Number needed to treat (NNT) for ketamine and esketamine in adults with treatment-resistant depression: A systematic review and meta-analysis.

BACKGROUND: Ketamine has been established as efficacious in adults living with Treatment-resistant Depression (TRD). Toward providing a quantifiable estimate of the clinical meaningfulness of the therapeutic benefit of ketamine, herein, we conduct a systematic review that aims to report the Number Needed to Treat (NNT) and the Number Needed to Harm (NNH). METHODS: This systematic review searched Embase, Medline/Pubmed, PsycINFO and ClinicalTrials.gov from inception up to October 15th 2023, for placebo-controlled, Randomized Controlled Trials (RCTs) assessing racemic ketamine or esketamine therapy for unipolar TRD. We calculated NNT and NNH for ketamine treatments over various time points. RESULTS: A total of 21 studies with 2042 participants were included. Racemic ketamine treatments had pooled NNTs for response of 7 at 4 h, 3 from one day to one week and 9 for studies at four weeks. Esketamine treatment was found to have a similar efficacy with an NNT of 2 at one day and 11 at four weeks. NNH values indicated low risk for ketamine treatments. LIMITATIONS: Limitations in the data used include the possibility of functional unblinding and selective reporting bias. At the same time, the meta-analysis may have been limited in its precision by including low threshold definitions of treatment resistance (≥ 1 failed antidepressant) and low-dose ketamine treatments. CONCLUSION: Herein, we determined that the NNT for ketamine treatment in adults living with TRD across different intervals of observation was <10. We conclude that the NNTs observed herein are highly clinically meaningful in this difficult to treat disorder.

A comparison between psilocybin and esketamine in treatment-resistant depression using number needed to treat (NNT): A systematic review.

BACKGROUND: Inadequate outcomes with monoamine-based treatments in depressive disorders are common and provide the impetus for mechanistically-novel treatments. Esketamine is a proven treatment recently approved for adults with Treatment-Resistant Depression (TRD) while psilocybin is an investigational treatment. Translation of the clinical meaningfulness for these foregoing agents in adults with TRD is required. Herein we evaluate the Number Needed to Treat (NNT) and Harm (NNH) of esketamine and psilocybin in adults with TRD. METHODS: We conducted a systematic review of randomized controlled trials, comparing the clinical efficacy of oral psilocybin to the co-commencement of intranasal esketamine with an oral antidepressant in adults with TRD. RESULTS: 25 mg psilocybin had a significant reduction in depressive symptoms at 21-days post-dose, the NNT was 5 [95 % CI = 3.1, 18.5]. Psilocybin-induced nausea had a significant NNH = 5. Fixed-dosed esketamine at 56 mg and 84 mg had a significant effect at 28-days post-dose, (NNT of 7 [95 % CI56mg = 3.5, 46.7], [95 % CI84mg = 3.6, 142.2]). Esketamine-induced headache, nausea, dizziness, and dissociation had NNHs <10. LIMITATIONS: The preliminary results may only reflect a small portion of the patient population. These results require replication and longer term studies investigating maintenance therapy. CONCLUSION: Relatively few pharmacologic agents are proven safe and effective in adults with TRD. NNT estimates for investigational psilocybin and esketamine in TRD indicate clinical meaningfulness. The NNH profile for both aforementioned agents is clinically acceptable. Our results underscore the clinical relevance of these treatment options in adults with TRD.

