit enrollment to members of this group. However, when eligibility is determined by observations of a continuous response variable, ineligible patients may be enrolled due to the misclassification resulting from truncated sampling. It is believed that these screening failures will have a negative impact on a study although the severity of the effect is unknown. This study examined the potential effects of truncated sampling under a variety of different situations Adopting a clinical model provided by cardiovascular research, computer simulations examined the potential effects of five experimental factors on clinical trials. Outcomes of interest included the true sample mean, probability of misclassification, cost of recruiting and power of ANOVA to detect a time by treatment interaction (which is known to exist). Simulation results demonstrated that sample characteristics were dependent upon the population variance structure, selection rule, and truncation limit. In addition, power was influenced by the truncation limit employed and size of the study sample. These latter effects were compared to evaluate the feasibility of employing the truncation limit as a design variable It was concluded that the conventional sample selection rule employing multiple qualifying observations performs best in terms of power. However, if safety and/or cost considerations are important, a modified plan requiring fewer screening observations provides a reasonable alternative. Based on the results of these simulations, the specification of truncation limits as a means of controlling power could not be recommended
acase@tulane.edu

Epilepsy is a common neurological disorder, with potentially devastating consequences, and thus, elucidating the etiology bears immense potential for developing methods for early detection and prevention, targeted treatment options, and overall improvements to quality of life for millions of people worldwide. In 2007, the Epilepsy Phenome/Genome Project (EPGP) set out to compile the largest ever, detailed phenotype-genotype dataset to begin to unravel the complex genetic underpinnings of epilepsy. Over the course of five years, the EPGP sought to enroll a total of 5,250 participants consisting of two cohorts: 1,500 pairs of first-degree relatives with idiopathic generalized epilepsy or localization related epilepsy and 750 triads, or individuals diagnosed with Infantile Spasms, Lennox-Gastaut Syndrome, or certain malformations of cortical development and their unaffected, biological parents. Enrolling an adequate number of eligible research participants is paramount to any study involving human subjects. Despite this, barriers to participant recruitment and accrual persist in a majority of trials, and literature pertaining to methods for overcoming such challenges remains scarce. Like most clinical trials, the EPGP encountered obstacles to participant accrual, and by the end of its first year, net participant enrollment was only 52% of the projected target for that time. To ameliorate this, the EPGP's central administrative team set in motion a multifaceted, dynamic participant recruitment campaign to bolster outreach and increase enrollment numbers. A systematic, retrospective review of the various participant recruitment methods and their respective outcomes was performed. Data was compiled from the EPGP's reporting server, central recruitment database, and other relevant reports and files compiled by the EPGP's administrative team. The various methods implemented by the EPGP to boost participant enrollment include hiring a full-time recruitment director, implementing a National Participant Recruitment Campaign and centralized eligibility pre-screening process, revising the protocol and eligibility criteria, and nearly doubling the size of the network of clinical centers. The centralized screening process facilitated a mechanism for tracking the amount of traffic each recruitment method generated, and this information was analyzed retrospectively. The most successful recruitment methods were found to be those that involved partnerships with healthcare providers and community organizations who have direct and widespread access to the EPGP's target patient population. Less effective methods, in terms of percent of contacts meeting eligibility criteria, were those that did not specifically target people with epilepsy but rather reached a larger demographic. In total, more than 2,000 individuals or families contacted the EPGP centrally, 80% of those underwent eligibility pre-screening with 242 units (579 participants) enrolled in the EPGP as of February 2014. This accounts for 14% of enrollment study-wide, which is analogous to the individual contributions of the EPGP' top enrolling clinical centers. Beyond the recruitment strategies and methods implemented by the campaign, revisions to the EPGP's protocol, modifications to the eligibility criteria, and network expansion resulted in an increase in participant accrual. The number of clinical centers involved in the EPGP was found to positively correlate with participant accrual. Ultimately, a total of 5,442 participants, or 104% of the total enrollment target, were consented to participate. Of those, 4,099 participants, or 78% of the total enrollment target, remain enrolled as of February 28, 2014. The EPGP enrolled more than 75% of target for five of the seven participant types and managed to enroll no less than 50% of target for all participant types. While the results reported are limited by an analysis of the resources required to initiate and carry out the various recruitment methods, the lessons learned during the course of the EPGP may serve to benefit other multi-institutional trials with similar considerations in their recruitment planning. The EPGP's approach to boosting participant accrual was not only successful but also essential to paving the way towards identifying the complex genetic causes and phenotypic manifestations of idiopathic epilepsy syndromes.

