Prognostic factors for the occurrence of post-operative shoulder stiffness after arthroscopic rotator cuff repair: a systematic review.

BACKGROUND: Post-operative shoulder stiffness (POSS) is one of the most frequent complications after arthroscopic rotator cuff repair (ARCR). Factors specifying clinical prediction models for the occurrence of POSS should rely on the literature and expert assessment. Our objective was to map prognostic factors for the occurrence of POSS in patients after an ARCR. METHODS: Longitudinal studies of ARCR reporting prognostic factors for the occurrence of POSS with an endpoint of at least 6 months were included. We systematically searched Embase, Medline, and Scopus for articles published between January 1, 2014 and February 12, 2020 and screened cited and citing literature of eligible records and identified reviews. The risk of bias of included studies and the quality of evidence were assessed using the Quality in Prognosis Studies tool and an adapted Grading of Recommendations, Assessment, Development and Evaluations framework. A database was implemented to report the results of individual studies. The review was registered on PROSPERO (CRD42020199257). RESULTS: Seven cohort studies including 23 257 patients were included after screening 5013 records. POSS prevalence ranged from 0.51 to 8.75% with an endpoint ranging from 6 to 24 months. Due to scarcity of data, no meta-analysis could be performed. Overall risk of bias and quality of evidence was deemed high and low or very low, respectively. Twenty-two potential prognostic factors were identified. Increased age and male sex emerged as protective factors against POSS. Additional factors were reported but do require further analyses to determine their prognostic value. DISCUSSION: Available evidence pointed to male sex and increased age as probable protective factors against POSS after ARCR. To establish a reliable pre-specified set of factors for clinical prediction models, our review results require complementation with an expert's opinion.

Antimicrobial Prophylaxis for Postoperative Urinary Tract Infections in Transurethral Resection of Bladder Tumors: A Systematic Review and Meta-Analysis.

PURPOSE: The administration of antimicrobial prophylaxis for postoperative urinary tract infections following transurethral resection of bladder tumors is controversial. We aimed to systematically review evidence on the potential effect of antimicrobial prophylaxis on postoperative urinary tract infections and asymptomatic bacteriuria. MATERIALS AND METHODS: We conducted a systematic search in Embase®, Medline® and the Cochrane Central Register of Controlled Trials. Randomized controlled trials and nonrandomized controlled trials assessing the effect of any form of antimicrobial prophylaxis in patients with transurethral resection of bladder tumors on postoperative urinary tract infections or asymptomatic bacteriuria were included. Risk of bias was assessed using RoB 2.0 or the Newcastle-Ottawa Scale. Fixed and random effects meta-analyses were conducted. As a potential basis for a scoping review, we exploratorily searched Medline for risk factors for urinary tract infections after transurethral resection of bladder tumors. The protocol was registered on PROSPERO (CRD42019131733). RESULTS: Of 986 screened publications, 7 studies with 1,725 participants were included; the reported effect sizes varied considerably. We found no significant effect of antimicrobial prophylaxis on urinary tract infections: the pooled odds ratio of the random effects model was 1.55 (95% CI 0.73-3.31). The random effects meta-analysis examining the effect of antimicrobial prophylaxis on asymptomatic bacteriuria showed an OR of 0.43 (0.18-1.04). Risk of bias was moderate. Our exploratory search identified 3 studies reporting age, preoperative pelvic radiation, preoperative hospital stay, duration of operation, tumor size, preoperative asymptomatic bacteriuria and pyuria as risk factors for urinary tract infections following transurethral resection of bladder tumors. CONCLUSIONS: We observed insufficient evidence supporting routine antimicrobial prophylaxis in patients undergoing transurethral resection of bladder tumors for the prevention of postoperative urinary tract infections; our findings may inform harmonization of international guidelines.

Most published meta-regression analyses based on aggregate data suffer from methodological pitfalls: a meta-epidemiological study.

