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Background The ramped position facilitates mask ventilation and endotracheal intubation in patients with obesity. This study aimed to determine whether the ramped position improves supraglottic airway (SGA) insertion in patients with obesity. Methods In this prospective, randomized, single-center trial, 48 obese patients undergoing elective surgery were randomized into either ramped or sniffing position groups. The Ambu® AuraGainTM (Ambu A/S), a second-generation SGA, was used. The primary outcome was the time required for the AuraGain insertion. Secondary outcomes included ease and number of insertion attempts, oropharyngeal leak pressure (OLP), and complications. The number needed to treat (NNT) was calculated to ensure ease of insertion. Results The time required for the AuraGain insertion was significantly shorter in the ramped group than in the sniffing group (13.0 [11.0, 16.0] vs. 24.0 [21.0, 28.0], P < 0.001). The insertion was easier in the ramped group than in the sniffing group (23/24 vs. 13/24, NNT = 2.4 [95% CI, 1.6, 5.0], P = 0.003). The first-attempt success rate was higher in the ramped group than in the sniffing group, although the difference was not statistically significant (22/24 vs. 18/24, P = 0.319). The OLP and postoperative complication rates were not significantly different between the groups. Conclusions The ramped position reduced the time required for the AuraGain insertion in obese patients while providing comparable airway sealing without increasing adverse events. Therefore, a ramped position may be a more suitable option for SGA insertion in this population.

Background: The number needed to treat (NNT) for efficacy and number needed to harm (NNH) for tolerability/safety were evaluated for adjunctive cariprazine in major depressive disorder (MDD)., Methods: Data were extracted from five randomized, double-blind, placebo-controlled trials of adjunctive cariprazine in MDD. NNTs (response, remission, severity shift) and NNHs (discontinuations due to adverse events [AEs], AEs, laboratory shifts) were determined in dose groupings; likelihood to be helped/harmed (LHH) was calculated., Results: NNTs (95 % CI) for adjunctive cariprazine versus placebo were statistically significant at week 6/early termination for response on the Montgomery-Åsberg Depression Rating Scale (MADRS), as defined by a decrease in total score ≥ 50 % (doses ≥ 1 mg/d = 12 [9-21]; 1-2 mg/d = 12 [8-25]; 2-4.5 mg/d = 14 [9-43]) and other response/remission outcomes. NNHs for cariprazine versus placebo were generally ≥ 10 for AEs that were statistically significant; an apparent dose-response was seen for akathisia (lower dose = 24 [17-43]; higher dose = 9 [7-11]). LHHs were ≥ 1 (acceptable benefit/harm ratio) for MADRS total score response versus most important cariprazine AEs in most dose groupings. For response versus discontinuation because of an AE, adjunctive cariprazine 1-2 mg/d had a more favorable response/tolerability profile in indirect comparison with other approved atypical antipsychotics., Limitations: Post hoc analysis; indirect comparisons., Conclusions: Patients receiving adjunctive cariprazine encountered benefits more often than harms; NNT values at week 6/early termination were statistically significant versus placebo on response/remission outcomes across dose groupings from the five pooled studies. Adjunctive cariprazine was well tolerated; NNH values versus placebo were generally > 10, with better akathisia tolerability in the lower-dose range., Competing Interests: Declaration of competing interest Leslie Citrome is a clinical professor in the Department of Psychiatry and Behavioral Sciences at New York Medical College in Valhalla, New York. He has served as consultant to AbbVie/Allergan, Acadia, Adamas, Alkermes, Angelini, Astellas, Avanir, Axsome, Biogen, BioXcel, Boehringer Ingelheim, Cadent Therapeutics, Cerevel, Clinilabs, COMPASS, Delpor, Eisai, Enteris BioPharma, HLS Therapeutics, Idorsia, INmune Bio, Impel, Intra-Cellular Therapies, Janssen, Karuna, Lundbeck, Luye, Lyndra, MapLight, Marvin, Medavante-ProPhase, Merck, Mitsubishi-Tanabe Pharma, Neumora, Neurocrine, Neurelis, Noema, Novartis, Noven, Otsuka, Ovid, Praxis, Recordati, Relmada, Reviva, Sage, Sumitomo/Sunovion, Supernus, Teva, University of Arizona, Vanda, Wells Fargo, and one-off ad hoc consulting for individuals/entities conducting marketing, commercial, or scientific scoping research; speaker for AbbVie/Allergan, Acadia, Alkermes, Angelini, Axsome, BioXcel, Eisai, Idorsia, Intra-Cellular Therapies, Janssen, Lundbeck, Neurocrine, Noven, Otsuka, Recordati, Sage, Sunovion, Takeda, Teva, and CME activities organized by medical education companies such as Medscape, NACCME, NEI, Vindico, and Universities and Professional Organizations/Societies; owns stocks (small number of shares of common stock): Bristol-Myers Squibb, Eli Lilly, J & J, Merck, Pfizer purchased >10 years ago, stock options: Reviva; and receives royalties/publishing Income from Taylor & Francis (Editor-in-Chief, Current Medical Research and Opinion, 2022-date), Wiley (Editor-in-Chief, International Journal of Clinical Practice, through end 2019), UpToDate (reviewer), Springer Healthcare (book), Elsevier (Topic Editor, Psychiatry, Clinical Therapeutics)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To evaluate the benefit-risk assessment of atogepant and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) vs. placebo based on the number needed to treat (NNT) and the number needed to harm (NNH) in a blended episodic migraine and chronic migraine (EM + CM) population., Methods: The NNT was calculated based on achievement of a ≥ 50% reduction in mean monthly migraine days (MMDs) from baseline across 12 weeks. The NNH was calculated using the proportion of participants reporting a discontinuation due to adverse events (AEs). The primary analysis included data from studies of atogepant, erenumab, galcanezumab, eptinezumab and fremanezumab., Results: In the primary analysis, the calculated NNT for atogepant 60 mg vs. placebo was 4.2 (95% credible interval (CrI) = 3.1-6.7), which was the lowest relative to the CGRP mAbs in the blended EM + CM population. Participants who received atogepant 60 mg or fremanezumab showed the most favorable NNH values (-1010 (95% Crl = 44 to ∞ to number needed to benefit 80) for atogepant) resulting from lower rates of discontinuation due to AEs compared with those receiving placebo., Conclusions: Atogepant demonstrated a favorable benefit-risk profile, with NNT and NNH values comparable (not statistically significant) with those of CGRP mAbs across all analyses., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Jessica Ailani, MD, has served as a consultant for AbbVie, Aeon, Amgen, Axsome, BioDelivery Sciences International, Biohaven, Eli Lilly and Company, GlaxoSmithKline, Gore, Impel, Ipsen, Linpharma, Lundbeck, Merz, Miravo, Nesos, Neurolief, Pfizer, Satsuma, Teva, and Theranica. She has owned stock shares in Ctrl M, has provided editorial services for SELF magazine, and has received clinical trial grants from AbbVie, Biohaven, Eli Lilly and Company, Ipsen, Parema, Satsuma and Zosano. Anjana Lalla, MS, Pranav Gandhi, PhD, and Krisztian Nagy, MD, are employees of AbbVie and may hold AbbVie stock. Rashmi B. Halker Singh, MD, serves on the editorial board of Current Neurology and Neuroscience Reports, serves as deputy editor for Headache, and previously received grants for research support from Amgen and Eli Lilly. In the past 3 years, she has received consulting fees from AbbVie and Pfizer. Dagny Holle-Lee, MD, PhD, has received honoraria for consulting from AbbVie/Allergan, Amgen, Eli Lilly, Hormosan, Lundbeck, Novartis, Teva and Zuellig Pharma. Patricia Pozo-Rosich, MD, PhD, has received, in the past 3 years, personal fees for advisory boards and speaker panels from AbbVie, Amgen, Chiesi, Eli Lilly, Lundbeck, Medscape, Novartis, Pfizer and Teva Pharmaceuticals, and for serving on a scientific advisory or data safety monitoring board for Lilly Foundation Spain; is the principal investigator for clinical trials sponsored by AbbVie, Eli Lilly, Lundbeck, Novartis and Teva; has received (through her group) grants from AbbVie, EraNet Neuron, Instituto de Salud Carlos III, Novartis and Teva; and serves as an associate editor for Cephalalgia, Headache, Neurologia, The Journal of Headache and Pain, and Revista de Neurologia. Kari Kelton, PhD, and Cristiano Piron, MPH, are employees of Medical Decision Modeling Inc., which received payment from AbbVie for the analysis.

