The effect of Tai Chi on functional mobility,balance and falls in Parkinson's disease: A systematic review and meta-analysis of systematic reviews

BackgroundThe aim of the study was to evaluate the effect of Tai Chi on functional mobility, balance and falls in Parkinson's disease.Materials and methodsA comprehensive literature search was conducted to identify the systematic reviews and meta-analyses up to the end of October 2021. 601 studies were identified, and 16 of them were included in our study.ResultsAccording to our meta-analysis; there was a significant effect of Tai Chi on balance (SMD, ?0.777 95% CI ?0.921 to -0.633; p = 0.000), functional mobility (SMD, ?0.719 95% CI ?0.944 to -0.494; p = 0.000), and falls (SMD, ?0.456 95% CI ?0.668 to -0.245; p = 0.000) in PD.ConclusionOur systematic review and meta-analysis found significant effects of Tai Chi on functional mobility, balance and falls in patients with PD.     

Efficacy of intravenous immunoglobulin in autoimmune neurological diseases. Literature systematic review and meta-analysis

BackgroundCorticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin (IVIg) and plasmapheresis, have shown mixed results in patient improvement.ObjectiveTo compare the efficacy of IVIg administration with that of corticosteroids, plasmapheresis, and placebo in autoimmune neurological diseases like Guillain-Barré syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, optic neuritis, and multiple sclerosis.MethodsA systematic review was performed on the databases PubMed, MEDLINE, Embase, and Cochrane. Controlled, randomized studies comparing the efficacy of IVIg with placebo, plasmapheresis, and/or glucocorticoid administration were selected. Only studies reporting the number of patients who improved after treatment were included, irrespective of language or publication year. In total, 23 reports were included in the meta-analysis study.ResultsOur meta-analysis showed a beneficial effect of IVIg administration on patient improvement over placebo (OR = 2.79, CI [95%] = 1.40–5.55, P = 0.01). Meanwhile, IVIg administration showed virtually identical effects to plasmapheresis (OR = 0.83, CI [95%] = 0.45–1.55, P < 0.01). Finally, no significant differences were found in the efficacy of IVIg and glucocorticoid administration (OR = 0.98, Cl [95%] = 0.58–1.68, P = 0.13).ConclusionIVIg can be regarded as a viable therapeutic approach, either as a first- or second-line therapy, and as an adjuvant therapy for autoimmune neurological diseases.     

The effects of aerobic exercise and transcranial direct current stimulation on cognitive function in older adults with and without cognitive impairment: A systematic review and meta-analysis

