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In this study, fractional flow reserve was used to identify patients with high-risk coronary stenoses, who received either PCI or medical therapy alone; patients with lower-risk lesions were entered in a registry. The PCI group had better outcomes than the medical-therapy group. The benefit of percutaneous coronary intervention (PCI) as an initial treatment strategy in patients with stable coronary artery disease remains controversial. 1 – 3 The potential result from revascularization depends on the extent and the degree of myocardial ischemia. 4 , 5 A fractional flow reserve (FFR) value of 0.80 or less (i.e., a drop in maximal blood flow of 20% or more caused by stenosis), as measured with the use of a coronary pressure wire during catheterization, indicates the potential of a stenosis to induce myocardial ischemia. 6 – 8 In such cases, robust clinical-outcome data favor FFR-guided revascularization, as compared with revascularization guided by . . .

To conduct a meta-analysis to determine specific computed tomography (CT) patterns and clinical features that discriminate between nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). The PubMed/Medline and Embase databases were searched for studies describing the radiological patterns of UIP and NSIP in chest CT images. Only studies involving histologically confirmed diagnoses and a consensus diagnosis by an interstitial lung disease (ILD) board were included in this analysis. The radiological patterns and patient demographics were extracted from suitable articles. We used random-effects meta-analysis by DerSimonian & Laird and calculated pooled odds ratios for binary data and pooled mean differences for continuous data. Of the 794 search results, 33 articles describing 2,318 patients met the inclusion criteria. Twelve of these studies included both NSIP (338 patients) and UIP (447 patients). NSIP-patients were significantly younger (NSIP: median age 54.8 years, UIP: 59.7 years; mean difference (MD) -4.4; p = 0.001; 95% CI: -6.97 to -1.77), less often male (NSIP: median 52.8%, UIP: 73.6%; pooled odds ratio (OR) 0.32; p<0.001; 95% CI: 0.17 to 0.60), and less often smokers (NSIP: median 55.1%, UIP: 73.9%; OR 0.42; p = 0.005; 95% CI: 0.23 to 0.77) than patients with UIP. The CT findings from patients with NSIP revealed significantly lower levels of the honeycombing pattern (NSIP: median 28.9%, UIP: 73.4%; OR 0.07; p<0.001; 95% CI: 0.02 to 0.30) with less peripheral predominance (NSIP: median 41.8%, UIP: 83.3%; OR 0.21; p<0.001; 95% CI: 0.11 to 0.38) and more subpleural sparing (NSIP: median 40.7%, UIP: 4.3%; OR 16.3; p = 0.005; 95% CI: 2.28 to 117). Honeycombing with a peripheral predominance was significantly associated with a diagnosis of UIP. The NSIP pattern showed more subpleural sparing. The UIP pattern was predominantly observed in elderly males with a history of smoking, whereas NSIP occurred in a younger patient population.

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/m 2 ; 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.

BackgroundImmune 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.MethodsWe 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.FindingsNinety 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.InterpretationPatients 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.FundingThis study was funded by Bern University Hospital.

Background Hip fractures are a common injury among older adults, leading to higher morbidity and mortality. Effective treatment pathways are needed. We aimed to compare an orthogeriatric model of care (OMC) and routine care in older hip fracture patients regarding discharge disposition, adherence to clinical care standards and functional outcomes. Methods We performed a retrospective cohort study in patients aged ≥ 70 years with acute hip fracture consecutively admitted to a tertiary Swiss hospital between January 1, 2023 and December 31, 2023 (n = 100). Patients meeting eligibility criteria (≥ 3 geriatric syndromes, no severe dementia) received OMC (n = 46) including an intensive multiprofessional rehabilitation program (MRP) comprising 7 physical, 2 nutritional, and 1 occupational therapy sessions led by a geriatrician during the acute hospital stay. All other patients received routine care (n = 56) on the same acute ward led by an orthopedic surgeon. Discharge destination, adherence to nine pre-specified clinical care standards and functional outcomes (Barthel index [BI] and De Morton Mobility index [DEMMI]), were assessed. Results Mean age was 83.6 years, 59% were female, and 66% frail (Clinical Frailty Scale ≥ 5). Overall, 30 patients (65.2%) in the OMC were discharged to inpatient geriatric rehabilitation compared to 15 patients (27.8%) in routine care. After post-acute rehabilitation, 23 patients (50%) in the OMC versus 16 patients (29.6%) in routine care were discharged home. Length of stay was similar in the OMC versus routine care (10.8 vs. 9.4 days). Mean adherence to nine clinical care standards was 87.9% in the OMC versus 58.7% in routine care. In OMC patients, adherence was lowest for pain management using a femoral nerve block (58.7%), and full-weight bearing (76.1%), while full adherence was observed for mobilization the first day after surgery. In the OMC, functional outcomes improved within 7 days (median increase BI 10 points, DEMMI 8 points). Conclusions The OMC including MRP resulted in higher numbers discharged to post-acute rehabilitation and to home afterwards, as well as improvement of adherence to clinical care standards and functional outcomes, suggesting that OMC is a promising care model. Refinement of OMC is needed to optimize adherence to full weight-bearing and femoral nerve block.