Abstract Background The well-established benefit of Low-Dense-Lipoprotein-cholesterol (LDL-c) lowering treatments (LLTs) has led clinical guidelines to lower the cardiovascular prevention targets. Despite this, there is a surprising scarcity of real-world studies (RWS) evaluating whether recommendations are applied in the routine clinical management of patients with type 2 diabetes (T2D). We therefore evaluated, in a large RWS, the pattern of LLTs use and the achievement of LDL-c targets in patients with T2D in Italian diabetes specialist clinics. Methods We collected data from 46 diabetes outpatient clinics (following 281,381 subjects), including 104,726 T2D patients, for whom use of LLTs between 2015 and 2016 was ascertained. We used the 2016 and 2019 European Atherosclerosis Society and European Society of Cardiology (EAS-ESC) guidelines to define cardiovascular risk categories, LDL-c targets, and the expected LDL-c reduction and cardiovascular benefit achievable with LLT intensification. Results 63,861 patients (61.0%) were on statin therapy, 9.2% of whom were also on ezetimibe. Almost all subjects were at high (29.3%) or very high (70.4%) cardiovascular risk, including 17% being in secondary prevention. Among very high-risk patients, 35% were not on statin despite half of them had LDL-c > 2.6 mmol/l, and only 15% of those on statins had LDL-c 1.8 mmol/l. Overall, 35% and 14% of subjects achieved the LDL-c targets as suggested by 2016 and 2019 EAS-ESC Guidelines, respectively. Based on anticipated response to treatment, we estimated that 38% of the entire population would require high-intensity-statin (HI-statin), 27% a combination of HI-statin plus ezetimibe, and 27% the addition of proprotein-convertase-subtilisin/kexin-9 (PCSK9) inhibitors. These LLT intensifications would reduce the incidence of cardiovascular events by 32%, from 23.511 to 16.022 events per 100.000 patients/10-years (incidence-rate-ratio 0.68; 95% C.I 0.67–0.70, p

Background: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease, development of end-stage renal disease, and all-cause mortality. It affects around 10% of the population worldwide. The prevalence of hypertension in people with CKD ranges from 22% in stage 1 to 80% in stage 4. Elevated arterial blood pressure is one of the major independent risk factors for adverse cardiovascular events. Thereby, reducing blood pressure to below standard targets may be beneficial but could also increase the risk of adverse events. The optimal blood pressure target in people with hypertension and CKD remains unknown., Objectives: Primary: to compare the effects of standard and lower-than-standard blood pressure targets for hypertension in people with chronic kidney disease on mortality and morbidity outcomes. Secondary: to assess the magnitude of reductions in systolic and diastolic blood pressure, the proportion of participants reaching blood pressure targets, and the number of drugs necessary to achieve the assigned target., Search Methods: We used standard, extensive Cochrane search methods. We searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, one other database, and two trial registers up to 8 February 2023. We also contacted authors of relevant papers regarding further published and unpublished work. We applied no language restrictions., Selection Criteria: We included randomized controlled trials (RCTs) in people with hypertension and CKD that provided at least twelve months' follow-up. Eligible interventions compared lower targets for systolic/diastolic blood pressure (130/80 mmHg or lower) to standard targets for blood pressure (140 to 160/90 to 100 mmHg or lower). Participants were adults with CKD and elevated blood pressure documented in a standard way on at least two occasions, or already receiving treatment for elevated blood pressure., Data Collection and Analysis: We used standard Cochrane methods. Our critical outcomes were: total mortality, total serious adverse events, total cardiovascular events, cardiovascular mortality, and progression to end-stage renal disease. Important outcomes were: participant withdrawals due to adverse effects, and number of participants with a doubling of serum creatinine level or at least a 50% reduction in the glomerular filtration rate (GFR) at the end of the study. We used GRADE to assess the certainty of the evidence for the critical outcomes. This review received no funding., Main Results: We included six RCTs that contributed data for meta-analysis, involving 7348 participants overall (range 840 to 4733 people per study). The mean follow-up was 3.6 years (range 1.0 to 8.0 years). Three studies were publicly funded, two were privately funded, and one had both public and private funding. All RCTs provided individual participant data. None of the included studies blinded participants or clinicians because of the need to titrate antihypertensive drugs to reach a specific blood pressure target. However, an independent committee blinded to group allocation assessed clinical events in all studies. Critical outcomes. Compared with standard blood pressure targets, lower targets likely result in little to no difference in total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.76 to 1.06; 6 studies, 7348 participants), total serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 6 studies, 7348 participants), and total cardiovascular events (RR 1.00, 95% CI 0.87 to 1.15; 5 studies, 6508 participants), all with moderate-certainty evidence. Compared with standard blood pressure targets, lower targets may result in little to no difference in cardiovascular mortality (RR 0.90, 95% CI 0.70 to 1.16; 6 studies, 7348 participants) and progression to end-stage renal disease (RR 0.94, 95% CI 0.80 to 1.11; 4 studies, 4788 participants), both with low-certainty evidence. Important outcomes. We found little to no differences in: participant withdrawals due to adverse effects; and the number of participants with a doubling of serum creatinine level, or at least a 50% reduction in GFR at the end of the study. Exploratory outcomes. Compared to the standard blood pressure target groups, participants in the lower target groups achieved lower systolic and diastolic blood pressure values after one year, and required a higher number of antihypertensive drugs at the end of the studies. A higher proportion of participants in the standard blood pressure target groups achieved the targets they were assigned than did participants in the intensive target groups., Authors' Conclusions: Compared to a standard blood pressure target, lower blood pressure targets probably result in little to no difference in total mortality, total serious adverse events, and total cardiovascular events, and may result in little to no difference in total cardiovascular mortality or in the progression to end-stage renal disease in people with hypertension and CKD. However, the evidence underpinning these conclusions has several limitations. All studies were open design, blood pressure measurement was performed at a medical office, and there was scant information about adverse events. Future research should include high-quality adverse event data, report results for people with different levels of proteinuria, and consider out-of-office blood pressure monitoring. Several studies are ongoing, and may provide new evidence for this topic in the near future., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Competing Interests: None declared.

