Number Needed To Treat Research Articles

Abstract 4139186: Bempedoic Acid and Limb Outcomes in Statin-Intolerant Patients with Peripheral Artery Disease

Introduction: Patients with peripheral artery disease (PAD) are at high risk of major adverse limb events (MALE) and CV events and have high rates of recurrence of these events. Recently, bempedoic acid was shown to reduce MACE in primary and secondary prevention patients. Whether bempedoic acid reduces the risk of MALE is unknown. Methods: CLEAR Outcomes randomized 13,970 patients to bempedoic acid 180 mg or placebo. A clinical history of PAD was reported by investigators at baseline. Two blinded vascular medicine specialists independently adjudicated all adverse events for limb outcomes including worsening PAD symptoms leading to revascularization, chronic limb threatening ischemia, and acute limb ischemia events with the composite defined as MALE. Outcomes were assessed as time to first event as well as total (including recurrent) events using a negative binomial approach. Results: A total of 1,624 of the enrolled patients had PAD at baseline. Over a median of 41.1 months the rate of first and total MALE events in patients with PAD in the placebo group were 8.3% and 13.7% respectively. Bempedoic acid reduced first MALE events by 36% (HR 0.64, 95% CI 0.44-0.93) with an absolute risk reduction (ARR) of 2.5% and number needed to treat (NNT) of 40, compared to placebo (figure, panel A). Similarly, when considering total events, bempedoic acid reduced MALE by 45% (RR 0.55, 95% CI 0.35 – 0.85, figure panel b). Consistent benefits were observed for MALE in the overall population as well as composites of MACE and MALE in both populations (Figure panel b). There was no evidence of effect modification for the benefit of bempedoic acid for MALE on the basis of PAD at baseline (p-interaction 0.09). Conclusions: Bempedoic acid significantly reduces MALE. Benefits appear potentially greater when considering total (i.e. recurrent) events. These findings support the importance of LDL-C lowering therapy in patients with PAD. In addition, these findings support the early use of therapies with proven MALE benefit, including bempedoic acid, to optimize outcomes in PAD.

Enhancing Air Quality Index Activity Guidelines for Preventing Cardiovascular Events in the General Adult Population

BackgroundThe public health relevance of daily Air Quality Index (AQI) activity guidelines for the general adult public in the United States to prevent atherosclerotic cardiovascular disease (ASCVD) events is questionable. ObjectivesThe purpose of the study was to explore the utility of a policy tailoring activity guidance to calculated ASCVD risk rather than uniform recommendations to the general adult public as currently provided. MethodsWe calculated the number needed to treat (NNT) to prevent one ASCVD event per day by following activity recommendations across 10-year ASCVD risk scores (1% to 20%). Second, we modeled the benefits of tailoring recommendations to ASCVD risk. ResultsThe NNT decreased as ASCVD risk and/or AQI levels increased. At AQIs up to 151 (68% of days with AQIs above moderate in the United States), the NNTs remained untenably high (>2.7-55.3 million) across ASCVD risk. Under unhealthy conditions (AQIs 151-200), 28% of elevated AQIs, NNTs <1 million could be achieved by current guidance (15% exposure reduction), but only among the highest-risk individuals (ASCVD 18% to 20%) on the most polluted days (AQIs 192-200). Tailoring guidance to ASCVD risk could yield NNTs <1 million at risk thresholds of 7.5% and 10% if activity restrictions were more stringent (35% to 50% exposure reductions) during unhealthy conditions. ConclusionsASCVD risk has a major influence on the NNT to prevent cardiovascular events by following AQI guidance. It may be possible for a future policy to improve the utility of AQI activity guidance for the general adult public by tailoring activity recommendations to ASCVD risk.