Antidepressants are frequently prescribed as co-analgesics in chronic pain. While their efficacy is well documented for neuropathic pain, the evidence is less clear in musculoskeletal pain conditions. The present study therefore evaluated the effect of the tricyclic antidepressant imipramine on chronic low-back pain in a randomized, double-blinded placebo-controlled design. To explore the mechanisms of action and the influence of drug metabolism, multimodal quantitative sensory tests (QST) and genotyping for cytochrome P450 2D6 (CYP2D6) were additionally performed. A single oral dose of imipramine 75 mg was compared to active placebo (tolterodine 1 mg) in 50 patients (32 females) with chronic non-specific low-back pain. Intensity of low-back pain was assessed on a 0-10 numeric rating scale at baseline and every 30 minutes after drug intake. Multimodal QST were performed at baseline and in hourly intervals for 2 hours. Pharmacogenetic influences of cytochrome P450 were addressed by CYP2D6 genotyping. No significant analgesic effect was detected neither on low-back pain nor on any of the sensory tests in the overall analyses. However, evidence for an interaction of the imipramine effect and CYP2D6 genotype was found for electrical and for pressure pain detection thresholds. Intermediate but not extensive metabolizers had a 1.20 times greater electrical pain threshold (95%-CI 1.10 to 1.31) and a 1.10 times greater pressure pain threshold (95%-CI 1.01 to 1.21) 60 minutes after imipramine than after placebo (p<0.001 and p = 0.034, respectively). The present study failed to demonstrate an immediate analgesic effect of imipramine on low-back pain. Anti-nociceptive effects as assessed by quantitative sensory tests may depend on CYP2D6 genotype, indicating that metabolizer status should be accounted for when future studies with tricyclic antidepressants are undertaken.

IntroductionThe analgesic and antipyretic paracetamol (acetaminophen) is generally considered safe in therapeutic doses. The most important toxic effect is hepatotoxicity after supratherapeutic doses or in the presence of risk factors (eg, malnutrition, alcoholism). According to the WHO analgesic ladder, a combination of a non-opioid analgesic such as paracetamol with a strong opioid is recommended as step III treatment of patients with chronic pain, despite limited evidence for this approach. The main aim of this study is to test the hypothesis that paracetamol does not provide clinically relevant benefits when added to strong opioids in patients with chronic pain.Methods and analysisInvestigator-initiated, randomised, double-blind, placebo-controlled, non-inferiority trial at two Swiss hospitals. A total of 140 patients with chronic pain requiring strong opioids and paracetamol ≥1.5 g/day for at least 7 days will be enrolled and randomised to either continued combination treatment or strong opioid plus placebo. In the first study phase (days 1–7), patients receive identically looking capsules containing either paracetamol at the exact dose previously used or a placebo. During a second study phase (days 7–14), all patients stop the blinded study medication (paracetamol and placebo) with follow-up to day 14. Adherence will be assessed by pill count and measurement of paracetamol and opioid serum concentrations. Patients are instructed to use a pain diary daily during the whole study. The primary outcome is the average pain score on day 7 using a 10 cm visual analogue scale (VAS). A difference between groups of ≤8 mm will be considered clinically irrelevant. Secondary outcomes will include VAS pain score on day 14, number of opioid rescue doses used, subjective ratings of overall feeling of well-being, quality of life, nausea/vomiting, drowsiness and constipation, and other adverse events, and potential effects of study drug concentrations and opioid receptor and cytochrome P450 (CYP) genotypes on the observed differences.Ethics and disseminationThe study was approved by the Ethics Committee (Ethikkommission Bern, reference number 2021-01518) and the Swiss Agency for Therapeutic Products (Swissmedic, reference number 701286). Results will be published in open-access policy peer-reviewed journals. The study is funded by the Swiss National Science Foundation (grant number 32 003B_201072).Trial registration numberNCT05088876.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in elderly patients. Extracellular DNA is a pro-inflammatory and pro-thrombotic mediator in vitro and in animal models. Levels of circulating extracellular DNA (ceDNA) are increased in VTE patients, but the association of ceDNA with VTE extent and clinical outcome is poorly understood. We analyzed the association of ceDNA with the extent of VTE, categorized as distal and proximal deep vein thrombosis and pulmonary embolism, and with the clinical outcomes VTE recurrence and mortality. We quantified ceDNA by a fluorescent probe, as well as circulating nucleosomes and neutrophil extracellular traps (NETs) by ELISA in plasma from 611 patients aged ≥ 65 years with acute VTE of a prospective cohort study (SWITCO65+). Levels of ceDNA and nucleosomes, but not NETs, correlated with VTE extent. Infectious comorbidities independently increased ceDNA levels in VTE. CeDNA strongly correlated with C-reactive protein and leukocytosis, suggesting an association of ceDNA with inflammation in VTE patients. CeDNA furthermore predicted PE-related and all-cause mortality, but not VTE recurrence, during a 3-year follow-up. Our study suggests that ceDNA levels in VTE patients reflect the degree of inflammation and may serve as a biomarker to stratify VTE patients at risk for mortality.

