A nomogram for predicting the risk of treatment failure of roxadustat in peritoneal dialysis with renal anemia.

The determinants of roxadustat treatment failure in renal anemia remain elusive. This study sought to develop a nomogram for predicting the risk of treatment failure of roxadustat in peritoneal dialysis (PD) with renal anemia. A retrospective cohort analysis from January 1, 2019, to January 31, 2023, included 204 PD patients with renal anemia, stratified by attainment group (Hb ≥ 110 g/L, n = 103) or non-attainment (Hb < 110 g/L, n = 101) within 1 year treatment. Univariate and multivariate Cox proportional hazards regressions were employed to ascertain predictive factors and construct the nomogram. Nomogram efficacy was evaluated via C-index, time-dependent ROC, calibration plots, and decision curve analysis, with internal validation via tenfold cross-validation and 1000 bootstrap resampling iterations. The study identified PD duration, serum transferrin, cardiovascular comorbidities, and stains as significant predictors. The nomogram demonstrated moderate discrimination at 6 months (AUC: 0.717) and enhanced predictive accuracy at 12 months (AUC: 0.741). The predicted and actual risk probabilities were concordant, with clinical net benefits observed at six-month (8 to 53%) and twelve-month (27 to 84%) risk thresholds. This nomogram is a valuable tool for effectively predicting non-attainment risk and facilitating personalized management of renal anemia in PD patients treated with roxadustat.

The efficacy of machine learning models in forecasting treatment failure in thoracolumbar burst fractures treated with short-segment posterior spinal fixation.

BACKGROUND: Although short-segment posterior spinal fixation (SSPSF) has shown promising clinical outcomes in thoracolumbar burst fractures, the treatment may be prone to a relatively high failure rate. This study aimed to assess the effectiveness of machine learning models (MLMs) in predicting factors associated with treatment failure in thoracolumbar burst fractures treated with SSPSF. METHODS: A retrospective review of 332 consecutive patients with traumatic thoracolumbar burst fractures who underwent SSPSF at our institution between May 2016 and May 2023 was conducted. Patients were categorized into two groups based on treatment outcome (failure or non-failure). Potential risk factors for treatment failure were compared between the groups. Four MLMs, including random forest (RF), logistic regression (LR), support vector machine (SVM), and k-nearest neighborhood (k-NN), were employed to predict treatment failure. Additionally, LR and RF models were used to assess factors associated with treatment failure. RESULTS: Of the 332 included patients, 61.4% were male (n = 204), and treatment failure was observed in 44 patients (13.3%). Logistic regression analysis identified Load Sharing Classification (LSC) score, lack of index level instrumentation, and interpedicular distance (IPD) as factors associated with treatment failure (P < 0.05). All models demonstrated satisfactory performance. RF exhibited the highest accuracy in predicting treatment failure (accuracy = 0.948), followed by SVM (0.933), k-NN (0.927), and LR (0.917). Moreover, the RF model outperformed other models in terms of sensitivity and specificity (sensitivity = 0.863, specificity = 0.959). The area under the curve (AUC) for RF, LR, SVM, and k-NN was 0.911, 0.823, 0.844, and 0.877, respectively. CONCLUSIONS: This study demonstrated the utility of machine learning models in predicting treatment failure in thoracolumbar burst fractures treated with SSPSF. The findings support the potential of MLMs to predict treatment failure in this patient population, offering valuable prognostic information for early intervention and cost savings.

Treatment Failure and Long-Term Prescription Risk for Guideline-Recommended Hypnotics in Japan.

