Investigating the influence of long-axial versus short-axial field of view PET/CT on stage migration in lymphoma and non-small cell lung cancer.

OBJECTIVES: The objective of this study was to evaluate the influence of a long-axial field-of-view (LAFOV) on stage migration using a large single-centre retrospective cohort in lymphoma and non-small cell lung cancer (NSCLC). METHODS: A retrospective study is performed for patients undergoing PET/computed tomography (CT) on either a short-axial field-of-view (SAFOV) or LAFOV PET/CT system for the staging of known or suspected NSCLC or for therapeutic response in lymphoma. The primary endpoint was the Deauville therapy response score for patients with lymphoma for the two systems. Secondary endpoints were the American Joint Committee on Cancer stage for NSCLC, the frequency of cN3 and cM1 findings, the probability for a positive nodal staging (cN1-3) for NSCLC and the diagnostic accuracy for nodal staging in NSCLC. RESULTS: One thousand two hundred eighteen records were screened and 597 patients were included for analysis ( N  = 367 for lymphoma and N  = 291 for NSCLC). For lymphoma, no significant differences were found in the proportion of patients with complete metabolic response versus non-complete metabolic response Deauville response scores ( P  = 0.66). For NSCLC no significant differences were observed between the two scanners for the frequency of cN3 and cM1 findings, for positive nodal staging, neither the sensitivity nor the specificity. CONCLUSIONS: In this study use of a LAFOV system was neither associated with upstaging in lymphoma nor NSCLC compared to a digital SAFOV system. Diagnostic accuracy was comparable between the two systems in NSCLC despite shorter acquisition times for LAFOV.

Accuracy of screening tests for cervical pre-cancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia.

Introduction: To provide evidence to improve cervical screening for women living with HIV (WLHIV), we assessed the accuracy of screening tests that can be used in low-resource settings and give results at the same visit. Methods: We conducted a paired, prospective study among consecutive eligible WLHIV, aged 18-65 years, receiving cervical cancer screening at one hospital in Lusaka, Zambia. The histopathological reference standard was multiple biopsies taken at two time points. The target condition was high-grade cervical intraepithelial neoplasia (CIN2+). The index tests were high-risk human papillomavirus detection (hrHPV, Xpert HPV, Cepheid), portable colposcopy (Gynocular, Gynius), and visual inspection with acetic acid (VIA). Accuracy of stand-alone and test combinations were calculated as the point estimate with 95% confidence intervals. A sensitivity analysis considered disease when only visible lesions were biopsied. Results: Among 371 participants with histopathological results, 27% (101/371) women had CIN2+ and 23% (23/101) was not detected by any index test. Sensitivity and specificity for stand-alone tests were: hrHPV, 67.3% (95% CI: 57.7-75.7) and 65.3% (59.4-70.7); Gynocular 51.5% (41.9-61.0) and 80.0% (74.8-84.3); and VIA 22.8% (15.7-31.9) and 92.6% (88.8-95.2), respectively. The combination of hrHPV testing followed by Gynocular had the best balance of sensitivity (42.6% [33.4-52.3]) and specificity (89.6% [85.3-92.7]). All test accuracies improved in sensitivity analysis. Conclusion: The low accuracy of screening tests assessed might be explained by our reference standard, which reduced verification and misclassification biases. Better screening strategies for WLHIV in low-resource settings are urgently needed. Registration number: The trial was registered prospectively at ClinicalTrials.gov (ref: NCT03931083 ). The study protocol has been previously published, and the statistical analysis plan can be accessed on ClinicalTrials.gov . Key messages: What is already known on this topic: The 2021 World Health Organization guidelines recommend that women living with HIV (WLHIV) receive screening for high risk human papillomavirus high-risk human papillomavirus (hrHPV) genotypes at three- to five-year intervals, followed by a triage test to determine whether treatment is needed but this is based on low and moderate certainty evidence.What this study adds: This study among WLHIV in Lusaka, Zambia evaluated three screening tests that allow same-day treatment; hrHPV test, portable colposcopy (Gynocular), and visual inspection with acetic acid (VIA), using strict methods to reduce verification and misclassification biases. The test accuracy of the different screening was poor, with sensitivities and specificity for stand-alone tests: hrHPV, 67.3% and 65.3%; Gynocular 51.5% and 80.0%; and VIA 22.8% and 92.6%; respectively.How this study might affect research, practice or policy: Our findings have implications for research and cervical cancer screening policies among WLHIV if test-accuracy in this high-risk population has been overestimated from a majority of exsisting studies that are affected by verification and misclassification biases. Methodologically robust studies are crucial to inform cervical cancer screening practices and policies for the successful implementation of a cervical cancer elimination plan in sub-Saharan Africa, where 85% of women with cervical cancer and HIV live.