Surgical site occurrence after prophylactic use of mesh for prevention of incisional hernia in midline laparotomy: systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The use of mesh is the standard for the prevention of incisional hernia (IH). However, the effect of surgical site occurrence (SSO) has never been compared. The aim of this meta-analysis was to evaluate the prevalence of SSO and measure its negative effect through the calculation of the number needed to treat for net effect (NNT net). METHODS: A meta-analysis was performed according to the PRISMA guidelines. The primary objective was to determine the prevalence of SSO and IH, and the secondary objective was to determine the NNT net as a metric to measure the combined benefits and harms. Only published clinical trials were included. The risk of bias was analyzed, and the random effects model was used to determine statistical significance. RESULTS: A total of 15 studies comparing 2344 patients were included. The incidence of IH was significantly lower in the mesh group than in the control group, with an OR of 0.29 (95% CI 0.16-0.49, p = 0.0001). The incidence of SSO was higher in the mesh group than in the control group, with an OR of 1.21 (95% CI 0.85-1.72, p = 0.0001) but without statistical significance. Therefore, the way to compare the benefits and risks of each of the studies was done with the calculation of the NNT net, which is the average number of patients who need to be treated to see the benefit exceeding the harm by one event, and the result was 5, which is the average number of patients who need to be treated to see the benefit exceeding the harm by one event. CONCLUSION: The use of mesh reduces the prevalence of IH and it does not increases the prevalence of SSO, the NNT net determined that the use of mesh continues to be beneficial for the patient.

Numbers needed to treat or harm and likelihood of being helped versus harmed for fremanezumab in patients who had prior inadequate response to two to four classes of migraine preventive medications: A post hoc analysis.

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.

Enhancing Cervical Cancer Prevention in South African Women: Primary HPV mRNA Screening with Different Genotype Combinations.

BACKGROUND: Cervical cancer prevention in regions with limited access to screening and HPV vaccination necessitates innovative approaches. This study explored the potential of a test-and-treat strategy using mRNA HPV tests to impact cervical cancer prevention in a high-prevalence HIV population. METHODS: A cervical screening study was conducted at three South African hospitals involving 710 under-screened, non-pregnant women (25 to 65 years) without known cervical diseases. Cytology, HPV testing, colposcopy, and biopsies were performed concurrently. Histopathologists determined final histological diagnoses based on biopsy and LLETZ histology. mRNA-HPV-genotyping for 3 (16, 18, 45) to 8 (16, 18, 31, 33, 35, 45, 52, 58) high-risk types was performed on leftover liquid-based cytology material. The preventive potential of the test-and-treat approach was estimated based on published data, reporting the causative HPV types in cervical cancer tissue from South African women. Treatment was provided as needed. RESULTS: The HPV positivity rate more than doubled from 3-type (15.2%; 95% CI: 12.6-17.8) to 8-type mRNA (31.5%; 95% CI: 28.8-34.9) combinations, significantly higher among HIV-positive women. CIN3+ prevalence among HIV-positive women (26.4%) was double that of HIV-negative women (12.9%) (p < 0.01). The 6-type combination showed the best balance of sensitivity, specificity and treatment group size, and effectiveness to prevent cervical cancer. A 4-type combination (16, 18, 35, 45) could potentially prevent 77.6% (95% CI: 71.2-84.0) of cervical cancer burden by treating 20% and detecting 41.1% of CIN3 cases in the study group. Similarly, a 6-type combination (16, 18, 31, 33, 35, 45), treating 25% and including 62% of CIN3 cases, might prevent 85% of cervical cancer cases (95% CI: 79.6-90.6) among HIV-positive and negative women. CONCLUSION: Employing mRNA HPV tests within a test-and-treat approach holds huge promise for targeted cervical cancer prevention in under-screened populations. Testing for mRNA of the 6 highest-risk HPV types in this population and treating them all is projected to effectively prevent progression from CIN3 to invasive cervical cancer while reducing overtreatment in resource-constrained settings.

Mineralocorticoid receptor antagonists for chronic heart failure: a meta-analysis focusing on the number needed to treat.