BackgroundAerobic exercise (AE) may slow age-related cognitive decline. However, such cognition-sparing effects are not uniform across cognitive domains and studies. Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation and is also emerging as a potential alternative to pharmaceutical therapies. Like AE, the effectiveness of tDCS is also inconsistent for reducing cognitive impairment in ageing. The unexplored possibility exists that pairing AE and tDCS could produce synergistic effects and reciprocally augment cognition-improving effects in older individuals with and without cognitive impairments.Previous research found such synergistic effects on cognition when cognitive training is paired with tDCS in older individuals with and without mild cognitive impairment (MCI) or dementia.AimThe purpose of this systematic review with meta-analysis was to explore if pairing AE with tDCS could augment singular effects of AE and tDCS on global cognition (GC), working memory (WM) and executive function (EF) in older individuals with or without MCI and dementia.MethodsUsing a PRISMA-based systematic review, we compiled studies that examined the effects of AE alone, tDCS alone, and AE and tDCS combined on cognitive function in older individuals with and without mild cognitive impairment (MCI) or dementia. Using a PICOS approach, we systematically searched PubMed, Scopus and Web of Science searches up to December 2021, we focused on ‘MoCA’, ‘MMSE’, ‘Mini-Cog’ (measures) and ‘cognition’, ‘cognitive function’, ‘cognitive’, ‘cognitive performance’, ‘executive function’, ‘executive process’, ‘attention’, ‘memory’, ‘memory performance’ (outcome terms). We included only randomized controlled trials (RTC) in humans if available in English full text over the past 20 years, with participants’ age over 60. We assessed the methodological quality of the included studies (RTC) by the Physiotherapy Evidence Database (PEDro) scale.ResultsOverall, 68 studies were included in the meta-analyses. AE (ES = 0.56 [95% CI: 0.28–0.83], p = 0.01) and tDCS (ES = 0.69 [95% CI: 0.12–1.26], p = 0.02) improved GC in all three groups of older adults combined (healthy, MCI, demented). In healthy population, AE improved GC (ES = 0.46 [95% CI: 0.22–0.69], p = 0.01) and EF (ES = 0.27 [95% CI: 0.05–0.49], p = 0.02). AE improved GC in older adults with MCI (ES = 0.76 [95% CI: 0.21–1.32], p = 0.01). tDCS improved GC (ES = 0.69 [90% CI: 0.12–1.26], p = 0.02), all three cognitive function (GC, WM and EF) combined in older adults with dementia (ES = 1.12 [95% CI: 0.04–2.19], p = 0.04) and improved cognitive function in older adults overall (ES = 0.69 [95% CI: 0.20–1,18], p = 0.01).ConclusionOur systematic review with meta-analysis provided evidence that beyond the cardiovascular and fitness benefits of AE, pairing AE with tDCS may have the potential to slow symptom progression of cognitive decline in MCI and dementia. Future studies will examine the hypothesis of this present review that a potentiating effect would incrementally improve cognition with increasing severity of cognitive impairment.     

Association between IFNL4 rs368234815 polymorphism and sustained virological response in chronic hepatitis C patients undergoing PEGylated interferon/ribavirin therapy: A meta-analysis

Background and aimsMany studies have been published on the association between IFNL4 rs368234815 single-nucleotide polymorphism (SNP) and sustained virological response (SVR) in chronic hepatitis C (CHC) patients undergoing treatment with PEGylated interferon (PEG-IFN) plus ribavirin (RBV). Because of the variable and sometimes inconsistent results, we performed a meta-analysis to estimate the association between these factors.MethodsWe conducted a search of the literature published prior to July 1, 2014. The pooled results were analyzed as the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effect model.ResultsThe pooled results revealed that the rs368234815 TT/TT genotype was significantly correlated with SVR in HCV-1/4-infected Caucasian patients (OR = 4.65, 95% CI = 3.36–6.42, P < 0.00001) but not in HCV-2/3-infected Caucasian patients (OR = 1.44, 95% CI: 0.89–2.33, P = 0.13). Conversely, the rs368234815 ΔG/ΔG genotype was significantly linked to treatment failure in Caucasian patients (OR = 0.49, 95% CI: 0.38–0.64, P < 0.00001), regardless of the HCV genotype.ConclusionThe results of the meta-analysis suggest that IFNL4 rs368234815 polymorphism may be a predictor of SVR in Caucasian HCV-1/4-infected patients.     

Accuracy of cholera rapid diagnostic tests: a systematic review and meta-analysis

