International trends in shoulder replacement: a meta-analysis from 11 public joint registers.

BACKGROUND AND PURPOSE: International variation exists in the types of shoulder replacement used for treatment of specific diseases. Implant choice continues to evolve without high-quality evidence. Our aim was to evaluate trends in incidence rates of shoulder replacement and assess any recent changes in practice between countries by using registry data. METHODS: Patient characteristics, indication and year of surgery, type of replacement, and collection methods of patient-reported outcomes (PROMs) was extracted from 11 public joint registries. Meta-analyses examined use of reverse total shoulder replacement (RTSR) for osteoarthritis, cuff tear arthropathy, and acute fracture; use of anatomical total shoulder replacement (TSR) for osteoarthritis; and use of humeral hemiarthroplasty for fracture. RESULTS: The annual growth rate of shoulder replacements performed is 6-15% (2011-2019). The use of RTSR has almost doubled (93%). RTSR is now universally performed for cuff tear arthropathy (97.3%, 95% confidence interval [CI] 96.0-98.1). Its use for avascular necrosis, trauma, and inflammatory arthropathy is increasing. The use of RTSR was similar (43.1%, CI 30.0-57.2) versus TSR (44.7%, CI 31.1-59.1) for osteoarthritis. The types of PROMs used, collection time points, and response rates lack standardization. COVID-19 had a varying inter-registry impact on incidence rates. CONCLUSION: The incidence of shoulder replacements has grown. Use of RTSR has increased for all disease indications despite limited high-quality evidence driving this change in indications outside of cuff arthropathy. Consequently, less variation is observed in international practice. Existing differences now relate to use of newer implant types and methodology of PROMs collection, which prevents international comparison and outcome analysis.

Viremia as a predictor of absence of serious bacterial infection in children with fever without source.

Most children with fever without source (FWS) require diagnostic laboratory tests to exclude a serious bacterial infection (SBI), often followed by admission and empirical antibiotics. As febrile children with a viral infection are less likely to have a SBI, identifying patients with systemic viral infection could contribute to exclude SBI. We evaluated whether the presence of virus in the blood could be used as a biomarker to rule out SBI. Children < 3 years old with FWS were prospectively enrolled and had real-time (reverse-transcription) PCR performed on the blood for adenovirus, enterovirus, parechovirus, and HHV6. 20/135 patients had SBI, and in 47/135, at least one virus was detected in the blood. Viremia had a higher sensitivity and negative predictive value (90% and 96%) to rule out SBI compared to CRP (65% and 93%) and PCT (55% and 90%). The odds ratio (OR) for the presence of SBI among non-viremic patients was 5.8 (p = 0.0225), compared to 5.5 for CRP ≥ 40 mg/l (p = 0.0009) and 3.7 for PCT ≥ 0.5 ng/mL (0.0093). This remained significant after adjusting for CRP and PCT (OR 5.6 and 5.9, respectively; p = 0.03 for both). Area under the ROC curve for CRP and PCT were 0.754 and 0.779, respectively, but increased to 0.803 and 0.832, respectively, when combined with viremia. CONCLUSION: The presence of viremia had a better performance than commonly used biomarkers to rule-out SBI and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS. Larger studies should evaluate the role of point-of-care testing of viruses by (revere-transcription) PCR in the plasma in management algorithms of children with FWS. WHAT IS KNOWN: • Most children with FWS have a viral infection, but up to 15% have a SBI; most require laboratory tests, and many admission and empirical antibiotics. • Children with a viral infection are less likely to have a SBI. WHAT IS NEW: • Children with a systemic viral infection are less likely to have an SBI. • Viremia is a better predictor of absence of SBI than commonly used biomarkers and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS.

Diffusion-magnetic resonance imaging predicts decline of kidney function in chronic kidney disease and in patients with a kidney allograft.

