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Objective The objective of this study was to present ways to graphically represent a number needed to treat (NNT) in (network) meta-analysis (NMA). Study Design and Setting A barrier to using NNT in NMA when an odds ratio (OR) or risk ratio (RR) is used is the determination of a single control event rate (CER). We discuss approaches to calculate a CER, and illustrate six graphical methods for NNT from NMA. We illustrate the graphical approaches using an NMA of cognitive enhancers for Alzheimer's dementia. Results The NNT calculation using a relative effect measure, such as OR and RR, requires a CER value, but different CERs, including mean CER across studies, pooled CER in meta-analysis, and expert opinion-based CER may result in different NNTs. An NNT from NMA can be presented in a bar plot, Cates plot, or forest plot for a single outcome, and a bubble plot, scatterplot, or rank-heat plot for ≥2 outcomes. Each plot is associated with different properties and can serve different needs. Conclusion Caution is needed in NNT interpretation, as considerations such as selection of effect size and CER, and CER assumption across multiple comparisons, may impact NNT and decision-making. The proposed graphs are helpful to interpret NNTs calculated from (network) meta-analyses.

Background There is currently insufficient evidence to support the use of lipid-lowering drug treatment (LLT) for primary prevention of cardiovascular disease (CVD) in the elderly. Objectives We examined the relationship of early initiation of LLT with short- and long-term all-cause and CVD mortality in persons older than 65 years in this post hoc study from the Second Australian National Blood Pressure study (ANBP2). Methods This was an in- and post-trial observational study. About 4257 hypertensive participants aged 65 to 84 years within Australian family practices were randomized to an angiotensin-converting enzyme inhibitor or a diuretic treatment group. After excluding participants with a prior history of CVD, the cohort was stratified into "LLT" and "no LLT" subgroups based on LLT status at randomization. Results At randomization, the participants had a mean age of 72 years, average blood pressure of 168/91 mm Hg and estimated 5-year CVD risk of 18.7 ± 8.3%. In the overall study population, the association of LLT with long-term (11-years) all-cause and non-CVD mortality was significant (hazard ratio [HR] 0.78 [95% confidence interval {CI} 0.66–0.92, P = .003] and HR 0.70 [95% CI 0.54–0.90, P = .006], respectively). Magnitudes of the association of LLT with long-term mortality and the association with short-term mortality were similar; however, no statistically significant association with short-term mortality was observed. In the subgroup analysis by baseline 5-year CVD risk, LLT participants in the highest risk tertile had a substantially lower relative risk for short-term all-cause mortality (HR 0.31, 95% CI 0.13–0.71, P for interaction .02) compared to those with lower estimated CVD risk. All analyses were adjusted for baseline and in-trial characteristics. Conclusion Our study showed a strong association between LLT and reduced long-term all-cause mortality. Thus, our findings support recommendations of the use of LLT in patients over 65 years, particularly those with high CVD risk who were more likely to obtain additional benefits in the short term. The findings also suggested that mortality benefits of LLT for the elderly may take longer to become evident.

Nowadays, guidelines are derived from the findings of randomized controlled therapeutic trials. However, an overall significant P value does not exclude that some patients may be harmed by or will not respond to the therapeutic agent being studied. Trials in patients with a low risk of events and/or a limited chance of providing significant differences in therapeutic effects require a large patient population to demonstrate a beneficial effect. Composite efficacy endpoints are often employed to obviate the need for a large patient population when low rates of events or limited therapeutic efficacy are anticipated. Results of randomized controlled therapeutic trials are commonly expressed in terms of relative risk reduction, whereas absolute risk reduction allows the calculation of the "number needed to treat" to prevent an adverse outcome. The number needed to treat is a far more clinically relevant variable than relative risk reduction. The clinician's mission is to match treatment to patient with the goal of achieving optimal therapeutic response. Drug-safety monitoring is also of major importance to avoid exposing patients to irreversible adverse effects. Unfortunately, drug-safety monitoring is often overlooked in routine clinical practice. Finally, the lack of long-term therapeutic data (>5-10 years) is an unsolved dilemma, as most trials are limited to a duration of a few months or years.

A reduction in relapse rate is the main primary outcome in most clinical trials in patients with multiple sclerosis (MS), with the effect of a treatment commonly expressed as relative risk reduction for this outcome. Physicians often assume that a drug with a higher relative risk reduction demonstrated in one trial is more effective than a drug with a lower relative risk reduction in another, and may pass this idea on to younger physicians and to patients. The use of the relative risk reduction as a measure of drug efficacy can be misleading, as it depends on the nature of the population studied: a treatment effect characterized by a lower relative risk reduction may be more clinically meaningful than one with a higher relative risk reduction. This concept is especially important with regard to clinical trials in patients with MS, where relapse rates in placebo groups have been declining in recent decades. Direct, head-to-head comparisons are the only way to compare the efficacy of the different treatments for MS.