Optimising prescribing in older adults with multimorbidity and polypharmacy in primary care (OPTICA): cluster randomised clinical trial.

OBJECTIVE: To study the effects of a primary care medication review intervention centred around an electronic clinical decision support system (eCDSS) on appropriateness of medication and the number of prescribing omissions in older adults with multimorbidity and polypharmacy compared with a discussion about medication in line with usual care. DESIGN: Cluster randomised clinical trial. SETTING: Swiss primary care, between December 2018 and February 2021. PARTICIPANTS: Eligible patients were ≥65 years of age with three or more chronic conditions and five or more long term medications. INTERVENTION: The intervention to optimise pharmacotherapy centred around an eCDSS was conducted by general practitioners, followed by shared decision making between general practitioners and patients, and was compared with a discussion about medication in line with usual care between patients and general practitioners. MAIN OUTCOME MEASURES: Primary outcomes were improvement in the Medication Appropriateness Index (MAI) and the Assessment of Underutilisation (AOU) at 12 months. Secondary outcomes included number of medications, falls, fractures, and quality of life. RESULTS: In 43 general practitioner clusters, 323 patients were recruited (median age 77 (interquartile range 73-83) years; 45% (n=146) women). Twenty one general practitioners with 160 patients were assigned to the intervention group and 22 general practitioners with 163 patients to the control group. On average, one recommendation to stop or start a medication was reported to be implemented per patient. At 12 months, the results of the intention-to-treat analysis of the improvement in appropriateness of medication (odds ratio 1.05, 95% confidence interval 0.59 to 1.87) and the number of prescribing omissions (0.90, 0.41 to 1.96) were inconclusive. The same was the case for the per protocol analysis. No clear evidence was found for a difference in safety outcomes at the 12 month follow-up, but fewer safety events were reported in the intervention group than in the control group at six and 12 months. CONCLUSIONS: In this randomised trial of general practitioners and older adults, the results were inconclusive as to whether the medication review intervention centred around the use of an eCDSS led to an improvement in appropriateness of medication or a reduction in prescribing omissions at 12 months compared with a discussion about medication in line with usual care. Nevertheless, the intervention could be safely delivered without causing any harm to patients. TRIAL REGISTRATION: NCT03724539Clinicaltrials.gov NCT03724539.

Thrombophilia and outcomes of venous thromboembolism in older patients.

Background: Limited data exist on thrombophilic risk factors and clinical outcomes in the elderly with venous thromboembolism (VTE). Objectives: To describe the prevalence of laboratory thrombophilic risk factors and their association with VTE recurrence or death in a cohort of elderly people with VTE. Methods: In 240 patients aged ≥65 years with acute VTE without active cancer or an indication for extended anticoagulation, we performed laboratory thrombophilia testing 1 year after the index VTE. Recurrence or death was assessed during the 2-year follow-up. Results: A total of 78% of patients had ≥1 laboratory thrombophilic risk factor(s). Elevated levels of von Willebrand factor, homocysteine, coagulant activity of factor VIII (FVIII:C), fibrinogen, FIX:C, and low antithrombin activity were the most prevalent risk factors (43%, 30%, 15%, 14%, 13%, and 11%, respectively). Additionally, 16.2% of patients experienced VTE recurrence and 5.8% of patients died. Patients with a von Willebrand factor of >182%, FVIII:C level >200%, homocysteine level >15µmol/L, or lupus anticoagulant had a significantly higher rate of recurrence than those without these risk factors (15.0 vs. 6.1 [P = .006], 23.5 vs. 8.2 [P = .01], 17.0 vs. 6.8 [P = .006], and 89.5 vs. 9.2 [P = .02] events per 100 patient-years, respectively). Furthermore, patients with a high fibrinogen level or hyperhomocysteinemia with a homocysteine level ≥30 µmol/L had significantly higher mortality than patients with normal levels (18.5 vs. 2.8 [P = .049] and 13.6 vs. 2 [P = .002] deaths per 100 patient-years, respectively). After adjustments for relevant confounders, these associations remained unchanged. Conclusion: Laboratory thrombophilic risk factors are common in elderly people with VTE and allow for the identification of a population at the risk of worse clinical outcomes.