Aims: Recent studies have shown that mineralocorticoid receptor antagonists (MRAs) can decrease mortality in patients with heart failure; however, the application of MRAs in current clinical practice is limited because of adverse effects such as hyperkalemia that occur with treatment. Therefore, this meta-analysis used the number needed to treat (NNT) to assess the efficacy and safety of MRAs in patients with chronic heart failure. Methods: We meta-analysed randomized controlled trials (RCTs) which contrasted the impacts of MRAs with placebo. As of March 2023, all articles are published in English. The primary outcome was major adverse cardiovascular events (MACE), and secondary outcomes included all-cause mortality, cardiovascular death, myocardial infarction (MI), stroke, and adverse events. Results: We incorporated seven studies with a total of 9,056 patients, 4,512 of whom received MRAs and 4,544 of whom received a placebo, with a mean follow-up period of 2.1 years. MACE, all-cause mortality, and cardiovascular mortality were all reduced by MRAs, with corresponding numbers needed to treat for benefit (NNTB) of 37, 28, and 34; as well as no impact on MI or stroke. MRAs increased the incidence of hyperkalemia and gynecomastia, with the corresponding mean number needed to treat for harm (NNTH) of 18 and 52. Conclusions: This study showed that enabling one patient with HF to avoid MACE required treating 37 patients with MRAs for 2.1 years. MRAs reduce MACE, all-cause mortality, and cardiovascular death; however, they increase the risk of hyperkalemia and gynecomastia.

Cost per Patient Achieving Treatment Targets and Number Needed to Treat with Tirzepatide Versus Semaglutide 1 mg in Patients with Type 2 Diabetes in the United States.

INTRODUCTION: Achieving glycemic control can help reduce complications of type 2 diabetes (T2D). This study compared the pharmacy cost per responder and number needed to treat (NNT) of tirzepatide 5 mg, 10 mg, and 15 mg versus semaglutide 1 mg to achieve glycemic, weight loss, and composite treatment endpoints in patients with T2D in the United States. METHODS: The proportions of patients achieving glycemic, weight loss, and composite treatment endpoints were obtained from the phase 3 SURPASS-2 randomized clinical trial which compared tirzepatide 5 mg, 10 mg, and 15 mg to semaglutide 1 mg. Annual pharmacy costs were calculated using 2022 wholesale acquisition costs. Cost per responder and NNT were calculated along with 95% confidence intervals and tests for statistical significance (P ≤ 0.05). RESULTS: Tirzepatide had a lower cost per responder to achieve glycated hemoglobin A1c (HbA1c) endpoints of ≤ 6.5% (10 mg and 15 mg doses) and < 5.7% (all doses) and weight loss endpoints of ≥ 5% (10 mg and 15 mg doses), ≥ 10% (all doses), and ≥ 15% (all doses). The cost per responder to achieve HbA1c < 7% (all doses of tirzepatide) and ≤ 6.5% (5 mg tirzepatide) were not statistically significantly different between tirzepatide and semaglutide 1 mg. The cost per patient to achieve the composite endpoints (HbA1c < 7.0%, ≤ 6.5%, or < 5.7%/weight loss ≥ 10%/no hypoglycemia) was statistically significantly lower for all doses of tirzepatide than for semaglutide 1 mg. The NNTs for all doses of tirzepatide were statistically significantly lower than that for semaglutide 1 mg to achieve all individual and composite endpoints, with the exception of the 5 mg dose for HbA1c < 7.0% and HbA1c ≤ 6.5%, where tirzepatide had numerically lower NNTs that were not statistically significant. CONCLUSION: Tirzepatide is a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) that may offer the potential to achieve stringent glycemic goals, weight loss targets, and composite treatment goals at a lower cost per responder compared to semaglutide 1 mg among people with T2D.

Number Needed to Treat (NNT): Evaluation Tool Used in Health and Wellness Program.

As life insurance companies evaluate prospective health and wellness programs, one frequently used tool is the number needed to treat (NNT) calculation. It is helpful to identify what the NNT might be for individual components of the program as well as for the whole program when all components are combined.

d-Amphetamine Transdermal System in Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: Secondary Endpoint Results and Post Hoc Effect Size Analyses from a Pivotal Trial.