Kidney cortical interstitial fibrosis is highly predictive of kidney prognosis and is currently assessed by evaluation of a biopsy. Diffusion-weighted magnetic resonance imaging is a promising non-invasive tool to evaluate kidney fibrosis. We recently adapted diffusion-weighted imaging sequence for discrimination between the kidney cortex and medulla and found that the cortico-medullary difference in apparent diffusion coefficient (ΔADC) correlated with histological interstitial fibrosis. Here, we assessed whether ΔADC as measured with diffusion-weighted magnetic resonance imaging is predictive of kidney function decline and dialysis initiation in chronic kidney disease (CKD) and patients with a kidney allograft in a prospective study encompassing 197 patients. We measured ΔADC in 43 patients with CKD (estimated GFR (eGFR) 55ml/min/1.73m2) and 154 patients with a kidney allograft (eGFR 53ml/min/1.73m2). Patients underwent a kidney biopsy and diffusion-weighted magnetic resonance imaging within one week of biopsy; median follow-up of 2.2 years with measured laboratory parameters. The primary outcome was a rapid decline of kidney function (eGFR decline over 30% or dialysis initiation) during follow up. Significantly, patients with a negative ΔADC had 5.4 times more risk of rapid decline of kidney function or dialysis (95% confidence interval: 2.29-12.58). After correction for kidney function at baseline and proteinuria, low ADC still predicted significant kidney function loss with a hazard ratio of 4.62 (95% confidence interval 1.56-13.67) independent of baseline age, sex, eGFR and proteinuria. Thus, low ΔADC can be a predictor of kidney function decline and dialysis initiation in patients with native kidney disease or kidney allograft, independent of baseline kidney function and proteinuria.

Impact of ischemia time on islet isolation success and posttransplantation outcomes: A retrospective study of 452 pancreas isolations.

Many variables impact islet isolation, including pancreas ischemia time. The ischemia time upper limit that should be respected to avoid a negative impact on the isolation outcome is not well defined. We have performed a retrospective analysis of all islet isolations in our center between 2008 and 2018. Total ischemia time, cold ischemia time, and organ removal time were analyzed. Isolation success was defined as an islet yield ≥200 000 IEQ. Of the 452 pancreases included, 288 (64%) were successfully isolated. Probability of isolation success showed a significant decrease after 8 hours of total ischemia time, 7 hours of cold ischemia time, and 80 minutes of organ removal time. Although we observed an impact of ischemia time on islet yield, a probability of isolation success of 50% was still present even when total ischemia time exceeds 12 hours. Posttransplantation clinical outcomes were assessed in 32 recipients and no significant difference was found regardless of ischemia time. These data indicate that although shorter ischemia times are associated with better islet isolation outcomes, total ischemia time >12 hours can provide excellent results in appropriately selected donors.

Predicting recurrence of hepatocellular carcinoma after liver transplantation using a novel model that incorporates tumor and donor-related factors.

Evidence suggests that liver graft quality impacts on posttransplant recurrence of hepatocellular carcinoma (HCC). As of today, selection criteria only use variables related to tumor characteristics. Within the Scientific Registry of Transplant Recipients, we identified patients with HCC who underwent liver transplantation between 2004 and 2016 (development cohort, n = 10 887). Based on tumor recurrence rates, we fitted a competing-risk regression incorporating tumor- and donor-related factors, and we developed a prognostic score. Results were validated both internally and externally in the Australia and New Zealand Liver Transplant Registry. Total tumor diameter (subhazard ratio [sub-HR] 1.52 [1.28-1.81]), alpha-feto protein (sub-HR 1.27 [1.23-1.32], recipient male gender (sub-HR 1.43 [1.18-1.74]), elevated donor body mass index (sub-HR 1.26 [1.01-1.58]), and shared graft allocation policy (sub-HR 1.20 [1.01-1.43]) were independently associated with tumor recurrence. We next developed the Darlica score (sub-HR 2.72 [2.41-3.08] P < 0.001) that allows identifying risky combinations between a given donor and a given recipient. Results were validated internally (n = 3 629) and externally in the Australia and New Zealand Liver Transplant Registry (n = 370). The current score is based on variables that are readily available at the time of graft offer. It allows identifying hazardous donor-recipient combinations in terms of risk of tumor recurrence and overall survival.

Prevalence of Metastatic Lateral Lymph Nodes in Asian Patients with Lateral Lymph Node Dissection for Rectal Cancer: A Meta-analysis.