External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection.

BACKGROUND & AIMS: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection. METHODS: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves. RESULTS: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10-17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03-3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61-1.25), and the pooled c-index was 0.77 (range 0.73-0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals. CONCLUSIONS: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. IMPACT AND IMPLICATIONS: Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. These results indicate that PAGE-B is a simple and valid risk prediction tool to determine the need for HCC screening among people living with HIV and HBV.

Incidence and clinical impact of bleeding events in older patients with acute venous thromboembolism.

Older patients anticoagulated for venous thromboembolism (VTE) have an increased risk of bleeding compared with younger patients. Little is known about the clinical impact of anticoagulation-related bleeding in this growing patient group. To prospectively assess the incidence, clinical impact, and predictors of bleeding in older patients anticoagulated for VTE, we analyzed 981 patients aged ≥65 years with acute VTE in a prospective multicenter cohort. Eight-eight percent were anticoagulated with vitamin K antagonists. Outcomes were the occurrence of major bleeding (MB) or clinically relevant nonmajor bleeding (CRNMB) event during the initial anticoagulation period up to 36 months. We described the incidence and clinical impact of bleeding and examined the association between risk factors and time to a first bleeding using competing risk regression; 100 MB and 125 CRNMB events occurred during follow-up. The incidence of MB and CRNMB was 8.5 (95% confidence interval [CI], 7.0-10.4) and 13.4 events (95% CI, 11.4-15.7) per 100 patient-years, respectively. In patients with MB, 79% required hospitalization, 18% required surgical intervention, and 19% required permanent discontinuation of anticoagulation; 15% of MB were intracranial and 6% were fatal. After adjustment, active cancer (subhazard ratio [SHR], 1.81; 95% CI, 1.12-2.93) and low physical activity (SHR, 1.88; 95% CI, 1.19-2.98) were associated with MB and high risk of falls with CRNMB (SHR, 2.04; 95% CI, 1.39-3.00). Older patients anticoagulated for VTE had a high incidence of MB and CRNMB, and these bleeding episodes caused a great burden of disease. Physicians should carefully weigh the risks/benefits of extended anticoagulation in the older population with VTE.

VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial.

BACKGROUND: Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap. METHODS: In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness - breathiness - hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported. DISCUSSION: To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506.

Profit-Influencing Factors in Orthopedic Surgery: An Analysis of Costs and Reimbursements.

The aging population and the associated demand for orthopedic surgeries are increasing health costs. Although the Diagnostic Related Groups (DRG) system was introduced to offer incentives for hospitals, concerns remain that reimbursements for older and frail patients do not cover all hospital expenses. We investigated further: (1) Does age influence net financial results in orthopedic surgery? (2) Are there patient or surgical factors that influence results? This retrospective, monocentric study compares costs and reimbursements for orthopedic patients in a tertiary care hospital in Switzerland between 2015 and 2017. The data of 1230 patients were analyzed. Overall, the net results for the hospital were positive, despite 19.5% of patients being treated at a loss. We did not find any correlation between age and profitability (p = 0.61). Patient-related factors associated with financial losses were female sex (p < 0.001) and diabetes (p = 0.013). Patients free of serious comorbidities (p = 0.012) or with a higher cost weight (p < 0.001) were more often profitable. A longer length of stay was associated with higher losses (p < 0.001). This is the first study to address the Swiss DRG reimbursement system in a broad orthopedic population, while also analyzing specific patient and surgical factors. Overall, the reimbursement system is fair, but could better account for certain interventions.

