The Interplay between Systolic Blood Pressure, Sauna Bathing, and Cardiovascular Mortality in Middle-Aged and Older Finnish Men: A Cohort Study.

OBJECTIVES: Elevated systolic blood pressure (SBP) is associated with an increased risk of cardiovascular disease (CVD) mortality, whereas frequent sauna bathing reduces the risk. Whether frequent sauna bathing mitigates CVD mortality among adults with elevated SBP has not been previously investigated. DESIGN AND SETTING: We examined the interactions between SBP and frequency of sauna bathing (FSB) with the risk of CVD mortality in a cohort of Caucasian men. PARTICIPANTS: The Kuopio Ischaemic Heart Disease Study cohort comprising of 2,575 men aged 42-61 years at baseline was employed for this prospective study analysis. MEASUREMENTS: Resting blood pressure was measured using a standardized protocol and sauna bathing habits were assessed by a self-administered questionnaire. Systolic blood pressure was categorized as normal and high (<140 and ≥140 mmHg, respectively) and FSB as low and high (defined as ≤ 2 and 3-7 sessions/week, respectively). RESULTS: A total of 744 CVD deaths were recorded during a median follow-up of 27.8 yr. Comparing high vs normal SBP, the multivariable-adjusted HR (95% CI) for CVD mortality was 1.44 (1.23-1.68). Comparing low vs high FSB, the multivariable-adjusted HR (95% CI) for CVD mortality was 1.24 (1.03-1.51). The associations persisted following mutual adjustment for each exposure. Compared with men with normal SBP-high FSB, high SBP-low FSB was associated with an increased risk of CVD mortality 1.81 (1.39-2.36), with attenuated but persisting evidence of an association for men with high SBP and high FSB 1.52 (1.06-2.16). When SBP was categorized as normal and high (<130 and ≥130 mmHg, respectively), there was no evidence of an association for men with high SBP and high FSB 1.11 (0.77-1.61). CONCLUSION: There might be an interaction between SBP, sauna bathing and CVD mortality risk in middle-aged and older Caucasian males. Frequent sauna baths may offset the increased risk of CVD mortality in men with high-normal SBP but not elevated SBP.

Effects of recurrent intra-articular corticosteroid injections for osteoarthritis at 3 months and beyond: a systematic review and meta-analysis in comparison to other injectables.

OBJECTIVE: Intra-articular corticosteroid injections (IACIs) provide temporary symptom relief in osteoarthritis (OA). This meta-analysis investigated the effects of recurrent IACIs at 3 months and beyond. DESIGN: We searched Medline, Embase and Cochrane from inception to January 2021 for randomised controlled trials (RCTs) of patients with OA who received recurrent IACIs compared with other injectables, placebo or no treatment (primary outcomes: pain, function). Mean differences (MDs) with 95% confidence intervals were reported. RESULTS: Ten RCTs were included (eight knee OA (n = 763), two trapeziometacarpal OA (n = 121)). Patients received between 2 and 8 injections, varying by trial. Trials compared recurrent IACIs with hyaluronic acid (HA), platelet-rich plasma (PRP), saline or orgotein (follow-up 3-24 months). Greater improvements in pain, function and QoL at 3-24 months were noted for the comparators than with IACIs, with comparators demonstrating an equal or superior effect, or the intervention effect attenuated during follow-up. Recurrent IACIs demonstrated no benefits in pain or function over placebo at 12-24 months. No serious adverse events were recorded. No studies reported on time-to-future interventions, risk of future prosthetic joint infection or other adverse events associated with subsequent joint replacement. CONCLUSIONS: Recurrent IACIs often provide inferior (or non-superior) symptom relief compared with other injectables (including placebo) at 3 months and beyond. Other injectables (HA, PRP) often yielded greater improvements in pain and function up to 24 months post-injection. Existing RCTs on recurrent IACIs lack sufficient follow-up data to assess disease progression and time-to-future interventions.

Starting dose and dose adjustment of non-vitamin K antagonist oral anticoagulation agents in a nationwide cohort of patients with atrial fibrillation.

This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in patients with atrial fibrillation (AF). In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. During the reference period, treatment was commenced for 866,539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA2DS2-VASc and HAS-BLED. A relative reduction of the proportion of patients treated with low dosages was evident overtime for dabigatran and rivaroxaban; whereas prescription of low dose apixaban and edoxaban increased progressively among elderly patients. Evidence based on real-world data shows a high frequency of low dose prescriptions of NOACs in AF patients. Except for older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, other factors that may determine the choice of reduced dose could not be ascertained. There may be potential under-treatment of AF patients, but further evaluation is warranted.