IMPORTANCE: Rectal cancers occupy the eighth position worldwide for new cases and deaths for both men and women. These cancers have a high tendency to form metastases in the mesorectum but also in the lateral lymph nodes. The therapeutic approach for the involved lateral lymph nodes remains controversial. OBJECTIVE: We performed a systematic review and meta-analysis to assess the prevalence of metastatic lateral lymph nodes in patients with lateral lymph node dissection (LLND) for rectal cancer, which seems to be a fundamental and necessary criterion to discuss any possible indications for LLND. METHODS: Data sources-study selection-data extraction and synthesis-main outcome and measures. We searched MEDLINE, EMBASE and COCHRANE from November 1, 2018, to November 19, 2018, for studies reporting the presence of metastatic lateral lymph nodes (iliac, obturator and middle sacral nodes) among patients undergoing rectal surgery with LLND. Pooled prevalence values were obtained by random effects models, and the robustness was tested by leave-one-out sensitivity analyses. Heterogeneity was assessed using the Q-test, quantified based on the I2 value and explored by subgroup analyses. RESULTS: Our final analysis included 31 studies from Asian countries, comprising 7599 patients. The pooled prevalence of metastatic lateral lymph nodes was 17.3% (95% CI: 14.6-20.5). The inter-study variability (heterogeneity) was high (I2 = 89%). The pooled prevalence was, however, robust and varied between 16.6% and 17.9% according to leave-one-out sensitivity analysis. The pooled prevalence of metastatic lymph nodes was not significantly different when pooling only studies including patients who received neoadjuvant treatment or those without neoadjuvant treatment (p = 0.44). Meta-regression showed that the pooled prevalence was associated with the sample size of studies (p < 0.05), as the prevalence decreased when the sample size increased. CONCLUSION: The pooled prevalence of metastatic lateral lymph nodes was 17.3% among patients who underwent rectal surgery with LLND in Asian countries. Further studies are necessary to determine whether this finding could impact the therapeutic strategy (total mesorectal excision with LLND versus total mesorectal excision with neoadjuvant radiochemotherapy).

International variation in distribution of ASA class in patients undergoing total hip arthroplasty and its influence on mortality: data from an international consortium of arthroplasty registries.

Background and purpose - A challenge comparing outcomes from total hip arthroplasty between countries is variation in preoperative characteristics, particularly comorbidity. Therefore, we investigated between-country variation in comorbidity in patients based on ASA class distribution, and determined any variation of ASA class to mortality risk between countries.Patients and methods - All arthroplasty registries collecting ASA class and mortality data in patients with elective primary THAs performed 2012-2016 were identified. Survival analyses of the influence of ASA class on 1-year mortality were performed by individual registries, followed by meta-analysis of aggregated data.Results - 6 national registries and 1 US healthcare organization registry with 418,916 THAs were included. There was substantial variation in the proportion of ASA class III/IV, ranging from 14% in the Netherlands to 39% in Finland. Overall, 1-year mortality was 0.93% (95% CI 0.87-1.01) and increased from 0.2% in ASA class I to 8.9% in class IV. The association between ASA class and mortality measured by hazard ratios (HR) was strong in all registries even after adjustment for age and sex, which reduced them by half in all registries. Combined adjusted HRs were 2.0, 6.1, and 22 for ASA class II-IV vs. I, respectively. Associations were moderately heterogeneous across registries.Interpretation - We observed large variation in ASA class distribution between registries, possibly explained by differences in background morbidity and/or international variation in access to surgery. The similar, strong mortality trends by ASA class between countries enhance the relevance of its use as an indicator of comorbidity in international registry studies.

Validation of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for kidney fibrosis detection: a cross-sectional study.