The purpose of the study is to compare outcomes between delayed repeat enema (DRE) and immediate surgery (IS) in children with ileocolic intussusception who fail initial enema reduction.Retrospective cohort study of children6 years-of-age from 2008 to 2012 in the Pediatric Health Information System (PHIS) database. Outcomes measured were bowel resection, length of stay (LOS), and adjusted hospital costs (AHC).4980 of 6889 (72.3%) children with intussusception were discharged without operation following a single successful enema. 1407 of 1909 (73.7%) remaining patients underwent IS while 502 (26.3%) had a DRE. Bowel resection was required in 372 of 1407 (26.4%) patients in IS group compared to 59 of 502 (11.8%) in the DRE group (p0.001). The number of patients needed to treat by DRE to prevent a bowel resection was 7. In multivariable analysis, the IS patients had a 2.5 times greater likelihood of undergoing bowel resection than the DRE patients (adjusted odds ratio [OR] 2.50, 95% confidence interval [CI] 1.83-3.41, p0.001). The DRE group had a mean LOS of 3.2 days (95% CI 2.9-3.6) and mean AHC of $9205 (95% CI $7673-$10,735). The IS group had a longer LOS (4.4days, 95% CI 4.0-4.8, p≤0.001) and higher AHC ($14,422, 95% CI $12,631-$16,214, p0.001).Delayed repeat enemas for ileocolic intussusception increase the success of nonoperative reduction, decrease the rate of bowel resection and reduce mean hospital length of stay and costs.

Summary Objectives To assess the potential use of a protein-based meningococcal group B (MenB) vaccine (Bexsero ® ) in addition to antibiotic chemoprophylaxis for preventing secondary cases. Methods Published studies on the risk of secondary meningococcal infections were used to estimate the numbers needed to vaccinate (NNV) with Bexsero ® to prevent a secondary case in household and educational settings. Results Most secondary cases occur within a few days of diagnosis in the index case. Unlike conjugate vaccines, early protection offered after a single dose of Bexsero ® is likely to be low, particularly in young children, who are at higher risk of secondary infection. NNV was dependent on predicted meningococcal strain coverage, estimated onset of protection after one Bexsero ® dose and estimated vaccine efficacy. Even in the most favourable scenario where we assume the vaccine is administered within 4 days of the index case and prevents 90% of cases occurring after 14 days, the NNV for household contacts was >1000. NNV in educational settings was much higher. Conclusions The estimated NNV should be taken into account when deciding policy to recommend Bexsero ® for close contacts of single cases in household or educational settings. Bexsero ® may have a protective role in clusters and outbreaks.

Purpose Inappropriate initial therapy for Candida -related septic shock is common and associated with a high mortality rate. This before-after pilot study was conducted to determine the feasibility of using empiric therapy for reducing the time to appropriate antifungal therapy in patients with Candida -related septic shock. Methods Patients aged 18–99years with septic shock presenting to Barnes-Jewish Hospital, St. Louis, Missouri, in 2012–2013 were assigned to 1 of 2 groups. Patients presenting between January 1, 2012, and December 31, 2012, were managed according to local standard of care for patients with septic shock, to include antifungal therapy at the discretion of the treating physician (standard therapy group). Patients presenting between January 1, 2013, and December 31, 2013, received empiric antifungal therapy (primarily micafungin 100 mg/d or fluconazole 800 mg on day 1, followed by 400 mg/d), facilitated by a clinical pharmacist in the medical intensive care unit, until microbiologic cultures were available to determine the cause of septic shock (empiric therapy group). The primary outcome was time to appropriate therapy after shock onset. Findings A total of 28 patients were enrolled (mean age, 56.3 [15.1] years [range, 30–92 years]; 16 [57.1%] men). The time to appropriate therapy after shock onset was statistically shorter with empiric therapy (n = 13) compared with standard therapy (n = 15) (10.6 [15.8] vs 40.5 [26.0] hours; P = 0.001). Patients receiving empiric therapy were more likely to have received appropriate therapy within 12 hours (69.2% vs 6.7%; P = 0.001) and within 24 hours (76.9% vs 40.0%; P = NS) of shock onset. In an analysis to determine the number of septic shock patients needed to be treated with empiric antifungal therapy for 1 patient with Candida -related septic shock to receive appropriate treatment, 256 patients without Candida infection received a total of 687 doses of empiric antifungal therapy (mean, 2.7 doses per patient) compared with 136 patients who received 382 doses of standard antifungal therapy (mean, 2.8 doses per patient); the number needed to treat was 19.6. Implications The present pilot study demonstrated that the use of empiric antifungal therapy for Candida -related septic shock was associated with a statistically shorter time to administration of appropriate treatment. ClinicalTrials.gov identifier.

