Association of HIV infection and cognitive impairment in older adults: A meta-analysis

ObjectiveTo synthesize evidence on the association between human immunodeficiency virus (HIV) infection and cognitive impairment in older adults.DesignMeta-analysis.ParticipantsAdults aged 50 years or older.MethodsIn this systematic literature review and meta-analysis, we searched PubMed, Scopus, Embase, and APA/PsycNet for studies published before July 21, 2020, that assessed the association between HIV-infection and cognitive impairment. We calculated pooled odds ratios (ORs) of cognitive impairment for people living with HIV (PLWH) and 95 % confidence intervals (CIs) using random-effect models and calculated pooled mean difference (MD) for major cognitive domains between PLWH and HIV-uninfected adults. We assessed risk of bias using the Newcastle-Ottawa scale.ResultsOf the 4432 studies identified, 21 cross-sectional studies were eligible for the meta-analysis, including 15 examining global cognitive impairment. The meta-analysis showed that older PLWH were more likely to be cognitively impaired than HIV-uninfected controls (OR = 2.44, 95 % CI = [1.69, 3.53], number of estimates (k) = 15, I² = 71 %). This higher likelihood was shown in studies from high income countries (OR = 2.63, 95 % CI = [1.76, 3.94], k = 12, I² = 55 %), but not from upper-middle income countries (OR = 1.96, 95 % CI = [0.26, 14.68], k = 3, I² = 91 %). PLWH had lower scores than HIV-uninfected adults in 5 out of 7 major cognitive domains, including executive function (MD = -0.42, 95 % CI = [-0.72, -0.11], k = 5, I² = 32 %), processing speed (MD = -0.33, 95 % CI = [-0.59, -0.08], k = 6, I² = 16 %), verbal (MD=-0.29, 95 % CI = [-0.48, -0.10], k = 6, I² = 0%), recall (MD = -0.24, 95 % CI = [-0.38, -0.10], k = 6, I² = 0%) and motor/psychomotor (MD = -0.38, 95 % CI = [-0.59, -0.16], k = 5, I² = 31 %) performance.Conclusions/implicationsOur meta-analysis provides empirical evidence that HIV infection is associated with an increased risk of cognitive impairment among older adults, especially in cognitive domains of executive function, processing speed, verbal, recall, and motor/psychomotor.     

The changing pattern of statin use in people with dementia: A population-based study

BackgroundAfter a dementia diagnosis, goals of care are often reassessed, including the use of preventive medications like statins.ObjectiveTo examine changes in statin use after initiating medication for managing dementia.MethodsA case-crossover study utilizing medication dispensing data from the Australian Pharmaceutical Benefits Scheme (PBS) 10% random sample was conducted. Use of statins was compared in the 12 months pre- and post-initiation (pre-period and post-period) of anti-dementia medications or risperidone for behavioural symptoms of dementia. Individuals aged ≥65 years who had their first dispensing of anti-dementia medication or risperidone between July 2006 and June 2017 and survived ≥12 months after their first supply were included. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for change in statin use in the discordant pairs.ResultsThe cohort (n = 19,809) had a median age of 81 years and 61% were female. Statins were less likely to be used after initiating anti-dementia medication or risperidone (OR 0.50; 95%CI 0.45–0.55). The OR for statin use in the post-period versus the pre-period decreased annually over the 11 years from 1.21; 95%CI 0.84–1.75 in 2006–7 to 0.31; 95%CI 0.24–0.41 in 2016–17 (p for interaction <0.05).ConclusionStatins are more likely to be ceased than started after initiating medication for dementia. This may reflect changes in goals of care, or changes in the interpretation of the available evidence for the safety and efficacy of statins in older people living with dementia.     