BACKGROUND: Kidney cortical interstitial fibrosis (IF) is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion magnetic resonance imaging (MRI) is a promising tool to evaluate kidney fibrosis via the apparent diffusion coefficient (ADC), but suffers from inter-individual variability. We recently applied a novel MRI protocol to allow calculation of the corticomedullary ADC difference (ΔADC). We here present the validation of ΔADC for fibrosis assessment in a cohort of 164 patients undergoing biopsy and compare it with estimated glomerular filtration rate (eGFR) and other plasmatic parameters for the detection of fibrosis. METHODS: This monocentric cross-sectional study included 164 patients undergoing renal biopsy at the Nephrology Department of the University Hospital of Geneva between October 2014 and May 2018. Patients underwent diffusion-weighted imaging, and T1 and T2 mappings, within 1 week after biopsy. MRI results were compared with gold standard histology for fibrosis assessment. RESULTS: Absolute cortical ADC or cortical T1 values correlated poorly to IF assessed by the biopsy, whereas ΔADC was highly correlated to IF (r=-0.52, P < 0.001) and eGFR (r = 0.37, P < 0.01), in both native and allograft patients. ΔT1 displayed a lower, but significant, correlation to IF and eGFR, whereas T2 did not correlate to IF nor to eGFR. ΔADC, ΔT1 and eGFR were independently associated with kidney fibrosis, and their combination allowed detection of extensive fibrosis with good specificity. CONCLUSION: ΔADC is better correlated to IF than absolute cortical or medullary ADC values. ΔADC, ΔT1 and eGFR are independently associated to IF and allow the identification of patients with extensive IF.

Mapping of aetiologies of gastroenteritis: a systematic review and meta-analysis of pathogens identified using a multiplex screening array.

OBJECTIVE: Emergence of molecular methods to screen stools could provide a more complete picture of pathogens causing gastroenteritis, allowing to adequately treat patients whenever required but, so far, no aggregate data have been released. Our objective was to report pathogens identified in patients suffering from gastroenteritis using a multiplex molecular array. DESIGN: Medline and Embase were searched for original publications reporting pathogens identified with FilmArray GI panel in patients suffering from gastroenteritis. Proportions of pathogens were extracted and pooled using a model with random effects. RESULTS: Fourteen studies (17,815 patients) were included in the analysis. Among the 7,071 patients (39.7%) with positive FilmArray, identified pathogens were EPEC (27.5%), Clostridium difficile (19.3%), Norovirus (15.1%), EAEC (15%), Campylobacter spp (11.8%), Salmonella spp (8.1%), ETEC (7.3%), Rotavirus (7.3%), Sapovirus (7.1%), STEC (5.2%), Shigella/EIEC (4.9%), Giardia lamblia (4%), Adenovirus (3.8%), Cryptosporidium spp (3.8%), Astrovirus (2.8%), Yersinia enterocolitica (1.7%), Escherichia coli O157 (1.1%), Plesiomonas shigelloides (1.1%), Cyclospora cayetanensis (0.7%), Vibrio spp (0.5%), Vibrio cholerae (0.3%) and Entamoeba histolytica (0.3%). When considering only studies with control group (microbiological examination of the stools performed by other methods), FilmArray identified at least one pathogen in 48.2% of patients versus 16.7% when using comparative diagnostic methods. CONCLUSIONS: FilmArray GI panel was positive in 39.7% of patients suffering from gastroenteritis. This proportion has to be mitigated by the carriage rates of identified organisms. Ultimately, restricted ordering of molecular panels to those patients who might benefit from specific treatment could provide medical value by swift identification of the pathogen and more targeted therapy.

Microbiologically documented infections after adult allogeneic hematopoietic cell transplantation: A 5-year analysis within the Swiss Transplant Cohort study.

BACKGROUND: Infections are an important complication after allogeneic hematopoietic cell transplantation (allo-HCT). The present study aimed at determining the landscape of infections occurring in a large cohort of allo-HCT patients, as well as associated risk factors for infections and for one-year non-relapse mortality. METHODS: This is a retrospective cohort study using STCS and EBMT databases to assess the one-year incidence rate of infection, as well as risk factors for infections and for one-year non-relapse mortality among adult allo-HCT patients transplanted between 2010 and 2014 in Switzerland. Univariable and multivariable quasi-Poisson and multivariable Cox regression models were used. RESULTS: Of 553 patients included, 486 had an infection with a global incidence rate of 3.66 infections per patient-year. Among a total of 1534 infections analyzed, viral infections were predominant (n = 1138, 74.2%), followed by bacterial (n = 343, 22.4%) and fungal (n = 53, 3.5%) infections. At one year, the cumulative incidence of relapse and non-relapse mortality was 26% and 16%, respectively. 195 (35.3%) of patients had at least one episode of severe graft-versus-host-disease (GvHD). A center effect was observed, and underlying disease, donor type, cytomegalovirus serological constellation, and GvHD were also associated with the incidence rate of infections. There was an increased risk for one-year non-relapse mortality associated with all pathogens, specifically within two months of infection, and this remained true beyond 2 months of a fungal infection. CONCLUSION: Despite advances to limit infections in this population, they still occur in most allo-HCT patients with a major impact on survival at 1 year.