The number needed to treat (NNT) is the inverse of the absolute risk difference, which is used as a secondary outcome to clinical trials as a measure relevant to a positive trial, supplementing statistical significance. The NNT requires dichotomous outcomes and is influenced by the baseline disease or symptom severity, the particular population, the type and intensity of the interventional, the duration of treatment, the time period to assessment of response, and the comparator response. Confidence intervals should always accompany NNT for the precision of its estimate. In this review, three meta-analyses are reviewed, which included the NNT in the analysis of response., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Considering clinical benefits of new combination therapies for metastatic renal-cell carcinoma (mRCC), this study aims to calculate the number needed to treat (NTT) and the cost of preventing an event (COPE) for pembrolizumab plus axitinib (PþA), and nivolumab plus ipilimumab (NþI) as first-line treatments, from the Brazilian private perspective. Methods: Overall survival (OS) and progression-free survival (PFS) data for intermediate- and poor-risk groups were obtained from KEYNOTE-426 and CHECKMATE-214 trials for PþA and NþI, respectively, versus sunitinib as mRCC first-line treatment. Results: Considering a 12-month time horizon, 6 patients should be treated with PþA to prevent one death with sunitinib use, resulting in a COPE of 3,893,903 BRL. Using NþI, NNT for 12-month OS rate was 13 compared to sunitinib, with a COPE of 6,357,965 BRL. Regarding PFS data, NNT was also 6 when comparing PþA versus sunitinib, with an estimated COPE of 3,893,903 BRL. Estimated NNT was 20 comparing NþI and sunitinib, resulting in a COPE of 10,172,744 BRL. Cost differences between two treatment options, reached more than 6 million BRL for PFS, and 2 million BRL for OS. Conclusion: At the 12-month landmark, PþA suggests better economic scenario versus NþI as firstline mRCC treatment option for intermediate- and poor-risk groups, through an indirect comparison using sunitinib as a common comparator. [ABSTRACT FROM AUTHOR]

Background: Despite using identical evidence to support practice guidelines for lipid-lowering treatment in primary prevention of cardiovascular disease (CVD), it is unclear to what extent the 2018 American Heart Association/American College of Cardiology/Multisociety, 2016 US Preventive Services Task Force (USPSTF), 2020 Department of Veterans Affairs/Department of Defense, 2021 Canadian Cardiovascular Society, and 2019 European Society of Cardiology/European Atherosclerosis Society guidelines differ in grading and assigning levels of evidence and classes of recommendations (LOE/class) at a population level.Methods: We included 7262 participants, aged 45 to 75 years, without history of CVD from the prospective population-based Rotterdam Study. Per guideline, proportions of the population recommended statin therapy by LOE/class, sensitivity and specificity for CVD events, and numbers needed to treat at 10 years were calculated.Results: Mean age was 61.1 (SD 6.9) years; 58.2% were women. American Heart Association/American College of Cardiology/Multisociety, USPSTF, Department of Veterans Affairs/Department of Defense, Canadian Cardiovascular Society, and European Society of Cardiology/European Atherosclerosis Society strongly recommended statin initiation in respective 59.4%, 40.2%, 45.2%, 73.7%, and 42.1% of the eligible population based on high-quality evidence. Sensitivity for CVD events for treatment recommendations supported with strong LOE/class was 86.3% for American Heart Association/American College of Cardiology/Multisociety (IA or IB), 69.4% for USPSTF (USPSTF-B), 74.5% for Department of Veterans Affairs/Department of Defense (strong for), 93.3% for Canadian Cardiovascular Society (strong), and 66.6% for European Society of Cardiology/European Atherosclerosis Society (IA). Specificity was highest for the USPSTF at 45.3% and lowest for European Society of Cardiology/European Atherosclerosis Society at 10.0%. Estimated numbers needed to treat at 10 years for those with the strongest LOE/class were ranging from 20 to 26 for moderate-intensity and 12 to 16 for high-intensity statins.Conclusions: Sensitivity, specificity, and numbers needed to treat at 10 years for assigned LOE/class varied greatly among 5 CVD prevention guidelines. The level of variability seems to be driven by differences in how the evidence is graded and translated into LOE/class underlying the treatment recommendations by different professional societies. Efforts towards harmonizing evidence grading systems for clinical guidelines in primary prevention of CVD may reduce ambiguity and reinforce updated evidence-based recommendations. [ABSTRACT FROM AUTHOR]

Regression models for continuous, binary, nominal, and ordinal outcomes almost completely rely on parametric models, whereas time-to-event outcomes are mainly analyzed by Cox's Proportional Hazards model, an essentially non-parametric method. This is done despite a long list of disadvantages that have been reported for the hazard ratio, and also for the odds ratio, another effect measure sometimes used for time-to-event modelling. In this paper, we propose a parametric proportional risk model for time-to-event outcomes in a two-group situation. Modelling explicitly a risk instead of a hazard or an odds solves the current interpretational and technical problems of the latter two effect measures. The model further allows for computing absolute effect measures like risk differences or numbers needed to treat. As an additional benefit, results from the model can also be communicated on the original time scale, as an accelerated or a prolongated failure time thus facilitating interpretation for a non-technical audience. Parameter estimation by maximum likelihood, while properly accounting for censoring, is straightforward and can be implemented in each statistical package that allows coding and maximizing a univariate likelihood function. We illustrate the model with an example from a randomized controlled trial on efficacy of a new glucose-lowering drug for the treatment of type 2 diabetes mellitus and give the results of a small simulation study. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this investigation is to examine the benefits and potential risks of these drugs in individuals by varying baseline low-density lipoprotein cholesterol (LDL-C) values, utilizing the concept of the number needed to treat (NNT)., Methods: We extensively searched electronic databases, such as PubMed, EMBASE, Cochrane, and Web of Science, up to 6 August 2023. Baseline LDL-C values were stratified into four categories: < 100, 100-129, 130-159, and ≥ 160 mg/dL. Risk ratios (RRs) and NNT values were computed., Results: This analysis incorporated data from 46 randomized controlled trials (RCTs), encompassing a total of 237,870 participants. The meta-regression analysis demonstrated an incremental diminishing risk of major adverse cardiovascular events (MACE) with increasing baseline LDL-C values. Statins exhibited a significant reduction in MACE [number needed to treat to benefit (NNTB) 31, 95% confidence interval (CI) 25-37], but this effect was observed only in individuals with baseline LDL-C values of 100 mg/dL or higher. Ezetimibe and PCSK9 inhibitors also were effective in reducing MACE (NNTB 18, 95% CI 11-41, and NNTB 18, 95% CI 16-24). Notably, the safety outcomes of statins and ezetimibe did not reach statistical significance, while the incidence of injection-site reactions with PCSK9 inhibitors was statistically significant [number needed to treat to harm (NNTH) 41, 95% CI 80-26]., Conclusion: Statins, ezetimibe, and PCSK9 inhibitors demonstrated a substantial capacity to reduce MACE, particularly among individuals whose baseline LDL-C values were relatively higher. The NNT visually demonstrates the gradient between baseline LDL-C and cardiovascular disease (CVD) risk., Systematic Review Registration: Registration: PROSPERO identifier number: CRD42023458630., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: Appraise the evidence for daridorexant 50 mg and 25 mg versus placebo when treating chronic insomnia disorder in terms of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH)., Methods: NNT, NNH, and LHH were calculated from a 3-month pivotal Phase 3 study ( N  = 930; randomized 1:1:1 to daridorexant 50 mg, daridorexant 25 mg, or placebo once nightly). Wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), and Insomnia Severity Index were used for the NNT efficacy analysis. NNH safety analysis was performed using rates of adverse events (AEs) occurring in >1% of the participants in any arm. LHH was assessed for all NNT estimates, contrasting them with NNH estimates for somnolence, headache, and fatigue AEs., Results: NNT estimates for daridorexant 50 mg versus placebo were <10 for clinically meaningful thresholds across all outcomes. NNT estimates for daridorexant 25 mg versus placebo were not as robust as those observed for daridorexant 50 mg, with many values exceeding 10. NNH estimates for daridorexant 50 mg and 25 mg versus placebo did not show a statistically significant treatment difference except for falls, where NNH was negative for the daridorexant 50 mg group (-44 [95% CI -328; -21]; rate of falls was greater with placebo than for daridorexant 50 mg). All LHH ratios at Months 1 and 3 were >1 (except for daridorexant 25 mg for the IDSIQ alert/cognition domain), indicating that patients were more likely to respond to daridorexant 50 mg and 25 mg than to experience an AE of somnolence, headache, or fatigue., Conclusion: Daridorexant 50 mg and 25 mg have a favorable benefit-risk ratio over 3 months. Daridorexant 50 mg demonstrated more robust (lower) NNT estimates versus placebo than daridorexant 25 mg.