Efficacy of topical progesterone versus topical clobetasol propionate in patients with vulvar Lichen sclerosus - A double-blind randomized phase II pilot study.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin disease that mostly affects the anogenital region of women and lowers patients' quality of life. Current standard treatment of LS is topical steroids. OBJECTIVE: To evaluate the efficacy of topical progesterone 8% ointment and compare to standard therapy with topical clobetasol propionate 0.05% in premenopausal women presenting with previously untreated early onset LS. STUDY DESIGN: Randomized, double-blind, 2-arm, single center superiority trial in premenopausal women with histologically confirmed vulvar LS who were randomized in a 1:1 ratio to receive clobetasol propionate 0.05% ointment or progesterone 8% ointment. The primary outcome was the clinical severity LS score after 12 weeks, which consists of six clinical features assessed by the physician. Secondary outcomes were the symptom severity LS score, which consists of three symptoms rated by the patient, the Short Form SF-12 physical and mental health scores, and adverse events. Response to medication was assessed by biopsy at the end of the treatment to evaluate inflammatory parameters. RESULTS: Overall, 105 women were screened, 102 underwent vulvar biopsy and 37 received a histologically confirmed diagnosis of LS and were randomized: 17 to progesterone and 20 to clobetasol propionate. At 12 weeks, the mean clinical LS scores improved from 4.6 (SD 2.0) to 4.5 (SD 1.7) in the progesterone arm, and from 4.6 (SD 2.8) to 2.9 (SD 2.2) in the clobetasol propionate arm (difference in favor of clobetasol 1.61; 95% CI 0.44 to 2.77, p = 0.009), and the mean symptom severity LS scores improved from 4.5 (SD 3.8) to 3.1 (SD 3.0) in the progesterone arm, and from 4.7 (SD 2.8) to 1.9 (SD 1.8) in the clobetasol propionate arm (difference in favor of clobetasol 1.32; 95% CI -0.25 to 2.89, p = 0.095). LS was in complete remission in 6 out of 10 patients (60%) with available biopsy in the progesterone arm, and in 13 out of 16 patients (81.3%) in the clobetasol propionate arm (odds ratio in favor of clobetasol 0.35; 95% CI 0.06 to 2.06, p = 0.234). No drug-related serious adverse event occurred during the trial. CONCLUSIONS: Topical progesterone 8% ointment is inferior to standard therapy with topical clobetasol propionate 0.05% in previously untreated premenopausal women with vulvar LS after 12 weeks treatment.

Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: a systematic review and meta-analysis of 1342 patients.

BACKGROUND: Immune responses on SARS-CoV-2 vaccination in patients receiving anti-CD20 therapies are impaired but vary considerably. We conducted a systematic review and meta-analysis of the literature on SARS-CoV-2 vaccine induced humoral and cell-mediated immune response in patients previously treated with anti-CD20 antibodies. METHODS: We searched PubMed, Embase, Medrxiv and SSRN using variations of search terms 'anti-CD20', 'vaccine' and 'COVID' and included original studies up to 21 August 2021. We excluded studies with missing data on humoral or cell-mediated immune response, unspecified methodology of response testing, unspecified timeframes between vaccination and blood sampling or low number of participants (≤3). We excluded individual patients with prior COVID-19 or incomplete vaccine courses. Primary endpoints were humoral and cell-mediated immune response rates. Subgroup analyses included time since anti-CD20 therapy, B cell depletion and indication for anti-CD20 therapy. We used random-effects models of proportions. FINDINGS: Ninety studies were assessed. Inclusion criteria were met by 23 studies comprising 1342 patients. Overall rate of humoral response was 0.40 (95% CI 0.35 to 0.47). Overall rate of cell-mediated immune responses was 0.71 (95% CI 0.57 to 0.87). A time interval >6 months since last anti-CD20 therapy was associated with higher humoral response rates with 0.63 (95% CI 0.53 to 0.72) versus <6 months 0.2 (95% CI 0.03 to 0.43); p=0<01. Similarly, patients with circulating B cells more frequently showed humoral responses. Anti-CD20-treated kidney transplant recipients showed lower humoral response rates than patients with haematological malignancies or autoimmune disease. INTERPRETATION: Patients on anti-CD20 therapies can develop humoral and cell-mediated immune responses after SARS-CoV-2 vaccination, but subgroups such as kidney transplant recipients or those with very recent therapy and depleted B cell are at high risk for non-seroconversion and should be individually assessed for personalised SARS-CoV-2 vaccination strategies. Potential limitations are small patient numbers and heterogeneity of studies included. FUNDING: This study was funded by Bern University Hospital.