Importance: Although insomnia guidelines recommend the use of several individual hypnotics, the most useful hypnotic for treating insomnia in a clinical setting remains unclear. Objective: To determine which guideline-recommended hypnotics have lower risks of monotherapy failure and which hypnotics have a higher risk of long-term prescription for insomnia treatment. Design, Setting, and Participants: This retrospective observational cohort study used data from the Japan Medical Data Center Claims Database from April 1, 2005, to March 31, 2021. Participants included adults whose first prescribed pharmaceutical treatment for insomnia was guideline-recommended hypnotic monotherapy. Data were analyzed from December 24, 2022, to September 26, 2023. Exposures: Suvorexant, ramelteon, eszopiclone, zolpidem, and triazolam monotherapy. Main Outcomes and Measures: The primary outcome was monotherapy failure, defined as a change in hypnotic or having an additional hypnotic prescribed for insomnia within 6 months of the first prescription of a guideline-recommended hypnotic monotherapy. The secondary outcome was monotherapy discontinuation, defined as no prescription of any hypnotic for 2 consecutive months within 6 months after prescribing a guideline-recommended hypnotic in patients for whom monotherapy did not fail. Monotherapy failure and discontinuation were compared using Cox proportional hazards and logistic regression models, respectively. Results: The study included 239 568 adults (median age, 45 [IQR, 34-55] years; 50.2% women) whose first prescription for insomnia was guideline-recommended hypnotic monotherapy. During the 6-month follow-up period, 24 778 patients (10.3%) experienced failure of monotherapy with a guideline-recommended hypnotic. In comparison with eszopiclone, there were more cases of monotherapy failure for ramelteon (adjusted hazard ratio [AHR], 1.23 [95% CI], 1.17-1.30; P < .001), fewer cases for zolpidem (AHR, 0.84 [95% CI, 0.81-0.87]; P < .001) and triazolam (AHR, 0.82 [95% CI, 0.78-0.87]; P < .001), and no significant difference between suvorexant and eszopiclone. Among those without monotherapy failure, monotherapy was discontinued in 84.6% of patients, with more discontinuations for ramelteon (adjusted odds ratio [AOR], 1.31 [95% CI, 1.24-1.40]; P < .001) and suvorexant (AOR, 1.20 [95% CI, 1.15-1.26]; P < .001) than for eszopiclone and no significant difference between zolpidem or triazolam and eszopiclone. Conclusions and Relevance: Due to uncontrolled confounding factors in this cohort study, no conclusions regarding the pharmacologic properties of guideline-recommended hypnotics can be drawn based on these results. Further studies accounting for confounding factors, including diagnoses of chronic vs acute insomnia disorder, insomnia and psychiatric symptom severity, and physician attitudes toward hypnotic prescription, are needed.

Association of blood eosinophils with corticosteroid treatment failure stratified by smoking status among inpatients with AECOPD.

BACKGROUND: Recent studies have suggested elevated blood eosinophils are independent predictors of response to corticosteroid therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Smoking status has been shown to affect corticosteroid response. Whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking has not been fully investigated so far. OBJECTIVES: This study aimed to assess whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking. METHODS: We included 3402 inpatients with AECOPD treated with corticosteroids at Beijing Chao-Yang Hospital from July 2013 to June 2021. Blood eosinophil counts were measured within 24 hours of admission. An eosinophil percentage ≥2% was considered as high eosinophilic. Smokers in this study were defined as current or former smokers. Treatment failure was defined as a worsening of AECOPD that led to adverse clinical outcomes or required further treatment or an extended hospital stay or hospitalisation following the exacerbation. Multivariate-adjusted logistic models were used to estimate the OR and 95% CI associated with treatment failure. RESULTS: There were 958 (28.2%) treatment failure events occurring. Patients with high eosinophils had a lower risk of treatment failure (OR 0.74, 95% CI 0.63 to 0.87) than patients with low eosinophils. Compared with never smoking and low eosinophilic group, the ORs for treatment failure were 0.70 (95% CI 0.52 to 0.96) for never smoking and high eosinophilic group, 0.82 (95% CI 0.64 to 1.05) for smoking and low eosinophilic group and 0.62 (95% CI 0.47 to 0.81) for smoking and high eosinophilic group. Furthermore, there was no significant interaction between eosinophils and smoking status in relation to treatment failure (p for interaction=0.73). Similar results were obtained from multiple secondary outcomes and subgroup analyses. CONCLUSION: Elevated blood eosinophils are associated with a lower rate of corticosteroid treatment failure, regardless of smoking status. Smoking does not modify the association between blood eosinophil level and corticosteroid treatment failure among inpatients with AECOPD.

Systematic review and meta-analysis of the management of acute uncomplicated diverticulitis: time to change traditional practice.