Objectives: Amphetamines are a preferred treatment for attention-deficit/hyperactivity disorder (ADHD), with the dextroamphetamine transdermal system (d-ATS) providing an alternative to oral formulations. A pivotal trial of d-ATS in children and adolescents with ADHD met primary and key secondary endpoints. This analysis reports additional endpoints and safety findings from the pivotal trial and evaluates effect size and number needed to treat (NNT) for d-ATS. Methods: In this study, a 5-week, open-label dose-optimization period (DOP) preceded a 2-week, randomized, crossover double-blind treatment period (DBP). Eligible patients received d-ATS 5 mg during the DOP, with weekly evaluations for increase to 10, 15, and 20 mg (equivalent to labeled doses of 4.5, 9, 13.5, and 18 mg/9 hours, respectively) until reaching and maintaining the optimal dose, which was utilized for the DBP. Secondary endpoints included assessment of Attention-Deficit/Hyperactivity Disorder Rating Scale IV (ADHD-RS-IV), Conners' Parent Rating Scale Revised Short Form (CPRS-R:S), and Clinical Global Impression (CGI) scores. NNT was calculated for ADHD-RS-IV and CGI-Improvement (CGI-I). Safety assessments included treatment-emergent adverse events (TEAEs) and dermal safety. Results: In total, 110 patients entered the DOP, with 106 patients randomized (DBP). During the DBP, the least-squares mean (95% confidence interval) difference for d-ATS versus placebo in ADHD-RS-IV total score was -13.1 (-16.2 to -10.0; p < 0.001), with effect size of 1.1 and NNT of 3 for ADHD-RS-IV remission, ≥30% improvement, and ≥50% improvement. Significant differences between placebo and d-ATS were also observed for CPRS-R:S and CGI-I scales (p < 0.001), with NNT of 2 for CGI-I response. Most TEAEs were mild or moderate, with three leading to study discontinuation in the DOP and none in the DBP. No patients discontinued due to dermal reactions. Conclusions: d-ATS was effective in treating ADHD in children and adolescents, meeting all secondary endpoints, with a large effect size and NNT of 2-3 to achieve a clinically meaningful response. d-ATS was safe and well tolerated, with minimal dermal reactions. Clinical Trial Registration: NCT01711021.

Practitioner characteristics, diagnostic accuracy metrics and discovering-individual with respect to 637 melanomas documented by 27 general practitioners on the Skin Cancer Audit Research Database.

BACKGROUND AND OBJECTIVE: Knowledge of accuracy for melanoma diagnosis and melanoma discovering-individual in primary care is limited. We describe general practitioner (GP) characteristics and analyse defined diagnostic accuracy metrics for GPs in the current study comparing this with a previous study for GPs common to both, and we analyse the individual first discovering each melanoma as a lesion of concern. METHODS: The characteristics and diagnostic accuracy of 27 Australasian GPs documenting 637 melanomas on the Skin Cancer Audit Research Database (SCARD) in 2013 were described and analysed. The number needed to treat (NNT) and percentage of melanomas that were in situ (percentage in situ) were analysed as surrogates for specificity and sensitivity, respectively. The discovering-individual was analysed according to patient age and sex and lesion Breslow thickness. RESULTS: The average NNT and percentage in situ were 5.73% and 65.07%, respectively. For 21 GPs in both a 2008-2010 study and the current study, the NNT was 10.78 and 5.56, respectively (p = 0.0037). A consistent trend of decreasing NNT and increasing percentage in situ through increasingly subspecialised GP categories did not reach statistical significance. NNT trended high at ages and sites for which melanoma was rare. While the patient or family member was more likely to discover thick melanomas and melanomas in patients under 40 years, GPs discovered 73.9% of the melanomas as lesions of concern. CONCLUSIONS: GPs were the discovering-individuals for the majority of melanomas in the current study and their accuracy metrics compared favourably with published figures for dermatologists and GPs.

Estimate of the cost per responder for treatment with biological therapies of moderate-to-severe plaque psoriasis in Colombia for first-year and maintenance periods.