Background Multimorbidity is associated with higher healthcare resource utilization, but we lack data on the association of specific combinations of comorbidities with healthcare resource utilization. We aimed to identify the combinations of comorbidities associated with high healthcare resource utilization among multimorbid medical inpatients. Methods We performed a multicentre retrospective cohort study including 33,871 multimorbid (≥2 chronic diseases) medical inpatients discharged from three Swiss hospitals in 2010–2011. Healthcare resource utilization was measured as 30-day potentially avoidable readmission (PAR), prolonged length of stay (LOS) and difference in median LOS. We identified the combinations of chronic comorbidities associated with the highest healthcare resource utilization and quantified this association using regression techniques. Results Three-fourths of the combinations with the strongest association with PAR included chronic kidney disease. Acute and unspecified renal failure combined with solid malignancy was most strongly associated with PAR (OR 2.64, 95%CI 1.79;3.90). Miscellaneous mental health disorders combined with mood disorders was the most strongly associated with LOS (difference in median LOS: 17 days) and prolonged LOS (OR 10.77, 95%CI 8.38;13.84). The number of chronic diseases was strongly associated with prolonged LOS (OR 9.07, 95%CI 8.04;10.24 for ≥10 chronic diseases), and to a lesser extent with PAR (OR 2.16, 95%CI 1.75;2.65 for ≥10 chronic diseases). Conclusions Multimorbidity appears to have a higher impact on LOS than on PAR. Combinations of comorbidities most strongly associated with healthcare utilization included kidney disorders for PAR, and mental health disorders for LOS.

Whether obesity is associated with recurrent venous thromboembolism (VTE) in elderly patients is unknown. To examine the association between two obesity measures, the body mass index (BMI) and the waist circumference (WC), and recurrent VTE in elderly patients. We studied 986 patients aged ≥65 years with an acute VTE from a prospective multicenter cohort study (09/2009-12/2013). The BMI was determined and categorized as <25, 25 to <30, or ≥30 kg/m2. The WC was categorized as <80 cm in women (w)/<94 cm in men (m), 80 to <88 cm (w)/94 to <102 cm (m), or ≥88 cm (w)/≥102 cm (m). We examined the association between the BMI and the WC and the time to a first symptomatic recurrent VTE using competing risk regression, adjusting for known risk factors of VTE recurrence and periods of anticoagulation. The mean follow-up was 28 months. The 3-year cumulative incidence of recurrent VTE did not vary by BMI and was 17.6% for a BMI <25 kg/m2, 11.5% for a BMI 25 to <30 kg/m2, and 16.9% for a BMI ≥30 kg/m2 (P = 0.09). The 3-year cumulative incidence of recurrent VTE did not vary by WC. After adjustment, neither the BMI (sub-hazard ratio [SHR] 1.02, 95% confidence interval [CI 0.98-1.05]) nor the WC (SHR 1.01, 95% CI 0.99-1.02) was associated with recurrent VTE. Measures of body weight were not associated with recurrent VTE in our cohort. Obesity does not appear to be a predictor of recurrent VTE in the elderly.