BACKGROUND: To evaluate comparative outcomes of outpatient (OP) versus inpatient (IP) treatment and antibiotics (ABX) versus no antibiotics (NABX) approach in the treatment of uncomplicated (Hinchey grade 1a) acute diverticulitis. METHODS: A systematic online search was conducted using electronic databases. Comparative studies of OP versus IP treatment and ABX versus NABX approach in the treatment of Hinchey grade 1a acute diverticulitis were included. Primary outcome was recurrence of diverticulitis. Emergency and elective surgical resections, development of complicated diverticulitis, mortality rate, and length of hospital stay were the other evaluated secondary outcome parameters. RESULTS: The literature search identified twelve studies (n = 3,875) comparing NABX (n = 2,008) versus ABX (n = 1,867). The NABX group showed a lower disease recurrence rate and shorter length of hospital stay compared with the ABX group (P = 0.01) and (P = 0.004). No significant difference was observed in emergency resections (P = 0.33), elective resections (P = 0.73), development of complicated diverticulitis (P = 0.65), hospital re-admissions (P = 0.65) and 30-day mortality rate (P = 0.91). Twelve studies (n = 2,286) compared OP (n = 1,021) versus IP (n = 1,265) management of uncomplicated acute diverticulitis. The two groups were comparable for the following outcomes: treatment failure (P = 0.10), emergency surgical resection (P = 0.40), elective resection (P = 0.30), disease recurrence (P = 0.22), and mortality rate (P = 0.61). CONCLUSION: Observation-only treatment is feasible and safe in selected clinically stable patients with uncomplicated acute diverticulitis (Hinchey 1a classification). It may provide better outcomes including decreased length of hospital stay. Moreover, the OP approach in treating patients with Hinchey 1a acute diverticulitis is comparable to IP management. Future high-quality randomised controlled studies are needed to understand the outcomes of the NABX approach used in an OP setting in managing patients with uncomplicated acute diverticulitis.

Risk factors for treatment failure in multidrug resistant tuberculosis in Tunisia: An analytic study.

INTRODUCTION-AIM: The emergence of multidrug resistant tuberculosis (MDR-TB) is a threat to global public health. The aim of our study was to determine risk factors for treatment failure in MDR-TB. METHODS: Retrospective study conducted between January 2000 and March 2019 including patients with MDR-TB. Characteristics of patients with therapeutic failure were compared to cured ones. Logistic regression analysis was used to identify risk factors for treatment failure. RESULTS: Our study included 140 patients aged of 42±13 years (18-80). Fifty-seven percent of patients had treatment success and 12% had treatment failure. In multivariate logistic regression analysis, treatment failure was associated with age over 45 years (OR=1.05; 95%CI, 1.024-7.736;p=0.014), primary education level and illiteracy (OR=5.022; 95%CI, 1.316-19.161;p=0,018), history of incarceration (OR=3.291; 95%CI, 1.291-21.083;p=0.016), undernutrition (OR=4.544; 95%CI, 2.304-54.231;p=0,027), extensive TB (OR=6.406; 95%CI, 1.761-23.922; p=0.038), initial high grade positive smears (OR=1.210; 95%CI, 1.187-32.657; p=0.045), positive smear culture at 90 days of treatment (OR=6.871, 95%CI, 3.824-23.541; p=0.003), poor adherence (OR=6.110; 95%CI, 2.740-12.450; p=0.021) and occurrence of psychiatric adverse events (OR=3.644 95%CI, 2.560- 27.268; p=0.041). CONCLUSION: Therapeutic education, nutritional and psychological support and close follow-up are strongly recommended to optimize the prognosis of MDR-TB.

Predictors of antiretroviral treatment failure to the first line therapy: a cross-sectional study among Iranian HIV-positive adults.