BackgroundCholera is an acute diarrheal disease caused by Vibrio cholerae O1 or O139. Cholera rapid diagnostic tests (RDTs) are widely used to screen for cholera cases. However, their accuracy has not been systematically reviewed.ObjectivesTo evaluate the diagnostic accuracy of cholera RDTs.MethodsSystematic review and meta-analysis.Data sourcesMedline, EMBASE and Web of science through to November 2020; references of included studies and a technical guidance on cholera RDTs. This review is registered with PROSPERO (CRD42021233124).Study eligibility criteriaCross-sectional studies comparing the performance of cholera RDTs either to stool culture or PCR.ParticipantsIndividuals with clinically suspected cholera.Data extractionTwo authors independently extracted data and assessed the quality using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria.ResultsEighteen studies were included in the systematic review of which 17 were used for meta-analysis. Crystal VC was the most frequently used RDT (13 studies), followed by Cholkit and Institut Pasteur cholera dipstick (three studies each), SD Bioline (two studies), Artron (one study) and Smart (one study). Using direct testing (n = 12 627 specimens), the bivariate random-effects model yielded a pooled sensitivity and specificity of 91% (95% CI 87%–94%) and 80% (95% CI 74%–84%), respectively. However, through alkaline peptone water (APW) enrichment (n = 3403 specimens), the pooled sensitivity and specificity were 89% (95% CI 79%–95%) and 98% (95% CI 95%–99%), respectively.ConclusionCholera RDTs, especially when enriched with APW, have moderate sensitivity and specificity. Although less useful for clinical management, the current generation of RDTs have clear utility for surveillance efforts if used in a principled manner. Enrichment of stool specimens in APW before using cholera RDTs reduces the possibility of obtaining false-positive results, despite the few cholera cases that go undetected. It is noteworthy that APW-enriched cholera RDTs are not necessarily rapid tests, and are not listed in the Global Task Force on Cholera Control/WHO target product profile.     

Divergent Effects of Novel Immunomodulatory Agents and Cyclophosphamide on the Risk of Engraftment Syndrome after Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma

Engraftment syndrome (ES) is an increasingly observed and occasionally fatal complication after autologous peripheral blood stem cell transplantation (PBSCT). In this study, we demonstrate that the incidence of ES is significantly increased in patients undergoing autologous PBSCT for multiple myeloma in comparison to patients with non-Hodgkin lymphoma or Hodgkin lymphoma. Multivariate analysis revealed that age > 60 (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.12 to 2.62; P = .013) and transplantation for multiple myeloma (HR, 2.80; 95% CI, 1.60 to 4.90; P = .0003) were associated with an increased risk of this complication. When stratified for myeloma patients only, age > 60 (HR, 1.80; 95% CI, 1.13 to 2.87; P = .013) and prior treatment with both lenalidomide and bortezomib (HR, 1.83; 95% CI, 1.11 to 3.04; P = .0001) were associated with an increased incidence of ES. Conversely, lack of exposure to cyclophosphamide from either chemomobilization or as a component of the pretransplantation therapeutic regimen increased the risk of this complication (HR, 3.05; 95% CI, 1.91 to 4.87; P <.0001). These studies demonstrate that the pretransplantation exposure of multiple myeloma patients to novel immunomodulatory agents and cyclophosphamide significantly affects the subsequent risk of developing ES.     

The level of thymic stromal lymphopoietin and its gene polymorphism are associated with rheumatoid arthritis

ObjectiveTo study the correlation between TSLP gene SNPs and RA in a Han Chinese population.MethodsThe genotypes of TSLP genes rs11466749, rs11466750 and rs10073816 among 197 RA patients and 197 controls were analysed by direct sequencing. ELISA was used to detect the plasma TSLP level. Logistic regression analysis was also conducted to identify risk factors for RA.ResultsThe rs11466749 locus GG genotype (OR = 5.30, 95% CI: 1.76–15.95, P < 0.01), dominant model (OR = 1.68, 95% CI: 1.03–2.73, P = 0.04), recessive model (OR = 5.15, 95% CI: 1.72–15.43, P < 0.01), and G allele (OR = 2.02, 95% CI: 1.33–3.09, P < 0.01) were associated with an increased risk of RA. The rs1073816 locus AA genotype (OR = 4.58, 95% CI: 1.49–14.01, P < 0.01), dominant model (OR = 1.75, 95% CI: 1.09–2.79, P = 0.03), recessive model (OR = 4.27, 95% CI: 1.40–13.00, P = 0.03) and A allele (OR = 1.94, 95% CI: 1.29–2.91, P < 0.01) were associated with an increased risk of RA. The rs1073816 locus GA genotype (OR = 0.29, 95% CI: 0.18–0.45, P < 0.01), dominant model (OR = 0.32, 95% CI: 0.21–0.49, P < 0.01) and A allele (OR = 0.45, 95% CI: 0.32–0.63, P < 0.01) were related to a decreased risk of RA susceptibility. The rs1466749 locus GG genotype, rs11466750 AA genotype, and rs10073816 GG genotype were independent risk factors for RA (P < 0.05). The AUC of plasma TSLP level in the diagnosis of RA was 0.8661 (95% CI: 0.8301–0.9002, P < 0.001). There were statistically significant differences in plasma TSLP levels among subjects with different genotypes at rs11466749, rs11466750, and rs10073816 in the TSLP gene (P < 0.05).ConclusionPlasma TSLP levels are a potential molecular marker of RA. SNPs at rs11466749, rs11466750 and rs10073816 of the TSLP gene are related to the susceptibility of the Han Chinese population to RA.     