GlycA, a novel pro-inflammatory glycoprotein biomarker is associated with mortality: results from the PREVEND study and meta-analysis.

BACKGROUND: Chronic diseases are associated with an inflammatory response. We determined the association of two inflammatory markers, GlycA and high-sensitivity C-reactive protein (hsCRP), with overall and cause-specific mortality in a cohort of men and women. METHODS: Cox regression analyses were used to examine associations of GlycA and hsCRP with all-cause, cancer and cardiovascular mortality in 5526 subjects (PREVEND cohort; average follow-up 12.6 years). RESULTS: GlycA was associated with all-cause mortality (n = 838), independent of clinical risk factors and hsCRP (hazard ratio 1.43 [95% confidence interval (CI): 1.09-1.87] for top versus bottom quartiles). For hsCRP, the association with all-cause mortality was nonsignificant after adjustment for GlycA. GlycA and hsCRP were associated with cancer mortality in men (n = 248), but not in women (n = 132). Neither GlycA nor hsCRP was independently associated with cardiovascular mortality (n = 201). In a meta-analysis of seven population-based studies, including 8153 deaths, the pooled multivariable-adjusted relative risk of GlycA for all-cause mortality was 1.74 (95% CI: 1.40-2.17) for top versus bottom quartiles. The association of GlycA with all-cause mortality was somewhat stronger than that of hsCRP. GlycA and hsCRP were not independently associated with cardiovascular mortality. The associations of GlycA and hsCRP with cancer mortality were present in men, but not in women. CONCLUSIONS: GlycA is significantly associated with all-cause mortality. GlycA and hsCRP were each not independently associated with cardiovascular mortality. The association of GlycA and hsCRP with cancer mortality appears to be driven by men.

Is social support associated with patient-reported outcomes after joint replacement? A systematic review and meta-analysis.

BACKGROUND: Identifying prognostic factors for outcomes after joint replacement could improve the provision of stratified care. This systematic review evaluated whether social support is a prognostic factor for better patient-reported outcomes after total hip replacement (THR) and total knee replacement (TKR). METHODS: MEDLINE, Embase and PsycINFO were searched from inception to April 2019. Cohort studies evaluating the association between social support and patient-reported outcomes at three months or longer after THR or TKR were included. Data were extracted from study reports. Study quality was assessed using the QUIPS tool. Data were synthesized using meta-analysis and narrative synthesis. The review was registered on PROSPERO (CRD42016041485). FINDINGS: Searches identified 5,810 articles and 56 studies with data from 119,165 patients were included. In meta-analysis, the presence of social support had a beneficial effect on long-term post-operative WOMAC (mean difference 2.88; 95% CIs 1.30; 4.46) and Oxford Knee Score (0.29; 0.12, 0.45). Social support measured using a validated questionnaire was found to be associated with WOMAC pain (0.04; 0.00, 0.08) but not WOMAC function (-0.01; -0.12, 0.11). The presence of social support had a positive association with some SF-36 subscales but not others. For all outcomes, results of narrative synthesis were inconsistent. INTERPRETATION: There is evidence that social support is a prognostic factor for some outcomes after joint replacement. Development and evaluation of complex interventions to improve social support and social integration is warranted. FUNDING: This study was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol.

Systematic review of the safety and efficacy of osseointegration prosthesis after limb amputation.

BACKGROUND: Osseointegration, an approach for direct skeletal attachment of a prosthesis to an amputated limb, may address many of the problems associated with socket prostheses. The safety of osseointegration remains uncertain. The aim of this study was to summarize evidence on functional and clinical outcomes, as well as adverse effects of osseointegration for patients with a limb amputation. METHODS: MEDLINE, Embase, Web of Science and the Cochrane Library were searched to April 2018. Eligible studies were observational, case and qualitative studies, and RCTs conducted in patients with a limb amputation, who were managed with osseointegrated prostheses and had follow-up data. RESULTS: Twenty-two eligible articles comprising 13 unique studies were included. No RCT was identified. Apart from three case reports that comprised one to five patients, the sample size of studies ranged from 11 to 100 participants. All relevant studies reported improvement in functional outcomes (walking ability, prosthetic use and mobility), satisfaction and quality of life following osseointegration, compared with their preoperative status or when using a conventional socket prosthesis. Infection rates ranged from 1 (95 per cent c.i. 0 to 5) to 77 (59 to 88) per cent. The majority of infections were described as low-grade soft tissue or superficial infections related to the skin-implant interface, and were treated effectively with antibiotics. None of the studies reported additional amputation or death as a result of osseointegration. CONCLUSION: Osseointegration after limb amputation improves prosthetic use, comfort when sitting, walking ability, mobility, gait and quality of life. However, it is associated with an increased risk of soft tissue infection.

