Journal articles: 'NNH'

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Raju, Gokaraju K., Sean Khozin, Karthik Gurumurthi, Reuben Domike, and Janet Woodcock. "Patient-Centered Approach to Benefit–Risk Characterization Using Number Needed to Benefit and Number Needed to Harm: Advanced Non–Small-Cell Lung Cancer." JCO Clinical Cancer Informatics, no. 4 (September 2020): 769–83. http://dx.doi.org/10.1200/cci.19.00103.

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This work summarizes the benefit and risk of the results of clinical trials submitted to the US Food and Drug Administration of therapies for the treatment of non–small cell lung cancer (NSCLC) using number needed to benefit (NNB) and number needed to harm (NNH) metrics. NNB and NNH metrics have been reported as potentially being more patient centric and more intuitive to medical practitioners than more common metrics, such as the hazard ratio, and valuable to medical practitioners in complementing other metrics, such as the median time to event. This approach involved the characterization of efficacy and safety results in terms of NNB and NNH of 30 clinical trials in advanced NSCLC supporting US Food and Drug Administration approval decisions from 2003 to 2017. We assessed trends of NNB over time of treatment (eg, for programmed death 1 inhibitors) and variation of NNB across subpopulations (eg, characterized by epidermal growth factor receptor mutation, programmed death ligand 1 expression, Eastern Cooperative Oncology Group performance status, age, and extent of disease progression). Furthermore, the evolution of NNB of treatments for advanced NSCLC was charted from 2003 to 2017. Across subpopulations, NNB, on average, was 4 patients for approved targeted therapies in molecularly enriched populations, 11 patients for approved therapies in nonmolecularly enriched populations, and 23 patients for withdrawn or unapproved therapies. Furthermore, the NNB analysis showed variation for attributes of epidermal growth factor receptor mutations, level of programmed death 1 expression, Eastern Cooperative Oncology Group performance status, etc. When considering the best-case subpopulations and available drugs, the NNB frontier reduced from an estimated value of 7.7 in 2003 to an estimated value of 2.5 in 2017 at the estimated median overall survival—equal to 6 months—of an untreated patient.

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Ma, Teng, Yuanlu Wang, Fengliang Wang, and Fei Li. "catena-Poly[[dichloridomercury(II)]-N′-nicotinoylnicotinohydrazide]." Acta Crystallographica Section E Structure Reports Online 68, no. 4 (March 3, 2012): m367. http://dx.doi.org/10.1107/s1600536812008884.

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The title complex, [HgCl2(C12H10N4O2)]n, is composed of one HgIIion, one nnh ligand (nnh =N′-nicotinoylnicotinohydrazide) and two coordinated chloride ions. The HgIIion shows a distorted tetrahedral geometry, being surrounded by two N atoms from two nnh ligands and two chloride ions. Due to the bridging role of nnh, the HgIIatoms are connected into polymeric chains along thecaxis, which are further interlinkedviaN—H...O and C—H...Cl hydrogen-bonding interactions, forming a three-dimensional network.

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Lehner, A., and C. Schlegel-Wagner. "Souvenir einer endoskopischen NNH-Operation." Laryngo-Rhino-Otologie 95, no. 09 (July 18, 2016): 636–38. http://dx.doi.org/10.1055/s-0042-107355.

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Bauer-Delto, Angelika. "Optimierte NNH-Chirurgie mit Powernavigation." HNO Nachrichten 43, no. 6 (December 2013): 44. http://dx.doi.org/10.1007/s00060-013-0226-0.

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Matsuura, Hideharu, Akinobu Takeshita, Tatsuya Imamura, Kota Takano, Kazuya Okuda, Atsuki Hidaka, Shi Yang Ji, et al. "Comparison of Conduction Mechanisms in Heavily Al-Doped 4H-SiC and Heavily Al- and N-Codoped 4H-SiC." Materials Science Forum 924 (June 2018): 188–91. http://dx.doi.org/10.4028/www.scientific.net/msf.924.188.

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The conduction mechanism in heavily Al-doped or heavily Al-and N-codoped p-type 4H-SiC epilayers was investigated. In both the singly-doped and codoped samples with an Al concentration (CAl) between 4x1019 and 2x1020 cm-3, band and nearest-neighbor hopping (NNH) conductions appeared in high and low temperature ranges, respectively. The codoping of N donors makes the NNH conduction dominant at temperatures higher than in the singly-doped samples. In both the singly-doped and codoped samples with CAl between 1x1019 and 4x1019 cm-3, an unexpected conduction appeared between the regions of the band and NNH conductions.

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Oussi, Ninos, Konstantinos Georgiou, Andreas Larentzakis, Dimitrios Thanasas, Markus Castegren, Evangelos Georgiou, and Lars Enochsson. "Validation of a Novel Needle Holder to Train Advanced Laparoscopy Skills to Novices in a Simulator Environment." Surgical Innovation 27, no. 2 (February 1, 2020): 211–19. http://dx.doi.org/10.1177/1553350619901222.

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Background. Our aim was to determine if a newly designed Najar needle holder (NNH) shortens the time for novices to improve advanced laparoscopy (AL) techniques (suturing/knot tying), compared with a conventional macro needle holder (MNH) in a simulator. Furthermore, we aimed to validate a new video scoring system determining AL skills. Methods. Forty-six medical students performed identical surgical tasks in a prospective, crossover study evaluating AL skills (NNH vs MNH). All subjects performed a double-throw knot, 2 single-throw knots following 3 running sutures in the Simball Box (SB) simulator. After resting, subjects switched needle holders. All tasks were videotaped and analyzed using SB software and by 2 independent reviewers using the Objective Video Evaluation Scoring Table (OVEST). Trial performance expressed as SB Overall Score (SBOS) and OVEST. Results. In the group starting with NNH (followed by MNH) OVEST was consistently high during both trials (median = 12.5, range = 6.5-18.0, and median = 13.5, range = 6.5-21.0; P = .2360). However, in the group starting with MNH, OVEST improved significantly when the participants changed to NNH (median = 10.0, range = 2.5-19.5, vs median = 14.5, range = 4.5-18.0; P = .0003); an improvement was also found with SBOS (median = 37%, range = 27% to 92%, vs median = 48%, range = 34% to 70%; P = .0289). In both trials, both independent reviewers’ OVEST measures correlated well: Trial 1: β = 0.97, P < .0001; and Trial 2: β = 0.95, P < .0001. A correlation also existed between SBOS and OVEST in both trials (β = 2.1, P < .0001; and β = 1.9, P = .0002). Conclusions. This study indicates a significantly higher improvement in laparoscopic suturing skills in novices training AL skills using NNH compared with MNH. Starting early, AL training in novices using NNH is a feasible option. Furthermore, OVEST used in experimental settings as an evaluation tool is comparable with the validated SBOS.

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George, Daniel J., A. Reginald Waldeck, Helen Guo, and Alexander J. Upton. "Number needed to harm (NNH) in patients with non-metastatic, castration-resistant prostate cancer (nmCRPC): A final analysis from the darolutamide (D), enzalutamide (E), and apalutamide (A) clinical trials." Journal of Clinical Oncology 40, no. 28_suppl (October 1, 2022): 326. http://dx.doi.org/10.1200/jco.2022.40.28_suppl.326.

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326 Background: Second generation androgen receptor inhibitors (ARI) D, A and E, approved for the treatment of nmCRPC, offer benefit in overall survival (OS) and metastasis-free survival (MFS), but do so with different risk-benefit profiles. Contextualizing risks of adverse events (AEs), or harm to patients, can be challenging. NNH is a trial-based measure that evaluates the number of patients who need to receive treatment before a harmful outcome occurs with the intervention, compared to the control. Thus, a higher NNH reflects a lower incremental likelihood of harm. This study is an update to a previous NNH analysis, utilizing final data from the ARI randomized controlled trials (RCTs). Methods: MEDLINE and EMBASE were searched for relevant RCTs. AEs occurring in ≥5% of either RCT arm were extracted from the final ARAMIS (D), SPARTAN (A) and PROSPER (E) publications. NNH by AE (all grade, grade 3 & 4) were calculated over the duration of each RCT based on reported rates, using the inverse of the absolute risk increase [1 / (experimental AE rate - control AE rate)]. An exploratory analysis considered the application of results to a US population, assuming trial-based AE rates to be representative of real-world rates. Results: Results show a trend of higher (i.e., favorable) NNH for AEs for D in ARAMIS across all grade and grade 3-4 AEs (Table), indicating a lower likelihood of incremental harm across AEs including fatigue, falls, hypertension and fracture for D versus A and E. Focusing on fatigue, fall and fractures, and selecting treatment with the highest (D) and lowest (A or E) NNH for an estimated 24,000 US high risk nmCRPC patients annually, treatment with D would translate to 4,073 fewer all-grade fatigue events, 2,928 fewer falls, and 2,383 fewer fractures compared to treatment with A (falls) or E (fatigue or fracture). Conclusions: The findings show a consistent trend of higher NNH (favorability) for D compared to A and E. The differences in their respective AE profiles are noteworthy not only for patients, but also for healthcare systems considering the overall risk-benefit amongst these three ARIs. Comparing D, A, and E directly in a single study may further inform their comparative profiles.[Table: see text]

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Wang, Qiying, and Ying Xiang Rachel Wang. "NONPARAMETRIC COINTEGRATING REGRESSION WITH NNH ERRORS." Econometric Theory 29, no. 1 (July 6, 2012): 1–27. http://dx.doi.org/10.1017/s0266466612000205.