BACKGROUND: HIV virological failure is one of the main problems in HIV-infected patients, and identifying the main predictors of such treatment failure may help in combating HIV/AIDS. METHODOLOGY: This cross-sectional study included 1800 HIV-infected patients with either virological failure or treatment response. HIV viral load, CD4 count, and other tests were performed. Statistical analysis was used to determine the predictors of virological failure. RESULTS: Clinical stage, treatment with reverse transcriptase inhibitors (RTIs), under therapy for three years or more, suboptimal adherence to antiretroviral treatment (ART), age > 40 years, CD4 count < 200 cells/mm3, unemployment, being infected through sex, and the presence of symptoms were the predominant risk factors for virological failure. In addition, 55% of patients who experienced virological failure failed to experience immunological and/or clinical failure. CONCLUSION: As the first study in southern Iran and the second in Iran, Iranian policymakers should focus on intensive counseling and adherence support and emphasize more effective treatment regimens such as protease and integrase inhibitors (PIs and INTIs), to increase the chance of a treatment response to ART. The accuracy of identifying clinical and immunological criteria in resource-limited settings is not promising. The present findings can be used to determine effective measures to control HIV treatment failure and design efficient strategies for the ambitious 95-95-95 plan.

Predicting early endodontic treatment failure following primary root canal treatment.

BACKGROUND: Understanding when and why endodontic treatments fail could help clinicians make prognoses and thus improve treatment outcomes. This study was aimed to assess potential predictors of early endodontic treatment failure. We explored factors contributing to the failure of initial root canal treatment were explored, with a specific emphasis on evaluating the influence of the time elapsed since the initial treatment. METHODS: This retrospective cohort study enrolled 1262 patients who sought endodontic treatment at our department and 175 patients were included for analysis. Potential causes of endodontic treatment failure were investigated, such as inadequate obturation quality, inadequate coronal status, the presence of additional untreated canals, anatomical complexity, instrument separation, iatrogenic perforation, cracks, and endodontic-periodontal lesions. The patients were divided into "short-term" and "long-term" groups depending on the time that had passed since the initial treatment (i.e., < 5 and > 10 years, respectively). The causes of failure in the short-term and long-term group were analyzed and compared using logistic regression analyses. Subgroup analysis was performed according to the number of years since the initial treatment in the short-term group to further investigate the association between the time and cause of failure (i.e., < 1, 2, 3, and 4 years, respectively). RESULTS: Untreated additional canals were present in 21.7% of all cases, and in 36.9 and 6.4% of cases in the short-term and long-term groups, respectively. Multivariable analysis showed that the presence of untreated additional canals was significantly associated with short-term compared to long-term failure. Untreated additional canals were also associated with endodontic failure within 1, 2, 3, and 4 years. CONCLUSIONS: The presence of untreated additional canals was a predictor of endodontic failure within 5 years following initial root canal treatment. To optimize long-term prognosis, it is important to detect and treat all root canals during the initial treatment.

A systematic review of failed endoscopic hemostasis for nonvariceal upper gastrointestinal bleeding.

BACKGROUND: Nonvariceal upper gastrointestinal bleeding (NVUGIB) is a surgical emergency, usually managed via endoscopy. Approximately 2% of patients will have another significant bleed after therapeutic endoscopy and may require either transarterial embolization (TAE) or surgery. In 2011, the National Institute for Health and Care Excellence guidelines recommended that TAE should be the preferred option offered in this setting. METHODS: This study aimed to conduct an appraisal of guidelines on NVUGIB using the Appraisal of Guidelines for Research and Evaluation II tool. A specific review of their recommendations on the management of adult patients with failed endoscopic hemostasis that required TAE or surgery was conducted. RESULTS: The quality of the guidelines was moderate; most could be recommended with changes. However, their recommendations regarding TAE vs surgery were widely heterogeneous. A closer review of the underpinning evidence showed that most studies were retrospective, with a small sample size and missing data. CONCLUSION: Because of the heterogeneity in evidence, the decision regarding TAE vs surgery requires further research. Deciding between these modalities is primarily based on TAE availability and patient comorbidities. However, surgery should not be dismissed as a key option after failed endoscopic hemostasis.

Does acute malnutrition in young children increase the risk of treatment failure following artemisinin-based combination therapy? A WWARN individual patient data meta-analysis.