BACKGROUND: Due to clinical and methodological diversity, clinical studies included in meta-analyses often differ in ways that lead to differences in treatment effects across studies. Meta-regression analysis is generally recommended to explore associations between study-level characteristics and treatment effect, however, three key pitfalls of meta-regression may lead to invalid conclusions. Our aims were to determine the frequency of these three pitfalls of meta-regression analyses, examine characteristics associated with the occurrence of these pitfalls, and explore changes between 2002 and 2012. METHODS: A meta-epidemiological study of studies including aggregate data meta-regression analysis in the years 2002 and 2012. We assessed the prevalence of meta-regression analyses with at least 1 of 3 pitfalls: ecological fallacy, overfitting, and inappropriate methods to regress treatment effects against the risk of the analysed outcome. We used logistic regression to investigate study characteristics associated with pitfalls and examined differences between 2002 and 2012. RESULTS: Our search yielded 580 studies with meta-analyses, of which 81 included meta-regression analyses with aggregated data. 57 meta-regression analyses were found to contain at least one pitfall (70%): 53 were susceptible to ecological fallacy (65%), 14 had a risk of overfitting (17%), and 5 inappropriately regressed treatment effects against the risk of the analysed outcome (6%). We found no difference in the prevalence of meta-regression analyses with methodological pitfalls between 2002 and 2012, nor any study-level characteristic that was clearly associated with the occurrence of any of the pitfalls. CONCLUSION: The majority of meta-regression analyses based on aggregate data contain methodological pitfalls that may result in misleading findings.

Quantitative Assessment of Point-of-Care 3D-Printed Patient-Specific Polyetheretherketone (PEEK) Cranial Implants.

Recent advancements in medical imaging, virtual surgical planning (VSP), and three-dimensional (3D) printing have potentially changed how today's craniomaxillofacial surgeons use patient information for customized treatments. Over the years, polyetheretherketone (PEEK) has emerged as the biomaterial of choice to reconstruct craniofacial defects. With advancements in additive manufacturing (AM) systems, prospects for the point-of-care (POC) 3D printing of PEEK patient-specific implants (PSIs) have emerged. Consequently, investigating the clinical reliability of POC-manufactured PEEK implants has become a necessary endeavor. Therefore, this paper aims to provide a quantitative assessment of POC-manufactured, 3D-printed PEEK PSIs for cranial reconstruction through characterization of the geometrical, morphological, and biomechanical aspects of the in-hospital 3D-printed PEEK cranial implants. The study results revealed that the printed customized cranial implants had high dimensional accuracy and repeatability, displaying clinically acceptable morphologic similarity concerning fit and contours continuity. From a biomechanical standpoint, it was noticed that the tested implants had variable peak load values with discrete fracture patterns and failed at a mean (SD) peak load of 798.38 ± 211.45 N. In conclusion, the results of this preclinical study are in line with cranial implant expectations; however, specific attributes have scope for further improvements.

Prognostic value of elevated lipoprotein(a) in patients with acute coronary syndromes.

BACKGROUND: Minimal lipoprotein(a) [Lp(a)] target values are advocated for high-risk cardiovascular patients. We investigated the prognostic value of Lp(a) in the acute setting of patients with acute coronary syndromes (ACS). MATERIALS AND METHODS: Plasma levels of Lp(a) were collected at time of angiography from 1711 patients hospitalized for ACS in a multicentre Swiss prospective cohort. Associations between elevated Lp(a) ≥30 mg/dL (cut-off corresponding to the 75th percentile of the assay) or Lp(a) tertiles at baseline, and major adverse cardiovascular events (MACE) at 1 year, defined as a composite of cardiac death, myocardial infarction or stroke, were assessed using hazard ratios (HR) and 95% confidence intervals (CI) adjusting for traditional cardiovascular risk factors (age, sex, smoking, diabetes, hypertension, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C] and triglycerides. RESULTS: Lp(a) levels range between 2.5 and 132 mg/dL with a median value of 6 mg/dL and a mean value of 14.2 mg/dL. A total of 276 patients (23.0%) had Lp(a) plasma levels ≥30 mg/dL. Patients with elevated Lp(a) were more likely to be of female gender and to have higher levels of total cholesterol, LDL-C, HDL-C and triglycerides. Higher Lp(a) was associated with failure to reach the LDL-C target <1.8 mmol/L at 1 year (HR 1.71, 95% CI 1.13-2.58, P = 0.01). No association was found between elevated Lp(a) and MACE at 1 year (HR 1.05, 95% CI 0.64-1.73), nor for Lp(a) tertiles (HR 0.82, 95% CI 0.52-1.28, P > 0.20) or standardized continuous variables (0.98, 95% CI 0.82-1.19 for each increase of standard deviation). CONCLUSIONS: Our real-world data suggest high Lp(a) levels at time of angiography are not predictive for cardiovascular outcomes in patients otherwise medically well controlled, but might be useful to identify patients who would not be on LDL-C targets 1 year after ACS.

Cysteine-rich angiogenic inducer 61 (Cyr61): a novel soluble biomarker of acute myocardial injury improves risk stratification after acute coronary syndromes.