Interplay between lifestyle factors and polygenic risk for incident coronary heart disease in a large multiethnic cohort

IntroductionThe objective of this study was to examine the interplay of polygenic risk and individual lifestyle factors (and a composite score of lifestyle) as antecedents of CHD in a large multiethnic cohort. MethodsWe used Genetic Epidemiology Resource in Adult Health and Aging (GERA) cohort participants free of CHD at baseline (n = 60,568; 67 % female; 18 % non-European). The individual and joint associations of smoking, Mediterranean diet pattern, level of physical activity and polygenic risk with incident CHD were assessed using Cox regression adjusting for genetic ancestry and non-mediating risk factors. Hazard ratios (HRs) and number needed to treat (NNT) were estimated according to these lifestyle factors and polygenic risk categories. Strengths included large sample size, long-follow-up, ethnic diversity, a clinically-validated polygenic risk score (PRS), and rich phenotype information. ResultsAfter 14 years of follow-up, there were 3159 incident CHD events. We observed no statistically significant interactions between individual lifestyle factors and polygenic risk (all p > 0.23). For individuals with a high genetic risk, moving from the worse lifestyle combination (no favorable lifestyle factors) to the best lifestyle combination (all three) is associated with 52 % lower rate of CHD. The NNT was highest in the low polygenic risk group (34), lowest in the high polygenic risk group [19] and in-between (Jin et al., 2011) [24] in the intermediate polygenic risk group. ConclusionsLifestyle and polygenic risk together influence the risk of incident CHD. Our results support consideration of polygenic risk in lifestyle interventions because those with high polygenic risk are likely to derive the most benefit.

NNT and NNH: statistics and stochastics in the evaluation of added therapeutic value

Any pharmacological, invasive, surgical health intervention should have an added therapeutic value as well as the requirements of quality, safety, efficacy, to be considered as a medical device based on scientific evidence and of clinical utility for the patient. The intervention should be shared between the doctor and the patient who should have rigorous but simple tools to decide on the best therapy to undertake. Assessment of relative risk reduction is commonly used in the scientific literature to quantify both statistical and clinical significance. The reduction of the relative risk is independent of the baseline risk and is useful for comparing the results of trials conducted on populations at different risk levels. A biased reading of relative risk reduction can be used to emphasize the magnitude of the benefit for market innovation. The absolute risk reduction, on the other hand, is proportional to the magnitude of the baseline risk and is a more useful parameter for physicians and patients to understand the extent of benefit and harm, especially if the parameter is expressed in terms of the number needed to treat (NNT) or to harm (NNH). The mode of scientific communication is important for doctors' choices and patients' trust. Even true data can be fake in communication and perception by resorting to verbose paraphrases. Presenting the results of clinical trials in stochastic as well as statistical terms is useful for doctors and patients to verify whether it is worth practicing a certain treatment whose success sometimes has the probability of winning the lottery, also considering side effects and adverse events. One of the most important challenges in precision medicine will be understanding the relationship between probability and randomness.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: target trial emulation studies.

To emulate target trials comparing recurrence of nephrolithiasis among patients with pre-existing nephrolithiasis (overall and stratified by concomitant gout) initiating sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus an active comparator. Target trial emulation studies. Canadian population database, January 2014 to June 2022. 20 146 patients with nephrolithiasis and type 2 diabetes, including those with concomitant gout at baseline, a high risk group. Initiation of an SGLT-2 inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist, with a dipeptidyl peptidase-4 (DPP-4) inhibitor as alternative comparator. The primary outcome was recurrent nephrolithiasis events ascertained from diagnoses during emergency department visits, hospital admissions, or outpatient visits. Secondary outcomes included nephrolithiasis resulting in hospital admission or emergency department visits and flare-up of gout, as well as a positive control outcome (genital infection) and negative control outcomes (osteoarthritis encounter and appendicitis). Poisson and Cox proportional hazards regression models were used (primary analyses), as well as overlap weighting. After inverse probability of treatment weighting, 1924 recurrent nephrolithiasis events occurred among the 14 456 weighted patients who used an SGLT-2 inhibitor (105.3 per 1000 person years), compared with 853 events among the 5877 weighted patients who used a GLP-1 receptor agonist (156.4 per 1000 person years). The adjusted rate ratio was 0.67 (95% confidence interval (CI) 0.57 to 0.79) and rate difference was -51 (95% CI -63 to -40) per 1000 person years, with a number needed to treat (NNT) of 20. Among those with recently active nephrolithiasis, the absolute rate difference was 219 per 1000 person years (NNT of 5). Protective associations persisted for nephrolithiasis events that required emergency department visits, hospital admissions, or procedures, and when an SGLT-2 inhibitor was compared with a DPP-4 inhibitor (rate ratio 0.73 (0.68 to 0.78), rate difference -38 (-46 to -29) per 1000 person years (NNT of 26)). Protective associations also persisted among patients with nephrolithiasis and concomitant gout, with a rate ratio of 0.67 (0.57 to 0.79) and rate difference of -53 (95% CI -78 to -27) per 1000 person years versus a GLP-1 receptor agonist (NNT of 19), and 0.63 (0.55 to 0.72) and-62 (-81 to -42) per 1000 person years, respectively, versus a DPP-4 inhibitor (NNT of 16). Furthermore, SGLT-2 inhibitor use was associated with a lower rate of gout flare-ups (rate ratio 0.72, 0.54 to 0.95, rate difference -16, -31 to -1 per 1000 person years) compared with GLP-1 receptor agonists (0.65, 0.52 to 0.82, and -21, -33 to -9 per 1000 person years) compared with DPP-4 inhibitors. SGLT-2 inhibitor initiators showed higher risk of genital infection (eg, hazard ratio 2.21, 95% CI 1.68 to 2.90, and rate difference 13 per 1000 person years), but no altered risk of osteoarthritis encounter (0.87, 0.68 to 1.1, and -2 per 1000 person years) or appendicitis (1.07, 0.69 to 1.67, and 1 per 1000 person years). Results were similar when propensity score overlap weighting was applied. The benefits associated with SGLT-2 inhibitor for patients with nephrolithiasis in these target trial emulations suggest they may be a useful addition to current treatments to simultaneously manage nephrolithiasis recurrence and comorbidities, including gout.