BACKGROUND: The geographical, demographic, and socioeconomic distributions of malaria and malnutrition largely overlap. It remains unknown whether malnutrition affects the efficacy of WHO-recommended artemisinin-based combination therapies (ACTs). A previous systematic review was inconclusive as data were sparse and heterogeneous, indicating that other methodological approaches, such as individual patient data meta-analysis, should be considered. The objective of this study was to conduct such a meta-analysis to assess the effect of malnutrition (wasting and stunting) on treatment outcomes in children younger than 5 years treated with an ACT for uncomplicated falciparum malaria. METHODS: We conducted a meta-analysis of individual patient data from studies identified through a systematic review of literature published between 1980 and 2018 in PubMed, Global Health, and Cochrane Libraries (PROSPERO CRD42017056934) and inspection of the WorldWide Antimalarial Resistance Network (WWARN) repository for ACT efficacy studies, including children younger than 5 years with uncomplicated falciparum malaria. The association of either acute (wasting) or chronic (stunting) malnutrition with day 42 PCR-adjusted risk of recrudescence (ie, return of the same infection) or reinfection after therapy was investigated using Cox regression, and with day 2 parasite positivity using logistic regression. FINDINGS: Data were included from all 36 studies targeted, 31 from Africa. Of 11 301 eligible children in 75 study sites, 11·5% were wasted (weight-for-height Z score [WHZ] <-2), and 31·8% were stunted (height-for-age Z score [HAZ] <-2). Decrease in WHZ was associated with increased risk of day 2 positivity (adjusted odds ratio 1·12, 95% CI 1·05-1·18 per unit; p=0·0002), treatment failure (adjusted hazard ratio [AHR] 1·14, 95% CI 1·02-1·26, p=0·016), and reinfection after therapy (AHR 1·09, 1·04-1·13, p=0·0003). Children with milder wasting (WHZ -2 to -1) also had a higher risk of recrudescence (AHR 1·85, 1·29-2·65, p=0·0008 vs WHZ ≥0). Stunting was not associated with reduced ACT efficacy. INTERPRETATION: Children younger than 5 years with acute malnutrition and presenting with uncomplicated falciparum malaria were at higher risk of delayed parasite clearance, ACT treatment failure, and reinfections. Stunting was more prevalent, but not associated with changes in ACT efficacy. Acute malnutrition is known to impact medicine absorption and metabolism. Further study to inform dose optimisation of ACTs in wasted children is urgently needed. FUNDING: Bill & Melinda Gates Foundation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Inhaled versus systemic corticosteroids for acute exacerbations of COPD: a systematic review and meta-analysis.

This meta-analysis compares the efficacy and safety of inhaled versus systemic corticosteroids for COPD exacerbations.Following a pre-registered protocol, we appraised eligible randomised controlled trials (RCTs) according to Cochrane methodology, performed random-effects meta-analyses for all outcomes prioritised in the European Respiratory Society COPD core outcome set and rated the certainty of evidence as per Grading of Recommendations Assessment, Development and Evaluation methodology.We included 20 RCTs totalling 2140 participants with moderate or severe exacerbations. All trials were at high risk of methodological bias. Low-certainty evidence did not reveal significant differences between inhaled and systemic corticosteroids for treatment failure rate (relative risk 1.75, 95% CI 0.76-4.02, n=569 participants); breathlessness (mean change: standardised mean difference (SMD) -0.11, 95% CI -0.36-0.15, n=239; post-treatment scores: SMD -0.18, 95% CI -0.41-0.05, n=293); serious adverse events (relative risk 1.47, 95% CI 0.56-3.88, n=246); or any other efficacy outcomes. Moderate-certainty evidence implied a tendency for fewer adverse events with inhaled compared to systemic corticosteroids (relative risk 0.80, 95% CI 0.64-1.0, n=480). Hyperglycaemia and oral fungal infections were observed more frequently with systemic and inhaled corticosteroids, respectively.Limited available evidence suggests potential noninferiority of inhaled to systemic corticosteroids in COPD exacerbations. Appropriately designed and powered RCTs are warranted to confirm these findings.

Explainable machine learning for early predicting treatment failure risk among patients with TB-diabetes comorbidity.