AIMS: We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification. METHODS AND RESULTS: Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls. Cyr61 levels were determined in human serum using an enzyme-linked immunosorbent assay. Cohorts of ACS (n = 2168) referred for coronary angiography, stable coronary artery disease (CAD) (n = 53), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n = 15) served to identify and evaluate the diagnostic and prognostic performance of the biomarker. Cyr61 was markedly elevated in ST-elevation myocardial infarction patients compared with non-ST-elevation myocardial infarction/unstable angina or stable CAD patients, irrespective of whether coronary thrombi were present. Cyr61 was rapidly released after occlusion of a septal branch in HOCM patients undergoing transcoronary ablation of septal hypertrophy. Cyr61 improved risk stratification for all-cause mortality when added to the reference GRACE risk score at 30 days (C-statistic 0.88 to 0.89, P = 0.001) and 1 year (C-statistic 0.77 to 0.80, P < 0.001) comparable to high-sensitivity troponin T (30 days: 0.88 to 0.89, P < 0.001; 1 year: 0.77 to 0.79, P < 0.001). Similar results were obtained for the composite endpoint of all-cause mortality or myocardial infarction. Conversely, in a population-based case-control cohort (n = 362), Cyr61 was not associated with adverse outcome. CONCLUSION: Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients.

Prognosis of Patients With Familial Hypercholesterolemia After Acute Coronary Syndromes.

BACKGROUND: Patients with heterozygous familial hypercholesterolemia (FH) and coronary heart disease have high mortality rates. However, in an era of high-dose statin prescription after acute coronary syndrome (ACS), the risk of recurrent coronary and cardiovascular events associated with FH might be mitigated. We compared coronary event rates between patients with and without FH after ACS. METHODS: We studied 4534 patients with ACS enrolled in a multicenter, prospective cohort study in Switzerland between 2009 and 2013 who were individually screened for FH on the basis of clinical criteria according to 3 definitions: the American Heart Association definition, the Simon Broome definition, and the Dutch Lipid Clinic definition. We used Cox proportional models to assess the 1-year risk of first recurrent coronary events defined as coronary death or myocardial infarction and adjusted for age, sex, body mass index, smoking, hypertension, diabetes mellitus, existing cardiovascular disease, high-dose statin at discharge, attendance at cardiac rehabilitation, and the GRACE (Global Registry of Acute Coronary Events) risk score for severity of ACS. RESULTS: At the 1-year follow-up, 153 patients (3.4%) had died, including 104 (2.3%) of fatal myocardial infarction. A further 113 patients (2.5%) experienced nonfatal myocardial infarction. The prevalence of FH was 2.5% with the American Heart Association definition, 5.5% with the Simon Broome definition, and 1.6% with the Dutch Lipid Clinic definition. Compared with patients without FH, the risk of coronary event recurrence after ACS was similar in patients with FH in unadjusted analyses, although patients with FH were >10 years younger. However, after multivariable adjustment including age, the risk was greater in patients with FH than without, with an adjusted hazard ratio of 2.46 (95% confidence interval, 1.07-5.65; P=0.034) for the American Heart Association definition, 2.73 (95% confidence interval, 1.46-5.11; P=0.002) for the Simon Broome definition, and 3.53 (95% confidence interval, 1.26-9.94; P=0.017) for the Dutch Lipid Clinic definition. Depending on which clinical definition of FH was used, between 94.5% and 99.1% of patients with FH were discharged on statins and between 74.0% and 82.3% on high-dose statins. CONCLUSIONS: Patients with FH and ACS have a >2-fold adjusted risk of coronary event recurrence within the first year after discharge than patients without FH despite the widespread use of high-intensity statins.

Prognostic value of PCSK9 levels in patients with acute coronary syndromes.

AIMS: Proprotein convertase subtilisin kexin 9 (PCSK9) is an emerging target for the treatment of hypercholesterolaemia, but the clinical utility of PCSK9 levels to guide treatment is unknown. We aimed to prospectively assess the prognostic value of plasma PCSK9 levels in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Plasma PCSK9 levels were measured in 2030 ACS patients undergoing coronary angiography in a Swiss prospective cohort. At 1 year, the association between PCSK9 tertiles and all-cause death was assessed adjusting for the Global Registry of Acute Coronary Events (GRACE) variables, as well as the achievement of LDL cholesterol targets of <1.8 mmol/L. Patients with higher PCSK9 levels at angiography were more likely to have clinical familial hypercholesterolaemia (rate ratio, RR 1.21, 95% confidence interval, CI 1.09-1.53), be treated with lipid-lowering therapy (RR 1.46, 95% CI 1.30-1.63), present with longer time interval of chest pain (RR 1.29, 95% CI 1.09-1.53) and higher C-reactive protein levels (RR 1.22, 95% CI 1.16-1.30). PCSK9 increased 12-24 h after ACS (374 ± 149 vs. 323 ± 134 ng/mL, P < 0.001). At 1 year follow-up, HRs for upper vs. lower PCSK9-level tertiles were 1.13 (95% CI 0.69-1.85) for all-cause death and remained similar after adjustment for the GRACE score. Patients with higher PCSK9 levels were less likely to reach the recommended LDL cholesterol targets (RR 0.81, 95% CI 0.66-0.99). CONCLUSION: In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year.