INTRODUCTION: Psoriasis is a chronic systemic inflammatory disease manifesting as erythematous and desquamative dermatoses. OBJECTIVES: This study estimated the cost per responder (CPR) for the treatment of moderate-to-severe plaque psoriasis with biologic therapies approved by the Colombian regulatory agency. METHODS: This secondary study used a modeling based CPR estimation to evaluate psoriasis therapies in Colombia. We calculated CPR of achieving Psoriasis Area and Severity Index (PASI) scores of 75, 90, and 100 for biological treatments based on the number needed to treat (NNT), reported in previously published network meta-analyses. We calculated CPR for the first year and for the maintenance period. We ranked alternatives using the estimated CPR from each literature source using the Borda count method. RESULTS: Adalimumab, infliximab and etanercept were the least expensive alternatives. Ixekizumab, guselkumab and secukinumab were the treatments with the lowest NNT for PASI 75, 90, and 100. For both first year and maintenance periods, adalimumab, infliximab, guselkumab and ixekizumab had the lowest CPR. Sensitivity analyzes showed consistent results. CONCLUSIONS: The application of CPR analysis of biologics to treat plaque psoriasis demonstrated that adalimumab, infliximab, guselkumab, and ixekizumab had the lowest CPR in the first year of treatment and during the maintenance period.

Number needed to treat and associated cost analysis of cenobamate versus third-generation anti-seizure medications for the treatment of focal-onset seizures in patients with drug-resistant epilepsy in Spain.

INTRODUCTION: Epilepsy is a serious neurological disease, ranking high in the top causes of disability. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, approximately 40% of patients suffer from Drug-Resistant Epilepsy (DRE) despite the availability of the latest options called third-generation Anti-Seizure Medications(ASMs). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. The introduction of a new drug increases the number of therapeutic options available, making it important to compare it with existing alternatives in terms of clinical benefit and efficiency. PURPOSE: This study aimed to compare the clinical benefit, in terms of the Number Needed to Treat (NNT), and the efficiency, in terms of Cost per NNT (CNT), associated with cenobamate versus third-generation ASMs used in Spain for the adjunctive treatment of FOS in patients with DRE. METHODS: The Number Needed to Treat data was calculated based on the ≥50% responder rate and seizure freedom endpoints (defined as the percentage of patients achieving 50% and 100% reduction in seizure frequency, respectively), obtained from pivotal clinical trials performed with cenobamate, brivaracetam, perampanel, lacosamide, and eslicarbazepine acetate. The NNT was established as the inverse of the treatment responder rate minus the placebo responder rate and was calculated based on the minimum, mid-range Daily Defined Dose (DDD), and maximum doses studied in the pivotal clinical trials of each ASM. CNT was calculated by multiplying the annual treatment cost by NNT values for each treatment option. RESULTS: In terms of NNT, cenobamate was the ASM associated with the lowest values at all doses for both ≥50% responder rate and seizure freedom compared with the alternatives. In terms of CNT, for ≥50% responder rate, cenobamate was the ASM associated with the lowest CNT values at DDD and lacosamide and eslicarbazepine acetate at the minimum and maximum dose, respectively. For seizure freedom, cenobamate was associated with the lowest CNT value at DDD and the maximum dose and lacosamide at the minimum dose. CONCLUSIONS: Cenobamate could represent the most effective ASM in all doses studied compared to the third-generation ASMs and the most efficient option at DDD for both ≥50% responder rate and seizure freedom. This study could represent an important contribution towards informed decision-making regarding the selection of the most appropriate therapy for FOS in adult patients with DRE from a clinical and economical perspective in Spain.

Number needed to treat and cost per responder of Janus kinase inhibitors approved for the treatment of moderate-to-severe rheumatoid arthritis in Japan.