Yes
Printed participant information about randomised controlled trials is often long, technical and difficult to navigate. Improving information materials is possible through optimisation and user-testing, and may impact on participant understanding and rates of recruitment. Methods: A study within a trial (SWAT) was undertaken within the CASPER trial. Potential CASPER participants were randomised to receive either the standard trial information or revised information that had been optimised through information design and user testing. Results: A total of 11,531 patients were randomised in the SWAT. Rates of recruitment to the CASPER trial were 2.0% in the optimised information group and 1.9% in the standard information group (odds ratio 1.027; 95% CI 0.79 to 1.33; p=0.202). Conclusions: Participant information that had been optimised through information design and user testing did not result in any change to rate of recruitment to the host trial. Registration: ISRCTN ID ISRCTN02202951; registered on 3 June 2009.
UK National Institute of Health Research Health Technology Assessment Programme (project number 08/19/04)
This article is included in the Studies Within A Trial (SWAT) collection (https://f1000research.com/collections/swat)

Indiana University-Purdue University Indianapolis (IUPUI)
Poor long-term kidney transplant outcomes are a significant problem in the U.S. Interventions must focus on preserving allograft function by managing modifiable risk factors. An instrument capable of identifying problems with post-kidney transplant self-management behaviors may enable the design and testing of self-management interventions. This study’s purpose was to test the psychometric properties of the new Kidney Transplant Self-Management Scale (KT–SM). The Zimmerman framework adapted for kidney transplant self-management guided the cross-sectional study. A total of 153 kidney recipients recruited from Facebook® completed the Self-Efficacy for Managing Chronic Disease (SEMCD), Patient Activation Measure (PAM), Kidney Transplant Questionnaire (KTQ), and KT–SM Scale instruments via a REDCap® survey. Most participants were female (65%), White (81.7%), and middle-aged (M = 46.7; SD = 12.4 years) with a history of dialysis (73%) and received a kidney transplant an average of 6.58 years previous (SD = 6.7). Exploratory factor analysis results supported the 16-item KT–SM Scale as a multidimensional scale with five domains with loadings ranging between .39 and .89: medication adherence, protecting kidney, cardiovascular risk reduction, ownership, and skin cancer prevention. Internal consistency reliability for the total scale (Cronbach’s α = .84) and five domains ranged from .71 to .83. The total and domains were positively correlated, ranging from r = .51 to .76, p = .01. Criterion-related validity was evidenced by significant correlations of KT–SM and domains with SEMCD (r =.22 to .53, p = .01), PAM (r = .31 to .52, p = .01), and the overall KTQ (r = .20 to .32, p = .01) except for one KT–SM domain: protecting kidney. Construct validity was evaluated using multivariate regression analysis. The linear combination of age, patient activation, and self-efficacy explained 45% of the variance in KT–SM behaviors; 47% of the variance in KTQ (measuring quality of life) was predicted by age, comorbidity, and self-efficacy. These findings provide beginning evidence of reliability and validity for the newly developed KT–SM scale. Instruments like this may provide a means to capture the self-management behaviors of the kidney transplant population, which is critical for future work on interventions.

To ensure quality patient care hospitals invest in nursing intellectual capital by allocating financial, human and material resources for nurses to acquire the knowledge and skills necessary to provide safe patient care. This study’s purpose was to test selected propositions of the middle-range theory of nursing intellectual capital which provides a conceptualization of the influence of nurses’ knowledge, skills and experience (nursing human capital) to patient and organizational outcomes. The theory was systematically developed after a critical review of the literature. It proposes that nursing human capital (registered nurses’ experience, and knowledge and skills acquired from continuing professional development including university courses, conferences, workshops, in-services, specialty certification) is related to variables within the work environment (nurse staffing, employer support for nurse continuing professional development), which in turn, is associated with the quality of patient care (adverse events) and the recruitment and retention of nurses. The theory also proposes that nursing structural capital, nursing knowledge available within practice guidelines, is associated with the quality of patient care. A cross-sectional design was used to test the proposed relationships. The study took place in 6 acute care hospitals in two provinces of Canada. Financial, human resource and risk management data were collected from hospital departmental databases and a survey of unit managers. Data from 91 inpatient units were used with structural equation modeling to test the theory’s propositions. The results indicated that nurses’ knowledge and skills represented by the proportion of RNs with degrees and proportion of RNs with specialty certification were directly associated with low hospital-acquired infection rates. Nurse experience, measured as mean years RN professional experience and RN unit tenure, was found to be significantly related to higher RN recruitment and retention. The proportion of RNs with degrees was found to partially mediate the influence of nurse staffing on hospital-acquired infections. The results provide preliminary evidence of the association of nursing intellectual capital with patient and organizational outcomes. The findings may assist administrators with fiscal and human resource decision-making related to the education of nurses within acute care hospitals, and professional organizations with policies governing nursing education and continuing professional development.