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This paper studies a nonlinear cointegrating regression model with nonlinear nonstationary heteroskedastic error processes. We establish uniform consistency for the conventional kernel estimate of the unknown regression function and develop atwo-stage approach for the estimation of the heterogeneity generating function.

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Davis, John W., and Susan C. Weller. "Intensity of statin therapy and muscle symptoms: a network meta-analysis of 153 000 patients." BMJ Open 11, no. 6 (June 2021): e043714. http://dx.doi.org/10.1136/bmjopen-2020-043714.

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ObjectiveTo estimate relative risk (RR) of statin-associated musculoskeletal symptoms by statin therapy intensity.SettingNetwork meta-analysis assessing multicentre randomised controlled trials (RCTs) across several countries.ParticipantsPubMed, Web of Science, Cochrane database and ClinicalTrials.gov were searched through January 2021 for doubled-blinded RCTs testing the effect of statin therapy on lipids with at least 1000 participants and 2 years of intended treatment. Two coders assessed articles for final inclusion, quality and outcomes. Treatment intensity was categorised according to American Heart Association definitions.OutcomesPairwise and network meta-analysis (NMA) estimated RR and risk difference with random effects modelling. Heterogeneity was evaluated with the I2 statistic. Outcomes included muscle symptoms (any, myalgia and attrition due to muscle symptoms), rhabdomyolysis and elevated creatine kinase (CK) (>10 × upper limit of normal).ResultsOf 2919 RCTs, 24 (n=152 461) met inclusion criteria. NMA results indicated risk was significantly greater for high compared with moderate intensity statin therapy for any muscle problem (RR=1.04, 95% CI 1.00 to 1.07; I2=0%), myalgia (RR=1.04, 95% CI 1.00 to 1.08; I2=0%, number needed to harm (NNH)=173), attrition due to muscle problems (RR=1.37, 95% CI 1.09 to 1.73, I2=0%, NNH=218) and elevated CK (RR=4.69, 95% CI 2.50 to 8.80; I2=7%, NNH=527). Risk also was significantly higher for high intensity compared with placebo for any muscle problem (RR=1.05, 95% CI 1.01 to 1.09, I2=0%), myalgia (RR=1.13, 95% CI 1.05 to 1.23; I2=0%, NNH=182), attrition due to muscle problems (RR=1.55, 95% CI 1.15 to 2.08, I2=0%, NNH=187) and elevated CK (RR=5.37, 95% CI 2.48 to 11.61; I2=7%, NNH=589). Due to inconsistency of results across sensitivity analyses, estimates were inconclusive for rhabdomyolysis and CK. There were no significant differences in risk between moderate intensity therapy and placebo for all outcomes.ConclusionsFor approximately each 200 patients on high intensity statins, one additional patient may experience myalgia or discontinue therapy due to muscle problems compared with moderate intensity therapy.Trial registration numberCRD42019112758.

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Cainzos-Achirica, Miguel, Michael D. Miedema, John W. McEvoy, Mahmoud Al Rifai, Philip Greenland, Zeina Dardari, Matthew Budoff, et al. "Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019." Circulation 141, no. 19 (May 12, 2020): 1541–53. http://dx.doi.org/10.1161/circulationaha.119.045010.

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Background: Recent American College of Cardiology/American Heart Association Primary Prevention Guidelines recommended considering low-dose aspirin therapy only among adults 40 to 70 years of age who are at higher atherosclerotic cardiovascular disease (ASCVD) risk but not at high risk of bleeding. However, it remains unclear how these patients are best identified. The present study aimed to assess the value of coronary artery calcium (CAC) for guiding aspirin allocation for primary prevention by using 2019 aspirin meta-analysis data on cardiovascular disease relative risk reduction and bleeding risk. Methods: The study included 6470 participants from the MESA Study (Multi-Ethnic Study of Atherosclerosis). ASCVD risk was estimated using the pooled cohort equations, and 3 strata were defined: <5%, 5% to 20%, and >20%. All participants underwent CAC scoring at baseline, and CAC scores were stratified as =0, 1 to 99, ≥100, and ≥400. A 12% relative risk reduction in cardiovascular disease events was used for the 5-year number needed to treat (NNT 5 ) calculations, and a 42% relative risk increase in major bleeding events was used for the 5-year number needed to harm (NNH 5 ) estimations. Results: Only 5% of MESA participants would qualify for aspirin consideration for primary prevention according to the American College of Cardiology/American Heart Association guidelines and using >20% estimated ASCVD risk to define higher risk. Benefit/harm calculations were restricted to aspirin-naive participants <70 years of age not at high risk of bleeding (n=3540). The overall NNT 5 with aspirin to prevent 1 cardiovascular disease event was 476 and the NNH 5 was 355. The NNT 5 was also greater than or similar to the NNH 5 among estimated ASCVD risk strata. Conversely, CAC≥100 and CAC≥400 identified subgroups in which NNT 5 was lower than NNH 5 . This was true both overall (for CAC≥100, NNT 5 =140 versus NNH 5 =518) and within ASCVD risk strata. Also, CAC=0 identified subgroups in which the NNT 5 was much higher than the NNH 5 (overall, NNT 5 =1190 versus NNH 5 =567). Conclusions: CAC may be superior to the pooled cohort equations to inform the allocation of aspirin in primary prevention. Implementation of current 2019 American College of Cardiology/American Heart Association guideline recommendations together with the use of CAC for further risk assessment may result in a more personalized, safer allocation of aspirin in primary prevention. Confirmation of these findings in experimental settings is needed.

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ZABRODSKII, A. G., and A. G. ANDREEV. "THE HOPPING CONDUCTION OF NEUTRON TRANSMUTED GERMANIUM." International Journal of Modern Physics B 08, no. 07 (March 30, 1994): 883–89. http://dx.doi.org/10.1142/s0217979294000427.

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An investigation was made of a batch of samples of neutron transmutation-doped (NTD) Ge:Ga with the degree of compensation K=0.3 and the concentration of the main impurity (Ga) from N=3.6 · 1014cm−3 to Nc=2.5 · 1017cm−3, corresponding to the MI transition. The following were studied: the parameters of NTD Ge:Ga, the temperature dependence of hopping transport, the ɛ3 region of the nearest neighbor hopping (NNH), the saturation of NNH, variable range hopping (VRH) and the Coulomb gap.

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Oberholzer, Katja, H. U. Kauczor, C. P. Heußel, G. Derigs, and M. Thelen. "Klinische Relevanz der NNH-CT vor Knochenmarktransplantation." RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren 166, no. 06 (June 1997): 493–97. http://dx.doi.org/10.1055/s-2007-1015465.

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Sedgwick, P. "What is number needed to harm (NNH)?" BMJ 347, aug02 1 (August 2, 2013): f4869. http://dx.doi.org/10.1136/bmj.f4869.

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Konnov, A. A., G. Colson, and J. De Ruyck. "The new route forming NO via NNH." Combustion and Flame 121, no. 3 (March 2000): 548–50. http://dx.doi.org/10.1016/s0010-2180(99)00164-9.

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Citrome, Leslie, James Norton, Kathy Chi-Burris, and George Demos. "152 Pimavanserin for the Treatment of Parkinson’s Disease Psychosis: Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed." CNS Spectrums 23, no. 1 (February 2018): 94–95. http://dx.doi.org/10.1017/s1092852918000469.