Considering clinical benefits of new combination therapies for metastatic renal-cell carcinoma (mRCC), this study aims to calculate the number needed to treat (NTT) and the cost of preventing an event (COPE) for pembrolizumab plus axitinib (P + A), and nivolumab plus ipilimumab (N + I) as first-line treatments, from the Brazilian private perspective. Overall survival (OS) and progression-free survival (PFS) data for intermediate- and poor-risk groups were obtained from KEYNOTE-426 and CHECKMATE-214 trials for P + A and N + I, respectively, versus sunitinib as mRCC first-line treatment. Considering a 12-month time horizon, 6 patients should be treated with P + A to prevent one death with sunitinib use, resulting in a COPE of 3,893,903 BRL. Using N + I, NNT for 12-month OS rate was 13 compared to sunitinib, with a COPE of 6,357,965 BRL. Regarding PFS data, NNT was also 6 when comparing P + A versus sunitinib, with an estimated COPE of 3,893,903 BRL. Estimated NNT was 20 comparing N + I and sunitinib, resulting in a COPE of 10,172,744 BRL. Cost differences between two treatment options, reached more than 6 million BRL for PFS, and 2 million BRL for OS. At the 12-month landmark, P + A suggests better economic scenario versus N + I as first-line mRCC treatment option for intermediate- and poor-risk groups, through an indirect comparison using sunitinib as a common comparator. [ABSTRACT FROM AUTHOR]

It is generally believed that pharmacologic prophylaxis for venous thromboembolism (VTE) is underused. However, previous studies have not shown associations between increased prophylaxis administration and reductions in VTE. We here investigated prophylaxis administration and VTE incidence among trauma patients at our facility to determine whether to further increase prophylaxis administration after implementation of a standardized monitoring protocol. Univariate analyses and regression models were used to evaluate the protocol's effect on VTE, identify clinical factors associated with VTE and with receiving prophylaxis, and identify over- or under-prophylaxed patients. A final prophylaxis rate of 71.2% was achieved, an increase from the 40.8% reported by the Trauma Quality Improvement Program in 2015, with no accompanying reduction in VTE (1.5% pre and postintervention). Factors that identified patients at lower probability of receiving prophylaxis were those that increased bleeding risk: severe head injuries (odds ratio [OR] 5 0.13) and preexisting bleeding (OR5 0.69) and renal/kidney (OR 50.46) disorders. A large group of patients was both at increased odds of receiving prophylaxis and at low risk of VTE, representing a group that may be considered for nonpharmacologic options. Examination of current prophylaxis practices and identification of underuse or overuse is beneficial before expending effort to increase prophylaxis administration to reduce VTE. [ABSTRACT FROM AUTHOR]

Background: The relationship between cholesterol levels and risk of venous thromboembolism (VTE) is uncertain. We set out to determine the effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition on the risk of VTE, explore potential mechanisms, and examine the efficacy in subgroups with clinically and genetically defined risk.Methods: We performed a post hoc analysis of the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) testing whether evolocumab reduces the risk of VTE events (deep venous thrombosis or pulmonary embolism). Data from FOURIER and ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment with Alirocumab) were then combined in a meta-analysis to assess the class effect of PCSK9 inhibition on the risk of VTE. We also analyzed baseline lipids in FOURIER to investigate potential mechanisms explaining the reduction in VTE with evolocumab. Last, an exploratory genetic analysis was performed in FOURIER to determine whether a VTE polygenic risk score could identify high-risk patients who would derive the greatest VTE reduction from evolocumab.Results: In FOURIER, the hazard ratio (HR) for VTE with evolocumab was 0.71 (95% CI, 0.50-1.00; P=0.05), with no effect in the 1st year (HR, 0.96 [95% CI, 0.57-1.62]) but a 46% reduction (HR, 0.54 [95% CI, 0.33-0.88]; P=0.014) beyond 1 year. A meta-analysis of FOURIER and ODYSSEY OUTCOMES demonstrated a 31% relative risk reduction in VTE with PCSK9 inhibition (HR, 0.69 [95% CI, 0.53-0.90]; P=0.007). There was no relation between baseline low-density lipoprotein cholesterol levels and magnitude of VTE risk reduction. In contrast, in patients with higher baseline lipoprotein(a) (Lp[a]) levels, evolocumab reduced Lp(a) by 33 nmol/L and risk of VTE by 48% (HR, 0.52 [95% CI, 0.30-0.89]; P=0.017), whereas, in patients with lower baseline Lp(a) levels, evolocumab reduced Lp(a) by only 7 nmol/L and had no effect on VTE risk (Pinteraction 0.087 for HR; Pheterogeneity 0.037 for absolute risk reduction). Modeled as a continuous variable, there was a significant interaction between baseline Lp(a) concentration and magnitude of VTE risk reduction (Pinteraction=0.04). A polygenic risk score identified patients who were at >2-fold increased risk for VTE and who derived greater relative (Pinteraction=0.04) and absolute VTE reduction (Pheterogeneity=0.009) in comparison with those without high genetic risk.Conclusions: PCSK9 inhibition significantly reduces the risk of VTE. Lp(a) reduction may be an important mediator of this effect, a finding of particular interest given the ongoing development of potent Lp(a) inhibitors. [ABSTRACT FROM AUTHOR]