Objective To quantify the influence of type 2 diabetes risk distribution on prevention benefit and apply a method to optimally identify population targets. Methods We used data from the 2011 Canadian Community Health Survey (N = 45,040) and the validated Diabetes Population Risk Tool to calculate 10-year diabetes risk. We calculated the Gini coefficient as a measure of risk dispersion. Intervention benefit was estimated using absolute risk reduction (ARR), number-needed-to-treat (NNT), and number of cases prevented. Results There is a wide variation of diabetes risk in Canada (Gini = 0.48) and with an inverse relation to risk (r = − 0.99). Risk dispersion is lower among individuals meeting an empirically derived risk cut-off (Gini = 0.18). Targeting prevention based on a risk cut-off (10-year risk ≥ 16.5%) resulted in a greater number of cases prevented (340 thousand), higher ARR (7.7%) and lower NNT (13) compared to targeting individuals based on risk factor targets. Conclusions This study provides empirical evidence to demonstrate that risk variability is an important consideration for estimating the prevention benefit. Prioritizing target populations using an empirically derived cut-off based on a multivariate risk score will result in greater benefit and efficiency compared to risk factor targets.

Clinical epidemiology studies are vulnerable to subtle confounding, leading skeptics to claim that an odds ratio below three rarely indicates a clinically important finding. We argue that such a high threshold is inappropriate when interpreting traffic death studies in clinical epidemiology research. We review 10 concepts that emphasize the value of modest effect sizes by taking into account the baseline frequency, nonfatal disability, numbers needed to treat, shared responsibility, event diversity, behavioral offsets, measurement error, indirect reinforcement, delayed progression, and economic affordability. An awareness of these concepts may help when interpreting effect sizes in studies of traffic deaths.

Background Although hyponatremia is a well-recognized complication of treatment with thiazide diuretics, the risk of thiazide-induced hyponatremia remains uncertain in routine care. Methods We conducted a retrospective cohort study using a multicenter clinical research registry to identify 2613 adult outpatients that were newly treated for hypertension between January 1, 2000 and December 31, 2005 at 2 teaching hospitals in Boston, Massachusetts, and followed them for up to 10 years. Results Two hundred twenty patients exposed to ongoing thiazide therapy were compared with 2393 patients who were not exposed. In the exposed group, 66 (30%) developed hyponatremia (sodium ≤130 mmol/L). The adjusted incidence rate of hyponatremia was 140 cases per 1000 person-years for patients treated with thiazides, compared with 87 cases per 1000 person-years in those without thiazides. Patients exposed to thiazides were more likely to develop hyponatremia (adjusted incidence rate ratio, 1.61; 95% confidence interval [CI], 1.15-2.25). There was no significant difference in the risk of hospitalizations associated with hyponatremia (adjusted rate ratio, 1.04; 95% CI, 0.46-2.32) or mortality (adjusted rate ratio, 0.41; 95% CI, 0.12-1.42). The number needed to harm (to result in one excess case of incident hyponatremia in 5 years) was 15.02 (95% CI, 7.88-160.30). Conclusions Approximately 3 in 10 patients exposed to thiazides who continue to take them develop hyponatremia.

INTRODUCTION Cerebrospinal fluid (CSF) fistula is a common neurosurgical complication, occurring in 1% to 27% of cases. The main clinical manifestations are postural headache, nausea, dizziness, photophobia, and tinnitus. This condition may be associated with inadequate wound healing and infection, meningitis, and pseudomeningocele, factors that increase patient morbidity and mortality. Despite the limitations, hermetic closure of the dura mater has been recommended for the prevention and treatment of CSF fistula. In recent years, techniques have been developed to reinforce the site of the dura mater closure, such as additional suture, autologous tissue grafts, fibrin sealants, and collagen sponges. DuraSeal is a dura mater sealant consisting of polyethylene glycol hydrogel (PEG hydrogel), to be applied at the site of suture, and has been indicated for head and spinal surgery with opening of the dura mater.