Sex Impacts Disease Activity But Not Symptoms or Quality of Life in Adults With Eosinophilic Esophagitis.

BACKGROUND: Eosinophilic esophagitis has a strong male predominance that appears at least partially due to genetic susceptibility. However, data regarding sex-related differences in patients with EoE are scarce. METHODS: We analyzed prospectively collected data from adults enrolled into the Swiss Eosinophilic Esophagitis Cohort Study. Patients with and without dilation in the past 12 months completed patient-reported Eosinophilic Esophagitis Activity Index (EEsAI) and EoE-specific quality of life in adults (EoE-QoL-A) and underwent endoscopy with biopsies. We used linear regression with EEsAI or EoE-QoL-A as the outcome, eosinophils per high power field, rings and strictures, current therapy use, and disease duration as predictors. RESULTS: A total of 266 patients (77% male, median age at diagnosis 35.8 years, median disease duration 10.4 years) were seen during 408 visits. Men had a longer diagnostic delay (62 months vs 36 months; P = .022), higher endoscopic disease activity (median endoscopic reference score 3.0 [interquartile range, 1.0-6.0] vs 2.0 [interquartile range, 0.0-4.0]; P = .010), more microabscesses (25% vs 13%; P = .025), and more often fibrosis of the lamina propria (mild/moderate 74.7% vs 61.5%, severe 9.1% vs 5.8%; P = .047) than women. When adjusting for objective measures of disease activity, disease duration, and current therapy use, we did not observe differences in EEsAI or EoE-QoL-A between women and men. CONCLUSIONS: Male EoE patients had higher endoscopic and histologic disease activity than female patients. When adjusting for biologic activity and therapy use, we did not identify differences in symptom severity or EoE-QoL between male and female eosinophilic esophagitis patients.

Readmissions after elective orthopedic surgery in a comprehensive co-management care system-a retrospective analysis.

BACKGROUND: No surgical intervention is without risk. Readmissions and reoperations after elective orthopedic surgery are common and are also stressful for the patient. It has been shown that a comprehensive ortho-medical co-management model decreases readmission rates in older patients suffering from hip fracture; but it is still unclear if this also applies to elective orthopedic surgery. The aim of the current study was to determine the proportion of unplanned readmissions or returns to operating room (for any reason) across a broad elective orthopedic population within 90 days after elective surgery. All cases took place in a tertiary care center using co-management care and were also assessed for risk factors leading to readmission or unplanned return to operating room (UROR). METHODS: In this observational study, 1295 patients undergoing elective orthopedic surgery between 2015 and 2017 at a tertiary care center in Switzerland were investigated. The proportion of reoperations and readmissions within 90 days was measured, and possible risk factors for reoperation or readmission were identified using logistic regression. RESULTS: In our cohort, 3.2% (42 of 1295 patients) had an UROR or readmission. Sixteen patients were readmitted without requiring further surgery-nine of which due to medical and seven to surgical reasons. Patient-related factors associated with UROR and readmission were older age (67 vs. 60 years; p = 0.014), and American Society of Anesthesiologists physical status (ASA PS) score ≥ 3 (43% vs. 18%; p < 0.001). Surgery-related factors were: implantation of foreign material (62% vs. 33%; p < 0.001), duration of operation (76 min. vs. 60 min; p < 0.001), and spine surgery (57% vs. 17%; p < 0.001). Notably, only spine surgery was also found to be independent risk factor. CONCLUSION: Rates of UROR during initial hospitalization and readmission were lower in the current study than described in the literature. However, several comorbidities and surgery-related risk factors were found to be associated with these events. Although no surgery is without risk, known threats should be reduced and every effort undertaken to minimize complications in high-risk populations. Further prospective controlled research is needed to investigate the potential benefits of a co-management model in elective orthopedic surgery.

Blood Omega-3 Fatty Acids Are Inversely Associated With Albumin-Creatinine Ratio in Young and Healthy Adults (The Omega-Kid Study).