Japanese encephalitis (JE) virus is the leading vaccine-preventable cause of encephalitis in Asia. For most travelers, JE risk is very low but varies based on several factors, including travel duration, location, and activities. To aid public health officials, health care providers, and travelers evaluate the worth of administering/ receiving pre-travel JE vaccinations, we estimated the numbers-needed-to-treat to prevent a case and the cost-effectiveness ratios of JE vaccination for U.S. travelers in different risk categories. We used a decision tree model to estimate cost per case averted from a societal and traveler perspective for hypothetical cohorts of vaccinated and unvaccinated travelers. Risk Category I included travelers planning to spend ≥1 month in JE-endemic areas, Risk Category II were shorter-term (<1 month) travelers spending ≥20% of their time doing outdoor activities in rural areas, and Risk Category III were all remaining travelers. We performed sensitivity analyses including examining changes in cost-effectiveness with 10- and 100-fold increases in incidence and medical treatment costs. The numbers-needed-to-treat to prevent a case and cost per case averted were approximately 0.7 million and $0.6 billion for Risk Category I, 1.6 million and $1.2 billion for Risk Category II, and 9.8 million and $7.6 billion for Risk Category III. Increases of 10-fold and 100-fold in disease incidence proportionately decreased cost-effectiveness ratios. Similar levels of increases in medical treatment costs resulted in negligible changes in cost-effectiveness ratios. Numbers-needed-to-treat and cost-effectiveness ratios associated with preventing JE cases in U.S. travelers by vaccination varied greatly by risk category and disease incidence. While cost effectiveness ratios are not the sole rationale for decision-making regarding JE vaccination, the results presented here can aid in making such decisions under very different risk and cost scenarios. [ABSTRACT FROM AUTHOR]

Abstract Background The number needed to treat (NNT) is an absolute effect measure that has been used to assess beneficial and harmful effects of medical interventions. Several methods can be used to calculate NNTs, and they should be applied depending on the different study characteristics, such as the design and type of variable used to measure outcomes. Whether or not the most recommended methods have been applied to calculate NNTs in studies published in the medical literature is yet to be determined. The aim of this study is to assess whether the methods used to calculate NNTs in studies published in medical journals are in line with basic methodological recommendations. Methods The top 25 high-impact factor journals in the “General and/or Internal Medicine” category were screened to identify studies assessing pharmacological interventions and reporting NNTs. Studies were categorized according to their design and the type of variables. NNTs were assessed for completeness (baseline risk, time horizon, and confidence intervals [CIs]). The methods used for calculating NNTs in selected studies were compared to basic methodological recommendations published in the literature. Data were analyzed using descriptive statistics. Results The search returned 138 citations, of which 51 were selected. Most were meta-analyses (n = 23, 45.1%), followed by clinical trials (n = 17, 33.3%), cohort (n = 9, 17.6%), and case–control studies (n = 2, 3.9%). Binary variables were more common (n = 41, 80.4%) than time-to-event (n = 10, 19.6%) outcomes. Twenty-six studies (51.0%) reported only NNT to benefit (NNTB), 14 (27.5%) reported both NNTB and NNT to harm (NNTH), and 11 (21.6%) reported only NNTH. Baseline risk (n = 37, 72.5%), time horizon (n = 38, 74.5%), and CI (n = 32, 62.7%) for NNTs were not always reported. Basic methodological recommendations to calculate NNTs were not followed in 15 studies (29.4%). The proportion of studies applying non-recommended methods was particularly high for meta-analyses (n = 13, 56.5%). Conclusions A considerable proportion of studies, particularly meta-analyses, applied methods that are not in line with basic methodological recommendations. Despite their usefulness in assisting clinical decisions, NNTs are uninterpretable if incompletely reported, and they may be misleading if calculating methods are inadequate to study designs and variables under evaluation. Further research is needed to confirm the present findings.

Objective: This study aimed to determine the number needed to treat (NNT), number needed to harm (NNH), and likelihood of being helped or harmed (LHH) in a post hoc analysis of the phase 3b FOCUS trial., Background: Fremanezumab, a humanized monoclonal antibody that selectively targets calcitonin gene-related peptide (CGRP), has demonstrated efficacy, tolerability, and safety in adults with episodic migraine (EM) or chronic migraine (CM), with documented previous inadequate response to two to four classes of migraine preventive medications., Methods: In the 12-week double-blind period of the FOCUS study, patients were randomized (1:1:1) to quarterly fremanezumab, monthly fremanezumab, or matched monthly placebo. NNT was based on responder analysis, defined as ≥50% reduction in monthly average number of migraine days at 12 weeks. NNH was based on discontinuations due to adverse events (AEs)., Results: Among patients with CM (n = 509), response rates and discontinuation rates were 27% (45/169) and 0 for quarterly fremanezumab, 29% (50/173) and 2% (3/173) for monthly fremanezumab, and 8% (13/167) and <1% (1/167) for placebo, respectively. These results translated to NNTs of 5.3 and 4.7, NNHs of 1000 and 88, and LHHs of 188 and 19 for quarterly and monthly fremanezumab, respectively. Among patients with EM (n = 328), response rates were 47% (50/107) for quarterly fremanezumab, 43% (47/110) for monthly fremanezumab, and 10% (11/111) for placebo. Discontinuation rates were <1% (n = 1) in all three groups. These results translated to NNTs of 2.7 and 3.0, NNHs of 1000 and 1000, and LHHs of 368 and 328 for quarterly and monthly fremanezumab, respectively., Conclusions: The NNT, NNH, and LHH for quarterly and monthly fremanezumab compare favorably with those for traditional oral preventive medications, including topiramate, valproate, and propranolol., (© 2023 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Multiple recent pharmacological clinical trials in neuropathic pain have failed to show beneficial effect of drugs with previously demonstrated efficacy, and estimates of drug efficacy seems to have decreased with accumulation of newer trials. However, this has not been systematically assessed. Here, we analyze time-dependent changes in estimated treatment effect size in pharmacological trials together with factors that may contribute to decreases in estimated effect size. This study is a secondary analysis of data from a previous published NeuPSIG systematic review and meta-analysis, updated to include studies published up till March 2017. We included double-blind, randomized, placebo-controlled trials examining the effect of drugs for which we had made strong or weak recommendations for use in neuropathic pain in the previously published review. As the primary outcome, we used an aggregated number needed to treat for 50% pain reduction (alternatively 30% pain reduction or moderate pain relief). Analyses involved 128 trials. Number needed to treat values increased from around 2 to 4 in trials published between 1982 and 1999 to much higher (less effective) values in studies published from 2010 onwards. Several factors that changed over time, such as larger study size, longer study duration, and more studies reporting 50% or 30% pain reduction, correlated with the decrease in estimated drug effect sizes. This suggests that issues related to the design, outcomes, and reporting have contributed to changes in the estimation of treatment effects. These factors are important to consider in design and interpretation of individual study data and in systematic reviews and meta-analyses. [ABSTRACT FROM AUTHOR]

The number needed to treat (NNT) with brentuximab vedotin consolidation therapy post-autologous stem cell transplant (ASCT) versus placebo in the phase 3 AETHERA trial to avoid one additional event of disease progression/death was evaluated. AETHERA included 329 Hodgkin lymphoma patients at increased risk of progression post-ASCT who received brentuximab vedotin 1.8 mg/kg (n = 165) or placebo (n = 164) on day 1 of each 21-d cycle (up to 16 cycles). Over 60 months, the NNT with brentuximab vedotin ranged from 4.08 to 7.79 for the intent-to-treat population, 3.18–6.07 for patients with ≥2 risk factors, and 2.98–5.65 for patients with ≥3 risk factors. At various time points, and dependent on the risk group, 3–8 patients would need to be treated with brentuximab vedotin consolidation therapy to prevent a disease progression/death, compared with placebo. Patients with increased risk of relapse may benefit most from brentuximab vedotin. [ABSTRACT FROM AUTHOR]