Variables of interest to predict glomerular filtration rate in preterm newborns in the first days of life.

BACKGROUND: Measurement of neonatal renal function is challenging, and accurate, easy-to-use markers to estimate glomerular filtration rate (eGFR) are lacking. This study aimed to evaluate principal determinants of GFR in neonates and develop a predictive equation. METHODS: GFR was measured, using single injection inulin clearance, at median day 3 of life in 48 newborns. Associations of clearance with height, gestational age, weight, creatinine, and cystatin C were explored and a multivariable model to estimate GFR developed. We also evaluated preexisting GFR equations (Schwartz, Zappitelli, combined Zappitelli). RESULTS: Forty-four clearances were measured, 36 very preterm neonates (28-32 weeks); 5 extremely preterm (< 28 weeks), and 3 term newborns. No patient presented acute renal insufficiency. Median inulin clearance in preterm infants was 18.83 ml/min/1.73 m2 (IQ 15.29; 24.99). Inulin clearance correlated with weight (ρ 0.74), gestational age (ρ 0.72), height (ρ 0.49), and creatinine (ρ - 0.42), but not cystatin C. In the multivariable model, predicted GFR equation was 2.32* (weight (g))0.64/(creatinine (mcmol/l))0.62. Mean error in predicting clearance was - 0.8 ml/min/1.73 m2 (- 3.0-1.4) ranging from - 14.9 to 13.3 ml/min/1.73 m2. Mean prediction error with Zappitelli and combined Zappitelli equations were 28.5 ml/min/1.73 m2 (95% CI 24.6-32.3) and 28.3 ml/min/1.73 m2 (95% CI 24.9-31.7), respectively, and 2 ml/min/1.73 m2 (95% CI - 0.6-4.6) for Schwartz equation. CONCLUSIONS: Weight and gestational age are crucial determinants of GFR in neonates. The Zappitelli models were not validated in our population. Our predictive model and Schwartz models performed better. Our model should be evaluated in another preterm population, particularly in those presenting renal insufficiency.

Overall and subgroup specific performance of the pediatric index of mortality 2 score in Switzerland: a national multicenter study.

Pediatric Index of Mortality (PIM) 2 score is used in pediatric intensive care unit (PICU) to predict the patients' risk of death. The performance of this model has never been assessed in Switzerland. The aim of this study was to evaluate the performance of the PIM2 score in the whole cohort and in pre-specified diagnostic subgroups of patients admitted to PICUs in Switzerland. All children younger than 16 years admitted to any PICU in Switzerland between January 1, 2012 and December 31, 2017 were included in the study. A total of 22,382 patients were analyzed. Observed mortality was 2%, whereas mortality predicted by PIM2 was 4.2% (SMR = 0.47, 95% CI, 0.42-0.52). Calibration was also poor across the deciles of mortality risks (p < 0.001). The AUC-ROC for the entire cohort was 0.88 (95% CI, 0.87-0.90). Calibration varied significantly according to primary diagnosis.Conclusion: The performance of the PIM 2 score in a cohort of Swiss patients is poor with adequate discrimination and poor calibration. The PIM 2 score tends to under predict the number of deaths among septic patients and in patients admitted after a cardiorespiratory arrest. What is Known: •PIM2 score is a widely used mortality prediction model in PICU. •PIM2 performance among uncommon but clinically relevant diagnostic subgroups of patients is unknown. •The performance of PIM2 score has never been assessed in Switzerland. What is New: •The performance of the PIM 2 score in a cohort of Swiss patients is poor with adequate discrimination and poor calibration. •Calibration varies significantly according to primary diagnosis. The PIM 2 score under predict the number of deaths among septic patients and in patients admitted after a cardiorespiratory arrest.