OBJECTIVE: This study evaluated the effectiveness and cost-effectiveness of baricitinib, tofacitinib, and upadacitinib regimens, compared to conventional synthetic disease-modifying antirheumatic drug (csDMARD) alone, among Japanese patients with moderate-to-severe rheumatoid arthritis (RA) inadequately responsive to csDMARD, measured in terms of number needed to treat (NNT) and cost per responder (CPR). METHODS: Efficacy data were derived from two recent network meta-analyses among global and Japanese population. The cost perspective was that of the Japanese Health Service. Both NNT and CPR were based on disease activity score for 28 joints with C-reactive protein (DAS28-CRP) remission and American College of Rheumatology (ACR) 20/50/70 at 12 and 24 weeks. RESULTS: Over 12 weeks, the median NNT and the median CPR to achieve DAS28-CRP remission were 4.3 and JPY 1,799,696 [USD 16,361], respectively, for upadacitinib 15 mg + csDMARD. The equivalent results were 6.0 and JPY 2,691,684 [USD 24,470] for baricitinib 4 mg + csDMARD and 5.6 and JPY 2,507,152 [USD 22,792] for tofacitinib 5 mg + csDMARD. Similar rankings were observed at 24 weeks and for other outcomes. CONCLUSIONS: Upadacitinib 15 mg was associated with the lowest NNT and CPR among the three Janus kinase inhibitors used in treatment regimens for Japanese patients with moderate-to-severe RA inadequately responsive to csDMARD.

Apalutamide or enzalutamide in castration-sensitive prostate cancer: a number needed to treat analysis.

The treatment of castration-sensitive prostate cancer (CSPC) has been revolutionized by the advent of apalutamide and enzalutamide in this setting; however, a direct comparison between these agents is still missing. In the current paper, we performed both Number Needed to Treat (NNT) and Number Needed to Harm (NNH) analyses aimed to compare clinical outcomes in CSPC patients treated with apalutamide or enzalutamide; data from 3323 CSPC patients enrolled in the ARCHES, ENZAMET and TITAN phase III studies were included. According to our results, apalutamide showed better results in terms of overall survival (OS) and safety in patients with CSPC, while better outcomes were observed with enzalutamide in the low-volume subgroup.

Mortality Reduction of Acute Surgery in Traumatic Acute Subdural Hematoma since the 19th Century: Systematic Review and Meta-Analysis with Dramatic Effect: Is Surgery the Obvious Parachute?

The rationale of performing surgery for acute subdural hematoma (ASDH) to reduce mortality is often compared with the self-evident effectiveness of a parachute when skydiving. Nevertheless, it is of clinical relevance to estimate the magnitude of the effectiveness of surgery. The aim of this study is to determine whether surgery reduces mortality in traumatic ASDH compared with initial conservative treatment. A systematic search was performed in the databases IndexCAT, PubMed, Embase, Web of Science, Cochrane library, CENTRAL, Academic Search Premier, Google Scholar, ScienceDirect, and CINAHL for studies investigating ASDH treated conservatively and surgically, without restriction to publication date, describing the mortality. Cohort studies or trials with at least five patients with ASDH, clearly describing surgical, conservative treatment, or both, with the mortality at discharge, reported in English or Dutch, were eligible. The search yielded 2025 reports of which 282 were considered for full-text review. After risk of bias assessment, we included 102 studies comprising 12,287 patients. The data were synthesized using meta-analysis of absolute risks; this was conducted in random-effects models, with dramatic effect estimation in subgroups. Overall mortality in surgically treated ASDH is 48% (95% confidence interval [CI] 44-53%). Mortality after surgery for comatose patients (Glasgow Coma Scale ≤8) is 41% (95% CI 31-51%) in contemporary series (after 2000). Mortality after surgery for non-comatose ASDH is 12% (95% CI 4-23%). Conservative treatment is associated with an overall mortality of 35% (95% CI 22-48%) and 81% (95% CI 56-98%) when restricting to comatose patients. The absolute risk reduction is 40% (95% CI 35-45%), with a number needed to treat of 2.5 (95% CI 2.2-2.9) to prevent one death in comatose ASDH. Thus, surgery is effective to reduce mortality among comatose patients with ASDH. The magnitude of the effect is large, although the effect size may not be sufficient to overcome any bias.