Gait function assessed using 3D gait analysis in patients with cervical spinal myelopathy before and after surgical decompression: a systematic review and meta-analysis.

BACKGROUND: Degenerative cervical myelopathy (DCM) is the most common cause of cervical spinal cord dysfunction in adults and the result of chronic degenerative changes of the cervical spine. The compression of the spinal cord can lead to ischemia, inflammation, and neuronal apoptosis with a consequent impairment of the neurological function. Gait impairment is one of the most frequent signs of DCM. PURPOSE: To investigate the changes in spatio-temporal gait parameters assessed using 3D gait analysis in patients affected by DCM compared with healthy controls and the effect of surgical decompression on these parameters. STUDY DESIGN/SETTING: Systematic review and meta-analysis. PATIENT SAMPLE: The meta-analysis included 267 patients with DCM and 276 healthy controls. OUTCOME MEASURES: Spatio-temporal parameters of gait were assessed. The primary outcome was gait speed; the secondary outcomes were cadence, stride length, step width, stride time, single-limb support time, and double-limb support time. METHODS: Studies reporting spatial and/or temporal gait parameters measured using 3D gait analysis in patients with DCM were included. Data sources were Embase, Medline, and the Core Collection of Web of Science. Meta-analyses were performed to investigate the influence of surgical decompression in patients measured before and after surgery as well as to compare gait parameters of patients with DCM with controls. RESULTS: Thirteen studies reporting on 267 patients with DCM and 276 healthy controls met the inclusion criteria. Seven studies compared patients with DCM with healthy controls, three studies compared gait in patients with DCM before and after surgical decompression, and three studies performed both comparisons. Compared with healthy controls, patients with DCM had slower gait speed (Standardized Mean Difference (SMD), -1.49; 95% confidence interval (CI) [-1.86; -1.13]; p<.001), lower cadence (SMD, -0.78; 95%CI [-1.00; -0.56]; p<.001), shorter stride length (SMD, -1.27; 95%CI [-1.53, -1.01]; p<.001), greater step width (SMD, 0.98; 95%CI [0.42, 1.54]; p=.003), longer stride time (SMD, 0.77; 95%CI [0.37, 1.16]; p=.009), single-limb support phase (SMD, -0.68; 95%CI [-1.06; -0.29]; p=.011), and double-limb support phase (SMD 0.84; 95%CI [0.35, 1.32]; p=.012). After surgical decompression, patients with DCM showed an improvement in gait speed (SMD, 0.57 (95%CI [0.29; 0.85]; p=.003) and no significant differences in other spatio-temporal parameters. CONCLUSIONS: Patients with DCM have clearly different spatio-temporal gait parameters than healthy controls. Gait speed is the only spatio-temporal gait parameter that improves significantly after surgical decompression suggesting that gait speed may be an important clinical outcome parameter in patients with DCM.

Impact of the COVID-19 pandemic on antibiotic prescribing in high-prescribing primary care physicians in Switzerland.

OBJECTIVES: The aim of this study was to evaluate antibiotic prescribing of medium-to-high prescribing primary care physicians being followed up after the completion of a Swiss national intervention trial of antibiotic prescription audit and feedback in the first SARS-CoV-2 pandemic year. METHODS: We used health insurer based claims data to calculate monthly antibiotic prescription rates per 100 consultations (primary endpoint) and applying interrupted time series (ITS) analysis methods, we estimated the immediate (step change) and sustained effects (slope) of the SARS-CoV-2 epidemic in 2020 on antibiotic prescribing compared to the pre-pandemic trial period from 2017-2019. RESULTS: We analysed data of 2945 of 3426 physicians (86.0%) from the trial with over 4 million consultations annually, who were in 2020 still in practice. Consultations dropped by 43% during the first pandemic year compared with 2017. Median monthly antibiotic prescription rates per 100 consultations in 2017 were 8.44 (Interquartile range [IQ] 6.32-11.50) and 8.35 (6.34-11.74) in the intervention and control groups, respectively, and increased to 15.63 (10.69-23.81) and 16.31 (10.65-24.72) per 100 consultations in 2020. ITS-derived incidence rate ratios for overall antibiotic prescriptions were 2.32 (95% CI 2.07-2.59) for the immediate pandemic effect, and 0.96 (0.95-0.98) for the sustained effect (change in slope in 2020 compared with 2017-2019). DISCUSSION: The SARS-CoV-2 pandemic had a major impact on antibiotic prescription patterns in primary care in Switzerland. For future viral pandemics, intervention plans with timely activation steps to minimize unjustified antibiotic consumption in primary care should be prepared.