Risk-Benefit Analysis of Novel Treatments for Patients with Generalized Myasthenia Gravis.

This study used network meta-analysis (NMA) to inform and compare the number needed to treat (NNT), number needed to harm (NNH), and cost per improved outcome (CPIO) associated with more recently approved treatments for anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) generalized myasthenia gravis (gMG). Clinical trials of neonatal Fc receptor (FcRn) inhibitors, efgartigimod intravenous (IV) and rozanolixizumab, and complement inhibitors, ravulizumab and zilucoplan, versus placebo (with background conventional treatment) were included in the primary NMA to compare efficacy and safety outcomes. The outputs from the NMAs were used to estimate NNT and NNH of each treatment versus placebo. CPIO (2024 USD) was estimated for a≥3- or≥5-point reduction from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores. Sensitivity analyses were performed adding efgartigimod PH20 subcutaneous (SC) and eculizumab to the NMA. Efgartigimod IV had the lowest NNT versus placebo for achieving a≥3- and≥5-point reduction in QMG, as well as a≥5-point reduction in MG-ADL, whereas rozanolixizumab had the lowest NNT for a≥3-point reduction in MG-ADL. The NNH versus placebo was similar across comparator treatments. Efgartigimod IV had the lowest CPIO among all treatments for all assessed efficacy outcomes. Sensitivity analyses yielded results consistent with primary analysis and indicated that efgartigimod PH20 SC had comparable NNT and CPIO values to efgartigimod IV, whereas eculizumab had comparable NNT and higher CPIO values compared to other complement inhibitors. FcRn inhibitors and complement inhibitors assessed in this study all demonstrated clinical benefit in terms of NNT as well as an acceptable safety profile in terms of NNH. Within the limitations of this meta-analysis, efgartigimod was associated with a favorable benefit-risk profile as well as a better economic value compared to ravulizumab, rozanolixizumab, and zilucoplan as treatments for anti-AChR Ab+gMG.

Implications of five different risk models in primary prevention guidelines

Abstract Background A lack of consensus exists across guidelines as to which risk model should be used for the primary prevention of cardiovascular disease (CVD). Purpose The objective of this study was to determine potential improvements in the number needed to treat (NNT) with statins using different risk models in patients eligible for risk stratification. Methods A retrospective observational cohort was assembled from primary care patients in Ontario, Canada between January 1st, 2010, to December 31st, 2014 and followed for up to 5 years. Risk estimation was undertaken in patients 40-75 years of age, without CVD, diabetes, or chronic kidney disease using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs), a recalibrated FRS (R-FRS), Systematic Coronary Risk Evaluation 2 (SCORE2), and the low-risk region recalibrated SCORE2 (LR-SCORE2). Results The cohort consisted of 47,399 patients (59% women, mean age 54). The NNT at 5 years with statins was lowest for SCORE2 at 40, followed by LR-SCORE2 at 41, R-FRS at 43, PCEs at 55, and FRS at 65. Models that selected for individuals with a lower NNT recommended statins to fewer, but higher risk patients. For instance, SCORE2 recommended statins to 7.9% of patients (5-year CVD incidence 5.92%). The FRS, however, recommended statins to 34.6% of patients (5-year CVD incidence 4.01%; Figure). Conclusions Newer models such as SCORE2 may improve statin allocation to higher risk groups with a lower NNT.Figure