Background: Omega-3 fatty acids are associated with a lower risk of cardiovascular disease (CVD) and with beneficial effects on CV risk factors. The albumin-creatinine ratio (ACR) is a risk factor for CVD, all-cause mortality and accelerated glomerular filtration rate (GFR) decline in the general population. We aimed to investigate the association between n-3 PUFAS and ACR in heathy individuals with preserved GFR. Design and Methods: The present cross-sectional analysis is part of the GAPP study, a population-based cohort of healthy adults aged 25-41 years. Individuals with known CVD, diabetes, or a BMI >35 kg/m2 were excluded. eGFR was calculated according to the combined Creatinine/Cystatin C CKD-EPI formula. ACR was obtained from a fasting morning urine sample. The Omega-3 Index (relative amount of EPA and DHA of total fatty acids in %) was obtained from whole blood aliquots. Results: Overall, 2001 participants (median age 37 years IQR 31; 40, 53% female) were included in this analysis. Median Omega-3 Index was 4.59 (IQR 4.06; 5.25) and median eGFR 111 ml/min/1.73 m2 (IQR 103; 118). Median ACR was 0.14 mg/mmol (IQR 0; 0.43). We found a significant inverse association of the Omega-3 Index with ACR (ratio 0.84, 95%CI 0.73-0.96; p = 0.011) which remained after comprehensive adjustment (ratio 0.86, 95%CI 0.74-1.00; p = 0.048). No association of the Omega-3 Index with eGFR was found. The adjusted difference in eGFR per 1-unit increase in Omega3-Index was -0.21 (95%CI -0.76; 0.35; p = 0.47). Conclusions: A higher Omega-3 Index was significantly associated with lower ACR in this young and healthy population with preserved eGFR. Omega-3 fatty acids may exhibit cardio- and nephroprotective effects in healthy individuals through modulation of ACR.

Prolonged antibiotic prophylaxis use in elective orthopaedic surgery - a cross-sectional analysis.

PURPOSE: Surgical antibiotic prophylaxis (SAP) prevents surgical site infections (SSI). In orthopaedic surgery, the use of prolonged SAP (PSAP) has been reported in daily routine, despite guidelines advising against it. Therefore, we asked: What is the proportion of PSAP use, defined as administration of SAP ≥24 h after elective orthopaedic surgery? Are there patient- and surgery-related predictors of PSAP use? METHODS: This cross-sectional analysis investigated 1292 patients who underwent elective orthopaedic surgery including total joint arthroplasties at one Swiss centre between 2015 and 2017. Patient comorbidities, surgical characteristics and occurrence of SSI at 90 days in PSAP group were compared to the SAP group (< 24 h post-operative). RESULTS: PSAP use was 12% (155 of 1292). Patient-related factors associated with PSAP compared to the SAP group included older age (63 vs. 58y; p < 0.001), higher BMI (29 vs. 27 kg/m2; p < 0.001), ASA classification ≥3 (31% vs. 17%; p < 0.001) and lung disease (17% vs. 9%; p = 0.002). Surgery-related factors associated with PSAP were use of prosthetics (62% vs. 45%; p < 0.001), surgery of the knee (65% vs. 25%; p < 0.001), longer surgery duration (87 vs. 68 min; p < 0.001) and presence of drains (90% vs. 65%; p < 0.001). All four SSI occurred in the SAP group (0 vs. 4; p = 1.0). Surgeons administered PSAP with varying frequencies; proportions ranged from 0 to 33%. CONCLUSION: PSAP use and SSI proportions were lower than reported in the literature. Several patient- and surgery-related factors associated with PSAP use were identified and some were potentially modifiable. Also, experienced surgeons seemed to implement differing approaches regarding the duration of SAP administration.

Return to Work and Quality of Life in Disease-Free Adult Patients with Soft-Tissue and Bone Sarcoma of the Extremity

Treatment of extremital sarcoma patients may be associated with significant functional disabilities and psychosocial distress affecting return to work (RtW) and quality of life (QoL). In this exploratory study we prospectively investigated the RtW rate, explored biomedical and psychosocial predictors of RtW, and compared generic QoL with Swiss population norms. Forty people (89 %) returned to work. Full-time employment before sarcoma diagnosis, high educational level, and low tumor grade showed an increased probability of RtW. The median age was lower in patients who returned to work, and they reported less fear of progression. Generic QoL (SF-36) was reduced in almost all dimensions when compared to a normative Swiss population. Physical functioning and fear of progression have to be addressed in the rehabilitation process.

Preoperative decolonization and periprosthetic joint infections-A randomized controlled trial with 2-year follow-up.