Risk of cancer in multiple sclerosis (MS): A systematic review and meta-analysis

Objective: To assess the pooled risk of cancer in patients with multiple sclerosis.Methods: We searched PubMed, Scopus, EMBASE, Web of Science, Ovid, google scholar and gray literature (references of studies, conference abstracts) which were published up to September 2019. The search strategy included the MeSH and text words as ((cancer) OR tumor) OR neoplasm) OR “malignant neoplasm) OR “benign neoplasm) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating).Results: The first literature search revealed 18,996 articles. After deletion of duplicate articles, finally, 264 articles remained. Excluding non-relevant articles, resulted in including 5 articles which met inclusion criteria.The RR estimated between 0.7 and 1.67 in included articles.The pooled RR estimated as 0.83 (95% CI:0.73–0.96) (I² = 90%, P < 0.001).Two studies provided prevalence of different cancers.The pooled prevalence of breast cancer in two studies was 2% (95%CI:2%–2%) (I² = 0%).The pooled prevalence of digestive system cancer in two studies was 2% (95%CI:1%–2%) (I² = 0%).The pooled prevalence of skin cancer in two studies was 1% (95%CI:0%–1%) (I² = 0).Conclusion: The result of this systematic review showed that the risk of cancer in patients with MS is less than the general population.     

Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis

ObjectivesCytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients.MethodsData sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I². We assessed the certainty of evidence using the GRADE approach.ResultsOf 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80–1.49, I² = 0%). Four RCTs with 771 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.71 (95%CI 0.52–0.96, I² = 0%), with a corresponding number needed to treat of 17 (95%CI 9–100). Among 18 cohorts at moderate risk of bias with 9850 patients, the pooled adjusted RR for mortality was 0.58 (95%CI 0.51–0.66, I² = 2.5%). This association was observed over all degrees of COVID-19 severity. Data from the RCTs did not show a higher risk of infections or adverse events with tocilizumab: pooled RR 0.63 (95%CI 0.38–1.06, five RCTs) and 0.83 (95%CI 0.55–1.24, five RCTs), respectively.ConclusionsCumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.     

Influenza vaccination reduces dementia risk: A systematic review and meta-analysis

Animal models have indicated that influenza vaccination may prevent or delay the onset of dementia. However, the epidemiological evidence in human beings is still limited. Given this background, this systematic review and meta-analysis aimed to summarize the current state of the art of observational studies investigating the association between influenza vaccination and the risk of dementia. We searched Scopus and Pubmed/Medline until 24 September 2021 for studies investigating the risk of dementia by influenza vaccination status. After adjustment for potentially important confounding variables, data were reported as risk ratios (RRs) with 95% confidence intervals (CIs). Among 273 articles initially evaluated, five were included for a total of 292,157 older people free from dementia at baseline (mean age=75.5 ± 7.4 years; 46.8% females). All studies were of high quality. Over a mean follow-up of 9 years, influenza vaccination mitigated the risk of dementia (RR=0.97; 95%CI: 0.94–1.00; I² =99%). This association held after adjustment for a mean of nine potential confounders (RR=0.71; 95%CI: 0.60–0.94; I² =95.9%). In sensitivity analysis, removing one study from the adjusted analyses, the adjusted RR remained similar (RR= 0.67; 95%CI: 0.63–0.70), but the heterogeneity disappears (I² =0%). In conclusion, influenza vaccination was associated with a significantly lower risk of dementia suggesting that the vaccination of older people against influenza may also aid in the prevention of dementia.     

Associations between loneliness and physical frailty in community-dwelling older adults: A systematic review and meta-analysis