Improving quality of life after breast cancer: a comparison of two microsurgical treatment options for breast cancer-related lymphedema (BCRL).

PURPOSE: Vascularized lymph node transfer (VLNT) entails the autologous relocation of lymph nodes to a lymphedematous region of the body, whereas lymphaticovenous anastomosis (LVA) creates a direct bypass between the lymphatic and venous system. Both techniques are meant to lastingly bolster the local lymphatic drainage capacity. This study compared safety and effectiveness of VLNT and LVA in patients with chronic breast cancer related lymphedema (BCRL). METHODS: A retrospective cohort study was conducted using data from our encrypted database composed of patients with chronic BCRL who were treated with either VLNT or LVA and had a minimum follow-up of two years. Patient-specific variables analyzed included pre- and postoperative arm circumferences, lymphedema stages and postoperative complications. RESULTS: A total of 105 patients met the inclusion criteria, of which 96 patients demonstrated a complete follow-up period of two years. The VLNT group displayed larger preoperative circumferential measurements, evident in both in the isolated examination of the affected arm, as well as when adjusted for the contralateral unaffected arm. Significant reduction in arm volume was achieved by both groups. However, VLNT demonstrated superior relative reduction rates than LVA, neutralizing any significant arm size disparities after 24 months. Surgery duration was slightly longer for VLNT than LVA. Postoperative complications, predominantly minor, were exclusively observed in the VLNT group. CONCLUSIONS: Both VLNT and LVA offer significant improvement for patients suffering from chronic BCRL. VLNT shows an even greater potential for improvement in more severe cases of BCRL, but involves a higher risk for (mostly minor) complications.

Development and internal validation of a model predicting patient-reported shoulder function after arthroscopic rotator cuff repair in a Swiss setting.

BACKGROUND: Prediction models for outcomes after orthopedic surgery provide patients with evidence-based postoperative outcome expectations. Our objectives were (1) to identify prognostic factors associated with the postoperative shoulder function outcome (the Oxford Shoulder Score (OSS)) and (2) to develop and validate a prediction model for postoperative OSS. METHODS: Patients undergoing arthroscopic rotator cuff repair (ARCR) were prospectively documented at a Swiss orthopedic tertiary care center. The first primary ARCR in adult patients with a partial or complete rotator cuff tear were included between October 2013 and June 2021. Thirty-two potential prognostic factors were used for prediction model development. Two sets of factors identified using the knowledge from three experienced surgeons (Set 1) and Bayesian projection predictive variable selection (Set 2) were compared in terms of model performance using R squared and root-mean-squared error (RMSE) across 45 multiple imputed data sets using chained equations and complete case data. RESULTS: Multiple imputation using data from 1510 patients was performed. Set 2 retained the following factors: American Society of Anesthesiologists (ASA) classification, baseline level of depression and anxiety, baseline OSS, operation duration, tear severity, and biceps status and treatment. Apparent model performance was R-squared = 0.174 and RMSE = 7.514, dropping to R-squared = 0.156, and RMSE = 7.603 after correction for optimism. CONCLUSION: A prediction model for patients undergoing ARCR was developed using solely baseline and operative data in order to provide patients and surgeons with individualized expectations for postoperative shoulder function outcomes. Yet, model performance should be improved before being used in clinical routine.

Doublecortin and Glypican-2 concentrations in the cerebrospinal fluid from infants are developmentally downregulated.