Purpose We systematically evaluated the Bosniak classification system with malignancy rates of each Bosniak category, and assessed the effectiveness related to surgical treatment and oncologic outcome based on recurrence and/or metastasis. Materials and Methods In a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria, we selected 39 publications for inclusion in this analysis and categorized them into 1) surgical cohorts—all cysts treated surgically and 2) radiological cohorts—cysts with surgical treatment or radiological followup. Results A total of 3,036 complex renal cysts were categorized into Bosniak II, IIF, III and IV. In surgical and radiological cohorts pooled estimates showed a malignancy prevalence of 0.51 (0.44, 0.58) in Bosniak III and 0.89 (0.83, 0.92) in Bosniak IV cysts, respectively. Stable Bosniak IIF cysts showed a malignancy rate of less than 1% during radiological followup (surveillance). Bosniak IIF cysts, which showed reclassification to the Bosniak III/IV category during radiological followup (12%), showed malignancy in 85%, comparable to Bosniak IV cysts. The estimated surgical number needed to treat to avoid metastatic disease of Bosniak III and IV cysts was 140 and 40, respectively. Conclusions The effectiveness of the Bosniak classification system for complex renal cysts was high in categories II, IIF and IV, but low in category III, and 49% of Bosniak III cysts was overtreated because of a benign outcome. This surgical overtreatment combined with the excellent outcome for Bosniak III cysts may suggest that surveillance is a rational alternative to surgery. This will require further study to assess whether surveillance of Bosniak III cysts will prove safe. [ABSTRACT FROM AUTHOR]

Background: The number needed to treat (NNT) is an absolute effect measure that has been used to assess beneficial and harmful effects of medical interventions. Several methods can be used to calculate NNTs, and they should be applied depending on the different study characteristics, such as the design and type of variable used to measure outcomes. Whether or not the most recommended methods have been applied to calculate NNTs in studies published in the medical literature is yet to be determined. The aim of this study is to assess whether the methods used to calculate NNTs in studies published in medical journals are in line with basic methodological recommendations.Methods: The top 25 high-impact factor journals in the "General and/or Internal Medicine" category were screened to identify studies assessing pharmacological interventions and reporting NNTs. Studies were categorized according to their design and the type of variables. NNTs were assessed for completeness (baseline risk, time horizon, and confidence intervals [CIs]). The methods used for calculating NNTs in selected studies were compared to basic methodological recommendations published in the literature. Data were analyzed using descriptive statistics.Results: The search returned 138 citations, of which 51 were selected. Most were meta-analyses (n = 23, 45.1%), followed by clinical trials (n = 17, 33.3%), cohort (n = 9, 17.6%), and case-control studies (n = 2, 3.9%). Binary variables were more common (n = 41, 80.4%) than time-to-event (n = 10, 19.6%) outcomes. Twenty-six studies (51.0%) reported only NNT to benefit (NNTB), 14 (27.5%) reported both NNTB and NNT to harm (NNTH), and 11 (21.6%) reported only NNTH. Baseline risk (n = 37, 72.5%), time horizon (n = 38, 74.5%), and CI (n = 32, 62.7%) for NNTs were not always reported. Basic methodological recommendations to calculate NNTs were not followed in 15 studies (29.4%). The proportion of studies applying non-recommended methods was particularly high for meta-analyses (n = 13, 56.5%).Conclusions: A considerable proportion of studies, particularly meta-analyses, applied methods that are not in line with basic methodological recommendations. Despite their usefulness in assisting clinical decisions, NNTs are uninterpretable if incompletely reported, and they may be misleading if calculating methods are inadequate to study designs and variables under evaluation. Further research is needed to confirm the present findings. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the short-term efficacy of venlafaxine extended release (ER) 75-225 mg/day compared with placebo for treating major depressive disorder (MDD) and to examine associations between baseline characteristics and efficacy outcomes in MDD patients treated with venlafaxine ER 75-225 mg/day.Research Design and Methods: This meta-analysis included published and unpublished short-term, double-blind, placebo-controlled, Wyeth/Pfizer sponsored studies of venlafaxine ER at doses up to 225 mg/day in adults with MDD.Clinical Trial Registration: All trials were conducted before trial registration became mandatory.Main Outcome Measures: Change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score was analyzed over time using a mixed-effects model for repeated measures with terms for study, treatment group, visit, interaction between treatment group and visit, and baseline score as a covariate. Associations between baseline demographic and clinical characteristics and the probability of HAM-D17 response and remission at week 8 were evaluated using logistic regression models, with terms for study, treatment group, and baseline characteristics in the models. Safety and tolerability was assessed based on adverse events (AEs) and discontinuations due to AEs.Results: The full analysis set included 1087 patients from five studies that fulfilled selection criteria. Statistically significant separation between venlafaxine ER and placebo groups for HAM-D17 total score was seen at week 2 and all subsequent assessments (p-values <.0001). There was no significant interaction between treatment and baseline HAM-D17 total score. Probability of HAM-D17 remission at week 8 decreased with increasing baseline HAM-D17 total score (p = .0012; OR: 0.94); however, baseline HAM-D17 total score did not predict response. Discontinuations due to AEs were reported for 9.4% of venlafaxine-ER-treated patients compared with 3.6% of placebo-treated patients. Key limitations: Five studies met the criteria for inclusion. Several differences in design between included studies limited the analysis: one study did not include a week 3 assessment (the week 3 time point was therefore dropped from the analysis), one study had two venlafaxine ER dose arms, which were combined into one group for the meta-analysis, and mixed- and flexible-dose studies were pooled.Conclusions: Venlafaxine ER 75-225 mg/day effectively reduced symptoms of depression in patients with MDD overall and in patients with either lower (≤23) or higher (>23) HAM-D17 total score at baseline. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Aims: Absolute treatment effects-i.e. numbers needed to treat (NNTs)-of novel antidiabetic drugs for cardiovascular outcomes have not been comprehensively evaluated. We aimed to perform a meta-analysis of digitalized individual patient outcomes to display and compare absolute treatment effects., Methods and Results: Individual patient time-to-event information from Kaplan-Meier plots of cardiovascular mortality (CM) and/or hospitalization for heart failure (HHF) endpoints from cardiovascular outcome trials (CVOTs) evaluating dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium glucose transporter 2 (SGLT2) inhibitors vs. placebo were digitalized using WebPlotDigitizer 4.2 and the R code of Guyot et al.; Weibull regression models were generated, validated, and used to estimate NNT for individual trials; random-effects meta-analysis generated Meta-NNT with 95% confidence intervals. Sixteen CVOTs reported time-to-event information (14 in primary diabetes and 2 in primary heart failure populations). Thirteen studies including 96 860 patients were meta-analysed for CM: At the median follow-up of 30 months, Meta-NNTs were 178 (64 to ∞ to -223) for DPP-4 inhibitors, 261 (158 to 745) for GLP-1 receptor agonists, and 118 (68 to 435) for SGLT2 inhibitors. Ten studies including 96 128 patients were meta-analysed for HHF: At the median follow-up of 29 months, estimated Meta-NNTs were -644 (229 to ∞ to -134) for DPP-4 inhibitors, 441 (184 to ∞ to -1100) for GLP-1 receptor agonists, and 126 (91 to 208) for SGLT2 inhibitors. SGLT2 inhibitors were especially effective for HHF in primary heart failure populations [Meta-NNT 25 (19 to 39)] vs. primary diabetes populations [Meta-NNT 233 (167 to 385)] at 16 months of follow-up., Conclusions: We found only modest treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors for CM and HHF in primary type 2 diabetes mellitus populations. In primary heart failure populations, SGLT2 inhibitor benefits were substantial and comparable in efficacy to established heart failure medication., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Conventional meta-analysis estimators are weighted means of study measures, meant to estimate an overall population measure. For measures such as means, mean differences and risk differences, a weighted arithmetic mean is the conventional estimator. When the measures are ratios, such as odds ratios, logarithms of the study measures are most frequently used, and the back-transform is a weighted geometric mean, rather than the arithmetic mean. For numbers needed to treat, a weighted harmonic mean is the back-transform. The Theorem of the Means effectively states that unless all of the studies have an equal result, the arithmetic mean must be greater than the geometric mean, which must be greater than the harmonic mean. When the weights are fixed sampling weights, the inequalities are in the expected direction. However, when the weights are the usual reciprocal variance estimates, the inequalities go in the opposite direction. The use of reciprocal variance weights is therefore questioned as perhaps having a fundamental flaw. An example is shown of a meta-analysis of frequencies of two classes of drug-resistant HIV-1 mutations. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Hazard ratios are ubiquitously used in time to event applications to quantify adjusted covariate effects. Although hazard ratios are invaluable for hypothesis testing, other adjusted measures of association, both relative and absolute, should be provided to fully appreciate studies results. The corrected group prognosis method is generally used to estimate the absolute risk reduction and the number needed to be treated for categorical covariates. Methods: The goal of this paper is to present transformation models for time-to-event outcomes to obtain, directly from estimated coefficients, the measures of association widely used in biostatistics together with their confidence interval. Pseudo-values are used for a practical estimation of transformation models. Results: Using the regression model estimated through pseudo-values with suitable link functions, relative risks, risk differences and the number needed to treat, are obtained together with their confidence intervals. One example based on literature data and one original application to the study of prognostic factors in primary retroperitoneal soft tissue sarcomas are presented. A simulation study is used to show some properties of the different estimation methods. Conclusions: Clinically useful measures of treatment or exposure effect are widely available in epidemiology. When time to event outcomes are present, the analysis is performed generally resorting to predicted values from Cox regression model. It is now possible to resort to more general regression models, adopting suitable link functions and pseudo values for estimation, to obtain alternative measures of effect directly from regression coefficients together with their confidence interval. This may be especially useful when, in presence of time dependent covariate effects, it is not straightforward to specify the correct, if any, time dependent functional form. The method can easily be implemented with standard software. [ABSTRACT FROM AUTHOR]