Trio genome sequencing for developmental delay and pediatric heart conditions: A comparative microcost analysis

PurposeGenome sequencing (GS) can aid clinical management of multiple pediatric conditions. Insurers require accurate cost information to inform funding and implementation decisions. The objective was to compare the laboratory workflows and microcosts of trio GS testing in children with developmental delay (DD) and in children with cardiac conditions.MethodsCost items related to each step in trio GS (child and 2 parents) for both populations were identified and measured. Program costs over 5 years were estimated. Probabilistic and deterministic analyses were conducted.ResultsThe mean cost per trio GS was CAD$6634.11 (95% CI = 6352.29-6913.40) for DD and CAD$8053.10 (95% CI = 7699.30-8558.10) for cardiac conditions. The 5-year program cost was CAD$28.11 million (95% CI = 26.91-29.29) for DD and CAD$5.63 million (95% CI = 5.38-5.98) for cardiac conditions. Supplies constituted the largest cost component for both populations. The higher cost per sample for the population with cardiac conditions was due to the inclusion of pharmacogenomics, higher bioinformatics labor costs, and a more labor intensive case review.ConclusionThis analysis indicated important variation in trio GS workflow and costs between pediatric populations in a single institution. Enhanced understanding of the clinical utility and costs of GS can inform harmonization and implementation decision-making.     

Efficacy and safety of intravenous and subcutaneous immunoglobulin therapy in idiopathic inflammatory myopathy: A systematic review and meta-analysis

ObjectiveTo perform a systematic review and meta-analysis on the efficacy and safety of intravenous (IVIg) and subcutaneous (SCIg) immunoglobulin (Ig) therapy in the treatment of idiopathic inflammatory myopathy (IIM) and juvenile dermatomyositis (JDM).MethodsPubMed, Embase and SCOPUS were searched to identify studies on Ig therapy in patients with IIM and/or JDM (2010?2020). Outcome measures were complete response (CR) or partial response (PR) in terms of muscle power and extramuscular disease activity measures on the International Myositis Assessment and Clinical Studies Group (IMACS) core set domains.ResultsTwenty-nine studies were included (n = 576, 544 IIM, 32 JDM). Muscle power PR with pooled Ig therapy was 88.5% (95% confidence interval (CI): 80.6–93.5, n = 499) and PR with SCIg treatment was 96.61% (95% CI: 87.43–99.15, n = 59). Pooled PR with first-line use of IVIg was 77.07% (95% CI: 61.25–92.89, n = 80). Overall, mean time to response was 2.9 months (95% CI: 1.9–4.1). Relapse was seen in 22.76% (95% CI: 14.9–33). Studies on cutaneous disease activity and dysphagia showed significant treatment responses. Glucocorticoid and immunosuppressant sparing effect was seen in 40.9% (95% CI: 20–61.7) and 42.2% (95% CI: 20.4–64.1) respectively. Ig therapy was generally safe with low risk of infection (1.37%, 95% CI: 0.1–2.6).ConclusionsAdd-on Ig therapy improves muscle strength in patients with refractory IIM, but evidence on Ig therapy in new-onset disease and extramuscular disease activity is uncertain.     