OBJECTIVE: Doublecortin (DCX) and glypican-2 (GPC2) are neurodevelopmental proteins involved in the differentiation of neural stem/progenitor cells (NSPCs) to neurons, and are developmentally downregulated in neurons after birth. In this study, we investigated whether the concentrations of DCX and GPC2 in the cerebrospinal fluid (CSF) from human pediatric patients reflect this developmental process or are associated with cerebral damage or inflammatory markers. METHODS: CSF was collected from pediatric patients requiring neurosurgical treatment. The concentrations of DCX, GPC2, neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IFN-γ, and TNF-⍺) were measured using immunoassays. RESULTS: From March 2013 until October 2018, 63 CSF samples were collected from 38 pediatric patients (20 females; 17 patients with repeated measurements); the median term born-adjusted age was 3.27 years [Q1: 0.31, Q3: 7.72]. The median concentration of DCX was 329 pg/ml [Q1: 192.5, Q3: 1179.6] and that of GPC2 was 26 pg/ml [Q1: 13.25, Q3: 149.25]. DCX and GPC2 concentrations independently significantly associated with age, and their concentration declined with advancing age, reaching undetectable levels at 0.3 years for DCX, and plateauing at 1.5 years for GPC2. Both DCX and GPC2 associated with hydrocephalus, NSE, IL-1ß, IL-2, IL-8, IL-13. No relationship was found between sex, acute infection, S100B, IL-4, IL-6, IL-10, IFN-γ, TNF-α and DCX or GPC2, respectively. CONCLUSIONS: Concentrations of DCX and GPC2 in the CSF from pediatric patients are developmentally downregulated, with the highest concentrations measured at the earliest adjusted age, and reflect a neurodevelopmental stage rather than a particular disease state.

Prognostic factors for improvement of shoulder function after arthroscopic rotator cuff repair: a systematic review.

Background: The identification of factors that specify prognostic models for postoperative results should be based on the best scientific evidence and expert assessment. We aimed to identify, map, and evaluate potential prognostic factors for the improvement of shoulder function in patients undergoing arthroscopic rotator cuff repair. Methods: Longitudinal primary studies of arthroscopic rotator cuff repair reporting any multivariable factor analyses for shoulder function improvement with an endpoint assessment of at least 6 months were included. We systematically searched EMBASE, Medline, and Scopus for articles published between January 2014 and June 2021. The risk of bias of included studies and the quality of evidence were assessed using the Quality in Prognosis Studies tool and an adapted Grading of Recommendations, Assessment, Development, and Evaluations framework. Results: Overall, 24 studies including 73 outcome analyses were included. We classified younger age and smaller tear size as probably prognostic for a greater improvement in objective outcomes. Shorter symptom duration, absence of a worker compensation claim, low preoperative level of functional status, and high preoperative pain level were classified as probably prognostic for greater improvement in patient-reported outcome measures. The quality of the synthesized evidence was low. Twenty-one studies had an overall high risk of bias. Conclusion: Six potential prognostic factors for shoulder function after arthroscopic rotator cuff repair were identified. Along with ongoing expert opinion assessments, they will feed into a prognostic model-building process.

Effect of Antibiotic Prescription Audit and Feedback on Antibiotic Prescribing in Primary Care: A Randomized Clinical Trial.

Importance: Antibiotics are commonly prescribed in primary care, increasing the risk of antimicrobial resistance in the population. Objective: To investigate the effect of quarterly audit and feedback on antibiotic prescribing among primary care physicians in Switzerland with medium to high antibiotic prescription rates. Design, Setting, and Participants: This pragmatic randomized clinical trial was conducted from January 1, 2018, to December 31, 2019, among 3426 registered primary care physicians and pediatricians in single or small practices in Switzerland who were among the top 75% prescribers of antibiotics. Intention-to-treat analysis was performed using analysis of covariance models and conducted from September 1, 2021, to January 31, 2022. Interventions: Primary care physicians were randomized in a 1:1 fashion to undergo quarterly antibiotic prescribing audit and feedback with peer benchmarking vs no intervention for 2 years, with 2017 used as the baseline year. Anonymized patient-level claims data from 3 health insurers serving roughly 50% of insurees in Switzerland were used for audit and feedback. The intervention group also received evidence-based guidelines for respiratory tract and urinary tract infection management and community antibiotic resistance information. Physicians in the intervention group were blinded regarding the nature of the trial, and physicians in the control group were not informed of the trial. Main Outcomes and Measures: The claims data used for audit and feedback were analyzed to assess outcomes. Primary outcome was the antibiotic prescribing rate per 100 consultations during the second year of the intervention. Secondary end points included overall antibiotic use in the first year and over 2 years, use of quinolones and oral cephalosporins, all-cause hospitalizations, and antibiotic use in 3 age groups. Results: A total of 3426 physicians were randomized to the intervention (n = 1713) and control groups (n = 1713) serving 629 825 and 622 344 patients, respectively, with a total of 4 790 525 consultations in the baseline year of 2017. In the entire cohort, a 4.2% (95% CI, 3.9%-4.6%) relative increase in the antibiotic prescribing rate was noted during the second year of the intervention compared with 2017. In the intervention group, the median annual antibiotic prescribing rate per 100 consultations was 8.2 (IQR, 6.1-11.4) in the second year of the intervention and was 8.4 (IQR, 6.0-11.8) in the control group. Relative to the overall increase, a -0.1% (95% CI, -1.2% to 1.0%) lower antibiotic prescribing rate per 100 consultations was found in the intervention group compared with the control group. No relevant reductions in specific antibiotic prescribing rates were noted between groups except for quinolones in the second year of the intervention (-0.9% [95% CI, -1.5% to -0.4%]). Conclusions and Relevance: This randomized clinical trial found that quarterly personalized antibiotic prescribing audit and feedback with peer benchmarking did not reduce antibiotic prescribing among primary care physicians in Switzerland with medium to high antibiotic prescription rates. Trial Registration: ClinicalTrials.gov Identifier: NCT03379194.