The present study aims to assess the treatment outcome of patients with diabetes and tuberculosis (TB-DM) at an early stage using machine learning (ML) based on electronic medical records (EMRs). A total of 429 patients were included at Chongqing Public Health Medical Center. The random-forest-based Boruta algorithm was employed to select the essential variables, and four models with a fivefold cross-validation scheme were used for modeling and model evaluation. Furthermore, we adopted SHapley additive explanations to interpret results from the tree-based model. 9 features out of 69 candidate features were chosen as predictors. Among these predictors, the type of resistance was the most important feature, followed by activated partial throm-boplastic time (APTT), thrombin time (TT), platelet distribution width (PDW), and prothrombin time (PT). All the models we established performed above an AUC 0.7 with good predictive performance. XGBoost, the optimal performing model, predicts the risk of treatment failure in the test set with an AUC 0.9281. This study suggests that machine learning approach (XGBoost) presented in this study identifies patients with TB-DM at higher risk of treatment failure at an early stage based on EMRs. The application of a convenient and economy EMRs based on machine learning provides new insight into TB-DM treatment strategies in low and middle-income countries.

Interaction between peripheral blood mononuclear cells and Trypanosoma cruzi-infected adipocytes: implications for treatment failure and induction of immunomodulatory mechanisms in adipose tissue.

Background/Introduction: Adipose tissue (AT) has been highlighted as a promising reservoir of infection for viruses, bacteria and parasites. Among them is Trypanosoma cruzi, which causes Chagas disease. The recommended treatment for the disease in Brazil is Benznidazole (BZ). However, its efficacy may vary according to the stage of the disease, geographical origin, age, immune background of the host and sensitivity of the strains to the drug. In this context, AT may act as an ally for the parasite survival and persistence in the host and a barrier for BZ action. Therefore, we investigated the immunomodulation of T. cruzi-infected human AT in the presence of peripheral blood mononuclear cells (PBMC) where BZ treatment was added. Methods: We performed indirect cultivation between T. cruzi-infected adipocytes, PBMC and the addition of BZ. After 72h of treatment, the supernatant was collected for cytokine, chemokine and adipokine assay. Infected adipocytes were removed to quantify T. cruzi DNA, and PBMC were removed for immunophenotyping. Results: Our findings showed elevated secretion of interleukin (IL)-6, IL-2 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in the AT+PBMC condition compared to the other controls. In contrast, there was a decrease in tumor necrosis factor (TNF) and IL-8/CXCL-8 in the groups with AT. We also found high adipsin secretion in PBMC+AT+T compared to the treated condition (PBMC+AT+T+BZ). Likewise, the expression of CD80+ and HLA-DR+ in CD14+ cells decreased in the presence of T. cruzi. Discussion: Thus, our findings indicate that AT promotes up-regulation of inflammatory products such as IL-6, IL-2, and MCP-1/CCL2. However, adipogenic inducers may have triggered the downregulation of TNF and IL-8/CXCL8 through the peroxisome proliferator agonist gamma (PPAR-g) or receptor expression. On the other hand, the administration of BZ only managed to reduce inflammation in the microenvironment by decreasing adipsin in the infected culture conditions. Therefore, given the findings, we can see that AT is an ally of the parasite in evading the host's immune response and the pharmacological action of BZ.

The effects of flow settings during high-flow nasal cannula oxygen therapy for neonates and young children.

BACKGROUND: During neonatal and paediatric high-flow nasal cannula therapy, optimising the flow setting is crucial for favourable physiological and clinical outcomes. However, considerable variability exists in clinical practice regarding initial flows and subsequent adjustments for these patients. Our review aimed to summarise the impact of various flows during high-flow nasal cannula treatment in neonates and children. METHODS: Two investigators independently searched PubMed, Embase, Web of Science, Scopus and Cochrane for in vitro and in vivo studies published in English before 30 April 2023. Studies enrolling adults (≥18 years) or those using a single flow setting were excluded. Data extraction and risk of bias assessments were performed independently by two investigators. The study protocol was prospectively registered with PROSPERO (CRD42022345419). RESULTS: 38 406 studies were identified, with 44 included. In vitro studies explored flow settings' effects on airway pressures, humidity and carbon dioxide clearance; all were flow-dependent. Observational clinical studies consistently reported that higher flows led to increased pharyngeal pressure and potentially increased intrathoracic airway pressure (especially among neonates), improved oxygenation, and reduced respiratory rate and work of breathing up to a certain threshold. Three randomised controlled trials found no significant differences in treatment failure among different flow settings. Flow impacts exhibited significant heterogeneity among different patients. CONCLUSION: Individualising flow settings in neonates and young children requires consideration of the patient's peak inspiratory flow, respiratory rate, heart rate, tolerance, work of breathing and lung aeration for optimal care.