Severe infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides receiving rituximab: A meta-analysis

IntroductionThe efficacy of rituximab (RTX) for remission induction and maintenance in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) is now established, but the safety, particularly concerning severe infection risk, is not well known.ObjectiveThe purpose of this meta-analysis is to assess the prevalence and incidence of severe infections and the factors explaining heterogeneity in AAV patients treated with RTX.MethodsPubMed and Embase were searched up to December 2017. Prevalence and incidence was pooled using a random-effects model in case of significant heterogeneity (I² > 50%). Severe infection was defined as severe when it led to hospitalization, intravenous antibiotics therapy, and/or death. The heterogeneity was explored by subgroup analyses and meta-regression.ResultsThe included studies encompassed 1434 patients with a median age of 51.9 years. The overall prevalence and incidence of severe infections was 15.4% (95% CI [8.9; 23.3], I² = 90%, 33 studies) and 6.5 per 100 person-years (PY) (95% CI [2.9; 11.4], I² = 76%, 18 studies), respectively. The most common infections were bacterial (9.4%, 95% CI [5.1; 14.8]). The prevalence of opportunistic infection was 1.5% (95% CI [0.5; 3.1], I² = 58%) including pneumocytis jirovecii infections (0.2%, 95% CI [0.0; 0.6], I² = 0), irrespective of prophylaxis administration. Mortality related to infection was estimated at 0.7% (95% CI [0.2; 1.2], I² = 27%). The RTX cumulative dose was positively associated with prevalence of infections (13 studies, prevalence increase of 4% per 100 mg, p < .0001). The incidence of infection was negatively associated with duration of follow-up (8 studies, incidence decrease of 9% per year, p = .03).ConclusionPrevalence and incidence of severe infections, mainly bacterial ones, were high in AAV patients treated with RTX. This meta-analysis highlights the need for prospective studies to stratify infectious risk and validate cumulative RTX dose and duration of follow-up as modifying factors.     

Clinical efficacy and safety of baloxavir marboxil in the treatment of influenza: A systematic review and meta-analysis of randomized controlled trials

PurposeThe aim of this meta-analysis is to compare the clinical efficacy and safety of baloxavir with other anti-influenza agents or placebo in the treatment of influenza.MethodsPubMed, Embase, Web of Science, Google Scholar, Scopus, CINAHL, Cochrane databases and clinical registration were searched from inception until February 15 2021 for relevant randomized controlled trials (RCTs). Only phase 3 RCTs evaluating the usefulness of baloxavir in the treatment of influenza were included.ResultsThree RCTs enrolling 3771 patients (baloxavir group, n = 1451; oseltamivir group, n = 1288; placebo group, n = 1032) were included. Compared with oseltamivir, baloxavir had an insignificantly shorter time to the alleviation of symptoms (mean difference [MD], −1.29 h; 95% CI, −6.80 to 4.21; I² = 0%). In contrast, baloxavir had a significantly shorter time to the alleviation of symptoms than placebo (MD, −26.32 h; 95% CI, −33.78 to −18.86; I² = 0%). Baloxavir was associated with a significant decline in influenza virus titers and viral RNA load compared to oseltamivir and placebo. Baloxavir was associated with a lower risk of any adverse events than oseltamivir (OR, 0.82; 95% CI, 0.69–0.98; I² = 0%) and placebo (OR, 0.79; 95% CI, 0.66–0.96; I² = 0%).ConclusionsThe findings of this meta-analysis suggested that baloxavir is superior to placebo in the treatment of influenza in both clinical outcome and virological response. Moreover, baloxavir was found to have a better virological response than oseltamivir and to be as effective as oseltamivir clinically. Compared with oseltamivir and placebo, baloxavir appears to be a relatively safe anti-influenza agent.     