Treatment effect measures under nonproportional hazards.

In a clinical trial with a time-to-event endpoint the treatment effect can be measured in various ways. Under proportional hazards all reasonable measures (such as the hazard ratio and the difference in restricted mean survival time) are consistent in the following sense: Take any control group survival distribution such that the hazard rate remains above zero; if there is no benefit by any measure there is no benefit by all measures, and as the magnitude of treatment benefit increases by any measure it increases by all measures. Under nonproportional hazards, however, survival curves can cross, and the direction of the effect for any pair of measures can be inconsistent. In this paper we critically evaluate a variety of treatment effect measures in common use and identify flaws with them. In particular, we demonstrate that a treatment's benefit has two distinct and independent dimensions which can be measured by the difference in the survival rate at the end of follow-up and the difference in restricted mean survival time, and that commonly used measures do not adequately capture both dimensions. We demonstrate that a generalized hazard difference, which can be estimated by the difference in exposure-adjusted subject incidence rates, captures both dimensions, and that its inverse, the number of patient-years of follow-up that results in one fewer event (the NYNT), is an easily interpretable measure of the magnitude of clinical benefit.

Cost Savings Associated with Vacuum-Assisted Closure in Trauma Patients Undergoing Posterior Spinal Fusion.

OBJECTIVE: To investigate the implications of vacuum-assisted closure (VAC) versus standard wound dressings on postoperative posterior spinal fusion (PSF) wounds with respect to potential cost savings associated with reduced incidence of surgical site infections. METHODS: This was a retrospective review of trauma patients who underwent open PSF under the care of a single surgeon at a Level I trauma center. Patients were postoperatively monitored for 90 days. Statistical analysis was performed with χ2 testing with the calculation of number needed to treat values. RESULTS: Inclusion criteria were met by 208 patients who underwent open PSF. The χ2 test revealed a significant increase in incidence of surgical site infections (20% vs. 8%; P = 0.021) in the non-VAC group (n = 112) compared with the VAC group (n = 96). Cost-benefit analysis revealed that use of VAC in patients undergoing open PSF could enable a mean cost savings of $163,492 per 100 patients. CONCLUSIONS: Use of VAC in patients undergoing open PSF was associated with a 2-fold decrease in incidence of surgical site infections and an infection-related cost savings of $163,492 per 100 patients. Further investigation is needed to ascertain additional benefits of VAC usage in patients undergoing open PSF.

A Simple and Interpretable Mortality-Based Value Metric for Condition- or Procedure-Specific Hospital Performance Reporting.

Objective: To develop a simple, interpretable value metric (VM) to assess the value of care of hospitals for specific procedures or conditions by operationalizing the value equation: Value = Quality/Cost. Patients and Methods: The present study was conducted on a retrospective cohort from 2015 to 2018 drawn from the 100% US sample of Medicare inpatient claims. The final cohort comprised 637,341 consecutive inpatient encounters with a cancer-related Medicare Severity-Diagnosis Related Grouping and 13,307 consecutive inpatient encounters with the International Classification of Diseases, Ninth Revision or International Classification of Diseases, Tenth Revision procedure code for partial or total gastrectomy. Claims-based demographic and clinical variables were used for risk adjustment, including age, sex, year, dual eligibility, reason for Medicare entitlement, and binary indicators for each of the Elixhauser comorbidities used in the Elixhauser mortality index. Risk-adjusted 30-day mortality and risk-adjusted encounter-specific costs were combined to form the VM, which was calculated as follows: number needed to treat = 1/(Mortalitynational - Mortalityhospital), and VM = number needed to treat × risk-adjusted cost per encounter. Results: Among hospitals with better-than-average 30-day cancer mortality rates, the cost to prevent 1 excess 30-day mortality for an inpatient cancer encounter ranged from $71,000 (best value) to $1.4 billion (worst value), with a median value of $543,000. Among hospitals with better-than-average 30-day gastrectomy mortality rates, the cost to prevent 1 excess 30-day mortality for an inpatient gastrectomy encounter ranged from $710,000 (best value) to $95 million (worst value), with a median value of $1.8 million. Conclusion: This simple VM may have utility for interpretable reporting of hospitals' value of care for specific conditions or procedures. We found substantial inter- and intrahospital variation in value when defined as the costs of preventing 1 excess cancer or gastrectomy mortality compared with the national average, implying that hospitals with similar quality of care may differ widely in the value of that care.