Preoperative decolonization, especially of Staphylococcus aureus carriers, has been proposed to reduce periprosthetic joint infections (PJI), but the evidence-based consensus is still lacking and data on long-term outcomes is scarce. In a previous randomized, single-blinded trial, decolonization produced no significant reduction of surgical site infections in overall elective orthopedic surgery at 3-month follow-up. A 2-year follow-up was then performed to specifically detect the impact of decolonization on delayed-onset PJI (3-24 months after surgery). Between November 2015 and September 2017, 613 of 1318 recruited patients underwent prosthetic surgery. Individuals were allocated into either the S. aureus carrier group (34%, 207 of 613 patients) or the noncarrier group (406 of 613 patients), according to nasal swab screening results. Both groups were then randomized into intervention and control arms. In the S. aureus group, the intervention consisted of daily chlorhexidine showers and application of mupirocin nasal ointment twice a day for 5 days before surgery. In noncarriers, only chlorhexidine showers were prescribed. Sample size calculation was based on the initial trial for overall and not for the prosthetic surgery group. No PJI was found at 2 years in either the carrier or in the noncarrier group. Therefore, no definite conclusion about the efficacy of preoperative decolonization to reduce PJI can be drawn. PJI proportions in this study were lower than described in the literature (mostly around 0.3%). Despite the insufficient sample size, this trial is the largest randomized trial on decolonization with a long-term follow-up, and results may be helpful for future meta-analyses.

Screening test accuracy to improve detection of precancerous lesions of the cervix in women living with HIV: a study protocol.

INTRODUCTION: The simplest and cheapest method for cervical cancer screening is visual inspection after application of acetic acid (VIA). However, this method has limitations for correctly identifying precancerous cervical lesions (sensitivity) and women free from these lesions (specificity). We will assess alternative screening methods that could improve sensitivity and specificity in women living with humanimmunodeficiency virus (WLHIV) in Southern Africa. METHODS AND ANALYSIS: We will conduct a paired, prospective, screening test accuracy study among consecutive, eligible women aged 18-65 years receiving treatment for HIV/AIDS at Kanyama Hospital, Lusaka, Zambia. We will assess a portable magnification device (Gynocular, Gynius Plus AB, Sweden) based on the Swede score assessment of the cervix, test for high-risk subtypes of human papillomavirus (HR-HPV, GeneXpert, Cepheid, USA) and VIA. All study participants will receive all three tests and the reference standard at baseline and at six-month follow-up. The reference standard is histological assessment of two to four biopsies of the transformation zone. The primary histological endpoint is cervical intraepithelial neoplasia grade two and above (CIN2+). Women who are VIA-positive or have histologically confirmed CIN2+ lesions will be treated as per national guidelines. We plan to enrol 450 women. Primary outcome measures for test accuracy include sensitivity and specificity of each stand-alone test. In the secondary analyses, we will evaluate the combination of tests. Pre-planned additional studies include use of cervigrams to test an automated visual assessment tool using image pattern recognition, cost-analysis and associations with trichomoniasis. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Zambia Biomedical Research Ethics Committee, Zambian National Health Regulatory Authority, Zambia Medicines Regulatory Authority, Swissethics and the International Agency for Research on Cancer Ethics Committee. Results of the study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03931083; Pre-results.

Association of patterns of multimorbidity with length of stay: A multinational observational study.

The aim of this study was to identify the combinations of chronic comorbidities associated with length of stay (LOS) among multimorbid medical inpatients.Multinational retrospective cohort of 126,828 medical inpatients with multimorbidity, defined as ≥2 chronic diseases (data collection: 2010-2011). We categorized the chronic diseases into comorbidities using the Clinical Classification Software. We described the 20 combinations of comorbidities with the strongest association with prolonged LOS, defined as longer than or equal to country-specific LOS, and reported the difference in median LOS for those combinations. We also assessed the association between the number of diseases or body systems involved and prolonged LOS.The strongest association with prolonged LOS (odds ratio [OR] 7.25, 95% confidence interval [CI] 6.64-7.91, P < 0.001) and the highest difference in median LOS (13 days, 95% CI 12.8-13.2, P < 0.001) were found for the combination of diseases of white blood cells and hematological malignancy. Other comorbidities found in the 20 top combinations had ORs between 2.37 and 3.65 (all with P < 0.001) and a difference in median LOS of 2 to 5 days (all with P < 0.001), and included mostly neurological disorders and chronic ulcer of skin. Prolonged LOS was associated with the number of chronic diseases and particularly with the number of body systems involved (≥7 body systems: OR 21.50, 95% CI 19.94-23.18, P < 0.001).LOS was strongly associated with specific combinations of comorbidities and particularly with the number of body systems involved. Describing patterns of multimorbidity associated with LOS may help hospitals anticipate resource utilization and judiciously allocate services to shorten LOS.