ObjectivesOlder adults may be at increased risk of loneliness. Frailty is also common in older adults, however, associations between loneliness and frailty have been understudied. This systematic review and meta-analysis aimed to explore evidence on how loneliness and frailty are correlated.MethodsA systematic search of the literature was conducted using 4 electronic databases in February 2022 for any studies published in 2000 or later that provided cross-sectional or longitudinal associations between loneliness and physical frailty in community-dwelling older adults. A meta-analysis was attempted to combine data when possible.ResultsFrom 1386 studies identified by the initial search, 16 studies were included for this review. Standardized mean difference (SMD) meta-analysis based on mean loneliness score across 3 frailty groups provided by 6 cross-sectional studies showed that worse frailty status was significantly associated with a higher degree of loneliness (SMD between frail and robust, frail and prefrail, and prefrail and robust were 0.77 (95% confidence interval (CI)= 0.57–0.96), 0.37 (95%CI=0.25–0.50), and 0.30 (95%CI=0.20–0.40), respectively.) Meta-analyses combining cross-sectional data from 6 studies revealed that frailty was significantly associated with a higher risk of loneliness compared with robustness (3 studies: pooled OR=3.51, 95%CI=2.70–4.56 for frailty, pooled OR=1.88, 95%CI=1.57–2.25 for prefrailty) and compared with non-frailty (4 studies: pooled OR=2.05, 95%CI=1.76–2.39). A meta-analysis involving two longitudinal studies showed that baseline loneliness was associated with a significantly higher risk of worsening frailty (2 studies: pooled OR=1.41, 95%CI=1.16–1.72).ConclusionsThis systematic review and meta-analysis was the first, to our knowledge, to quantitatively demonstrate significant cross-sectional and longitudinal associations between loneliness and frailty in community-dwelling older adults.     

Efficacy of repetitive transcranial magnetic stimulation for post-stroke depression: a systematic review and meta-analysis of randomized clinical trials

We aimed to conduct a meta-analysis to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with post-stroke depression (PSD). Six relevant electronic databases (PubMed, CENTRAL, Embase, Web of Science, CINAHL, and PsycINFO) were searched. Randomized controlled trials (RCTs) that compared rTMS with control condition for PSD were included. The mean change in depression symptom scores was defined as the primary efficacy outcome. Secondary outcomes included the remission rate of depression, stroke recovery, and cognitive function recovery. In total, 7 RCTs with 351 participants were included. At post-treatment, rTMS was significantly more effective than the control condition, with a standardized mean difference (SMD) of -1.15 (95%CI: -1.62 to -0.69; P<0.001, I²=71%) and remission with an odds ratio (OR) of 3.46 (95%CI: 1.68 to 7.12; P<0.001; I²=11%). As for stroke recovery, rTMS was also better than the control condition (SMD=-0.67, 95%CI: -1.02 to -0.32; P<0.001). However, no significant difference was found for cognitive function recovery between the two groups (SMD=4.07, 95%CI: -1.41 to 9.55; P=0.15). To explore the potential moderators for the primary outcome, a series of subgroup and sensitivity analyses were performed. The results implied that rTMS may be more effective in Asian samples than in North American samples (P=0.03). In conclusion, from the current evidence in this study, rTMS could be an effective treatment for patients with PSD. Further clinical studies with larger sample sizes and clearer subgroup definitions are needed to confirm these outcomes.     

Prognostic and clinicopathological significance of SR-B1 in solid tumors: A meta-analysis

BackgroundThe expression of cell surface receptors is abnormal in malignant tumors. The scavenger receptor class B type I (SR-B1) is an integral membrane glycoprotein receptor that facilitates the selective uptake of cholesterol by malignant cells. Accumulated studies investigated the prognostic role of SR-B1 in many solid tumors, such as breast cancer, lung cancer and so on. However, the conclusions remain undefined. Therefore, we conducted this meta-analysis to obtain more accurate evaluation of prognostic significance of SR-B1 in solid tumors.Materials and methodsWe searched PubMed, Embase, Web of science and Cochrane library for eligible studies published before November 2018. The included studies investigated the association between the SR-B1 level and clinicopathological features including survival outcomes in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were adopted to assess the survival outcomes and odds ratio (ORs) with 95% confidence intervals (CIs) were pooled to evaluated the clinicopathological features.ResultsA total of 10 studies involving 2585 patients were included in this meta-analysis. The results showed that low SR-B1 level was significantly correlated with earlier tumor grade (pooled OR = 2.09, 95%CI = 1.28–3.43, P = 0.001), less nodal involvement (pooled OR = 2.07, 95%CI = 1.43–3.0, P < 0.001), less distant metastasis (OR = 19.8, 95%CI = 2.58–151.65, P = 0.004), smaller tumor size (OR = 2.34, 95%CI = 1.53–3.57, P < 0.001), earlier TNM stage (OR = 3.77, 95%CI = 1.67–8.48, P = 0.001), lower recurrence (HR = 1.98, 95%CI = 1.57–2.49, P = 0.000), and better OS (HR = 1.99, 95%CI = 1.70–2.31, P = 0.000).ConclusionThe low expression of SR-B1 was significantly associated with better clinicopathological status and longer survival in patients with solid tumors. SR-B1 might act as a promising prognostic biomarker for solid tumors.     