Time to Treatment and Outcomes of Hemorrhagic Stroke, Comparing Patients Entering Surgery before and after 120 Minutes Upon Arrival at the Emergency Department Pattani Hospital

Background: The duration between a patient’s hospital arrival and the point at which they enter surgery for hemorrhagic stroke affects survival, length of stay, health care costs, and outcome (Glasgow Outcome Scale). Therefore, a study to explore the effects of time on these outcomes is warranted. Objective: To compare treatment outcomes of patients with hemorrhagic stroke having entered surgery before and after 120 minutes upon arrival at the emergency department. Materials and Methods: A therapeutic and interventional study with a retrospective observational cohort design at Pattani Hospital in patients with hemorrhagic stroke who received treatment between October 2018 and April 2023. A retrospective review of medical records, which collected clinical characteristics and the time to treatment. Glasgow Outcome Scale was evaluated at 72 hours, two weeks, one month, and date of hospital discharge. Length of stay, health care costs, and survival status at date of hospital discharge were analyzed. Comparative analysis was performed by Fisher’s exact probability test and t-test, and prognostic analysis was performed by risk ratio. Results: Of all the patients in the present study, 49 and 182 received treatment before and after 120 minutes, respectively, upon arrival at the emergency department. Clinical characteristics of gender, age, underlying conditions, regular medications, and level of consciousness were not significantly different between the two groups. Patients who entered surgery within 120 minutes of arrival had more occurrences of basal ganglia hemorrhage compared with those who received surgery thereafter. Furthermore, patients who received surgery within 120 minutes had a 11.4% increased chance of survival. The number needed to treat (NNT) hemorrhagic stroke patients with a time to treatment of under 120 minutes is 9. However, there was an associated increase in complications, health care cost, and length of stay. The Glasgow Outcome Scale improvement was greater only in the two-week follow-up period. These results were similar when subarachnoid hemorrhage and anticoagulating medication used were excluded. Conclusion: Patients with hemorrhagic stroke who receive early surgical treatment have lower mortality rates. Adequate provision of personnel and facilities for delivering prompt care should be made available. Measures should be taken to reduce the complications of patients who receive surgical treatment after 120 minutes upon arrival at the emergency department.

Comparison of three management approaches for dental caries in primary molars: A two-year randomized clinical trial

Aimto compare two-year clinical success rates of caries management in children (Hall Technique HT, Nonrestorative caries treatment NRCT, Conventional restorations CR), and to evaluate pain perception, behaviour, technique acceptability by patients, parents and dentists. Methods122, 3–8–year-olds were enrolled in 2-year parallel group randomised controlled trial (CR, n = 52, HT, n = 35, NRCT, n = 35). Caries was recorded using Nyvad criteria to measure clinical success/ failure rates. Child's pain perception (Visual Analogue Scale of Faces), child behaviour (Frankl scale), parents’ and dentists’ treatment opinions (5-point Likert scale) were assessed. Statistical analysis included Chi-square, non-parametric Kruskal–Wallis, Bonferroni-corrected Mann-Whitney U tests (p < 0.05), absolute risk reduction (ARR) and number needed to treat (NNT). ResultsAfter two years, with 116 participants, clinical success rates were: CR=60.8 % (n = 31), HT=93.8 % (n = 30), NRCT=42.5 % (n = 14) (p < 0.001). Major/minor failure rates differed: CR=17.6 % (n = 9) / 21.6 % (n = 11); HT=6.2 % (n = 2)/ 0 %, NRCT=33.3 % (n = 11)/ 24.2 % (n = 8), (p < 0.05). When comparing HT to CR, ARR = 0.33; NNT= 3 (95 % CI 0.02 -0.58); NRCT to CR, - no observed benefit from NRCT. More than 70 % of children demonstrated “positive/definitely positive” behaviour during treatment. Pain intensity was “very low/low” in 92.3 % of cases for CR, 88.6 % for HT, and 77.1 % for NRCT . NRCT was “very easy” to perform for 82.9 % of participants, compared to 42.3 % for CR and 17.1 % for HT (p < 0.05). CR were reported to take longer than NRCT and HT (p < 0.05). ConclusionClinical success rates of HT were superior to CR and NRCT. All treatment techniques were well tolerated by children, CR was more time-consuming and HT – technically more difficult to perform. Clinical significancecaries management in primary molars can be successfully performed using minimal intervention, particularly, sealing in caries lesions with Hall technique. NRCT can prevent caries progression when adequate access to mechanical plaque disruption and fluoride is provided. However, occasional fluoride application, and uncontrolled toothbrushing with fluoride toothpaste cannot replace restorative procedures.