Efficacy of various forms of acupuncture for the treatment of urinary incontinence in women: A systematic review and meta-analysis

Background and purposeEvidence regarding the efficacy of various forms of acupuncture for the treatment of urinary incontinence (UI) in women is outdated and inconclusive. This review aims to determine the efficacy of different forms of acupuncture for the treatment of UI in women.MethodsMultiple databases were searched from inception to June 2020. Randomized controlled trials that compared various forms of acupuncture to control were included.ResultsTen trials were included in this review. The pooled analysis demonstrated that an increased proportion of women with stress UI (SUI) reported fewer UI episodes (1.73 [95% CI 1.46, 2.04]; p < 0.00001) in the electroacupuncture group than in the sham group. The meta-analysis also revealed a significantly increased number of women who reported the complete cure of SUI in the electroacupuncture combined with pelvic floor muscle training group than in the medication group (RR 2.67 [95% CI 1.51, 4.71]; p = 0.0007). Body and laser acupuncture caused significant decreases in the number of urge accidents (-2.70 [95% CI -4.86, -0.54]; p = 0.01) and the occurrence of urgency symptoms (-3.60[95% CI -5.34, -1.86]; p < 0.0001), compared with sham acupuncture.ConclusionsBased on the findings of this review, electroacupuncture may be able to improve SUI in women in clinical settings. This review also identified evidence supporting the use of body, electro,- and laser acupuncture for the treatment of urge UI; however, these results were obtained from single studies, and further research remains necessary to confirm the effects of these interventions on the treatment of urge UI in women.     

Self-efficacy and health-related quality of life in chronic obstructive pulmonary disease: A meta-analysis

ObjectiveTo determine the association between self-efficacy and health-related quality of life (HRQoL) in people with Chronic Obstructive Pulmonary Disease (COPD) and the moderating effect of self-efficacy type (exercise task, exercise barrier, COPD symptom, general) and HRQoL type (generic, COPD specific).MethodsDatabases were searched systematically from inception to January 2019. Methodological quality was assessed, and a meta-analysis was conducted following PRISMA guidelines (PROSPERO protocol: CRD42018114846).ResultsAcross 31 coefficients, there was a positive relationship between self-efficacy and HRQoL (r = 0.38, 95 %CI [0.32, 0.45]). Exercise barrier self-efficacy had the strongest relationship to HRQoL (r = 0.42, 95 % CI [0.30, 0.52]), followed by COPD symptoms (r = 0.41, 95 % CI [0.33, 0.49]), exercise tasks (r = 0.40, 95 % CI [0.29, 0.50]), and general self-efficacy (r = 0.21, 95 % CI [0.14, 0.28]). Generic HRQoL had a similar relationship to self-efficacy (r = 0.38, 95 % CI [0.28, 0.47]) as COPD specific HRQoL (r = 0.38, 95 % CI [0.30, 0.46]).ConclusionThere is a moderate positive relationship between self-efficacy and HRQoL in COPD, with the relationship stronger for exercise and COPD symptoms than general self-efficacy.     

The effects of acupressure on postoperative nausea and vomiting among patients undergoing laparoscopic surgery: A meta-analysis of randomized controlled trials