Hyperhomocysteinemia and risk of incident cognitive outcomes: An updated dose-response meta-analysis of prospective cohort studies

ObjectiveThis study aimed to comprehensively assess the dose-response relationship between blood homocysteine levels and risk of all cause, Alzheimer and vascular dementia, as well as cognitive impairment without dementia (CIND).MethodWe searched for all related prospective cohort studies reporting homocysteine as an exposure from patients with cognitive disorders as a result in the PubMed and EMBASE databases up to June 18, 2018. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were extracted. The dose-response meta-analyses were conducted to assess potential linear and non-linear dose-response relations. Summary RRs and 95% CIs were calculated using a random- or fixed-effects model.ResultsTwenty-eight prospective cohort studies were eligible in this meta-analysis. During average follow-up periods ranging from 2.7 to 35 years there were 2557 cases (1035 all-cause dementia, 530 Alzheimer’s disease, 92 vascular dementia and > 900 CIND) among 28,257 participants. There was a clear linear dose-response relationship between blood homocysteine concentration and risk of Alzheimer-type dementia (P > 0.05 for non-linearity). The pooled RR of Alzheimer-type dementia was 1.15 (95% CI: 1.04 to 1.26; I² = 56.6%, n = 5) for every 5 μmol/L increase in blood homocysteine. Sensitivity analysis showed similar results, and there was no clear evidence of publication bias with Begg’s and Egger’s tests for Alzheimer dementia (P = 0.806, 0.084, respectively), strengthening the linear relationship between blood homocysteine levels and risk of Alzheimer dementia. Due to the presence of publication bias and low statistical power, elevated levels of blood homocysteine were not appreciably associated with risk of all-cause, vascular dementia and CIND.ConclusionsEvery 5 μmol/L increase in blood homocysteine is linearly associated with a 15% increase in relative risk of Alzheimer-type dementia. This meta-analysis provides further evidence that a higher concentration of blood homocysteine is associated with a higher risk of Alzheimer-type dementia.     

Risk of seizures and subclinical epileptiform activity in patients with dementia: A systematic review and meta-analysis

BackgroundSeizures and subclinical epileptiform activity are common yet easily overlooked among demented patients. We aimed to investigate their epidemiological characteristics in patients with dementia from various aspects.MethodsWe retrieved relevant observational studies from PubMed and Embase Library until March 2021. Pooled estimate effects were calculated using random-effects models. This study is registered with PROSPERO, number CRD42020200949.ResultsOf the 19144 identified studies, 27 were eligible for inclusion. The pooled period prevalence rates of seizures were 4.86% (95%CI: 3.43–6.51%), 2.68% (95%CI: 2.13–3.28%), 2.81% (95%CI: 2.02–3.71%）and 7.13% (95%CI: 2.67–13.14%) among patients with Alzheimer’s disease (AD), Dementia of Lewy Body (DLB), Frontotemporal dementia (FTD) and Vascular dementia (VaD), respectively. The pooled incidence rate of seizures was [8.4 (95%CI: 4.2–12.7) per 1000 person-years] in AD patients. And the pooled relative risk of seizures in patients with AD was 3.35 (95%CI: 2.69–4.19). Besides, the pooled cumulative incidence rate and prevalence rate of subclinical epileptiform activity among AD patients were [21.41% (95%CI: 0.001–63.60%)] and 9.73% (95%CI: 0.26–28.38%), respectively.ConclusionsThe accurate rates of seizures and subclinical epileptiform activities in the four major dementia types are high. Besides, patients with AD are likely at a higher risk of seizures.     