Cross-country skiing is associated with lower all-cause mortality: A population-based follow-up study.

The prospective relationship between leisure-time cross-country skiing and any fatal events is uncertain. We aimed to assess the associations of leisure-time cross-country skiing habits with the risk of all-cause mortality in a general population. A 12-month physical activity questionnaire was used at baseline to assess the frequency, average duration, and intensity of cross-country skiing in a prospective population-based cohort of 2087 middle-aged men from eastern Finland. Hazard ratios (HRs; 95% confidence intervals) were calculated for all-cause mortality. During a median (interquartile range) follow-up of 26.1 (18.7-28.0) years, 1028 all-cause mortality outcomes were recorded. In analyses adjusted for several established risk factors and other potential confounders, when compared to men who did not do any cross-country skiing, the HRs (95% CIs) of all-cause mortality were 0.84 (0.73-0.97) and 0.80 (0.67-0.96) for men who did 1-200 and >200 metabolic equivalent-hours per year of cross-country skiing, respectively. Similarly, compared to men who did not do any cross-country skiing, the corresponding adjusted HRs (95% CIs) for all-cause mortality were 0.84 (0.72-0.97) and 0.82 (0.69-0.97) for men who did 1-60 min/wk and >60 min/wk of cross-country skiing, respectively. The associations were similar across several subgroups, except for evidence of effect modification by body mass index and history of diabetes. Total volume as well as duration of leisure-time cross-country skiing is each inversely and independently associated with all-cause mortality in a middle-aged Caucasian male population.

Systematic review of risk prediction scores for surgical site infection or periprosthetic joint infection following joint arthroplasty.

Accurate identification of individuals at high risk of surgical site infections (SSIs) or periprosthetic joint infections (PJIs) influences clinical decisions and development of preventive strategies. We aimed to determine progress in the development and validation of risk prediction models for SSI or PJI using a systematic review. We searched for studies that have developed or validated a risk prediction tool for SSI or PJI following joint replacement in MEDLINE, EMBASE, Web of Science and Cochrane databases; trial registers and reference lists of studies up to September 2016. Nine studies describing 16 risk scores for SSI or PJI were identified. The number of component variables in a risk score ranged from 4 to 45. The C-index ranged from 0·56 to 0·74, with only three risk scores reporting a discriminative ability of >0·70. Five risk scores were validated internally. The National Healthcare Safety Network SSIs risk models for hip and knee arthroplasties (HPRO and KPRO) were the only scores to be externally validated. Except for HPRO which shows some promise for use in a clinical setting (based on predictive performance and external validation), none of the identified risk scores can be considered ready for use. Further research is urgently warranted within the field.

Aspirin for primary prevention of cardiovascular and all-cause mortality events in diabetes: updated meta-analysis of randomized controlled trials.

AIMS: To evaluate the benefits and harms of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in people with diabetes by conducting a systematic review and meta-analysis. METHODS: Randomized controlled trials of aspirin compared with placebo (or no treatment) in people with diabetes with no history of cardiovascular disease were identified from MEDLINE, EMBASE, Web of Science, the Cochrane Library and a manual search of bibliographies to November 2015. Study-specific relative risks with 95% CIs were aggregated using random effects models. RESULTS: A total of 10 randomized trials were included in the review. There was a significant reduction in risk of major adverse cardiovascular events: relative risk of 0.90 (95% CI 0.81-0.99) in groups taking aspirin compared with placebo or no treatment. Limited subgroup analyses suggested that the effect of aspirin on major adverse cardiovascular events differed by baseline cardiovascular disease risk, medication compliance and sex (P for interaction for all > 0.05).There was no significant reduction in the risk of myocardial infarction, coronary heart disease, stroke, cardiovascular mortality or all-cause mortality. Aspirin significantly reduced the risk of myocardial infarction for a treatment duration of ≤ 5 years. There were differences in the effect of aspirin by dosage and treatment duration on overall stroke outcomes (P for interaction for all < 0.05). There was an increase in risk of major or gastrointestinal bleeding events, but estimates were imprecise and not significant. CONCLUSIONS: The emerging data do not clearly support guidelines that encourage the use of aspirin for the primary prevention of cardiovascular disease in adults with diabetes who are at increased cardiovascular disease risk.