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AbstractStudy ObjectivePsychosis is common in Parkinson’s disease (PD) and increases in both frequency and severity with disease duration. It is associated with increased morbidity/mortality, complicates management of motor symptoms and often leads to long-term care placement. Pimavanserin (PIM) is a highly selective serotonin 5-HT2A receptor antagonist/inverse agonist indicated for the treatment of hallucinations and delusions associated with PD psychosis (PDP). The study aim is to review theevidence-base for PIM for the treatment of PDP using the metrics of evidence-based medicine, namely number needed to treat (NNT), number needed to harm (NNH), andlikelihood to be helped or harmed (LHH), in order to better place this intervention into clinical perspective.MethodsNNT and NNH are measures of effect size and indicate how many patients would need to be treated with one agent instead of the comparator in order to encounter one additional outcome of interest. A useful medication is one with a low NNT and a high NNH when comparing it with another intervention; a low NNT and a high NNH would mean one is more likely to encounter a benefit than a harm. Categorical efficacy and tolerability data was extracted from the clinical trial databases of the double-blind placebo-controlled studies of PIM in persons with PDP. The studies were 6 weeks in duration and fixed dose with the exception of study ACP-103-006 which was 4-weeks in duration. NNT and NNH values were calculated with their respective 95% confidence intervals. Efficacy endpoints were defined based on 2 definitions: a) Scale for the Assessment ofPositive Symptoms in Parkinson’s Disease (SAPS-PD) total score decrease ≥3 points from baseline and b) Clinical Global Impressions-Improvement scale (CGI-I) score of 1 (very much improved) or 2 (much improved). Tolerability outcomes of clinical interest, occurring at any time in available studies were assessed, including discontinuation due toan adverse event (AE). Likelihood to be helped or harmed (LHH) was then calculated contrasting therapeutic response vs. discontinuation because of an AE.ResultsNNT values for PIM 34 mg/d vs. placebo for several definitions of clinical response are <10, and as robust as 4, denoting that PIM is a potentially efficacious intervention. NNH values for tolerability outcomes for PIM 34 mg/d (as well as for doses that range from 8.5 mg/d to 51 mg/d) are >10, and/or are not statistically significant, and/or show an advantage for PIM over placebo (such as for postural hypotension), denoting that PIM is a potentially tolerable intervention. In terms of LHH, PIM 34 mg/d is about 5 times more likely to result in clinical response (as measured by ≥3 point decrease from baseline on the SAPS-PD) vs. discontinuation due to an adverse event.ConclusionsUsing the metrics of NNT, NNH, and LHH, PIM 34 mg/d for the treatment of PDP appears to have a compelling benefit-risk profile.Funding AcknowledgementsClinical study was funded by ACADIA Pharmaceuticals Inc.

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Citrome, Leslie, James C. Norton, Kathy Chi-Burris, and George Demos. "Pimavanserin for the treatment of Parkinson’s disease psychosis: number needed to treat, number needed to harm, and likelihood to be helped or harmed." CNS Spectrums 23, no. 3 (November 3, 2017): 228–38. http://dx.doi.org/10.1017/s1092852917000736.

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ObjectiveOur aim was to describe the efficacy and tolerability of pimavanserin, a highly selective serotonin 5-HT2A receptor inverse agonist/antagonist indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis (PDP), using the metrics of number needed to treat (NNT) and number needed to harm (NNH).MethodsCategorical efficacy and tolerability data were extracted from the clinical trial databases of the double-blind placebo-controlled studies of pimavanserin in persons with PDP. NNT and NNH values were calculated with their respective 95% confidence intervals. The likelihood to be helped or harmed (LHH) was then calculated contrasting therapeutic response versus discontinuation because of an adverse event.ResultsNNT values for pimavanserin 34 mg/d versus placebo for several definitions of clinical response are <10, and as robust as 4. NNH values for tolerability outcomes for pimavanserin 34 mg/d (as well as for doses that range from 8.5 to 51 mg/d) are >10, and/or are not statistically significant, and/or show an advantage for pimavanserin over placebo (such as for postural hypotension). In terms of LHH, pimavanserin 34 mg/d is about five times more likely to result in clinical response (as measured by a ≥3 point decrease from baseline on the Scale for the Assessment of Positive Symptoms adapted for Parkinson’s disease) versus discontinuation due to an adverse event.ConclusionsUsing the metrics of NNT, NNH, and LHH, pimavanserin 34 mg/d for the treatment of PDP appears to have a compelling benefit/risk profile.

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Liang, Jane, David Bergqvist, Roger Yusen, and Russell Hull. "Benefit-to-harm ratio of thromboprophylaxis for patients undergoing major orthopaedic surgery." Thrombosis and Haemostasis 111, no. 02 (2014): 199–212. http://dx.doi.org/10.1160/th13-08-0654.

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SummarySurgeons consider the benefit-to-harm ratio when making decisions regarding the use of anticoagulant venous thromboembolism (VTE) prophylaxis. We evaluated the benefit-to-harm ratio of the use of newer anticoagulants as thromboprophylaxis in patients undergoing major orthopaedic surgery using the likelihood of being helped or harmed (LHH), and assessed the effects of variation in the definition of major bleeding on the results. A systematic literature search was performed to identify phase II and phase III studies that compared regulatory authority-approved newer anticoagulants to the low-molecularweight heparin enoxaparin in patients undergoing major orthopaedic surgery. Analysis of outcomes data estimated the clinical benefit (number-needed-to-treat [NNT] to prevent one symptomatic VTE) and clinical harm (number-needed-to-harm [NNH] or the NNT to cause one major bleeding event) of therapies. We estimated each trial’s benefitto-harm ratio from NNT and NNH values, and expressed this as LHH = (1/NNT)/(1/NNH) = NNH/NNT. Based on reporting of efficacy and safety outcomes, most studies favoured enoxaparin over fondaparinux, and rivaroxaban over enoxaparin. However, when using the LHH metric, most trials favoured enoxaparin over both fondaparinux and rivaroxaban when they included surgical-site bleeding that did not require reoperation in the definition of major bleeding. The exclusion of bleeding at surgical site which did not require reoperation shifted the benefit-to-harm ratio in favour of the newer agents. Variations in the definitions of major bleeding may change the benefit-to-harm ratio and subsequently affect its interpretation. Clinical trials should attempt to improve the consistency of major bleeding reporting.

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S., Chandramohan Reddy, and Sam Varghese. "A study on risk factors associated with neonatal hyperbilirubinemia among newborns at tertiary care level in Kerala, India." International Journal of Contemporary Pediatrics 7, no. 6 (May 22, 2020): 1415. http://dx.doi.org/10.18203/2349-3291.ijcp20202157.

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Background: Neonatal hyperbilirubinemia is defined as serum bilirubin levels >7 mg/dl around 85% of all term newborns and most of the premature babies develop clinical jaundice and various associated risk factors are involved in NNH and treatment for this condition depends on gestational age, serum bilirubin levels at different time interval during early life of these newborns and treating them with phototherapy or exchange transfusion. Objective of the study was to establish the relation with the NNH and risk factors among newborns and treatment with the phototherapy if required.Methods: The present prospective study was conducted at Karuna Medical College, Chittur Palakkad from January 2019 to December 2019. A total of 40 samples which are born during the study period were included in the study. All types of gestations (preterm, full term, post term), both genders (male and female), new-borns with risk factors, serum bilirubin (TSB) >7 mg/dl at 48 hrs of life were included in the studyResults: In our study, female samples consists of 55% and male samples were 45% during the study period minimum gestational age was 35 weeks and maximum was 40 weeks. 5% sample with a serum bilirubin level of 9 mg/dl, with risk factor as a Rh(-ve) incompatibility was treated with phototherapy up to 96 hrs of life.Conclusions: Study conveys various risk factors responsible for NNH and treatment with phototherapy given to the affected new-borns. With good clinical history, risk factors involved in new-borns, antenatal counseling is needed to all pregnant women’s it is necessary to check the serum bilirubin levels and treated with phototherapy to avoid further NNH related complications in the new-borns.

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Citrome, Leslie, Allitia DiBernardo, and Jaskaran Singh. "144 Esketamine Nasal Spray for Management of Treatment-Resistant Depression: Number Needed to Treat, Number Needed to Harm, Likelihood to be Helped/Harmed." CNS Spectrums 25, no. 2 (April 2020): 291–92. http://dx.doi.org/10.1017/s1092852920000607.

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Abstract:Background:Targeting of glutamate receptors is a novel approach for the treatment of major depressive disorder (MDD). This study aimed to review the usefulness for esketamine nasal spray for the management of treatment-resistant depression (TRD) using the tools of evidence-based medicine: number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).Methods:Data sources were four completed Phase 3 randomized, double-blind, placebo-controlled, studies, including two pivotal registration studies of esketamine nasal spray in TRD in non-elderly adults (acute flexible-dose study NCT02418585, maintenance study NCT02493868) Efficacy outcomes included acute response (≥50% decrease from baseline on Montgomery-Asberg Depression Rating Scale [MADRS] total score), acute remission (MADRS scores ≤12; and other thresholds using the MADRS and Clinical Global Impressions-Severity [CGI-S] scales), categorical shifts in MADRS and CGI-S scores, and avoidance of relapse/recurrence (observed relapse rates). NNT, NNH and LLH are calculated for combination of esketamine nasal spray and oral antidepressant (esketamine+AD) vs AD+placebo in patients with TRD.Results:In the acute flexible-dose study of esketamine nasal spray (56-84 mg twice-weekly for 4 weeks), MADRS response with esketamine+AD vs AD+placebo at endpoint (rates 63.4% vs 49.5%, respectively) yielded an NNT value of 8, and MADRS remission at endpoint (48.2% vs 30.3%) resulted in a NNT vs AD+placebo of 6. NNH values vs AD+placebo were <10 for the adverse events (AE) of dissociation (26.1% vs 3.7%), vertigo (26.1% vs 2.8%), nausea (26.1% vs 6.4%), dizziness (20.9% vs 4.6%), and dysgeusia (24.3% vs 11.9%), the NNH values were 5, 5, 6, 7, and 9, respectively. Discontinuation rates due to AE (7.0% vs 0.9%) yielded a NNH of 17. LHH comparing MADRS remission vs discontinuation was 17/6, or approximately 3. The pattern of results was similar for the other acute studies and for the pooled data combining all 3 acute studies. Maintenance use of esketamine (dose 56-84 mg once-weekly or once-every-other-week) plus an oral AD demonstrated NNT values <10 for relapse and/or maintenance of remission in favor of esketamine+AD vs AD+placebo, a NNT of 4 was observed for outcome of relapse in patients with stable response at the time of randomization (relapse rates were 25.8% vs 57.6%, respectively). In the maintenance study, discontinuation rates due to an AE (2.6% vs 2.1%) yielded a non-significant NNH value of 178.Conclusion:The low NNT values <10 for efficacy outcomes suggest potential benefits of esketamine+AD for both acute and maintenance use. LHH was favorable: esketamine+AD was 3 times more likely to result in acute remission vs discontinuation due to an AE.Funding Acknowledgements:Janssen Global Services, LLC

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K. Jack, Tonye. "NOx Formation and Control: On Thermochemistry of NNH." International Journal of ChemTech Research 11, no. 8 (2018): 98–107. http://dx.doi.org/10.20902/ijctr.2018.110811.

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Dammann, F. "Bildgebung der Nasennebenhöhlen (NNH) in der heutigen Zeit." Der Radiologe 47, no. 7 (May 22, 2007): 576–83. http://dx.doi.org/10.1007/s00117-007-1502-z.

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Barki, Hadjer, Latifa Khaouane, and Salah Hanini. "Modelling of Adsorption of Methane, Nitrogen, Carbon Dioxide, Their Binary Mixtures, and Their Ternary Mixture on Activated Carbons Using Artificial Neural Network." Kemija u industriji 68, no. 7-8 (2019): 289–302. http://dx.doi.org/10.15255/kui.2019.002.

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This work examines the use of neural networks in modelling the adsorption process of gas mixtures (CO2, CH4, and N2) on different activated carbons. Seven feed-forward neural network models, characterized by different structures, were constructed with the aim of predicting the adsorption of gas mixtures. A set of 417, 625, 143, 87, 64, 64, and 40 data points for NN1 to NN7, respectively, were used to test the neural networks. Of the total data, 60 %, 20 %, and 20 % were used, respectively, for training, validation, and testing of the seven models. Results show a good fit between the predicted and experimental values for each model; good correlations were found (R = 0.99656 for NN1, R = 0.99284 for NN2, R = 0.99388 for NN3, R = 0.99639 for Q1 for NN4, R = 0.99472 for Q2 for NN4, R = 0.99716 for Q1 for NN5, R = 0.99752 for Q3 for NN5, R = 0.99746 for Q2 for NN6, R = 0.99783 for Q3 for NN6, R = 0.9946 for Q1 for NN7, R = 0.99089 for Q2 for NN7, and R = 0.9947 for Q3 for NN7). Moreover, the comparison between the predicted results and the classical models (Gibbs model, Generalized dual-site Langmuir model, and Ideal Adsorption Solution Theory) shows that the neural network models gave far better results.

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Vázquez, Gustavo H., Anees Bahji, Juan Undurraga, Leonardo Tondo, and Ross J. Baldessarini. "Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium." Journal of Psychopharmacology 35, no. 8 (July 9, 2021): 890–900. http://dx.doi.org/10.1177/02698811211013579.

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Background: Successful treatment of major depressive disorder (MDD) can be challenging, and failures ("treatment-resistant depression" [TRD]) are frequent. Steps to address TRD include increasing antidepressant dose, combining antidepressants, adding adjunctive agents, or using nonpharmacological treatments. Their relative efficacy and tolerability remain inadequately tested. In particular, the value and safety of increasingly employed second-generation antipsychotics (SGAs) and new esketamine, compared to lithium as antidepressant adjuncts remain unclear. Methods: We reviewed randomized, placebo-controlled trials and used random-effects meta-analysis to compare odds ratio (OR) versus placebo, as well as numbers-needed-to-treat (NNT) and to-harm (NNH), for adding SGAs, esketamine, or lithium to antidepressants for major depressive episodes. Results: Analyses involved 49 drug-placebo pairs. By NNT, SGAs were more effective than placebo (NNT = 11 [CI: 9–15]); esketamine (7 [5–10]) and lithium (5 [4–10]) were even more effective. Individually, aripiprazole, olanzapine+fluoxetine, risperidone, and ziprasidone all were more effective (all NNT < 10) than quetiapine (NNT = 13), brexpiprazole (16), or cariprazine (16), with overlapping NNT CIs. Risk of adverse effects, as NNH for most-frequently reported effects, among SGAs versus placebo was 5 [4–6] overall, and highest with quetiapine (NNH = 3), lowest with brexpiprazole (19), 5 (4–6) for esketamine, and 9 (5–106) with lithium. The risk/benefit ratio (NNH/NNT) was 1.80 (1.25–10.60) for lithium and much less favorable for esketamine (0.71 [0.60–0.80]) or SGAs (0.45 [0.17–0.77]). Conclusions: Several modern antipsychotics and esketamine appeared to be useful adjuncts to antidepressants for acute major depressive episodes, but lithium was somewhat more effective and better tolerated. Limitations: Most trials of adding lithium involved older, mainly tricyclic, antidepressants, and the dosing of adjunctive treatments were not optimized.

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Melamed, Nir, Elizabeth Asztalos, Kellie Murphy, Arthur Zaltz, Donald Redelmeier, Baiju R. Shah, and Jon Barrett. "Neurodevelopmental disorders among term infants exposed to antenatal corticosteroids during pregnancy: a population-based study." BMJ Open 9, no. 9 (September 2019): e031197. http://dx.doi.org/10.1136/bmjopen-2019-031197.