Interpreting study results is an essential component of decision-making. Both laypeople and healthcare professionals often misinterpret treatment effects that are presented as relative risk reduction. Therefore, we developed and piloted a web-based tool to teach the difference between relative and absolute risk reductions. This project follows the UKMRC-guidance for complex interventions. The tool was developed based on adult learning and design theories. This was followed by a qualitative feasibility study focusing on acceptance, applicability, and comprehensibility with healthcare professionals and laypersons. We conducted think-aloud and semi-structured interviews and analysed them using qualitative content analysis. In addition, we explored calculation skills. Between January 2020 and April 2021, we conducted 22 interviews with 8 laypeople and 14 healthcare professionals from different settings. Overall, the tool proved to be feasible and relevant. With regard to comprehension, we observed an awareness of the interpretation of risk reduction, presented therapy effects were questioned more critically, and the influence of relative effects was recognized. Nevertheless, there were comprehension problems in some of the participants, especially with calculations in connection with low mathematical skills. The tool can be used to improve the interpretation of risk reductions in various target groups and to supplement existing educational programs.

Objectives To explore consumers' beliefs and preferences for benefit information in medicine leaflets and examine their understanding and reaction to treatment benefits. Methods Forty-five participants were recruited to eight focus groups, run concurrently in Australia (23 participants in four groups) and the UK (22 participants in four groups). Participants were provided with amended leaflets based on the medicine clopidogrel, containing textual and numerical benefit information presented using numbers needed to treat ( NNT). A topic guide which explored use of leaflets, preferences and opinions was used to direct discussion. Focus group discussions were recorded, transcribed verbatim and content analysed using adapted cross-case study analysis. Key findings The consensus was that the inclusion of benefit information was a positive factor. Many participants felt that textual benefit information offered an incentive to take a medicine, although some Australian participants had concerns that included benefit information could create anxiety. The presentation of numerical benefit information provoked strong feelings of disbelief and shock. Participants were surprised that so few people would benefit. Some participants struggled to understand and interpret the NNT and others found it difficult to comprehend the magnitude of the benefit information, instead operating on initial and often crude assumptions of what the data meant. In both countries the provision of numerical benefit information appeared to shake participants' faith in drug treatments. Participants were concerned about how this might affect the 'less-informed' patient. However, in the UK, participants stated that their adherence to treatment was also reinforced by their doctor's advice. Conclusions Participants wanted to receive information about the benefits of their medicines. However, they may misinterpret the numerical information provided. [ABSTRACT FROM AUTHOR]

To compare the clinical efficiency of different modes of treatment of infertile couples and to estimate the possible benefit of nutraceutical food supplementation ( NFS), the numbers needed to treat ( NNT) was calculated in 4143 infertile couples based on controlled trials in recent literature and personal data. The NNT expresses the number of individuals who need to be treated to obtain one complementary pregnancy. In female infertility, the NNT of mild or moderate endometriosis was 8.4, and in anti-estrogens treatment of anovulation, it was 5.9. In tamoxifen treatment of idiopathic oligozoospermia, NNT was 3.9, and in antioxidant supplementation, it was 7.8. Treatment of varicocele yielded NNT of 6.3 and 6.8 after 1 year in multi- or single-centre trials, respectively, and NFS lowered the NNT after 3 months to 2.6. Adding NFS to the male partner increased the ongoing pregnancy rate by IVF with NNT of 8.3, and adding NFS to both partners reduced the NNT to 4.0. Although these results were obtained in heterogeneous trials and populations, it is suggested that the NNT should be useful for comparing the effectiveness of different modes of treatment of the infertile couple, and that complementary nutraceutical food supplementation may be beneficial. [ABSTRACT FROM AUTHOR]