Efficacy of migraine prophylaxis treatments for treatment-naïve patients and those with prior treatment failure: a protocol for systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Migraine headache is a significant health problem affecting patients' psychological well-being and quality of life. Several network meta-analyses (NMAs) have compared the efficacy of migraine prophylaxis medications. However, some have focused exclusively on oral medications, while others were limited to injectable medications. Moreover, none of these NMAs conducted a stratified analysis between treatment-naïve patients and those with prior treatment failure. Therefore, this systematic review and NMA will compare the efficacy among all treatments for migraine prophylaxis, stratified by the treatment status of patients (ie, treatment-naïve and previous treatment failure). METHODS AND ANALYSIS: Randomised-controlled trials that included patients with chronic or episodic migraine, assessed the efficacy of oral or injectable treatments for migraine prophylaxis and measured the outcomes as monthly migraine day, monthly headache day, migraine-related disability, health-related quality of life or adverse drug events will be eligible for inclusion in this review. Relevant studies will be searched from Medline, Scopus, the US National Institutes of Health Register, and the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) databases since inception through 15 August 2023. Risk of bias assessment will be performed using a revised tool for assessing the risk of bias in randomised trials. Two-stage NMA will be applied to compare relative treatment effects among all treatments of migraine prophylaxis. Surface under the cumulative ranking curve will be applied to estimate and rank the probability to be the best treatment. Consistency assumption will be assessed using a design-by-treatment interaction model. Publication bias will be assessed by comparison-adjusted funnel plot. All analyses will be stratified according to patients' status (ie, treatment-naïve and prior treatment failure). ETHICS AND DISSEMINATION: This study is a systematic review protocol collecting data from published literature and does not require approval from an institutional review board. Results from this systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020171843.

Endobronchial silicone spigot in prolonged air leaks: Nationwide study on outcomes and risk factors for treatment failure.

BACKGROUND: The endobronchial silicone spigot, also known as the endobronchial Watanabe spigot, is used in bronchoscopic interventions to manage prolonged pulmonary air leakage. However, the outcomes of this procedure have not been thoroughly investigated. METHODS: Using a Japanese national inpatient database from April 2014 to March 2022, we assessed the clinical characteristics and outcomes of all eligible patients who received the endobronchial spigot. We also investigated risk factors associated with treatment failure. Treatment failure was defined as in-hospital death or the need for surgery after bronchial occlusion. RESULTS: We analyzed data of 1095 patients who underwent bronchial occlusion using the endobronchial spigot. Among them, 252 patients (23.0%) died during hospitalization, and 403 patients (36.8%) experienced treatment failure. Factors associated with treatment failure included age between 85 and 94 years (odds ratio [OR] 1.83; 95% confidence intervals [CI], 1.04-3.21); male sex (OR 2.43; 95% CI, 1.44-4.11); low Barthel index score; comorbidities of interstitial pneumonia (OR 1.71; 95% CI, 1.18-2.48); antibiotics treatment (OR 1.45; 95% CI, 1.02-2.07); steroids treatment (OR 1.59; 95% CI, 1.07-2.36); and surgery prior to bronchial occlusion (OR 2.08; 95% CI, 1.29-3.35). In contrast, pleurodesis after bronchial occlusion (OR 0.49; 95% CI, 0.32-0.75), and admission to high-volume hospitals were inversely associated with treatment failure (OR 0.58; 95% CI, 0.37-0.90). CONCLUSIONS: The endobronchial Watanabe spigot could be a nonsurgical treatment option for patients with prolonged pulmonary air leaks. Our findings will help identify patients who may benefit from such bronchial interventions.

Impacts of armed conflicts on tuberculosis burden and treatment outcomes: a systematic review.

OBJECTIVES: This systematic review aimed to summarise existing literature on the impacts of armed conflicts on tuberculosis burden and treatment outcomes. DESIGN: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature Plus, Scopus, ScienceDirect, Embase and medRxiv. DATA EXTRACTION AND SYNTHESIS: Three reviewers independently screened, selected eligible studies and extracted data. A narrative review was undertaken to summarise the findings qualitatively. RESULTS: Eleven studies were included in this review, reporting on tuberculosis incidence rates, prevalence and treatment outcomes, including mortality. Overall, the impact of armed conflicts on case notifications was variable. Six studies reported overall increases in tuberculosis case notifications following the onset of conflicts, while three studies reported overall decreases in tuberculosis case notifications. Factors, including limited access to healthcare services, challenges in surveillance and laboratory confirmation, the destruction of health systems and incapacitating the healthcare workforce, contributed to a decrease in the number of notified cases. The higher tuberculosis notification in some of the studies could be attributed to the disruption of tuberculosis prevention and control programmes as well as increased socioeconomic deprivation, including malnutrition, mass migration, poor living conditions and overcrowding that are worsened during conflicts. Armed conflicts without effective interventions were associated with worse tuberculosis treatment outcomes, including lower proportions of people with treatment success and higher proportions of people with loss to follow-up, mortality and treatment failure. However, implementing various interventions in conflict settings (such as establishing a National Tuberculosis Control Programme) led to higher tuberculosis notification rates and treatment success. CONCLUSION: The impact of armed conflicts on tuberculosis notification is complex and is influenced by multiple factors. The findings of this review underscore the importance of concerted efforts to control tuberculosis in conflict settings using available resources.

Selection strategy of second-line biologic therapies in adult patients with ulcerative colitis following prior biologic treatment failure: Systematic review and meta-analysis.

BACKGROUND: Optimizing second-line biologic therapies for adult ulcerative colitis (UC) post first-line failure is essential. OBJECTIVE: Compare second-line biologic therapy efficacy in adult UC patients with prior treatment failure. METHODS: A comprehensive search of electronic databases up to May 2023 was conducted to assess second-line biologic therapy efficacy using a random effects model. Parameters analyzed included clinical remission rate, clinical response rate, mucosal healing rate, annual discontinuation rate, and colectomy rates. RESULTS: Forty-three research papers were analyzed. Clinical remission rates for second-line biologics were ranked at 6-14 weeks: Infliximab (30%) was followed by Vedolizumab (29%), Ustekinumab (27%), and Adalimumab (19%). At 52-54 weeks, the order shifted, with Vedolizumab (35%) followed by Infliximab (32%), Ustekinumab (31%), and Adalimumab (26%). The mucosal healing rate was 21%, ranked as: Infliximab (31%), Vedolizumab (21%), Adalimumab (21%), and Ustekinumab (14%). The annual discontinuation rate stood at 20%, with Adalimumab (25%), Vedolizumab (18%), Infliximab (17%), and Ustekinumab (16%). Discontinuation rates due to primary failure (PF), secondary failure (SF), and adverse events (AE) were 6%, 12%, and 3%, respectively. The annual colectomy rate was 9%, with Adalimumab (15%) followed by Vedolizumab (10%), Ustekinumab (9%), and Infliximab (5%), and colectomy rates of 10% due to PF, 12% due to SF, and 4% due to AE. CONCLUSION: For UC patients with first-line treatment failure, it is recommended to prioritize infliximab or vedolizumab as second-line biologic therapies, while avoiding adalimumab as the primary choice. Further clinical trials are necessary to assess ustekinumab efficacy accurately.

Can Decision Support Tools Improve Empiric Antibiotic Prescribing?

Decision Support Tools for Antibiotic PrescribingChoosing the right antibiotic is challenging. Unnecessarily broad-spectrum antibiotic treatment promotes antimicrobial resistance; inappropriately narrow-spectrum antibiotic use can lead to treatment failure. A cluster-randomized trial of a model-informed clinical decision support tool is proposed for guiding empiric antibiotic therapy for hospitalized patients with suspected infection.