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ObjectiveAn increasing proportion of fetuses are exposed to antenatal corticosteroids (ACS). Despite their immediate beneficial effects, the long-term safety of ACS has been an ongoing source of concern. In the current study, we assessed the likelihood of neurodevelopmental problems among term infants exposed to ACS earlier in pregnancy compared with non-exposed term infants.DesignRetrospective cohort study (2006–2011). Median duration of follow-up was 7.8 (IQR 6.4–9.2) years.SettingPopulation-based study, Ontario, Canada.ParticipantsAll live singleton infants born at term (≥370/7weeks gestation) (n=529 205).ExposureACS during pregnancy.Primary and secondary outcome measuresA composite of diagnostic or billing codes reflecting proven or suspected neurodevelopmental problems during childhood including audiometry testing, visual testing or physician service claim with a diagnosis code related to a suspected neurocognitive disorder.ResultsAt 5 years of age, the cumulative rate for the primary outcome was higher among infants exposed to ACS compared with non-exposed infants: 61.7% (3346/5423) vs 57.8% (302 520/523 782), respectively (p<0.001; number needed to harm (NNH)=25, 95% CI 19 to 38; adjusted HR (aHR) 1.12, 95% CI 1.08 to 1.16). Similar findings were observed for each of the individual components of the primary outcome: 15.3% vs 12.7% for audiometry testing (p<0.001; NNH=39, 95% CI 29 to 63; aHR 1.18, 95% CI 1.11 to 1.25); 45.4% vs 43.5% for visual testing (p=0.006; NNH=54, 95% CI 31 to 200; aHR 1.08, 95% CI 1.04 to 1.12) and 25.8% vs 21.6% for suspected neurocognitive disorder (p<0.001; NNH=24, 95% CI 19 to 33; aHR 1.16, 95% CI 1.10 to 1.21).ConclusionsWe found an association among term infants between exposure to ACS during pregnancy and healthcare utilisation during childhood related to suspected neurocognitive and neurosensory disorders.

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Larkin, Andrew, Howard Waitzkin, Ella Fassler, and Kesavan Rajasekharan Nayar. "How missing evidence-based medicine indicators can inform COVID-19 vaccine distribution policies: a scoping review and calculation of indicators from data in randomised controlled trials." BMJ Open 12, no. 12 (December 2022): e063525. http://dx.doi.org/10.1136/bmjopen-2022-063525.

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ObjectiveReports of efficacy, effectiveness and harms of COVID-19 vaccines have not used key indicators from evidence-based medicine (EBM) that can inform policies about vaccine distribution. This study aims to clarify EBM indicators that consider baseline risks when assessing vaccines’ benefits versus harms: absolute risk reduction (ARR) and number needed to be vaccinated (NNV), versus absolute risk of the intervention (ARI) and number needed to harm (NNH).MethodsWe used a multimethod approach, including a scoping review of the literature; calculation of risk reductions and harms from data concerning five major vaccines; analysis of risk reductions in population subgroups with varying baseline risks; and comparisons with prior vaccines.FindingsThe scoping review showed few reports regarding ARR, NNV, ARI and NNH; comparisons of benefits versus harms using these EBM methods; or analyses of varying baseline risks. Calculated ARRs for symptomatic infection and hospitalisation were approximately 1% and 0.1%, respectively, as compared with relative risk reduction of 50%–95% and 58%–100%. NNV to prevent one symptomatic infection and one hospitalisation was in the range of 80–500 and 500–4000. Based on available data, ARI and NNH as measures of harm were difficult to calculate, and the balance between benefits and harms using EBM measures remained uncertain. The effectiveness of COVID-19 vaccines as measured by ARR and NNV was substantially higher in population subgroups with high versus low baseline risks.ConclusionsPriorities for vaccine distribution should target subpopulations with higher baseline risks. Similar analyses using ARR/NNV and ARI/NNH would strengthen evaluations of vaccines’ benefits versus harms. An EBM perspective on vaccine distribution that emphasises baseline risks becomes especially important as the world’s population continues to face major barriers to vaccine access—sometimes termed ‘vaccine apartheid’.

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CASTRO, Paula Marcela Vilela, Felipe Piccarone Gonçalves RIBEIRO, Amanda de Freitas ROCHA, Mônica MAZZURANA, and Guines Antunes ALVAREZ. "Hand-sewn versus stapler esophagogastric anastomosis after esophageal ressection: sistematic review and meta-analysis." ABCD. Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) 27, no. 3 (September 2014): 216–21. http://dx.doi.org/10.1590/s0102-67202014000300014.

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INTRODUCTION: Postoperative anastomotic leak and stricture are dramatic events that cause increased morbidity and mortality, for this reason it's important to evaluate which is the best way to perform the anastomosis. AIM: To compare the techniques of manual (hand-sewn) and mechanic (stapler) esophagogastric anastomosis after resection of malignant neoplasm of esophagus, as the occurrence of anastomotic leak, anastomotic stricture, blood loss, cardiac and pulmonary complications, mortality and surgical time. METHODS: A systematic review of randomized clinical trials, which included studies from four databases (Medline, Embase, Cochrane and Lilacs) using the combination of descriptors (anastomosis, surgical) and (esophagectomy) was performed. RESULTS: Thirteen randomized trials were included, totaling 1778 patients, 889 in the hand-sewn group and 889 in the stapler group. The stapler reduced bleeding (p <0.03) and operating time (p<0.00001) when compared to hand-sewn after esophageal resection. However, stapler increased the risk of anastomotic stricture (NNH=33), pulmonary complications (NNH=12) and mortality (NNH=33). There was no significant difference in relation to anastomotic leak (p=0.76) and cardiac complications (p=0.96). CONCLUSION: After resection of esophageal cancer, the use of stapler shown to reduce blood loss and surgical time, but increased the incidence of anastomotic stricture, pulmonary complications and mortality.

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Citrome, Leslie. "Treatment of bipolar depression: making sensible decisions." CNS Spectrums 19, S1 (November 19, 2014): 1–12. http://dx.doi.org/10.1017/s109285291400056x.

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A major challenge in the treatment of major depressive episodes associated with bipolar disorder is differentiating this illness from major depressive episodes associated with major depressive disorder. Mistaking the former for the latter will lead to incorrect treatment and poor outcomes. None of the classic antidepressants, serotonin specific reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors have ever received regulatory approval as monotherapies for the treatment of bipolar depression. At present, there are only 3 approved medication treatments for bipolar depression: olanzapine/fluoxetine combination, quetiapine (immediate or extended release), and lurasidone (monotherapy or adjunctive to lithium or valproate). All 3 have similar efficacy profiles, but they differ in terms of tolerability. Number needed to treat (NNT) and number needed to harm (NNH) can be used to quantify these similarities and differences. The NNTs for response and remission for each of these interventions vs placebo range from 4 to 7, and 5 to 7, respectively, with overlap in terms of their 95% confidence intervals. NNH values less than 10 (vs placebo) were observed for the spontaneously reported adverse events of weight gain and diarrhea for olanzapine/fluoxetine combination (7 and 9, respectively) and somnolence and dry mouth for quetiapine (3 and 4, respectively). There were no NNH values less than 10 (vs placebo) observed with lurasidone treatment. NNH values vs placebo for weight gain of at least 7% from baseline were 6, 16, 58, and 36, for olanzapine/fluoxetine combination, quetiapine, lurasidone monotherapy, and lurasidone combined with lithium or valproate, respectively. Individualizing treatment decisions will require consideration of the different potential adverse events that are more likely to occur with each medication. The metric of the likelihood to be helped or harmed (LHH) is the ratio of NNH to NNT and can illustrate the tradeoffs inherent in selecting medications. A more favorable LHH was noted for treatment with lurasidone. However, OFC and quetiapine monotherapy may still have utility in high urgency situations, particularly in persons who have demonstrated good outcomes with these interventions in the past, and where a pressing clinical need for efficacy mitigates their potential tolerability shortcomings. In terms of maintenance therapy, adjunctive quetiapine is the only agent where the NNT vs lithium or valproate alone is less than 10 for both the prevention of mania and the prevention of depression.

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Goodsite, Michael E., Werner Rom, Jan Heinemeier, Todd Lange, Suat Ooi, Peter G. Appleby, William Shotyk, W. O. van der Knaap, Christian Lohse, and Torben S. Hansen. "High-Resolution AMS 14C Dating of Post-Bomb Peat Archives of Atmospheric Pollutants." Radiocarbon 43, no. 2B (2001): 495–515. http://dx.doi.org/10.1017/s0033822200041163.

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Peat deposits in Greenland and Denmark were investigated to show that high-resolution dating of these archives of atmospheric deposition can be provided for the last 50 years by radiocarbon dating using the atmospheric bomb pulse. 14C was determined in macrofossils from sequential one cm slices using accelerator mass spectrometry (AMS). Values were calibrated with a general-purpose curve derived from annually averaged atmospheric 14CO2 values in the northernmost northern hemisphere (NNH, 30°–90°N). We present a thorough review of 14C bomb-pulse data from the NNH including our own measurements made in tree rings and seeds from Arizona as well as other previously published data. We show that our general-purpose calibration curve is valid for the whole NNH producing accurate dates within 1–2 years. In consequence, 14C AMS can precisely date individual points in recent peat deposits within the range of the bomb-pulse (from the mid-1950s on). Comparing the 14C AMS results with the customary dating method for recent peat profiles by 210Pb, we show that the use of 137Cs to validate and correct 210Pb dates proves to be more problematic than previously supposed.As a unique example of our technique, we show how this chronometer can be applied to identify temporal changes in Hg concentrations from Danish and Greenland peat cores.

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Goldvaser, Hadar, Domen Ribnikar, Tristan Alexandra Barnes, David W. Cescon, Alberto Ocana, and Eitan Amir. "Toxicity of extended adjuvant aromatase inhibitors therapy in postmenopausal breast cancer patients: A systematic review and meta-analysis." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 549. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.549.

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549 Background: Aromatase inhibitors (AI) are a gold standard adjuvant endocrine therapy for postmenopausal women with breast cancer. A number of randomized trials (RCTs) have reported modest improvements in breast cancer outcomes from extending treatment with AI beyond the initial 5 years after diagnosis. However, less in known about the toxicity of extended AI compared with no therapy. Methods: We conducted a systematic review of MEDLINE to identify RCTs that compared extended AI to placebo or no treatment. The search was supplemented by a review of abstracts from the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium meetings between 2013 and 2016. Odds ratios (ORs), 95% confidence intervals (CI), absolute risks, and the number needed to harm (NNH) associated with one adverse event were computed for prespecified safety and tolerability outcomes including cardiovascular disease, bone fractures, second cancers (excluding new breast cancer), treatment discontinuation due to adverse events and death without recurrence. Results: Seven trials comprising 16349 patients met the inclusion criteria. Longer treatment with AI was associated with increased odds of cardiovascular disease (OR = 1.18, 95% CI 1.00-1.40, P=0.05; NNH = 122) and bone fractures (OR = 1.34, 95% CI 1.16 - 1.55, P < 0.001; NNH = 72). Compared to control, longer AI therapy was associated with a higher odds of treatment discontinuation due to adverse events (OR = 1.45, 95% CI 1.25 - 1.68, P < 0.001; NNH = 20). Longer AI therapy did not influence the odds of second cancers (OR = 0.93, 95% CI 0.73-1.18, P = 0.56). There was a numerical excess of death without recurrence with longer AI therapy, but this was not statistically significant (OR = 1.11, 95% CI 0.9 - 1.36, P = 0.34). Conclusions: Longer durations of AI use are associated with increased cardiovascular events and bone fracture. There is a numerical, but non-statistically significant excess of deaths without breast cancer recurrence among patients receiving longer AI therapy. These data should be taken into account when considering extended adjuvant AI therapy for breast cancer patients.

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Maroulis, George. "Electrical Properties for HCO+ and NNH+ from Fourth-Order Møller-Plesset Perturbation Theory." Zeitschrift für Naturforschung A 43, no. 5 (May 1, 1988): 419–29. http://dx.doi.org/10.1515/zna-1988-0505.

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Electric multipole moments and static polarizabilities are reported for HCO+ and NNH+ . Both molecular ions are of great importance to interstellar matter chemistry. All properties were calculated from the energy of the molecule in the presence of distant electric charges. Electron correlation effects were taken into account via SDQ-MPPT(4), fourth-order Møller-Plesset Perturbation Theory with single, double and quadrupole substitutions from the reference SCF wavefunction. With the exception of the dipole moment, values for the other properties studied in this work appear in the literature for the first time. The dipole moment (relative to the centre of mass) and the axial and perpendicular components of the dipole polarizability are 1.515 ea0, 13.39 and 6.88 e2a2Eh+1 respectively for HCO+ and 1.328 ea0, 13.81 and 5.70 e2a20Eh-1 for NNH+ .

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Chalk, Andrew J., and Leo Radom. "Ion-Transport Catalysis: Catalyzed Isomerizations of NNH+and NNCH3+." Journal of the American Chemical Society 121, no. 7 (February 1999): 1574–81. http://dx.doi.org/10.1021/ja982928l.

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Kaschke, O., and H. Behrbohm. "Nasensplint - Platzhalter für die Nachbehandlung nach endoskopischen NNH-Operationen." Laryngo-Rhino-Otologie 77, no. 07 (July 1998): 414–17. http://dx.doi.org/10.1055/s-2007-997000.

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Citrome, Leslie, and Terence A. Ketter. "NNT and NNH remain helpful in evidence-based medicine." British Journal of Psychiatry 209, no. 3 (September 2016): 262–63. http://dx.doi.org/10.1192/bjp.209.3.262b.

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Klippenstein, Stephen J., Lawrence B. Harding, Peter Glarborg, and James A. Miller. "The role of NNH in NO formation and control." Combustion and Flame 158, no. 4 (April 2011): 774–89. http://dx.doi.org/10.1016/j.combustflame.2010.12.013.

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Oeken, J., and J. Törpel. "Der Einfluss der Navigation auf die endoskopische NNH-Chirurgie." HNO 56, no. 2 (May 23, 2007): 151–57. http://dx.doi.org/10.1007/s00106-007-1580-2.

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Andia, A., B. Souleymane, M. Daou, M. Zara, S. Beydou, MS Aminou, and E. Adehossi. "Geriatric in Patient Profile at the Department of Internal Medicine at Niamey National Hospital, Niger." European Scientific Journal, ESJ 13, no. 27 (September 30, 2017): 279. http://dx.doi.org/10.19044/esj.2017.v13n27p279.

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Background: The ageing population in developing countries has brought a demographic and an epidemiological transition, with the impact of chronic diseases resulting from life style changes on the health status of the population. Objective: To describ a profile geriatrics patient, specifically to identify epidemiologic, clinical, etiologic and outcome of this group at the department of internal medicine to NNH Patients and method: Medical records of all geriatric patients aged ≥65 years admitted at the department of NNH Between January 2012 and December 2015 were retrieved and reviewed retrospectively. Results: A total of 6074 admissions at the internal medicine department of NNH over three years were reported and 1130 (18, 6%) were geriatrics patients, the average age was 75, 95 years and more than half were men (50,7%). 80 % of patients were in the young old group (65-74 years), 13% in the old group (75-84 years) and 7% in the oldest old group (≥85 years). High blood pressure was the frequent comorbidity (12, 3%) and the most symptoms caused hospitalization were stroke (17, 6%), fevers (16, 5%) and worst health (13, 1%). Frequent illnesses were cardiovascular diseases (38.4%), infections, (19.2%) and endocrine diseases (11%). The average length of hospital stays was 8, 7 days. The mortality rate was 18, 2% and the worst outcomes factors were female sex, frail elderly group in 75 to 84 years and high blood pressure. Conclusion: Chronic diseases were responsible of morbidity and mortality for the majority elderly’s patient.

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Garg, Bhawan Deep, Anju Bansal, and Nandkishor S. Kabra. "Role of Kangaroo Mother Care in the Management of Neonatal Hyperbilirubinemia in Both Term and Preterm Neonates: A Systematic Review." Journal of Perinatal Education 29, no. 3 (June 29, 2020): 123–33. http://dx.doi.org/10.1891/j-pe-d-18-00043.

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BackgroundNeonatal hyperbilirubinemia (NNH) is the most common clinical sign seen in neonatal practice. Kangaroo mother care (KMC), a new strategy has been tried for the management of hyperbilirubinemia.AimsTo evaluate the role of KMC for reduction of bilirubin and duration of phototherapy in term and preterm neonates.MethodThe literature search was done for various randomized control trials by searching the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, ongoing clinical trials and abstracts of conferences.ResultsThis review included five RCTs that fulfilled inclusion criteria. Out of five trials, two trials reported a significant reduction in bilirubin and three trials reported a significant reduction in duration of phototherapy.ConclusionKMC may be a novel strategy in the management of NNH. However, due to small sample size and heterogeneity between the trials, the current evidence is not sufficient. Hence, large trials with adequate sample sizes are needed.

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Kajikawa, Yasutomo. "Deconvolution of local activation energy of hopping conductivity: Application to p-Ge." International Journal of Modern Physics B 34, no. 08 (March 27, 2020): 2050069. http://dx.doi.org/10.1142/s0217979220500691.

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A new method for analyzing the local reduced activation energy [Formula: see text] of the impurity conductivity is applied to Ga-doped [Formula: see text]-Ge samples with a constant compensation ratio of [Formula: see text] reported by Zabrodskii and Andreev [Int. J. Mod. Phys. B 8, 883 (1994)]. Here, the local reduced activation energy is defined as [Formula: see text], where [Formula: see text] and [Formula: see text] denote conductivity and absolute temperature, respectively. The method enables us to deconvolute the [Formula: see text] curve into contributions from different conduction mechanisms such as free-hole conduction, nearest-neighbor hopping (NNH) conduction and variable-range hopping (VRH) conduction. As a result, it is shown that both the power exponents of the pre-exponential factors of NNH and VRH conductivity tend to decrease with increasing impurity concentration.