Cerebral small vessel disease and the risk of Alzheimer’s disease: A systematic review

BackgroundCerebral small vessel disease (CSVD) comprises a variety of disorders affecting small arteries and microvessels of the brain, manifesting as white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and deep brain infarcts. In addition to its contribution to vascular dementia (VaD), it has also been suggested to contribute to the pathogenesis of Alzheimer’s disease (AD).MethodA systematic review of the literature available on Medline, Embase and Pubmed was undertaken, whereby CSVD was divided into WMHs, CMBs and deep brain infarcts. Biomarkers of AD pathology in the cerebrospinal fluid or plasma, or positron emission tomographic imaging for amyloid and/or tau deposition were used for AD pathology.ResultsA total of 4117 articles were identified and 41 articles met criteria for inclusion. These consisted of 17 articles on vascular risk factors for clinical AD, 21 articles on Aβ pathology and 15 articles on tau pathology, permitting ten meta-analyses. CMBs or lobar CMBs were associated with pooled relative risk (RR) of AD at 1.546, (95%CI 0.842–2.838, z = 1.41 p = 0.160) and 1.526(95%CI 0.760–3.063, z = 1.19, p = 0.235) respectively, both non-significant. Microinfarcts were associated with significantly increased AD risk, with pooled odds ratio OR at 1.203(95%CI 1.014–1.428, 2.12 p = 0.034). Aβ pathology was significantly associated with WMHs in AD patients but not in normal age-matched controls. The pooled β (linear regression) for total WMHs with CSF Aβ42 in AD patients was -0.19(95%CI -0.26–0.11, z = 4.83 p = 0.000) and the pooled r (correlation coefficient) for WMHs and PiB in the normal population was -0.10 (95%CI -0.11–0.30, 0.93 p = 0.351). CMBs were significantly associated with Aβ pathology in AD patients. The pooled standardized mean difference (SMD) was -0.453, 95%CI -0.697– -0.208, z = 3.63 p = 0.000. There was no significant relationship between the incidence of lacunes and levels of CSFAβ, with a pooled β of 0.057 (95%CI -0.050–0.163, z = 1.05 p = 0.295). No significant relationship was found between CMBs and the levels of CSFt-tau/CSFp-tau in AD patients (-0.014, 95%CI -0.556–0.529, z = 0.05 p = 0.960; -0.058, 95%CI -0.630–0.515, z = 0.20 p = 0.844) and cortical CMBs and CSF p-tau in the normal population (0.000, 95%CI -0.706–0.706, z = 0.00 p = 0.999).ConclusionsSome CSVD markers were significantly associated with clinical AD pathology and may be associated with Aβ/tau pathology. WMHs and microinfarcts were associated with increased risk of AD. It remains unclear whether they precede or follow AD pathology.     

Affective symptoms and risk of progression to mild cognitive impairment or dementia in subjective cognitive decline: A systematic review and meta-analysis

AimsTo systematically review the literature on outcomes for individuals with subjective cognitive decline (SCD) with concurrent affective symptoms. To conduct a meta-analysis to establish whether either higher depressive symptoms or higher levels of anxiety increased the risk of progression SCD to mild cognitive impairment (MCI) or dementia.MethodsFive databases were searched from inception to February 2021 for longitudinal studies of older adults with SCD, reporting depressive and anxiety symptoms at baseline and risk of MCI or dementia at follow-up. Data were extracted and pooled using a random-effects meta-analysis.ResultsTwelve studies were identified. Pooled effect sizes indicated higher depressive symptoms did not increase risk of clinical progression to either MCI (RR = 0.98; 95 % CI: 0.75–1.26) or dementia (RR = 0.69; 95 % CI: 0.27–1.79). However, presence of anxiety or SCD-related worry did significantly increase risk of progression from subjective to objective cognitive impairment by 40 % (RR = 1.40; 95 % CI:1.20 – 1.63).ConclusionsAffective symptoms in the form of anxiety, but not depressive symptoms, increase the risk of progression to objective cognitive impairment in individuals with SCD. Further research should focus on establishing whether psychological interventions aimed at reducing anxiety and worry also reduce the risk of clinical progression.     