Adjunctive cariprazine for the treatment of major depressive disorder: Number needed to treat, number needed to harm, and likelihood to be helped or harmed

BackgroundThe 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). MethodsData 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. ResultsNNTs (95 % CI) for adjunctive cariprazine versus placebo were statistically significant at week 6/early termination for Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥ 50 % response (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. LimitationsPost hoc analysis; indirect comparisons. ConclusionsPatients receiving adjunctive cariprazine encountered benefits more often than harm; NNT values at week 6/ET were statistically significant versus placebo on response/remission outcomes across dose groupings from the 5 pooled studies. Adjunctive cariprazine was well tolerated; NNH values versus placebo were generally >10, with better akathisia tolerability in the lower-dose range.

Comparative Efficacy and Safety of Upadacitinib vs. Vedolizumab, Ustekinumab, and Tofacitinib After Induction and Maintenance for Ulcerative Colitis: Three Matching-Adjusted Indirect Comparisons.

Evidence on the comparative efficacy and safety of approved therapies for ulcerative colitis (UC) during induction and maintenance, including upadacitinib (UPA), vedolizumab (VEDO), ustekinumab (UST), and tofacitinib (TOFA), is limited. Using data from phase 3 trials, three placebo (PBO)-anchored matching-adjusted indirect comparisons of the efficacy and safety of UPA versus VEDO, UST, and TOFA (U-ACHIEVE and U-ACCOMPLISH, GEMINI-1, UNIFI, and OCTAVE induction and maintenance trials) have been conducted. Baseline characteristics from UPA trials were weighted separately to match each comparator trial. Induction responders were re-randomized to oral UPA 15 or 30mg, VEDO 300mg intravenously every 8weeks (Q8W), UST 90mg SC Q8W, or oral TOFA 5mg, or PBO in maintenance. Treat-through efficacy outcomes at weeks 44(UST)/46(VEDO)/52(UPA/TOFA) were adjusted by the likelihood of induction response and included clinical response, clinical remission, and endoscopic improvement. Safety outcomes included adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation (except UPA vs. VEDO). Benefit-risk was assessed by numbers needed to treat (NNT)/harm, calculated as the inverse of the difference in proportions of patients achieving each efficacy/safety outcome for UPA versus comparator. The proportions of patients who demonstrated clinical response or endoscopic improvement was greater with UPA 15mg versus VEDO and TOFA (p<0.05). The proportions of patients demonstrating all treat-through efficacy outcomes were significantly greater with UPA 30mg versus VEDO, UST, or TOFA with NNTs 3.2-8.7. No significant differences in proportions of AEs, SAEs, and AEs leading to discontinuation were observed between the two doses of UPA and comparators. In patients with active UC, greater clinical efficacy, and similar safety after 1year of maintenance were observed with UPA versus VEDO, UST, and TOFA, suggesting a favorable benefit-risk profile for UPA. Despite matched baseline characteristics, differences in trial design and endpoints may persist.

Ramped versus sniffing position for Ambu® AuraGainTM insertion in patients with obesity: a randomized controlled study.

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. 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. 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. 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.

Antioxidative effects of N-acetylcysteine in patients with β-thalassemia: A quick review on clinical trials.

Several studies have highlighted the potent antioxidant properties of N-acetyl cysteine (NAC). This review aimed to assess the impact of NAC on oxidative stress biomarkers in patients with β-thalassemia. The review included articles published before 2024 that investigated the effects of NAC on oxidative stress in individuals with β-thalassemia. A comprehensive search was conducted across various databases, including Scopus, PubMed, Web of Science, Trip, and CENTRAL. Only English-language clinical trials were considered for inclusion in this review. Besides, the number needed to treat (NNT) was calculated based on the included studies. Ninety-nine articles were retrieved from electronic databases, and after a thorough review, eight articles were selected for comprehensive text analysis. The highest dose of NAC administered was 10 mg/kg/day (equivalent to 600 mg/day) over a period of 3-6 months. All the studies assessing the impact of NAC on oxidative stress indicators in β-thalassemia patients demonstrated positive effects during the 3-month follow-up period. Most estimated NNTs fell into 1-5, suggesting significant clinical therapeutic value in this context. The current potency of NAC alone appears to be effective in ameliorating oxidative stress in patients with β-thalassemia major. While a 3-month duration seems adequate to demonstrate the antioxidant properties of NAC in this population, larger and well-designed clinical trials are warranted. Current clinical evidence possesses a high risk of bias.

"Metabolic Bridge Therapy Prior to Microvascular Breast Reconstruction in the Morbidly Obese: A Proof-of-Concept Risk Analysis".

Obese patients experience more complications after autologous breast reconstruction. This study evaluates how bariatric surgery modulates risk of complications in the setting of microvascular breast reconstruction. Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) databases were queried for patients with body mass index (BMI) ≥35 kg/m2 undergoing bariatric surgery from 2017-2022. Outcomes included BMI and obesity-related comorbidities before and 1 year after bariatric surgery. Paired Breast Reconstruction Risk Assessment (BRA) scores were analyzed to evaluate risk modulation before and after bariatric surgery in the setting of microvascular breast reconstruction. A total of 1,026 patients were included with an average age of 47 and BMI of 44.7 kg/m2. Comorbidities included hypertension (601, 59%), type 2 diabetes (291, 28%), and cardiovascular disease (10, 1%). One-year outcomes after bariatric surgery included an average BMI of 32.7 kg/m2, with remission of type 2 diabetes in 29% of patients. Paired BRA risk analysis for microvascular breast reconstruction before and after bariatric surgery showed reduction in 30-day surgical complications (40.4% vs. 24.8%, P<0.0001), with an absolute risk reduction (ARR) of 15%, relative risk reduction (RRR) of 36%, and a number needed to treat (NNT) of 7. Each 1 kg/m2 reduction in preoperative BMI was associated with a 3.4% reduction in surgical complications (P<0.0001). There is potential efficacy for metabolic bridge therapy in reducing complications for obese patients undergoing microvascular breast reconstruction.

The association of obstetric anal sphincter injury and mediolateral episiotomy with increasing birth weight and duration of second stage of labour in spontaneous vaginal delivery

ObjectivesAnalysis of the association of mediolateral episiotomy (MLE) with obstetric anal sphincter injury (OASI) in women with spontaneous vaginal delivery.Design.Population-based cohort study with data from the Netherlands Perinatal Registry, describing 541 055 women who delivered a singleton live born infant in cephalic presentation spontaneously at term. Risk indicators for OASI were tested using univariate and multivariate analysis. Additional analysis for the interaction of MLE with other risk indicators was performed. ResultsThe rate of OASI was 4.2 % in 215 241 nulliparous and 1.4 % in 325 814 multiparous women. In nulliparous and multiparous women MLE was associated with a reduction of OASI (adjusted OR (aOR) 0.3, 95 % CI 0.30–0.34 and aOR 0.32, 95 % CI 0.30–0.34).The association of MLE with a reduced rate of OASI was stronger in high birthweight and in prolonged 2nd stage groups.In nulliparous women, the number needed to treat (NNT) for the use of MLE to prevent one OASI is 31 in general. With MLE, the OASI rate reduced from 11.5 % to 2.9 with a NNT of 12 in the group with a birth weight ≥ 4000 g and a duration of the second stage of labour of 60–120 min. The NNT is 9 In the group with a birth weight ≥ 4000 g and a duration of the second stage of labour ≥ 120 min (reduction rate of OASI from 14.2 % to 3.5 %). ConclusionsUse of MLE is associated with a reduction of OASI in spontaneous vaginal delivery.In nulliparous women, an episiotomy with an anticipated birth weight > 4000 g and a duration of the 2nd stage of more than 60 min should be considered.

Effectiveness of Public Health Education on the Uptake of Iron-And Folic Acid Supplements Among Pregnant Women: Findings from a Stepped Wedge Cluster Randomized Trial

Objective: To determine the effectiveness of public health education on the uptake of iron and folic acid supplements (IFAS) among pregnant women. Design: A stepped wedge cluster randomized trial. Setting: 12 antenatal care clinics (ANC) in Embu County - Kenya. The clinics are outpatient departments in health facilities dedicated to providing care for pregnant women. Participants: Pregnant women receiving antenatal care services in the study sites. Intervention: After a baseline observational phase, a multifaceted intervention bundle was implemented. The intervention included a 60-minute IFAS information session for health workers at the start of intervention. Health workers then provided daily IFAS literacy sessions to all the pregnant women and issued them with IFAS related information materials (a pill reminder card, and a personalized calendar). The study team conducted biweekly facility audits for quality assurance. The total duration of the study was 8 months, starting June 2022. Primary outcome: The primary outcome was the proportion of pregnant women taking IFAS daily in the intervention phase compared with control phase. This was measured through IFAS residual pill count during every ANC visit. Results: A total of 4,749 ANC visits were monitored for 2,132 women receiving antenatal care in the 12 clinics. Participant characteristics were similar across control and intervention phases. The uptake of IFAS significantly improved from 44.8% (95% CI 34.7 to 55.0) in control phase to 83.3% (95% CI 75.9 to 90.9) during the intervention. This translates to a 38.5 (95% CI 26.0 to 51.1) percentage points improvement. The number needed to treat (NNT) for this intervention was 3 patients (95% CI 2 to 4). Conclusion: IFAS uptake significantly improved following the intervention. The findings support public health education as an effective strategy for improving the uptake of IFAS in ANC settings.

Shouldice versus Lichtenstein inguinal hernia repair: A meta-analysis of randomized controlled trials.

The Lichtenstein technique is the standard treatment for adult open inguinal hernia repair. Among the non-mesh repair techniques, Shouldice has shown the best results and is comparable to mesh repairs in selected cases. Due to the risk of chronic groin pain associated with the Lichtenstein technique, Shouldice has increased in popularity, and some surgeons have adopted it as a viable first-line option. MEDLINE, Cochrane, Central Register of Clinical Trials, and EMBASE for randomized controlled trials (RCT) published until February 2024. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed using the Cochran Q test and I2 statistics with p-values <0.10 and I2 > 25% considered significant. Statistical analysis was performed using R Software, version 4.1.2. Fourteen RCTs comprising 2784 patients were included, of whom 1379 (47.5%) were submitted to the Shouldice hernia repair and 1513 (52.5%) to the Lichtenstein technique. Shouldice was associated with a significant increase in the recurrence rate (4.2% vs. 0.9%; RR 3.68; 95% CI 2.05-6.60; p<0.001; I2=0%) compared with Lichtenstein. The number needed to treat (NNT) to prevent one Shouldice recurrence was 30.3. There were no significant differences between groups in chronic pain, urinary retention, bladder injury, testicular atrophy, wound infection, hematoma-seroma, or hypesthesia. The Lichtenstein technique was associated with reduced recurrence rates compared with Shouldice in patients undergoing inguinal hernia repair. However, the overall recurrence rate with the Shouldice technique was still low (4.2%), suggesting that it may be a viable option in selected patients.

Meta-analysis of sotagliflozin, a dual sodium-glucose-cotransporter 1/2 inhibitor, for heart failure in type 2 diabetes.

Sodium-glucose co-transporters (SGLTs) mediate sodium and glucose transport across cell membranes. SGLT2 inhibitors have a recognized place within heart failure (HF) guidelines. We evaluated the effect of sotagliflozin on HF and cardiovascular outcomes in participants with type 2 diabetes. Scopus, Medline, Embase and Central were searched from inception until 2 June 2023. Randomized controlled trials evaluating sotagliflozin in type 2 diabetes participants and reporting HF events were selected. Major adverse cardiovascular events (MACE) and systolic blood pressure were evaluated. The Cochrane risk of bias tool (RoB 2.0) was used. Pooled mean difference (MD), relative risk (RR), 95% confidence intervals and the number needed to treat (NNT) were estimated (PROSPERO: CRD42023432732). We selected nine studies (n=15320 participants: n=8040 intervention and n=7280 control). The median follow-up was 13.4months (Q1=13, Q3=21). One study recruited participants with HF at baseline. After a follow-up of >52weeks, sotagliflozin significantly reduced the risk of HF [n=8 studies; RR=0.66 (0.64, 0.69)], stroke [n=6 studies; RR=0.75 (0.58, 0.97)] and MACE [n=8 studies; RR=0.73 (0.66, 0.81)]. The NNT was 20 and 26 for HF and MACE, respectively. Sotagliflozin lowered systolic blood pressure [n=7; MD=-2.38mmHg (-2.79, -1.97)]. No dose-dependent effect was identified for HF [200mg: RR=0.38 (0.16, 0.89), 400mg: RR=0.57 (0.39, 0.85), P-value=0.22]. The high risk of bias was a limitation of this review. Sotagliflozin reduced HF and cardiovascular events in type 2 diabetes participants. Research exploring its effects in HF and comparisons with SGLT2 inhibitors is warranted to determine if dual SGLT inhibition surpasses selective inhibition.

Abstract P115: Hypothetical Blood Pressure Lowering Interventions and Risk of Mortality in Middle-Aged and Older Chinese Adults: A Population-Based Modelling Study

Background: Improving hypertension control is an important global health priority. We aimed to study the effects of hypothetical interventions on systolic blood pressure (SBP) on mortality risk at the population level. Methods: We estimated the relationship between SBP and all-cause mortality in adults aged 45 years and older from the China Health and Retirement Longitudinal Study and compared the mortality reductions associated with lowering SBP to different hypothetical targets (120, 130, 140, 150 mm Hg). Using the parametric g-computation modeling technique, we estimated the mean blood pressure reduction required to achieve each target, the share of the population in need of management, and the number needed to treat (NNT) to avert one death under different hypothetical population-wide scale-up scenarios. Results: Among 12355 participants, 1203 died over 7-year follow-up. We found a weak, non-linear relationship between SBP and mortality, with larger incremental mortality benefits at higher SBP values: reducing SBP from 160 mm Hg to 120 mm Hg was associated with a relative risk of mortality of 0.75 (95% CI 0.65 to 0.86). At the population level, reducing SBP to 120 mm Hg among all those with a starting SBP of more than 120 mm Hg (120 mm Hg scenario) was associated with 13.7 deaths averted per 1000 population (95% CI -19.3 to -8.1), compared with 3.8 deaths averted per 1000 population (95% CI -6.0 to -1.6) associated with reducing SBP to 150 mm Hg among all those with a starting SBP of more than 150 mm Hg (150 mm Hg scenario). However, there were large differences between scenarios in the proportion of the population that would require treatment, ranging from 64.3% (95% CI 63.4 to 65.1) in the 120 mm Hg scenario to 16.7% (6.0 to 17.3) in the 150 mm Hg scenario. To achieve the target, the 120 mm Hg scenario required a mean shift of -14.4 mm Hg in SBP (95% CI -14.7 to -14.1) compared with a -2.9 mm Hg mean change (-3.0 to -2.7) for the 150 mm Hg scenario. Based on the ratio of number of deaths averted to the proportion requiring treatment, the 150 mm Hg scenario had the smallest NNT (n=44), followed by the 120 mm Hg scenario (n=47), the 140 mm Hg scenario (n=49), and the 130 mm Hg scenario (n=51). Conclusions: These findings highlight the possible substantial benefits of reducing blood pressure. We find that scaling up management based on a 150 mm Hg target is more efficient in terms of the NNT compared with strategies to reduce SBP to lower levels.

Designing and validating a clinical decision support algorithm for diabetic nephroprotection in older patients

BackgroundOlder patients with diabetic kidney disease (DKD) often do not receive optimal pharmacological treatment. Current clinical practice guidelines (CPGs) do not incorporate the concept of personalised care. Clinical decision support...