Patient satisfaction and survey response in 717 hospital surveys in Switzerland: a cross-sectional study.

BACKGROUND: The association between patient satisfaction and survey response is only partly understood. In this study, we describe the association between average satisfaction and survey response rate across hospital surveys, and model the association between satisfaction and propensity to respond for individual patients. METHODS: Secondary analysis of patient responses (166'014 respondents) and of average satisfaction scores and response rates obtained in 717 annual patient satisfaction surveys conducted between 2011 and 2015 at 164 Swiss hospitals. The satisfaction score was the average of 5 items scored between 0 and 10. The association between satisfaction and response propensity in individuals was modeled as the function that predicted best the observed response rates across surveys. RESULTS: Among the 717 surveys, response rates ranged from 16.1 to 80.0% (pooled average 49.8%), and average satisfaction scores ranged from 8.36 to 9.79 (pooled mean 9.15). At the survey level, the mean satisfaction score and response rate were correlated (r = 0.61). This correlation held for all subgroups of surveys, except for the 5 large university hospitals. The estimated individual response propensity function was "J-shaped": the probability of responding was lowest (around 20%) for satisfaction scores between 3 and 7, increased sharply to about 70% for those maximally satisfied, and increased slightly for the least satisfied. Average satisfaction scores projected for 100% participation were lower than observed average scores. CONCLUSIONS: The most satisfied patients were the most likely to participate in a post-hospitalization satisfaction survey. This tendency produces an upward bias in observed satisfaction scores, and a positive correlation between average satisfaction and response rate across surveys.

Usefulness of a systematic approach at listing for vaccine prevention in solid organ transplant candidates.

Solid organ transplant (SOT) candidates may not be immune against potentially vaccine-preventable diseases because of insufficient immunizations and/or limited vaccine responses. We evaluated the impact on vaccine immunity at transplant of a systematic vaccinology workup at listing that included (1) pneumococcal with and without influenza immunization, (2) serology-based vaccine recommendations against measles, varicella, hepatitis B virus, hepatitis A virus, and tetanus, and (3) the documentation of vaccines and serology tests in a national electronic immunization registry (www.myvaccines.ch). Among 219 SOT candidates assessed between January 2014 and November 2015, 54 patients were transplanted during the study. Between listing and transplant, catch-up immunizations increased the patients' immunity from 70% to 87% (hepatitis A virus, P = .008), from 22% to 41% (hepatitis B virus, P = .008), from 77% to 91% (tetanus, P = .03), and from 78% to 98% (Streptococcus pneumoniae, P = .002). Their immunity at transplant was significantly higher against S. pneumoniae (P = .006) and slightly higher against hepatitis A virus (P = .07), but not against hepatitis B virus, than that of 65 SOT recipients transplanted in 2013. This demonstrates the value of a systematic multimodal serology-based approach of immunizations of SOT candidates at listing and the need for optimized strategies to increase their hepatitis B virus vaccine responses.

Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

BACKGROUND: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. METHODS: We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. RESULTS: No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. CONCLUSIONS: In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.).

Risk of Colorectal Cancer in Patients With Acute Diverticulitis: A Systematic Review and Meta-analysis of Observational Studies.