Background and objectiveLaparoscopic surgery is one of the most commonly performed surgeries in general surgery, with fewer side effects and rapid recovery. Postoperative nausea and vomiting (PONV) remains the main challenge that confronts the prognosis of this minimally invasive surgery. We aimed to evaluate the effect of acupressure, a nonpharmacological non-invasive method, on the incidence of nausea and vomiting following laparoscopic surgery within the early phase (first six hours postoperatively) and the extended phase (for at least 24 h postoperatively).MethodsWe searched PubMed, Cochran, Scopus, Web of Science, Google scholar, and Wiley for randomized controlled trials that evaluated the effect of acupressure on PONV in patients undergoing laparoscopy. Data were extracted and analyzed in a random model, and pooled risk ratios (RRs) with their respective 95% confidence intervals (CIs) were calculated.ResultsEleven trials were included in the meta-analysis, comprising 941 patients. Most of the included patients were females undergoing gynecological laparoscopy or laparoscopic cholecystectomy. Acupressure significantly lowered the incidence of nausea and vomiting, within the early phase (RR = 0.62, 95% CI [0.44 to 0.88]; p = 0.008), (RR = 0.5, 95% CI [0.30 to 0.84]; p = 0.008), and the extended phase (RR = 0.65, 95% CI [0.52 to 0.83]; p = 0.0003), (RR = 0.44, 95% CI [0.32 to 0.61]; p < 0.00001), respectively. Moreover, acupressure significantly reduced the need for rescue antiemetic drugs in both phases (p < 0.05).ConclusionAcupressure is an effective procedure for reducing nausea, vomiting, and the need for antiemetic drugs after laparoscopic surgery.     

Novel point-of-care biomarker combination tests to differentiate acute bacterial from viral respiratory tract infections to guide antibiotic prescribing: a systematic review

BackgroundAcute respiratory tract infections (RTIs) are the most common reason to seek medical care, with many patients receiving inappropriate antibiotics. Novel testing approaches to identify aetiology at the point-of-care are required to accurately guide antibiotic treatment.ObjectiveTo assess the diagnostic accuracy of biomarker combinations to rapidly differentiate between acute bacterial or viral RTI aetiology.Data sourcesMEDLINE, Embase and Web of Science databases were searched to February 2021.Study eligibility criteriaDiagnostic accuracy studies comparing accuracy of point-of-care and rapid diagnostic tests in primary or secondary care, consisting of biomarker combinations, to identify bacterial or viral aetiology of RTI.MethodsRisk of bias was assessed using the QUADAS-2 tool. Sensitivity and specificity of tests reported by more than one study were meta-analysed using a random effects model.ResultsTwenty observational studies (3514 patients) were identified. Eighteen were judged at high risk of bias. For bacterial aetiologies, sensitivity ranged from 61% to 100% and specificity from 18% to 96%. For viral aetiologies, sensitivity ranged from 59% to 97% and specificity from 74% to 100%. Studies evaluating two commercial tests were meta-analysed. For ImmunoXpert, the summary sensitivity and specificity were 85% (95% CI 75%–91%, k = 4) and 86% (95% CI 73%–93%, k = 4) for bacterial infections, and 90% (95% CI 79%–96%, k = 3) and 92% (95% CI 83%–96%, k = 3) for viral infections, respectively. FebriDx had pooled sensitivity and specificity of 84% (95% CI 75%–90%, k = 4) and 93% (95% CI 90%–95%, k = 4) for bacterial infections, and 87% (95% CI 72%–95%; k = 4) and 82% (95% CI 66%–86%, k = 4) for viral infections, respectively.ConclusionCombinations of biomarkers show potential clinical utility in discriminating the aetiology of RTIs. However, the limitations in the evidence base, due to a high proportion of studies with high risk of bias, preclude firm conclusions. Future research should be in primary care and evaluate patient outcomes and cost-effectiveness with experimental study designs.Clinical trialPROSPERO registration number: CRD42020178973.     

Prenatal and early-life exposure to indoor air-polluting factors and allergic sensitization at 2 years of age