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Yoo, Jung Bo, Han Sol Kim, Seung Hee Kang, Byeongno Lee, and Nam Hwi Hur. "Hollow nickel-coated silica microspheres containing rhodium nanoparticles for highly selective production of hydrogen from hydrous hydrazine." J. Mater. Chem. A 2, no. 44 (2014): 18929–37. http://dx.doi.org/10.1039/c4ta03550j.

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Hollow nickel-coated microspheres containing Rh nanoparticles (Rh/Ni@SiO₂) generate hydrogen (H₂) from hydrazine (H₂NNH₂) with over 99% selectivity within 1.5 h at 25 °C.

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Riedel-Baima, Bozena, Roman Zielinski, and Kornelia Polok. "Efficacy and safety parameters of a novel COVID-19 vaccine." Frontiers in Molecular Immunology 2, no. 1 (2021): 13–15. http://dx.doi.org/10.25082/fmi.2021.01.001.

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Considering the fact that vaccine efficacy may be a difficult concept for physicians and health officials alike, we decided to explain it using data from the first publication on the efficacy and safety of a COVID-19 vaccine produced by Pfizer/BioNTech. We examined the published data and calculated common epidemiological parameters such as RRR (relative risk reduction), RR (relative risk), ARR (absolute risk reduction) and NNT (number needed to treat) for 3 groups of patients as described in the original paper. Further, we calculated safety parameters for the vaccine as NNH (number needed to harm) for any, related and severe side effects as mentioned by the investigators. We argue that both NNT and NNH are necessary estimates of how a vaccine might perform in real life and that a robust understanding of efficacy is vital for patients and health care providers as well as health officials in order to make responsible and balanced policy decisions regarding vaccination.

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Gawel, Marek J., Irene Worthington, and Anne Maggisano. "Progress in Clinical Neurosciences A Systematic Review of the Use of Triptans in Acute Migraine." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 28, no. 1 (February 2001): 30–41. http://dx.doi.org/10.1017/s0317167100052525.

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ABSTRACT:Objective:A systematic review of the literature was undertaken, to consolidate evidence concerning the efficacy and safety of triptans currently available in Canada (sumatriptan, rizatriptan, naratriptan, zolmitriptan), and to provide guidelines for selection of a triptan.Methods:Data from published, randomized, placebo-controlled trials were pooled and a combined number needed to treat (NNT) and number needed to harm (NNH) was generated for each triptan. Direct comparative trials of triptans were also examined.Results:The lowest NNTfor headache response/pain-free at one/two hours is observed with subcutaneous sumatriptan. Among the oral formulations, the lowest NNT is observed with rizatriptan and the highest NENT with naratriptan. The lowest NNH is observed with subcutaneous sumatriptan.Conclusions:Triptans are relatively safe and effective medications for acute migraine attacks. However, differences among them are relatively small. Considerations in selecting a triptan include individual patient response/tolerance, characteristics of the attacks, relief of associated symptoms, consistency of response, headache recurrence, delivery systems and patient preference.

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Qualls, Clifford, Mario Kornfeld, Nancy Joste, Abdul-Mehdi Ali, and Otto Appenzeller. "MPV17-related hepatocerebral mitochondrial DNA depletion syndrome (MPV17-NNH) revisited." eNeurologicalSci 2 (March 2016): 8–13. http://dx.doi.org/10.1016/j.ensci.2016.01.004.

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Greener, Mark. "Keys to understanding the clinical significance of NNT and NNH." Nurse Prescribing 9, no. 8 (August 2011): 400–401. http://dx.doi.org/10.12968/npre.2011.9.8.400.

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Yenikomshian, MBA, Mihran Ara, Alan G. White, PhD, Louis P. Garrison, PhD, Gary M. Oderda, PharmD, MPH, Joseph E. Biskupiak, PhD, MBA, Patrick R. Hlavacek, MPH, and Carl L. Roland, PharmD, MS. "Projecting the cost, utilization, and patient care impact of prescribing extended release non-abuse-deterrent opioids to chronic pain patients." Journal of Opioid Management 13, no. 5 (September 1, 2017): 291. http://dx.doi.org/10.5055/jom.2017.0398.

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Objectives: To estimate healthcare resource utilization, associated costs, and number needed to harm (NNH) from a physician's decision to prescribe extended-release (ER) non-abuse-deterrent opioids (non-ADO) as compared to ER ADOs in a chronic pain population.Design: A 12-month probabilistic simulation model was developed to estimate the reduction of misuse and/or abuse from a physician's prescribing decisions for 10,000 patients. Model inputs included probabilities for opioid misuse and/ or abuse-related events, opioid discontinuation, and switching from ADO to non- ADO. Estimated reductions in abuse associated with ADOs were obtained from positive subjective measures using human abuse liability studies. The model was run separately for commercial, Medicare, Medicaid, and Veterans Administration (VA) populations. The difference in healthcare resource utilization and associated costs (2015 USD) between the ADO and non-ADO simulations was calculated. NNH for non-ADO was also calculated.Results: Misuse and/or abuse-related events for patients prescribed ER non-ADOs ranged from 223−1,410 and associated costs ranged from $20−$98 per patient for commercial and Medicare populations, respectively. Prescribing ER ADOs were associated with 87, 289, 264, and 417 fewer misuse and/or abuse−related events, saving $8, $35, $21, and $29 per patient in commercial, VA, Medicaid, and Medicare populations, respectively. NNH ranged from 185 in the commercial population to 40 in the Medicare population. Results were sensitive to decreases in the probability of misuse and/or abuse events but showed reductions.Conclusions: A physician's decision to prescribe ER ADOs could lead to large reductions in misuse and/or abuse-related events and associated costs across many patient populations.

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Bitter, Thomas, and Orlando Guntinas-Lichius. "Funktionelle endoskopische Nasennebenhöhlenchirurgie (FESS)." Laryngo-Rhino-Otologie 98, no. 06 (June 2019): 429–43. http://dx.doi.org/10.1055/a-0830-3960.

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ZusammenfassungDie funktionelle endoskopische Nasennebenhöhlenchirurgie ist das minimalinvasive chirurgische Standardverfahren zur operativen Behandlung von Patienten mit chronischer Rhinosinusitis. Sie verfolgt das Grundprinzip, die Erkrankung in den NNH zu entfernen und dabei möglichst gesunde Schleimhaut sowie funktionell relevante Strukturen zu schonen. In dieser Übersicht werden Operationsverfahren, Ausstattung, Komplikationen und ihr Management erläutert.

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Kishi, T., H. Y. Meltzer, Y. Matsuda, and N. Iwata. "Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder: systematic review and meta-analysis." Psychological Medicine 44, no. 11 (November 21, 2013): 2255–69. http://dx.doi.org/10.1017/s0033291713002857.

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BackgroundA meta-analysis of the serotonin1A (5-HT1A) receptor partial agonist of the azapirone class as an anxiolytic drug for the treatment of major depressive disorder (MDD) has not previously been reported.MethodWe carried out a systematic review of the literature available in PubMed, the Cochrane Library database and PsycINFO up to 12 October 2013, and conducted a meta-analysis of randomized controlled trials (RCTs) comparing 5-HT1A agonists with placebo and RCTs of 5-HT1A agonist augmentation therapies for MDD treatment. We calculated the risk ratio (RR), number needed to treat (NNT)/number needed to harm (NNH) and 95% confidence intervals (CIs).ResultsFifteen RCTs comparing 5-HT1A agonists with placebo (total n = 2469, four studies with buspirone, seven with gepirone, three with ipsapirone and one with zalospirone) were identified. Pooled 5-HT1A agonists had significantly more responders (RR 0.74, 95% CI 0.65–083, p < 0.00001, NNT = 6, 12 trials, n = 1816) than placebo. Pooled 5-HT1A agonists were superior to placebo in discontinuation due to inefficacy (RR 0.49, p = 0.02, NNH = 16, p = 0.03, 10 trials, n = 1494) but were inferior to placebo in discontinuation due to side-effects (RR 1.88, p < 0.0001, NNH = 17, p = 0.001, 13 trials, n = 2196). However, all-cause discontinuation was similar in both groups (RR 0.99, p = 0.85, 14 trials, n = 2402). Four 5-HT1A agonist augmentation studies were identified (total n = 365, three buspirone studies and one tandospirone study). There were no statistically significant effects of 5-HT1A agonist augmentation therapies on response rate (RR 0.98, p = 0.85, four trials, n = 341). 5-HT1A agonist-related side-effects including gastrointestinal symptoms, dizziness, insomnia, palpitation, paresthesia and sweating were greater than with placebo (p < 0.00001 to p = 0.03).ConclusionsOur results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.