The Alpha-Defensin Immunoassay and Leukocyte Esterase Colorimetric Strip Test for the Diagnosis of Periprosthetic Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Synovial biomarkers have recently been adopted as diagnostic tools for periprosthetic joint infection (PJI), but their utility is uncertain. The purpose of this systematic review and meta-analysis was to synthesize the evidence on the accuracy of the alpha-defensin immunoassay and leukocyte esterase colorimetric strip test for the diagnosis of PJI compared with the Musculoskeletal Infection Society diagnostic criteria. METHODS: We performed a systematic review to identify diagnostic technique studies evaluating the accuracy of alpha-defensin or leukocyte esterase in the diagnosis of PJI. MEDLINE and Embase on Ovid, ACM, ADS, arXiv, CERN DS (Conseil Européen pour la Recherche Nucléaire Document Server), CrossRef DOI (Digital Object Identifier), DBLP (Digital Bibliography & Library Project), Espacenet, Google Scholar, Gutenberg, HighWire, IEEE Xplore (Institute of Electrical and Electronics Engineers digital library), INSPIRE, JSTOR (Journal Storage), OAlster (Open Archives Initiative Protocol for Metadata Harvesting), Open Content, Pubget, PubMed, and Web of Science were searched for appropriate studies indexed from inception until May 30, 2015, along with unpublished or gray literature. The classification of studies and data extraction were performed independently by 2 reviewers. Data extraction permitted meta-analysis of sensitivity and specificity with construction of receiver operating characteristic curves for each test. RESULTS: We included 11 eligible studies. The pooled diagnostic sensitivity and specificity of alpha-defensin (6 studies) for PJI were 1.00 (95% confidence interval [CI], 0.82 to 1.00) and 0.96 (95% CI, 0.89 to 0.99), respectively. The area under the curve (AUC) for alpha-defensin and PJI was 0.99 (95% CI, 0.98 to 1.00). The pooled diagnostic sensitivity and specificity of leukocyte esterase (5 studies) for PJI were 0.81 (95% CI, 0.49 to 0.95) and 0.97 (95% CI, 0.82 to 0.99), respectively. The AUC for leukocyte esterase and PJI was 0.97 (95% CI, 0.95 to 0.98). There was substantial heterogeneity among studies for both diagnostic tests. CONCLUSIONS: The diagnostic accuracy for PJI was high for both tests. Given the limited number of studies and the large cost difference between the tests, more independent research on these tests is warranted. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Gamma glutamyltransferase and metabolic syndrome risk: a systematic review and dose-response meta-analysis.

AIMS: We aimed to quantify and characterise in detail the nature of the dose-response relationship between baseline gamma glutamyltransferase (GGT) level and risk of incident metabolic syndrome (MetS) in the general population and determine the precise estimate of the magnitude of the association. METHODS: We performed a systematic review and dose-response meta-analysis of published prospective cohort studies. Relevant studies were identified in a literature search of MEDLINE, EMBASE and Web of Science up to May 2014. A potential nonlinear relationship between GGT levels and MetS was examined using restricted cubic splines. Study-specific estimates were combined using random-effects models. RESULTS: Of the 323 studies reviewed, we included 10 prospective cohort studies with data on 67,905 participants comprising of 6595 incident MetS cases. In pooled analysis of seven studies with relevant data, baseline GGT level was statistically significantly positively associated with risk of MetS in a nonlinear fashion (p for nonlinearity = 0.003). Comparing individuals in the top vs. bottom thirds of baseline GGT levels, relative risk for MetS in pooled analysis of all 10 eligible studies was 1.88 (95% confidence interval: 1.49-2.38). Evidence was lacking of publication bias among the contributing studies. CONCLUSION: Baseline GGT level is positively and strongly associated with risk of the MetS in a nonlinear dose-response manner.