Pain Reduction With AbobotulinumtoxinA for the Treatment of Hallux Valgus in Adult Participants: Results of a Randomized and Placebo-Controlled Phase 2 Trial.

AbobotulinumtoxinA (aboBoNT-A, Dysport® [Ipsen, Paris, France]) inhibits acetylcholine release at the neuromuscular junction and may modulate pain signaling in hallux valgus (HV). This randomized study (NCT03569098) included a double-blind phase (aboBoNT-A 300U, 500U or placebo injections into forefoot muscles) and an open-label aboBoNT-A treatment period in participants with an HV diagnosis and no HV surgery. The primary endpoint was change from baseline in numeric pain rating scale (NPRS) score at week 8. Secondary endpoints included change in NPRS (other time points) and proportion of participants with ≥20% reduction from baseline NPRS (responders). Post-hoc analyses assessed number of days in a 7-day evaluation period that participants spent in a lower pain state than at baseline. Participants received aboBoNT-A 300U (n = 63), 500U (n = 60) or placebo (n = 63). Superiority to placebo was not observed with either aboBoNT-A dose at week 8, thus the primary endpoint was unmet. At week 12, a trend toward efficacy was observed with aboBoNT-A 500U versus placebo and the proportion of participants with ≥20% reduction from baseline NPRS was greater with aboBoNT-A 500U versus placebo (p = .006). Participants in the aboBoNT-A 500U group spent more days with lower NPRS than their lowest baseline score, and with NPRS ≥2 points lower than their mean baseline NPRS at weeks 8 and 12 versus placebo (all p < .05; post-hoc). AboBoNT-A was well tolerated. Although the primary endpoint was unmet, other endpoints showed a nominal advantage for aboBoNT versus placebo for treatment of HV-related pain, particularly at week 12. Further clinical evaluation is needed to establish whether botulinum toxins represent a viable non-operative treatment option for HV-associated pain. PLAIN LANGUAGE SUMMARY: Hallux valgus is the medical name for a bunion, a foot deformity that can worsen over time. Patients with bunions experience pain and walking can become difficult, which can affect their quality of life. Foot support aids (e.g., braces, splints and inserts) are available, but surgery is the standard treatment. This study looked at how injections of a specific type of botulinum toxin, called abobotulinumtoxinA or "aboBoNT-A", into the foot may help to reduce pain in patients with bunions. The study included 186 patients aged 18 to 75 years who had not had surgery on their bunion. The researchers looked at how well the injections worked using scales that measure the pain levels the patient experienced. The main outcome was whether patients who had aboBoNT-A injections had less pain after 8 weeks than they did before treatment. The study included patients who were injected with saltwater (no treatment) to check that any treatment effect was real. Researchers also looked at the results after 12 weeks, as well as how many patients had less pain after treatment than before and how many days in a given week patients experienced less pain after treatment than they did before. There was no reduction in pain levels with aboBoNT-A injections after 8 weeks compared with no treatment. However, the other study outcomes suggested that aboBoNT-A resulted in a small benefit compared with no treatment, especially after 12 weeks. Further medical research is needed to establish whether botulinum toxins represent an alternative treatment to surgery for the pain associated with bunions.