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da Silva, Fernando de C., Vitor F. Ferreira, Patrícia de O. Lopes, James L. Wardell, and Solange M. S. V. Wardell. "Stereochemistry of Products of Reactions between 3-diazo-naphthalene-1,2,4-trione and β-dicarbonyl Compounds. Structure of ethyl 2-[(3-hydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-yl)-hydrazono]-3-phenyl-3-oxo-propionate." Journal of Chemical Research 2009, no. 5 (May 2009): 308–11. http://dx.doi.org/10.3184/030823409x440850.

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3-Hydroxy-2-[(R1CO)(R2CO)]C=NNH-1,4-naphthoquinones, obtained from reactions of 3-diazonaphthalene-1,2,4-trione with β-diketones, R1C(O)CH2COR2, have been previously found to have high antibacterial activity. However, confirmation of the stereochemistry about the C=N bond could not be achieved by spectroscopic means for products having different R1 and R2 groups, thereby limiting the utility of the reaction. Full characterisation of the product isolated from reaction of 3-diazonaphthalene-1,2,4-trione with PhC(O)CH2CO2Et is now reported, from a single crystal X-ray structure determination: the product, 3-hydroxy-2-[(PhCO)(EtCO2)]C=NNH-1,4-naphthoquinone has a ( Z)-stereochemistry. The Z-isomer is obtained rather than the E form due to the preferred formation of the stronger intramolecular N–H—O hydrogen-bond with the ester carbonyl oxygen rather than a weaker one with the ketone oxygen. Weaker C–H—O hydrogen bonds link the molecules into columns. It is suggested that similar Z geometries will arise from other RC(O)CH2CO2Ri reactants.

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Kishi, Taro, Yuki Matsui, Yuki Matsuda, Asuka Katsuki, Hikaru Hori, Hiroko Yanagimoto, Kenji Sanada, et al. "Efficacy, Tolerability, and Safety of Blonanserin in Schizophrenia: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials." Pharmacopsychiatry 52, no. 02 (March 7, 2018): 52–62. http://dx.doi.org/10.1055/a-0574-0088.

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Abstract Introduction We conducted an updated systematic review and meta-analysis of randomized controlled trials (RCTs) comparing blonanserin with other antipsychotics (amisulpride, aripiprazole, haloperidol, paliperidone, and risperidone). Methods Weighted mean difference (WMD), risk ratio, and number needed to harm (NNH) with 95% confidence intervals (95% CIs) were calculated using random-effects model. Results Ten RCTs (n=1521) were included in this study. Blonanserin was superior to aripiprazole in improvement of Positive and Negative Syndrome Scale total scores (WMD=−10.62, 95% CI=−17.67 to −3.560, p=0.003). Blonanserin was associated with a higher incidence of all-cause discontinuation (RR=1.373, 95% CI=1.088–1.734, p=0.008, NNH=11), akathisia, extrapyramidal disorder, and agitation/excitement and a lower risk of hyperprolactinemia compared with risperidone + paliperidone. Discussion The current meta-analytic study did not update the comparison of blonanserin vs. haloperidol because there were no new RCTs. Our results suggest that the efficacy of blonanserin for schizophrenia is comparable with that of other antipsychotics, and blonanserin seems to be well tolerated.

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Hidaka, Atsuki, Akinobu Takeshita, Kohei Ogawa, Tatsuya Imamura, Kota Takano, Kazuya Okuda, Hideharu Matsuura, et al. "Anomalous Conduction between the Band and Nearest-Neighbor Hopping Conduction Regions in Heavily Al-Doped p-Type 4H-SiC." Materials Science Forum 1004 (July 2020): 224–30. http://dx.doi.org/10.4028/www.scientific.net/msf.1004.224.

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We measure the temperature-dependent resistivity (ρ(T)) for thick heavily Al- and Ncodoped p-type 4H-SiC samples grown by chemical vapor deposition (CVD), physical vapor transport (PVT), and solution growth (SG), and investigate their conduction mechanisms. For samples with an Al concentration (CAl) of 3.5×1019 to 1×1020 cm-3 grown by CVD, PVT, and SG, the conduction mechanisms at high and low temperatures are band and nearest-neighbor hopping (NNH) conduction, respectively. In the range CAl of 1×1019 to 3.5×1019 cm-3, on the other hand, an anomalous conduction, referred to as X conduction here, is observed between the band and NNH conduction regions for the samples grown by CVD and PVT, but not those grown by SG. One of the differences between the samples grown by CVD and PVT and those grown by SG is the off-orientation toward [11-20] of the (0001) 4H-SiC substrate. We discuss the reason for the appearance of X conduction, which appears to be consistent with dopant-concentration inhomogeneity model.

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Blumenstein, I., S. Xuan, R. Panaccione, F. Baert, M. Barreiro-de Acosta, B. D. Ye, J. Klaff, et al. "P179 Comparative benefit-risk profile of induction and maintenance therapy with upadacitinib versus placebo in patients with moderately to severely active ulcerative colitis." Journal of Crohn's and Colitis 17, Supplement_1 (January 30, 2023): i333—i334. http://dx.doi.org/10.1093/ecco-jcc/jjac190.0309.

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Abstract Background Upadacitinib (UPA) demonstrated efficacy and safety as induction and maintenance therapy for ulcerative colitis (UC) in Phase 3 trials U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026). This post-hoc analysis aims to characterise the benefit-risk profile of UPA induction and maintenance therapy vs placebo (PBO) in patients (pts) with moderately to severely active UC based on a number needed to treat/harm (NNT/NNH) analysis. Methods Efficacy and safety data from the pooled intention-to-treat population of U-ACHIEVE and U-ACCOMPLISH trials were included. Pts received UPA 45 mg (UPA45) once daily (QD) or PBO for 8 weeks (induction trials). Clinical responders (per Adapted Mayo score) at Week 8 of induction were re-randomised to receive UPA 15 mg (UPA15) or 30 mg (UPA30) QD, or PBO in the 52-week maintenance study. The primary efficacy endpoint was clinical remission per Adapted Mayo score. Secondary outcomes are listed in Table 1 and safety outcomes are listed in Table 2. N, percentages, and outcome differences compared by Z test were reported. NNT/NNH was calculated as the inverse of the difference in proportions achieving efficacy/safety outcomes for UPA vs PBO. Positive NNT values indicate greater efficacy and negative NNH values imply lower safety risk for UPA vs PBO. Results A significantly greater proportion of pts achieved clinical remission at induction (UPA45 29.9% vs PBO 4.4%) and maintenance (UPA15 40.4%, UPA30 53.6% vs PBO 10.8%) with UPA vs PBO, as well as all secondary endpoints (all p<0.001; Table 1). The NNT for clinical remission at Week 8 was 4.0, ranging from 2.1 to 9.6 for secondary endpoints. At Week 52, the NNT for clinical remission was 2.4; NNTs for secondary endpoints ranged from 1.8 to 5.9 (Table 1). At Week 8, adverse events (AEs) were lower for worsening of UC for UPA45 vs PBO-treated pts and greater for creatine phosphokinase (CPK) elevation, acne, neutropenia, and lymphopenia (p≤0.01). At Week 52, AEs were lower for UPA15 and UPA30 vs PBO for worsening of UC, AEs leading to discontinuation (UPA15 only), and arthralgia (UPA30 only), and greater for CPK elevation, herpes zoster, hepatic disorder (UPA15 only), and neutropenia (UPA30 only) (p≤0.05; Table 2). All other AEs were similar between UPA and PBO. Among the safety outcomes significantly different between UPA and PBO, the NNH for UPA vs PBO ranged from –16.1 to 25.6 (Table 2). Conclusion This post-hoc Phase 3 analysis demonstrates greater efficacy and generally comparable safety of UPA vs PBO, indicating a favourable benefit-risk profile for UPA in pts with moderately to severely active UC.

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Journal articles on the topic 'NNH'

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