Background: The numbers needed to treat (NNT) and the corresponding confidence intervals for patients with prostate cancer and defined annual PSA increases (PSA velocity, PSAV) have not been described previously. Aim: The objective of this study is to assess NNT, numbers needed to treat to harm and corresponding confidence intervals for radical prostatectomy (RP) in patients with prostate cancer defined as a PSAV ≤2 ng/ml/year. Methods: NNT following RP were estimated in risk groups defined by PSAV using mortality statistics and hazard ratios obtained in a noncontrolled trial. As no suited control group and no appropriate randomized trials were available for doing this calculation and as such trials are unlikely to become available in the near future we have calculated our NNTs as published previously by using relative risk reduction from an earlier randomized trial (RCT) comparing RP with watchful waiting (WW) [Can J Urol 2006;13(suppl 1):48-55]. Results: For preoperative PSAV >2 ng/ml/year, NNT for RP were estimated at 25, whereas for preoperative PSAV ≤2 ng/ml/year, the estimate was 618. The lower 95% confidence limits (NNTBl) were 9 and 126, respectively (treatment with benefit). The implications emerging from these findings are discussed by comparison with published NNT values from other RCTs. The lower 95% confidence limit for preoperative PSAV ≤2 ng/ml/year was found to be large in comparison. Conclusion: The NNT estimate obtained here for PSAV >2 ng/ml/year and its lower 95% confidence interval is comparable to values in other studies on prostate cancer for therapies considered to be effective, while the estimated NNT for patients with PSAV ≤2 ng/ml/year is large in comparison. We conclude that the benefits of RP for localized prostate cancer with preoperative PSAV ≤2 ng/ml/year may be considered small. There are several limitations to our findings, the most important of which lies in the fact that while PSAV remains significantly associated with outcomes, the predictive value of PSA measurements is low. While PSAV >2 ng/ml/year clearly indicates a need for surgery, a PSAV ≤2 ng/ml/year should imply further decision making. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Randomized, double-blind, placebo-controlled trials on neuropathic pain treatment are accumulating, so an updated review of the available evidence is needed. Studies were identified using MEDLINE and EMBASE searches. Numbers needed to treat (NNT) and numbers needed to harm (NNH) values were used to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions. One hundred and seventy-four studies were included, representing a 66% increase in published randomized, placebo-controlled trials in the last 5years. Painful poly-neuropathy (most often due to diabetes) was examined in 69 studies, postherpetic neuralgia in 23, while peripheral nerve injury, central pain, HIV neuropathy, and trigeminal neuralgia were less often studied. Tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, the anticonvulsants gabapentin and pregabalin, and opioids are the drug classes for which there is the best evidence for a clinical relevant effect. Despite a 66% increase in published trials only a limited improvement of neuropathic pain treatment has been obtained. A large proportion of neuropathic pain patients are left with insufficient pain relief. This fact calls for other treatment options to target chronic neuropathic pain. Large-scale drug trials that aim to identify possible subgroups of patients who are likely to respond to specific drugs are needed to test the hypothesis that a mechanism-based classification may help improve treatment of the individual patients. [ABSTRACT FROM AUTHOR]

Biological processes are full of variations and so are responses to therapy as measured in clinical research. Estimators of clinical efficacy are, therefore, usually reported with a measure of uncertainty, otherwise called dispersion. This study aimed to review both the flaws of data reports without measure of dispersion and those with over-dispersion. Examples of estimators commonly reported without a measure of dispersion include: 1) number needed to treat; 2) reproducibility of quantitative diagnostic tests; 3) sensitivity/specificity; 4) Markov predictors; 5) risk profiles predicted from multiple logistic models. Data with large differences between response magnitudes can be assessed for over-dispersion by goodness of fit tests. The χ² goodness of fit test allows adjustment for over-dispersion. For most clinical estimators, the calculation of standard errors or confidence intervals is possible. Sometimes, the choice is deliberately made not to use the data fully, but to skip the standard errors and to use the summary measures only. The problem with this approach is that it may suggest inflated results. We recommend that analytical methods in clinical research should always attempt to include a measure of dispersion in the data. When large differences exist in the data, the presence of over-dispersion should be assessed and appropriate adjustments made. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Cox proportional hazards regression models are frequently used to determine the association between exposure and time-to-event outcomes in both randomized controlled trials and in observational cohort studies. The resultant hazard ratio is a relative measure of effect that provides limited clinical information. Study Design and Setting: A method is described for deriving absolute reductions in the risk of an event occurring within a given duration of follow-up time from a Cox regression model. The associated number needed to treat can be derived from this quantity. The method involves determining the probability of the outcome occurring within the specified duration of follow-up if each subject in the cohort was treated and if each subject was untreated, based on the covariates in the regression model. These probabilities are then averaged across the study population to determine the average probability of the occurrence of an event within a specific duration of follow-up in the population if all subjects were treated and if all subjects were untreated. Results: Risk differences and numbers needed to treat. Conclusions: Absolute measures of treatment effect can be derived in prospective studies when Cox regression is used to adjust for possible imbalance in prognostically important baseline covariates. [Copyright &y& Elsevier]

Abstract: Understanding a change score is indispensable for interpretation of results from clinical studies. One way of determining the relevance of change scores is through the use of transition questions that assesses patients’ retrospective perception of treatment effect. Unfortunately, results from studies using transition questions are difficult to compare since wording of questions and definitions of important improvements vary between studies. The objectives of this study were to determine the consequence of using different transition questions on pain and disability measures and make proposals for a standardised use of such questions. Two hundred and thirty-three patients with low back pain and/or leg pain were recruited. Participants were followed over an 8-week period and randomised to two groups receiving a 7- (TQ1) and 15-point (TQ2) transition question, respectively, in addition to a numeric rating scale evaluating the importance of the perceived change. Four external criteria were generated using both stringent and less stringent standards to dichotomise patients. Discrimination was determined using area under the receiver operating characteristic curve (ROCauc) and responsiveness using standardised response mean (SRM). Results demonstrated small variations in ROCauc across the external criteria for all outcome measures. 7% more patients were classified as improved in the group receiving the 15-point TQ compared to the 7-point TQ (stringent standard). SRMs were higher for the retrospective TQs in primary sector patients compared to the serial measures with no difference between TQ1 and TQ2. On the basis of our findings we have outlined a proposal for a standardised use of transition questions. [Copyright &y& Elsevier]

A better understanding of the risk concept in relation to treatment of chronic disease processes is warranted. Consequences of therapies may be described in terms of risk reductions or postponement of adverse outcomes. This review argues that for most interventions, neither of these measures adequately characterize the distribution of treatment benefit across patients. More focus should be placed on choosing the context-relevant outcome measure and on developing techniques for extracting and communicating 2D outcome measures where the distribution of outcomes across patients is explicitly reflected. Since the distribution of outcomes affects patients' valuation of interventions, more research into risk communication is likely to lead to improved decision making. [ABSTRACT FROM AUTHOR]

Introduction Memantine is currently the only treatment approved for moderately severe to severe Alzheimer's disease (AD). There is still some discussion as to its place in clinical practice and many UK clinicians are discouraged for economic reasons from prescribing it. We adopt a ‘number needed to treat’ (NNT) approach to assess the benefits reported in memantine trials. Method We searched Medline and the Cochrane Dementia and Cognitive Improvement Specialised Register for double-blind, randomised and controlled trials of memantine in AD. If efficacy was only reported in terms of mean change, rather than as number of individuals who responded or were harmed by an intervention, we contacted the drug companies (Merz and Lundbeck) to ask for more data. We also calculated effect size. Results We found two trials of memantine in AD that met our criteria. We found that NNTs for global outcome were 3 and 6, for cognitive outcome 7 and for activities of daily living 4 and 8. The effect size for memantine varied between 0.32 and 0.62. For NNH memantine was no more harmful than placebo and significantly less so for the outcome of agitation. Conclusion The small NNTs and the lack of harm shown by the NNHs strongly suggest that memantine, as with cholinesterase inhibitors, has a valuable place in the current clinical management of AD. The effect sizes are mainly in the ‘medium’ range for clinical effect, which also suggests that memantine has a clinical place in terms of cognition and dependency. There remains a need for more studies that examine carer burden, behavioural and psychological effects, and quality of life for both the person with dementia and the caregiver. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]