BackgroundPrevious studies have suggested that exposures to indoor air-polluting factors during pregnancy and early life can influence childhood allergy development. These exposures have been investigated in singularity; however, the effect of simultaneous exposure to multiple factors remains unclear.ObjectiveTo evaluate the effect of prenatal and early-life exposure to 7 air-polluting factors on allergic sensitization at 2 years of age.MethodsMother-child pairs (n = 108) enrolled in the Kingston Allergy Birth Cohort were followed up from birth to 2 years of age. Exposure to air fresheners, candles, mold, cats, dogs, carpet, and environmental tobacco smoke (ETS) during the prenatal, 6-month, 1-year, and 2-year time points were obtained. A skin prick test (SPT) was performed on both the mother and the 2-year-old child.ResultsExposure to candles during the prenatal window, cats during the 6-month window, and ETS at 2 years significantly increased the odds ratio (OR) of a positive SPT result (candles: OR, 5.096; 95% CI, 1.69-13.86; P = .006; cat: OR, 4.267; 95% CI, 1.096-15.68; P = .048; and ETS: OR, 3.78; 95% CI, 1.189-11.18; P = .04). Children with a positive SPT result had significantly more exposures than SPT-negative children (prenatal P = .005, 1-year P = .03, and 2-year P = .008). As the total number of exposures increased, the percentage of SPT-positive children increased (prenatal P = .005, 1-year P = .03, and 2-year P = .01).ConclusionWe have provided evidence supporting the role of the indoor environment on atopic disease development. The combined effect of multiple exposures may be more influential to allergy development than a single exposure.     

Exercise interventions in Alzheimer’s disease: A systematic review and meta-analysis of randomized controlled trials

AimsTo assess the potential multi-domain benefits of exercise interventions on patients with Alzheimer’s disease (AD), as well as to determine the specific effects of different exercise modalities (aerobic, strength, or combined training).MethodsA systematic search was conducted in PubMed and Web of Science until March 2021 for randomized controlled trials assessing the effect of exercise interventions (compared with no exercise) on patients with AD. Outcomes included cognitive function (mini-mental state examination [MMSE] test), physical function (e.g., 6-minute walking test [6MWT]), functional independence (Barthel index), and neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI]). A random-effects meta-analysis was conducted.Results28 studies (total n = 1337 participants, average age 79–90 years) were included in the systematic review, of which 21 could be meta-analyzed. Although considerable heterogeneity was found, exercise interventions induced several significant benefits, including in Barthel index (n = 147 patients, mean difference [MD]=8.36 points, 95% confidence interval [CI]=0.63–16.09), 6MWT (n = 369, MD=84 m, 95% CI=44–133)), and NPI (n = 263, MD=−4.4 points, 95% CI=−8.42 to −0.38). Benefits were also found in the MMSE test, albeit significance was only reached for aerobic exercise (n = 187, MD=2.31 points, 95% CI 0.45–4.27).ConclusionsExercise interventions appear to exert multi-domain benefits in patients with AD.     

The personal utility and uptake of genomic sequencing in pediatric and adult conditions: eliciting societal preferences with three discrete choice experiments

PurposeTo estimate the personal utility and uptake of genomic sequencing (GS) across pediatric and adult-onset genetic conditions.MethodsThree discrete choice experiment (DCE) surveys were designed and administered to separate representative samples of the Australian public. Bayesian D-efficient explicit partial profile designs were used. Choice data were analyzed using a panel error component random parameter logit model.ResultsOverall, 1913 participants completed the pediatric (n = 533), symptomatic adult (n = 700) and at-risk adult (n = 680) surveys. The willingness-to-pay for GS information in pediatric conditions was estimated at $5470–$15,250 (US$3830–$10,675) depending on the benefits of genomic information. Uptake ranged between 60% and 81%. For symptomatic adults, the value of GS was estimated at $1573–$8102 (US$1100–$5671) and uptake at 34–82%. For at-risk adults, GS was valued at $2036–$5004 (US$1425–$3503) and uptake was predicted at 35–61%.ConclusionThere is substantial personal utility in GS, particularly for pediatric conditions. Personal utility increased as the perceived benefits of genomic information increased. The clinical and regulatory context, and individuals’ sociodemographic and attitudinal characteristics influenced the value and uptake of GS. Society values highly the diagnostic, clinical, and nonclinical benefits of GS. The personal utility of GS should be considered in health-care decision-making.