Duration of Pre-Operative Antibiotic Treatment and Culture Results in Patients With Infective Endocarditis.

BACKGROUND: Bacterial growth in cultures of resected heart valves of patients with infective endocarditis (IE) is influenced by pre-operative antibiotic treatment (preop-AT). OBJECTIVES: This study sought to evaluate the time dependency of valve culture results (positive valve culture [PVC] vs. negative valve culture) on preop-AT. METHODS: A total of 352 IE episodes in 344 adult patients of our tertiary referral hospital were retrospectively investigated (2005 to 2016). The primary endpoint was PVC results. The study used a logistic additive model adjusted for bacterial species, the McCabe-Jackson classification, and the existence of foreign valve material as covariables. RESULTS: The 231 included IE cases (187 [81%] men, median age 62 years, 153 [66%] native valves) comprised 58 (25%) PVC results and 173 (75%) negative valve culture results. A multivariable analysis adjusted for bacterial species, McCabe-Jackson classification, and valve type resulted in odds ratios for PVC of 6.35 (95% confidence interval [CI]: 1.94 to 20.78; p = 0.002) and 3.93 (95% CI: 1.57 to 9.84; p = 0.003) for Enterococcus spp. and Staphylococcus spp., respectively. Model-based odds ratios for PVC risk reduction in 2-day intervals of preop-AT ranged from 0.64 (95% CI: 0.61 to 0.68) at day 7 to 0.74 (95% CI: 0.70 to 0.78) at day 13 and 0.98 (95% CI: 0.93 to 1.02) at day 21. CONCLUSIONS: In IE cases treated with valve surgery, Staphylococcus aureus and Enterococcus spp. were associated with valve culture growth. After 7 days of antibiotic treatment, the additional effect of preop-AT on valve culture results per 2-day interval was minor. Antibiotic treatment beyond 21 days had no influence on culture results.

Prognosis in patients with cancer-associated venous thromboembolism: Comparison of the RIETE-VTE and modified Ottawa score.

BACKGROUND: The RIETE-VTE score was derived to risk-stratify patients with cancer-associated venous thromboembolism (CAT). OBJECTIVES: To externally validate the RIETE-VTE score and to compare its prognostic performance with the modified Ottawa score. PATIENTS/METHODS: We studied 178 elderly patients with CAT in a prospective multicenter cohort and assessed 30-day all-cause mortality, 90-day overall complications (mortality, major bleeding, or venous thromboembolism [VTE] recurrence), and 6-month VTE recurrence. Patients were stratified into RIETE-VTE and modified Ottawa score risk classes (low, intermediate, high). We compared the discriminative power (area under the receiver operating characteristic [ROC] curve) to predict mortality, overall complications, and VTE recurrence. RESULTS: Fifteen patients (8.4%) died within 30 days, 42 (23.6%) experienced an overall complication by day 90, and 6 (3.4%) had recurrent VTE within 6 months. The RIETE-VTE and the modified Ottawa score classified similar proportions of patients as low risk (35.4% versus 31.5%; P = .37). No low-risk patient died within 30 days. Low-risk patients identified by the RIETE-VTE and modified Ottawa score had similar rates of overall complications (7.9% versus 8.9%) and VTE recurrence (1.6% versus 1.8%). The modified Ottawa score and the RIETE-VTE score had similar areas under the ROC curve for predicting all-cause mortality (0.84 versus 0.75; P = .21), overall complications (0.74 versus 0.68; P = .26), and VTE recurrence (0.67 versus 0.64; P = .78). CONCLUSIONS: Both the RIETE-VTE and modified Ottawa score accurately identified elderly patients with CAT who are at low risk for short-term mortality and who are potential candidates for outpatient care.