BACKGROUND: Bradford, one of the most deprived cities in the United Kingdom, has a wide range of public health problems associated with socioeconomic deprivation, including an infant mortality rate almost double that for England and Wales. Infant mortality is highest for babies of Pakistani origin, who comprise almost half the babies born in Bradford. The Born in Bradford cohort study aims to examine environmental, psychological and genetic factors that impact on health and development perinatally, during childhood and subsequent adult life, and those that influence their parents' health and wellbeing. This protocol outlines methods for the recruitment phase of the study. METHODS: Most Bradford women attend for antenatal care and give birth at the Bradford Royal Infirmary, which has approximately 5,800 births per year. Women are eligible for recruitment if they plan to give birth here. Babies born from March 2007 are eligible to participate, recruitment is planned to continue until 2010. Fathers of babies recruited are invited to participate. Women are usually recruited when they attend for a routine oral glucose tolerance test at 26-28 weeks gestation. Recruitment of babies is at birth. Fathers are recruited whenever possible during the antenatal period, or soon after the birth. The aim is to recruit 10,000 women, their babies, and the babies' fathers. At recruitment women have blood samples taken, are interviewed to complete a semi-structured questionnaire, weighed, and have height, arm circumference and triceps skinfold measured. Umbilical cord blood is collected at birth. Within two weeks of birth babies have their head, arm and abdominal circumference measured, along with subscapular and triceps skinfold thickness. Fathers self-complete a questionnaire at recruitment, have height and weight measured, and provide a saliva sample. Participants are allocated a unique study number. NHS numbers will be used to facilitate record linkage and access to routine data. A wide range of hospital and community sources is being accessed to provide data for the women and children. Data are checked for accuracy and consistency. CONCLUSION: Born in Bradford will increase understanding of the factors that contribute to health and wellbeing, and identify factors that influence differences in them between people of Pakistani and European origin.

Dissertação de Mestrado em Farmacologia Aplicada apresentada à Faculdade de Farmácia
A investigação clínica representa uma atividade de valor no desenvolvimento de novos medicamentos, encontrando-se em exponencial evolução em Portugal. Esta apresenta benefícios sociais e económicos importantes e possibilita o acesso precoce, por parte dos doentes, a moléculas inovadoras, contribuindo igualmente para uma melhoria da prestação de cuidados de saúde e favorecendo a esperança e qualidade de vida da população portuguesa.Os ensaios clínicos possuem grande relevância, promovendo o desenvolvimento nacional. Constata-se, no entanto, que a realização de ensaios clínicos em Portugal é significativamente inferior à de outros países de dimensão semelhante, pelo que se pode concluir que ainda não foi alcançado todo o potencial nacional em ensaios clínicos. Portugal tem perdido competitividade nesta área, sendo necessário investir na Investigação e Desenvolvimento (I&D). Existem diversas barreiras à evolução e desenvolvimento de ensaios clínicos sob a perspetiva dos profissionais de equipas de investigação, promotores e CROs (Organizações de Investigação Contratadas), que através da resposta a questionários desenvolvidos para o efeito classificaram em termos de relevância, numa escala de Likert, diversos aspetos que podem contribuir para um centro de ensaios clínicos de excelência. Destes destacaram aqueles que constituem um impedimento à seleção de centros de ensaios clínicos em Portugal. Estes incluem a alocação insuficiente de recursos humanos, a inadequação de instalações e equipamentos disponíveis, constrangimentos no recrutamento e participação em ensaios clínicos e a fraca dedicação à qualidade de todos os procedimentos. No entanto, observa-se que Portugal possui uma grande capacidade de desenvolvimento e aperfeiçoamento, apresentando equipas com crescente grau de formação académica e tempo de dedicação, nomeadamente os seus investigadores e coordenadores de ensaios clínicos, e, portanto, com grande potencial para se tornar uma referência a nível internacional na área de I&D.Neste sentido, de modo a tornar Portugal um país competitivo, é de grande importância a identificação e monitorização dos principais fatores que contribuem para o progresso dos ensaios clínicos, sendo determinantes para a seleção dos centros de ensaios clínicos portugueses, dinamizando esta atividade em Portugal.
Clinical research represents a valuable activity in the development of new therapies and is undergoing an exponential evolution in Portugal. It has significant social and economic benefits and allows patients to have early access to innovative molecules, contributing to an improvement in health care services, improving life expectancy and quality of life of the Portuguese population.Clinical trials have great relevance, promoting national development. However, it is observed that the conduct of clinical trials in Portugal is significantly lower than in other countries of similar size, so it can be concluded that the full national potential in clinical trials has not yet been achieved. Portugal has lost competitiveness in this area, making it necessary to invest in Research and Development (R&D). There are several barriers to the evolution and development of clinical trials, from the perspective of professionals from research teams, sponsors and CROs (Contract Research Organizations), who, by responding to questionnaires developed for this purpose, rated in terms of relevance, on a Likert scale, several aspects that may contribute to a clinical trial site of excellence. Of these, they highlighted those that constitute an impediment to the selection of clinical trial sites in Portugal. These include insufficient allocation of human resources, inadequacy of available facilities and equipment, constraints on recruitment and participation in clinical trials, and poor dedication to the quality of all procedures. However, it is observed that Portugal has a great capacity for development and improvement, presenting teams with increasing degrees of academic formation and time dedication, namely its researchers and clinical trial coordinators, and, therefore, with great potential to become an international reference in R&D.In this sense, to make Portugal a competitive country, it is of great importance to identify and monitor the main factors that enable and contribute to the progress of clinical trials, being determinant for the selection of Portuguese clinical trial sites, dynamizing this activity in Portugal.