Is living alone a risk factor of frailty? A systematic review and meta-analysis

ObjectivesTo examine the association of living alone with frailty in cross-sectional and longitudinal studies by a systematic review and meta-analysis.DesignSystematic review and meta-analysis.Setting and participantsCommunity-dwelling older adults with a mean age of >60 years.MethodsA systematic search of the literature was conducted according to the PRISMA guidelines. We searched PubMed in February 2019 without language restriction for cohort studies that examined the associations between living alone and frailty. The reference lists of the relevant articles and the included articles were reviewed for additional studies. We calculated pooled odds ratios (OR) of the presence and incidence of frailty for living alone from cross-sectional and longitudinal studies.ResultsAmong the 203 studies identified, data of 44 cross-sectional studies (46 cohorts) and 6 longitudinal studies were included in this review. The meta-analysis showed that older adults living alone were more likely to be frail than those who were not (46 cohorts: pooled OR = 1.28, 95 % confidence interval (CI) = 1.13–1.45, p < 0.001). Gender-stratified analysis showed that only men living alone were at an increased risk of being frail (20 cohorts: pooled OR = 1.71, 95 %CI = 1.49–1.96), while women were not (22 cohorts: pooled OR = 1.00, 95 %CI = 0.83–1.20). No significant association was observed in a meta-analysis of longitudinal studies (6 cohorts: pooled OR = 0.88, 95 %CI = 0.76–1.03).Conclusions/ImplicationsThe present systematic review and meta-analysis showed a significant cross-sectional association between living alone and frailty, especially in men. However, living alone did not predict incident frailty. More studies controlling for important confounders, such as social networks, are needed to further enhance our understanding of how living alone is associated with frailty among older adults.     

The Effect of Flavonoids on Chronic Prostatitis: A Meta-analysis of Published Randomized Controlled Trials

ObjectiveTo assess the effect of flavonoids on chronic prostatitis, a meta-analysis of randomized controlled trials was performed.MethodsThrough using subject word and random word, PubMed, Scopus, Web of Science, and Cochrane Library were searched for related records up to July 2018. The response rate and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) were used to evaluate the therapeutic efficacy of the flavonoids. The Cochrane handbook for systematic reviews of interventions version was used to evaluate the quality of included studies. The model of determining odds ratio (OR) was chose according to the value of I².ResultsA total of 11 studies involving 975 subjects (experiment 516, control 459) were included. The overall OR of response rate was 0.31 (95%CI 0.11–0.89, P = 0.03). At the subgroup analysis, the OR of response rate of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) was 0.57 (95%CI 0.18–1.77, P = 0.33), while the OR of response rate of chronic bacterial prostatitis (CBP) was 0.08 (95%CI 0.02–0.33, P = 0.0005). The OR of response rate of CP/CPPS (control was placebo) was 0.29 (95%CI 0.16–0.52, P < 0.0001). The overall OR of baseline NIH-CPSI was ?0.1 (95%CI -0.61–0.41, P = 0.70). The overall OR of posttreatment NIH-CPSI was ?6.96 (95%CI -8.32～ ?5.60, P < 0.00001).ConclusionsThis meta-analysis indicates that the flavonoids may be clinically beneficial through significantly improving the response rate and NIH-CPSI in chronic prostatitis patients and short-lasting antibiotics therapy in association with the flavonoids could be a better choose for CBP. Moreover, the flavonoids therapy has an excellent safety profile with minor adverse effects.     