The role of muscle degeneration and spinal balance in the pathophysiology of lumbar spinal stenosis: Study protocol of a translational approach combining in vivo biomechanical experiments with clinical and radiological parameters.

OBJECTIVE: To describe a study protocol for investigating the functional association between posture, spinal balance, ambulatory biomechanics, paraspinal muscle fatigue, paraspinal muscle quality and symptoms in patients with symptomatic lumbar spinal stenosis (sLSS) before and 1-year after elective surgical intervention. DESIGN: Single-centre prospective, experimental, multimodal (clinical, biomechanical, radiological) study with three instances of data collection: baseline (study visit 1), 6-month follow-up (remote) and 1-year follow-up (study visit 2). Both study visits include an in vivo experiment aiming to elicit paraspinal muscle fatigue for postural assessment in a non-fatigued and fatigued state. EXPERIMENTAL PROTOCOL: At baseline and 1-year follow-up, 122 patients with sLSS will be assessed clinically, perform the back-performance scale assessment and complete several patient-reported outcome measure (PROMs) questionnaires regarding overall health, disease-related symptoms and kinesiophobia. Posture and biomechanical parameters (joint kinematics, kinetics, surface electromyography, back curvature) will be recorded using an optoelectronic system and retroreflective markers during different tasks including overground walking and movement assessments before and after a modified Biering-Sørensen test, used to elicit paraspinal muscle fatigue. Measurements of muscle size and quality and the severity of spinal stenosis will be obtained using magnetic resonance imaging (MRI) and sagittal postural alignment data from EOS radiographies. After each study visit, physical activity level will be assessed during 9 days using a wrist-worn activity monitor. In addition, physical activity level and PROMs will be assessed remotely at 6-month follow-up. CONCLUSION: The multimodal set of data obtained using the study protocol described in this paper will help to expand our current knowledge on the pathophysiology, biomechanics, and treatment outcome of degenerative sLSS. The results of this study may contribute to defining and/or altering patient treatment norms, surgery indication criteria and post-surgery rehabilitation schedules. TRIAL REGISTRATION: The protocol was approved by the regional ethics committee and has been registered at clinicaltrials.gov (NCT05523388).

Impact of Very Small Aneurysm Size and Anterior Communicating Segment Location on Outcome after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Very small anterior communicating artery aneurysms (vsACoA) of <5 mm in size are detected in a considerable number of patients with aneurysmal subarachnoid hemorrhage (aSAH). Single-center studies report that vsACoA harbor particular risks when treated. OBJECTIVE: To assess the clinical and radiological outcome(s) of patients with aSAH diagnosed with vsACoA after aneurysm treatment and at discharge. METHODS: Information on n = 1868 patients was collected in the Swiss Subarachnoid Hemorrhage Outcome Study registry between 2009 and 2014. The presence of a new focal neurological deficit at discharge, functional status (modified Rankin scale), mortality rates, and procedural complications (in-hospital rebleeding and presence of a new stroke on computed tomography) was assessed for vsACoA and compared with the results observed for aneurysms in other locations and with diameters of 5 to 25 mm. RESULTS: This study analyzed n = 1258 patients with aSAH, n = 439 of which had a documented ruptured ACoA. ACoA location was found in 38% (n = 144/384) of all very small ruptured aneurysms. A higher in-hospital bleeding rate was found in vsACoA compared with non-ACoA locations (2.8 vs 2.1%), especially when endovascularly treated (2.1% vs 0.5%). In multivariate analysis, aneurysm size of 5 to 25 mm, and not ACoA location, was an independent risk factor for a new focal neurological deficit and a higher modified Rankin scale at discharge. Neither very small aneurysm size nor ACoA location was associated with higher mortality rates at discharge or the occurrence of a peri-interventional stroke. CONCLUSION: Very small ruptured ACoA have a higher in-hospital rebleeding rate but are not associated with worse morbidity or mortality.

Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials.

BACKGROUND: Interpretation of the evidence from randomised controlled trials (RCTs) of remdesivir in patients treated in hospital for COVID-19 is conflicting. We aimed to assess the benefits and harms of remdesivir compared with placebo or usual care in these patients, and whether treatment effects differed between prespecified patient subgroups. METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane COVID-19 trial registry, ClinicalTrials.gov, the International Clinical Trials Registry Platform, and preprint servers from Jan 1, 2020, until April 11, 2022, for RCTs of remdesivir in adult patients hospitalised with COVID-19, and contacted the authors of eligible trials to request individual patient data. The primary outcome was all-cause mortality at day 28 after randomisation. We used multivariable hierarchical regression-adjusting for respiratory support, age, and enrollment period-to investigate effect modifiers. This study was registered with PROSPERO, CRD42021257134. FINDINGS: Our search identified 857 records, yielding nine RCTs eligible for inclusion. Of these nine eligible RCTs, individual data were provided for eight, covering 10 480 patients hospitalised with COVID-19 (99% of such patients included in such RCTs worldwide) recruited between Feb 6, 2020, and April 1, 2021. Within 28 days of randomisation, 662 (12·5%) of 5317 patients assigned to remdesivir and 706 (14·1%) of 5005 patients assigned to no remdesivir died (adjusted odds ratio [aOR] 0·88, 95% CI 0·78-1·00, p=0·045). We found evidence for a credible subgroup effect according to respiratory support at baseline (pinteraction=0·019). Of patients who were ventilated-including those who received high-flow oxygen-253 (30·0%) of 844 patients assigned to remdesivir died compared with 241 (28·5%) of 846 patients assigned to no remdesivir (aOR 1·10 [0·88-1·38]; low-certainty evidence). Of patients who received no oxygen or low-flow oxygen, 409 (9·1%) of 4473 patients assigned to remdesivir died compared with 465 (11·2%) of 4159 patients assigned to no remdesivir (0·80 [0·70-0·93]; high-certainty evidence). No credible subgroup effect was found for time to start of remdesivir after symptom onset, age, presence of comorbidities, enrolment period, or corticosteroid use. Remdesivir did not increase the frequency of severe or serious adverse events. INTERPRETATION: This individual patient data meta-analysis showed that remdesivir reduced mortality in patients hospitalised with COVID-19 who required no or conventional oxygen support, but was underpowered to evaluate patients who were ventilated when receiving remdesivir. The effect size of remdesivir in patients with more respiratory support or acquired immunity and the cost-effectiveness of remdesivir remain to be further elucidated. FUNDING: EU-RESPONSE.

Load-Induced Glenohumeral Translation After Rotator Cuff Tears: Protocol for an In Vivo Study.

BACKGROUND: Rotator cuff tears are a common shoulder injury, but they sometimes remain undiagnosed, as symptoms can be limited. Altered shoulder biomechanics can lead to secondary damage and degeneration. In biomechanical analyses, the shoulder (ie, the glenohumeral joint) is normally idealized as a ball-and-socket joint, even though a translation is often observed clinically. To date, no conclusive changes in glenohumeral translation have been reported in patients with rotator cuff tears, and it is unknown how an additional handheld weight that is comparable to those used during daily activities will affect glenohumeral translations in patients with rotator cuff tears. OBJECTIVE: This study aims to assess the load-induced glenohumeral translation (liTr) in patients with rotator cuff tears and its association with the load-induced changes in muscle activation (liMA). METHODS: Patients and asymptomatic controls will be recruited. Participants will fill out health questionnaires and perform 30° arm abduction and adduction trials, during which they will hold different handheld weights of a maximum of 4 kg while motion capture and electromyographic data are collected. In addition, fluoroscopic images of the shoulders will be taken for the same movements. Isometric shoulder muscle strength for abduction and rotation will be assessed with a dynamometer. Finally, shoulder magnetic resonance images will be acquired to assess muscle status and injury presence. The dose-response relationship between additional weight, liTr, and liMA will be evaluated. RESULTS: Recruitment and data collection began in May 2021, and they will last until the recruitment target is achieved. Data collection is expected to be completed by the end of 2022. As of November 2022, data processing and analysis are in progress, and the first results are expected to be submitted for publication in 2023. CONCLUSIONS: This study will aid our understanding of biological variations in liTr, the influence of disease pathology on liTr, the potential compensation of rotator cuff tears by muscle activation and size, and the association between liTr and patient outcomes. The outcomes will be relevant for diagnosis, treatment, and rehabilitation planning in patients with rotator cuff tears. TRIAL REGISTRATION: ClinicalTrials.gov NCT04819724; https://clinicaltrials.gov/ct2/show/NCT04819724. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43769.