BACKGROUND & AIMS: We performed a systematic review and meta-analysis to assess the prevalence of colorectal cancer in patients with acute diverticulitis. METHODS: We searched MEDLINE from inception through November 2nd, 2017 for studies reporting the prevalence of colorectal cancer in patients with diverticulitis, identified based on the protocol CRD42017083272. This systematic review was conducted in accordance to the MOOSE guidelines. Pooled prevalence values were obtained by random effects models and robustness was tested by leave-one out sensitivity analyses. Heterogeneity was assessed using the Q-test and quantified based on I2 value. The critical appraisal of included studies was performed using the Newcastle-Ottawa scale. RESULTS: Our final analysis included 31 studies, comprising 50,445 patients. The pooled prevalence of colorectal cancer was 1.9% (95% CI, 1.5%-2.3%). Patients with complicated diverticulitis had a significantly higher risk for colorectal cancer (prevalence, 7.9%; 95% CI, 3.9%-15.3%) than patients with uncomplicated diverticulitis (prevalence, 1.3%; 95% CI, 0.1%-2%), corresponding to a pooled prevalence ratio of 6.7 (95% CI, 2.5-18.3). Subgroup analyses did not find significant difference in prevalence when separately pooling studies according to ranking on the Newcastle-Ottawa scale, geographical location or length of follow-up. Meta-regression did not find any association between age and colorectal cancer. Among patients who underwent endoscopy, the pooled prevalence of polyps was 22.7% (95% CI, 19.6%-26.0%), of advanced adenomas was 4.4% (95% CI, 3.4%-5.8%), of adenomas was 14.2% (95% CI, 11.7%-17.1%), and of hyperplastic polyps was 9.2% (95% CI, 7.6%-11.2%). CONCLUSION: In a meta-analysis of observational studies of patients with acute diverticulitis, we found the pooled prevalence of colorectal cancer to be 1.9%. The risk of colorectal cancer was significantly higher in patients with complicated diverticulitis than in patients with uncomplicated diverticulitis.

Cost-effectiveness evaluation of HPV self-testing offered to non-attendees in cervical cancer screening in Switzerland.

OBJECTIVE: About 30% of women who are eligible for cervical cancer (CC) screening remain un-screened or under-screened in Switzerland. HPV testing on self-collected vaginal samples (Self-HPV) has shown to be more sensitive than cytology while also reaching non-attendees. The objective of this study was to explore the cost-effectiveness of offering Self-HPV to non-attendees in Switzerland. METHODS: A recursive decision-tree with one-year cycles was used to model the life-long natural HPV history. Markov cohort simulations were used to assess the expected outcomes from the model. The outcomes of three strategies were compared with the absence of screening: Self-HPV and triage with colposcopy (Self-HPV/colpo), Self-HPV and triage with Pap cytology (Self-HPV/PAP), cytological screening and triage with HPV (PAP/HPV). Sensitivity analyses for the key parameters of the model were conducted to check the robustness of findings. RESULTS: Offering a Self-HPV screening to non-attendees could prevent 90% of CC and 94% of CC-related deaths in the study population. The current cytology-based program could reduce by 83% the number of CC cases and by 88% the number of CC-related deaths over the population's lifetime. Compared to the absence of screening, incremental cost-effectiveness ratios (ICER) were estimated to be, per saved Quality Adjusted Life Year (QALY), 12413US$ for the strategy Self-HPV/colpo, 11138US$ for the strategy Self-HPV/Pap and 22488US$ for the strategy PAP/HPV. CONCLUSIONS: Offering Self-HPV as a CC screening strategy to non-attendees in Switzerland is a cost-effective solution that is associated with a reduction of CC cases and related deaths. Self-HPV is more cost-effective than the currently used cytology-based screening.

Work overload is related to increased risk of error during chemotherapy preparation.

PURPOSE: Chemotherapy preparation units face peaks in activity leading to high workloads and increased stress. The present study evaluated the impact of work overloads on the safety and accuracy of manual preparations. METHOD: Simulating overwork, operators were asked to produce increasing numbers of syringes (8, 16, and 24), with markers (phenylephrine or lidocaine), within 1 h, in an isolator, under aseptic conditions. Results were analyzed using qualitative and quantitative criteria. Concentration deviations of < 5%, 5%-10%, 10%-30%, and >30% from the expected concentration were considered as accurate, weakly accurate, inaccurate, and wrong concentrations, respectively. RESULTS: Twenty-one pharmacy technicians and pharmacists carried out 63 preparation sessions (n = 1007 syringes). A statistically significant decrease in the manufacturing time for one syringe was observed when workload increased (p < 0.0001). Thirty-nine preparation errors were recorded: 30 wrong concentrations (deviation > 30%), 6 mislabeling, 2 wrong diluents, and 1 wrong drug. There was no statistically significant difference in the mean concentration accuracy of final preparations across the three workloads. The overall error rate increased with the number of preparations made in 1 h: 1.8% for 8 preparations, 2.7% for 16 preparations, and 5.4% for 24 preparations (p < 0.05). CONCLUSION: Although pharmacy technicians and pharmacists were able to increase production speeds with no effect on mean concentration accuracy under stressful conditions, there were greater probability errors being made. These results should encourage actions to spread workloads out over the day to avoid peaks in activity.

The impact of a transversus abdominis plane block including clonidine vs. intrathecal morphine on nausea and vomiting after caesarean section: A randomised controlled trial.

BACKGROUND: Intrathecal morphine (ITM) is a widely used technique for postcaesarean section analgesia but entails a high risk of postoperative nausea and vomiting (PONV). The transversus abdominis plane (TAP) block is an alternative. OBJECTIVE: We tested the hypothesis that a TAP block including clonidine reduces the incidence of PONV after caesarean section when compared with ITM. DESIGN: A randomised, controlled, double-blinded study. SETTING: Geneva University Hospitals, Switzerland, from October 2013 to February 2017. PATIENTS: A total of 182 patients undergoing elective caesarean section were studied. Reasons for noninclusion were complicated pregnancy, contraindication to spinal anaesthesia or TAP block, extreme weight or height, allergy to any medication or previous median abdominal incision. INTERVENTIONS: Patients were allocated randomly to one of two groups (quadruple blinded): 100 µg of morphine added to the spinal local anaesthetic or a bilateral TAP block with 20 ml of ropivacaine 0.375% + 75 µg of clonidine on each side. MAIN OUTCOME MEASURES: The primary outcome measure was the total number of patients presenting with PONV at 24 h. Secondary aims were to compare other adverse effects (pruritus, respiratory depression, hypotension, bradycardia, sedation), analgesic efficacy and the quality of postoperative recovery. RESULTS: At 24 h, there was no significant difference between ITM and TAP groups in the total number of patients presenting with PONV: 17/92 patients (18.5%, 95% confidence interval 11.1 to 27.9) and 27/88 patients (30.7%, 95% confidence interval 21.3 to 41.4) in TAP and ITM groups, respectively (P = 0.065). Pain scores at 6 h and cumulative morphine consumption at 24 h were lower in the ITM group (P < 0.0001 for morphine consumption at 24 h). The incidence of hypotension was higher in the TAP group (54.3 vs. 29.2%, P = 0.0006). Maternal satisfaction was high and not different between groups. CONCLUSION: A TAP block with clonidine and local anaesthetic does not reduce significantly the incidence of PONV compared with ITM. We confirm the superiority of ITM on acute postcaesarean section analgesia compared with a TAP block, even with clonidine as an adjunct. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01931215.

ASA class is associated with early revision and reoperation after total hip arthroplasty: an analysis of the Geneva and Swedish Hip Arthroplasty Registries.

Background and purpose - Data from several joint replacement registries suggest that the rate of early revision surgery after primary total hip arthroplasty (THA) is increasing. The ASA class, now widely recorded in arthroplasty registries, may predict early revision. We investigated the influence of ASA class on the risk of revision and other reoperation within 3 months and within 5 years of primary THA. Patients and methods - We used data from the Geneva and Swedish Hip Arthroplasty Registries, on primary elective THAs performed in 1996-2016 and 2008-2016, respectively. 5,319 and 122,241 THAs were included, respectively. Outcomes were all-cause revision and other reoperations evaluated using Kaplan-Meier survival and Cox regression analyses. Results - Within 3 months after surgery, higher ASA class was associated with greater risk of revision and other reoperation. 3-month cumulative incidences of revision by ASA class I, II, and III-IV respectively, were 0.6%, 0.7%, and 2.3% in Geneva and 0.5%, 0.8%, and 1.6% in Sweden. 3-month cumulative incidences of other reoperation were 0.4%, 0.7%, and 0.9% in Geneva and 0.2%, 0.4%, and 0.7% in Sweden. Adjusted hazard ratios (ASA III-IV vs. I) for revision within 3 months were 2.7 (95% CI 1.2-5.9) in Geneva and 3.3 (CI 2.6-4.0) in Sweden. Interpretation - Assessment of ASA class of patients prior to THA will facilitate risk stratification. Targeted risk-reduction strategies may be appropriate during the very early postoperative period for patients identified as at higher risk. Systematically recording ASA class in arthroplasty registries will permit risk adjustment and facilitate comparison of revision rates internationally.