Primary Sjögren's syndrome is associated with increased risk of malignancies besides lymphoma: A systematic review and meta-analysis

ObjectivePatients with primary Sjögren's syndrome(pSS) have increased risk of non-Hodgkin lymphoma (NHL). However, whether pSS patients have increased risk of other malignancies is unclear. The aim of this study is to investigate the association between pSS and the risk of malignancy, with a focus on hematological malignancies besides lymphoma and solid tumors through a systematic review and meta-analysis.MethodWe searched PubMed and EMBASE by March 21st 2021. Inclusion criteria were as follows: (1) pSS was the exposure of interest; (2) newly developed malignancies were the outcome of interest; (3) standardized incidence ratio or relative risk with 95% confidence interval or essential data to calculate them were reported. (4) Study design was cohort study. Patient with other connective diseases were excluded. Quality assessment was conducted according to Newcastle-Ottawa Scale for cohort study. Random or fixed effect models were used to calculate the pooled SIR according to heterogeneity measured by I².ResultsA total of 1003 articles were found by a comprehensive search in PubMed and EMBASE. Twenty-eight articles were eligible. Four of them were from the same database, and the one with longest observational span was chosen. Therefore, twenty-five articles were included for final analysis, which involved more than 47,607 pSS patients with the follow-up of more than 452,468 person-year. We found that pSS was significantly associated with increased risks of overall malignancy(pooled SIR 2.17, 95%1.57–3.00), hematological malignancy(pooled SIR 11.55, 95%CI 4.32–30.90) including NHL(pooled SIR 13.71, 95%CI 8.83–21.29), Hodgkin lymphoma(pooled SIR 8.84, 95%CI 5.00–15.61), multiple myeloma(pooled SIR 8.27, 95%CI 3.08–22.24), leukemia(pooled SIR 2.56, 95%CI 1.78–3.69) and solid tumors(pooled SIR 1.39, 95%CI 0.90–2.13) including lung cancer(pooled SIR 1.55, 95%CI 1.29–1.85), thyroid cancer(pooled SIR 2.05, 95%CI 1.20–3.48), non-melanoma skin cancer(pooled SIR 1.71, 95%CI 1.08–2.72), kidney/urinary tract cancer(pooled SIR 1.36, 95%CI 1.02; 1.81), liver cancer(pooled SIR 1.70, 95%CI 1.13–2.57) and prostate cancer(pooled SIR 1.50, 95%CI 1.02–2.22).ConclusionThis meta-analysis showed that pSS patients had increased risk of overall cancer, which not only contributed by NHL, but also by other hematological malignancies and solid tumors.     

Clinical usefulness of gastric adenocarcinoma predictive long intergenic noncoding RNA in human malignancies: A meta-analysis

BackgroundGastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC), a newly identified lincRNA, was reported to be aberrantly expressed in several kinds of cancers and played an important role in tumor progression. This study was performed to systematically estimate the prognostic role of GAPLINC expression in cancer patients.MethodsSeveral electronic databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched for potential literature (updated to September 3, 2018). The pooled hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a fixed effects model using Stata12.0 software.ResultsThe pooled results indicated that elevated GAPLINC was significantly related to shorter overall survival (OS) (HR = 1.66, 95%CI: 1.40–1.93, p < 0.001), which was further validated using The Cancer Genome Atlas (TCGA) dataset. Furthermore, high GAPLINC expression was correlated with higher tumor grade (OR = 1.91, 95%CI: 1.35–2.70, p < 0.001), positive lymph node metastasis (OR = 2.80, 95%CI: 1.69–4.64, p < 0.001), deeper infiltration depth (OR = 2.44, 95%CI: 1.43–4.17, p = 0.001) and advanced clinical stage (OR = 3.54, 95%CI: 2.13–5.88, p < 0.001).ConclusionsOur results suggest that elevated GAPLINC was associated with poor clinical outcomes and might serve as a promising prognostic biomarker in cancer survivors.     

Proton pump inhibitor use and risk for recurrent Clostridioides difficile infection: a systematic review and meta-analysis

ObjectivesProton pump inhibitor (PPI) therapy is a potentially modifiable risk factor for recurrent Clostridioides difficile infection (CDI). Citing an absence of clinical trials, many guidelines do not provide recommendations for addressing PPI management. Our aim was to perform an updated systematic review and meta-analysis evaluating the association between PPI use and recurrent CDI addressing prior methodological limitations.MethodsData sources were MEDLINE and EMBASE. Eligible studies were cohort and case–control studies; there were no restrictions on study setting or duration of follow-up. Participants were adults with prior CDI who did or did not receive PPI therapy and were assessed for recurrent CDI. Summary (unadjusted) odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Prespecified subgroup analyses were performed to explore heterogeneity including study design, study quality, duration of follow-up, adjustment for confounders, and outcome definition.ResultsSixteen studies were included in the meta-analysis, comprising 57 477 patients with CDI, of whom 6870 (12%) received PPIs. The rate of recurrent CDI was 24% in patients treated with PPIs versus 18% in those who were not. A meta-analysis that pooled unadjusted odds ratios demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.69, 95%CI 1.46–1.96) versus those who did not. There was moderate heterogeneity between studies (I² 56%); however, a sensitivity analysis restricted to studies with 56 days of follow-up substantially reduced the heterogeneity (OR 1.59, 95%CI 1.36–1.85; I² 12%). An analysis restricted to multivariate studies that combined adjusted ORs also demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.49, 95%CI 1.12–2.00). No publication bias was identified.ConclusionsWe found significantly higher odds of recurrent CDI among users of PPIs that persisted across multiple sensitivity analyses. These results support stronger recommendations for PPI stewardship at CDI diagnosis.     

Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic review and meta-analysis

ObjectivesThe treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic review about seroconversion after SARS-CoV-2 vaccination in patients with IMIDs and impact of various drugs on seroconversion rates.MethodsElectronic databases were searched to identify relevant studies reporting seroconversion rates following SARS-CoV-2 vaccination in IMIDs. We calculated the pooled seroconversion rates after a single or two doses of vaccination, pooled seroconversion rates in patients with specific IMIDs, and rates in patients on various drugs/drug classes.ResultsTwenty-five studies were included in the systematic review. The pooled seroconversion rates after two doses of mRNA vaccination were higher (83.1, 95%CI: 74.9–89.0, I² = 90%) as compared to a single dose (69.3, 52.4–82.3, I² = 95%). The odds of seroconversion were lower in IMIDs as compared to healthy controls (0.05, 0.02–0.13, I² = 21%). The seroconversion rates in patients with inflammatory bowel disease (95.2, 95%CI: 92.6–96.9, I² = 0%), spondyloarthropathy (95.6, 95% CI: 83.4–98.9, I² = 35%), and systemic lupus erythematosus (90.7, 95%CI: 85.4–94.2, I² = 0%) were higher as compared to rheumatoid arthritis (79.5, 95% CI: 65.1–88.9, I² = 85%), and vasculitis (70.5, 95% CI: 52.9–83.5, I² = 51%). The seroconversion rates following double dose of mRNA were excellent (>90%) in those on anti-tumour necrosis factor (TNF), anti-integrin (vedolizumab), anti-IL 17 (secukinumab), anti-IL6 (Tocilizumab) and anti-IL12/23 (Ustekinumab) therapies but attenuated (<70%) in patients on anti-CD20 (Rituximab) or anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapies (Abatacept). The seroconversion rates were good (70–90%) with steroids, hydroxychloroquine, JAK inhibitors, mycophenolate mofetil and leflunomide. Combination of anti-TNF with immunomodulators (azathioprine, 6-meracptopurine, methotrexate) resulted in an attenuated vaccine response as compared to anti-TNF monotherapy.ConclusionSeroconversion rates after SARS-CoV-2 vaccination are lower in patients with IMIDs. Certain therapies (anti-TNF, anti-integrin, anti-IL 17, anti-IL6, anti-12/23) do not impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses.