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Background: Data on reference values for lean mass (LM) and fat mass (FM) in the Southeast Asian populations are currently lacking. Therefore, we aimed to estimate the normative values and generate anthropometric prediction models for LM and FM in the Thai population. Methods: Consecutive community-dwelling individuals aged 20-90 years were recruited from Srinagarind Hospital, Khon Kaen, Thailand, between 2010 and 2015. LM and FM were measured using dual energy X-ray absorptiometry. Age and sex stratified percentile of LM and FM were presented. Anthropometric prediction models for LM and FM were developed by using linear regression to generate competing models. Results: A total of 832 individuals (334 males and 498 females) were included in the study. The mean ± SD age, LM, and FM were 50.0 ± 16.2 years, 38.9 ± 8.0 kg, and 15.5 ± 7.7 kg, respectively. LM decreased with age from 49.4 kg in 20-29 years group to 42.3 kg in ≥70 years group in male and 34.6 kg in 30-39 years group to 30.8 kg in ≥70 years group in females. FM has an inverse U-shaped association with age, which peaked at 11.9 kg in 60-69 years group in males and 20.7 kg in 50-59 years group in females. Among the various anthropometric models, the models incorporating age, sex, weight, and height were considered the best fit for predicting both LM and FM. Conclusion: In the Thai population, peak LM was reached during early adulthood and decline with age, whereas FM showed an inverse U-shaped association with age. The prediction models incorporating age, sex, weight, and height were proposed as practical tools for assessing LM and FM in clinical practice.

In conducting a scoping review on the health effects of high-concentration cannabis products, we have uncovered pervasive methodological shortcomings within the cannabis literature. This paper begins by defining the 'causal effect' of interest for public health and delineating the desirable features of study design that can address crucial questions pertaining to public health and policy. We further delve into the methodological complexities inherent in studying the health effects of high-concentration cannabis products, describing challenges associated with the measurement of exposures and outcomes, confounding, selection bias, and the generalizability of findings. We introduce causal inference methods to mitigate potential biases in observational cannabis use studies. We identify specific areas that necessitate further development and investigation to deepen our understanding of this topic. Finally, this paper extends actionable recommendations, serving as a roadmap for upcoming research initiatives in this domain., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The current study aimed to investigate the prevalence trends of osteoporosis from 2003 to 2022 using data from the largest tertiary care referral center hospital in Northeastern Thailand. We reviewed 36,306 bone mineral density measurements of community-dwelling individuals aged > 45 years from the medical record database of Srinagarind Hospital, Khon Kaen, Thailand, between 2003 and 2022. We observed a significant increase in the crude prevalence of osteoporosis from 2003 to 2022. Meanwhile, the age-standardized prevalence increased more gradually., Purpose: To investigate the prevalence trends of osteoporosis from 2003 to 2022 using data from the largest tertiary care referral center in Northeastern Thailand., Methods: Bone mineral density (BMD) measurements of community-dwelling individuals aged > 45 years were reviewed from the medical record database of Srinagarind Hospital, Khon Kaen, Thailand, between 2003 and 2022. Osteoporosis was defined by a T-score of ≤  - 2.5. For each year, crude and age-standardized prevalence rates for osteoporosis stratified by site of measurement were calculated. Trend analysis was performed using the joinpoint regression method., Results: A total of 36,306 BMD measurements were identified between 2003 and 2022. The crude prevalence of femoral neck (FN) osteoporosis increased from 2.4% to 9.2% in men and from 2.5% to 11.2% in women, while the age-standardized prevalence increased less, from 2.6% to 8.3% in men, and slightly decreased from 8.7% to 7.6% in women. Trend analysis revealed increased crude and age-standardized prevalence rates of FN osteoporosis in men, with an annual percent change (APC) of 4.0 (95%CI: - 4.1 to 14.7) and 2.3 (95%CI: - 4.9 to 10.0), respectively. In women, the crude prevalence increased significantly from 2003 to 2011 (APC: 20.8, 95%CI: 5.8-249.3) and plateaued from 2011 to 2022 (APC: 0.8, 95%CI: - 30.3 to 5.9). The age-standardized prevalence was relatively unchanged (APC: 0.1, 95%CI: - 4.2 to 5.4)., Conclusion: We observed a significant increase in the crude prevalence of osteoporosis from 2003 to 2022 among individuals receiving BMD measurements in a tertiary care referral center in Northeastern Thailand. Meanwhile, the age-standardized prevalence increased more gradually., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

This study aimed to evaluate the prevalence and risk of malignant neoplasm in primary hyperparathyroidism (PHPT) patients. Potentially eligible studies were retrieved from PubMed and Embase databases from inception to November 2023 using search strategy consisting of terms for "Primary hyperparathyroidism" and "Malignant neoplasm". Eligible study must report prevalence of malignant neoplasm among patients with PHPT or compare the risk of malignant neoplasm between patients with PHPT and comparators. Point estimates with standard errors were extracted from each study and combined using the generic inverse variance method.A total of 11,926 articles were identified. After two rounds of systematic review, 50 studies were included. The meta-analysis revealed that pooled prevalence rates of overall cancer was 0.19 (95%CI: 0.13-0.25; I 2 94%). The two most prevalent types of malignancy among patients with PHPT ware papillary thyroid cancer (pooled prevalence: 0.07; 95%CI: 0.06-0.08; I 2 85%) and breast cancer (pooled prevalence: 0.05; 95%CI: 0.03-0.07; I 2 87%). Subgroup analysis of studies focusing on patients undergoing parathyroidectomy reported a fourfold higher prevalence of papillary thyroid cancer than the remaining studies (0.08 versus 0.02). The meta-analysis of cohort studies found a significant association between PHPT and overall cancer with the pooled risk ratio of 1.28 (95%CI: 1.23-1.33; I 2 66.9%).We found that the pooled prevalence of malignant neoplasm in PHPT was 19%, with papillary thyroid cancer and breast cancer being the most prevalent types. The meta-analysis of cohort studies showed that patient with PHPT carried an approximately 28% increased risk of malignancy., (© 2024. The Author(s).)

Background. The concentration of pharmacologically active tetrahydrocannabinol (THC) in cannabis products has been increasing over the past decade. Concerns about potential harmful health effects of using these increasingly higher-concentration products have led some states to consider regulation of cannabis product THC concentration. We conducted a scoping review of health effects of high-concentration cannabis products to inform policy on whether the THC concentrations of cannabis product should be regulated or limited. Objectives. We conducted a scoping review to (1) identify and describe human studies that explore the relationship of high-concentration cannabis products with any health outcomes in the literature and (2) create an interactive evidence map of the included studies to facilitate further analyses. Search Methods. An experienced medical information specialist designed a comprehensive search strategy of 7 electronic databases. Selection Criteria. We included human studies of any epidemiological design with no restrictions by age, sex, health status, country, or outcome measured that reported THC concentration or included a known high-concentration cannabis product. Data Collection and Analysis. We imported search results into Distiller SR, and trained coders conducted artificial intelligence‒assisted screening. We developed, piloted, and revised data abstraction forms. One person performed data abstraction, and a senior reviewer verified a subset. We provide a tabular description of study characteristics, including exposures and outcomes measured, for each included study. We interrogated the evidence map published in Tableau to answer specific questions and provide the results as text and visual displays. Main Results. We included 452 studies in the scoping review and evidence map. There was incomplete reporting of exposure characteristics including THC concentration, duration and frequency of use, and products used. The evidence map shows considerable heterogeneity among studies in exposures, outcomes, and populations studied. A limited number of reports provided data that would facilitate further quantitative synthesis of the results across studies. Conclusions. This scoping review and evidence map support strong conclusions concerning the utility of the literature for characterizing risks and benefits of the current cannabis marketplace and the research approaches followed in the studies identified. Relevance of the studies to today's products is limited. Public Health Implications. High-quality evidence to address the policy question of whether the THC concentration of cannabis products should be regulated is scarce. The publicly available interactive evidence map is a timely resource for other entities concerned with burgeoning access to high-concentration cannabis. ( Am J Public Health. 2023;113(12):1332-1342. https://doi.org/10.2105/AJPH.2023.307414).

Background: Macular hole (MH) is a full-thickness defect in the central portion of the retina that causes loss of central vision. According to the usual definition, a large MH has a diameter greater than 400 µm at the narrowest point. For closure of MH, there is evidence that pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling achieves better anatomical outcomes than standard PPV. PPV with ILM peeling is currently the standard of care for MH management; however, the failure rate of this technique is higher for large MHs than for smaller MHs. Some studies have shown that the inverted ILM flap technique is superior to conventional ILM peeling for the management of large MHs., Objectives: To evaluate the clinical effectiveness and safety of pars plana vitrectomy with the inverted internal limiting membrane flap technique versus pars plana vitrectomy with conventional internal limiting membrane peeling for treating large macular holes, including idiopathic, traumatic, and myopic macular holes., Search Methods: The Cochrane Eyes and Vision Information Specialist searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registries on 12 December 2022., Selection Criteria: We included randomized controlled trials (RCTs) that evaluated PPV with ILM peeling versus PPV with inverted ILM flap for treatment of large MHs (with a basal diameter greater than 400 µm at the narrowest point measured by optical coherence tomography) of any type (idiopathic, traumatic, or myopic)., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane and assessed the certainty of the body of evidence using GRADE., Main Results: We included four RCTs (285 eyes of 275 participants; range per study 24 to 91 eyes). Most participants were women (63%), and of older age (range of means 59.4 to 66 years). Three RCTs were single-center trials, and the same surgeon performed all surgeries in two RCTs (the third single-center RCT did not report the number of surgeons). One RCT was a multicenter trial (three sites), and four surgeons performed all surgeries. Two RCTs took place in India, one in Poland, and one in Mexico. Maximum follow-up ranged from three months (2 RCTs) to 12 months (1 RCT). No RCTs reported conflicts of interest or disclosed financial support. All four RCTs enrolled people with large idiopathic MHs and compared conventional PPV with ILM peeling versus PPV with inverted ILM flap techniques. Variations in technique across the four RCTs were minimal. There was some heterogeneity in interventions: in two RCTs, all participants underwent combined cataract-PPV surgery, whereas in one RCT, some participants underwent cataract surgery after PPV (the fourth RCT did not mention cataract surgery). The critical outcomes for this review were mean best-corrected visual acuity (BCVA) and MH closure rates. All four RCTs provided data for meta-analyses of both critical outcomes. We assessed the risk of bias for both outcomes using the Cochrane risk of bias tool (RoB 2); there were some concerns for risk of bias associated with lack of masking of outcome assessors and selective reporting of outcomes in all RCTs. All RCTs reported postoperative BCVA values; only one RCT reported the change in BCVA from baseline. Based on evidence from the four RCTs, it is unclear if the inverted ILM flap technique compared with ILM peeling reduces (improves) postoperative BCVA measured on a logarithm of the minimum angle of resolution (logMAR) chart at one month (mean difference [MD] -0.08 logMAR, 95% confidence interval [CI] -0.20 to 0.05; P = 0.23, I 2 = 65%; 4 studies, 254 eyes; very low-certainty evidence), but it may improve BCVA at three months or more (MD -0.17 logMAR, 95% CI -0.23 to -0.10; P < 0.001, I 2 = 0%; 4 studies, 276 eyes; low-certainty evidence). PPV with an inverted ILM flap compared to PPV with ILM peeling probably increases the proportion of eyes achieving MH closure (risk ratio [RR] 1.10, 95% CI 1.02 to 1.18; P = 0.01, I 2 = 0%; 4 studies, 276 eyes; moderate-certainty evidence) and type 1 MH closure (RR 1.31, 95% CI 1.03 to 1.66; P = 0.03, I² = 69%; 4 studies, 276 eyes; moderate-certainty evidence). One study reported that none of the 38 participants experienced postoperative retinal detachment., Authors' Conclusions: We found low-certainty evidence from four small RCTs that PPV with the inverted ILM flap technique is superior to PPV with ILM peeling with respect to BCVA gains at three or more months after surgery. We also found moderate-certainty evidence that the inverted ILM flap technique achieves more overall and type 1 MH closures. There is a need for high-quality multicenter RCTs to ascertain whether the inverted ILM flap technique is superior to ILM peeling with regard to anatomical and functional outcomes. Investigators should use the standard logMAR charts when measuring BCVA to facilitate comparison across trials., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background and Aims: Studies have suggested that high parathyroid hormone (PTH) was associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), although the results from existing studies are inconsistent. Using systematic review and meta-analysis, we aimed to determine the association of PTH with NAFLD and NASH., Methods: Potentially eligible studies were identified from Embase and Medline databases from using search strategy consisting of terms for "NAFLD/NASH", and "PTH". Eligible study must consist of one group of patients with NAFLD/NASH and another group without NAFLD/NASH. The study must provide mean ± SD PTH in both groups. We extracted such data to calculate mean difference (MD). Pooled MD was then calculated by combining MDs of each study using random-effects model. Funnel plot was used to assess for the presence of publication bias., Results: A total of 388 articles were identified. After systematic review, 12 studies fulfilled the eligibility criteria and were included into the meta-analysis. The meta-analysis of 10 studies revealed the significant association between high PTH and NAFLD, with the pooled MD of 5.479 (95%CI 0.947-10.011, I 2 82.4%). The funnel plot was symmetric and did not suggest publication bias. The meta-analysis of 4 studies revealed the non-significant association between high PTH and NASH, with the pooled MD of 11.955 (95%CI -4.703 - 28.614, I 2 81.0%)., Conclusions: High PTH level is significantly associated with NAFLD and can be used as a marker of NAFLD. However, high PTH level is non-significantly associated with NASH. Further studies are needed to increase the sample size and eliminate the confounding factors., Competing Interests: Conflict of interest/competing interest All the authors declare no conflicts of interest., (Copyright © 2023 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate bone fragility in patients with hereditary connective tissue disorders (HCTD), including Ehlers-Danlos syndrome (EDS), Marfan's syndrome (MFS) and Loeys-Dietz syndrome (LDS)., Methods: From inception to June 2022, potentially eligible studies were identified in the Medline and EMBASE databases using search strategy that included terms for "HCTD", "Fracture" and "Osteoporosis". Eligible studies must consist of a group of patients with HCTD and report prevalence/incidence of fracture/osteoporosis in their participants, with or without comparison with healthy individuals. Point estimates with standard errors were obtained from each study and combined using the generic inverse variance method., Results: Among the 4206 articles identified, 19 studies were included. The pooled prevalence of fracture in EDS, MFS, and LDS were 44% (95% confidence interval [CI], 25% to 65%, I 2 88%), 17% (95% CI, 11% to 26%, I 2 68%), 69% (95% CI, 47% to 85%, I 2 83%), respectively. The pooled prevalence of osteoporosis in EDS was 17% (95% CI, 8% to 34%, I 2 96%). EDS was associated with fracture [pooled odds ratio {OR} 4.90 (95% CI, 1.49 - 16.08, I 2 86%)], but not osteoporosis [pooled OR 1.34 (95% CI, 0.28 - 6.36, I 2 87%). One study reported a 5% (95% CI, 3% to 8%) prevalence of osteoporosis in MFS, which was associated with fracture [incidence rate ratio 1.35 (95% CI, 1.18 - 1.55)] and osteoporosis [subhazard ratio 3.97 (95% CI, 2.53 - 6.25)]., Conclusion: EDS was associated with fracture, which could be independent of osteoporosis status. MFS had a milder degree of increased risk of fracture and osteoporosis. Despite no data from cohort studies, there was a significantly higher rate of fracture in LDS., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Objective : This systematic review and meta-analysis compared the patient-reported outcomes of intra-articular facet joint injections of normal saline and selected active substances to identify a more effective agent for treating subacute and chronic low back pain (LBP). Methods : The PubMed, Embase, Scopus, Web of Science, and CENTRAL databases were searched for randomized controlled trials and observational studies published in English. A research quality assessment was performed using ROB2 and ROBINS-I. A meta-analysis was conducted using a random-effects model, and the mean differences (MD) with 95% confidence intervals (CI) in efficacy outcomes, including pain, numbness, disability, and quality of life, were assessed. Results: Of the 2467 potential studies, 3 were included (247 patients). The active substances and normal saline had similar therapeutic effects on pain within 1 h, after 1-1.5 months, and after 3-6 months, with MD and 95% CI of 2.43 and -11.61 to 16.50, -0.63 and -7.97 to 6.72, and 1.90 and -16.03 to 19.83, respectively, as well as on the quality of life after 1 and 6 months. Conclusions : The short- and long-term clinical effects of intra-articular facet joint injections of normal saline are comparable to those of other active substances in patients with LBP.

Background: Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear. In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020., Methods: Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15 months pre-COVID (January 2019-March 2020). We used the Oxford COVID-19 Government Response Tracker (OxCGRT) index and multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors., Findings: Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model., Conclusions: Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks., (© 2023. The Author(s).)

Background: Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG., Objectives: To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more types of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG., Search Methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register); MEDLINE; Embase; PubMed; and LILACS to 19 October 2021; metaRegister of Controlled Trials to 19 October 2021; and two additional trial registers to 19 October 2021. We did not use any date or language restrictions in the electronic search for trials., Selection Criteria: We included randomized controlled trials (RCTs) of people treated with anti-VEGF medications for NVG., Data Collection and Analysis: Two review authors independently assessed the search results for trials, extracted data, and assessed risk of bias, and the certainty of the evidence. We resolved discrepancies through discussion., Main Results: We included five RCTs (356 eyes of 353 participants). Each trial was conducted in a different country: two in China, and one each in Brazil, Egypt, and Japan. All five RCTs included both men and women; the mean age of participants was 55 years or older. Two RCTs compared intravitreal bevacizumab combined with Ahmed valve implantation and panretinal photocoagulation (PRP) with Ahmed valve implantation and PRP alone. One RCT randomized participants to receive an injection of either intravitreal aflibercept or placebo at the first visit, followed by non-randomized treatment according to clinical findings after one week. The remaining two RCTs randomized participants to PRP with and without ranibizumab, one of which had insufficient details for further analysis. We assessed the RCTs to have an unclear risk of bias for most domains due to insufficient information to permit judgment.   Four RCTs examined achieving control of IOP, three of which reported our time points of interest. Only one RCT reported our critical time point at one month; it found that the anti-VEGF group had a 1.3-fold higher chance of achieving control of IOP at one month (RR 1.32, 95% 1.10 to 1.59; 93 participants) than the non-anti-VEGF group (low certainty of evidence). For other time points, one RCT found a three-fold greater achievement in control of IOP in the anti-VEGF group when compared with the non-anti-VEGF group at one year (RR 3.00; 95% CI:1.35 to 6.68; 40 participants). However, another RCT found an inconclusive result at the time period ranging from 1.5 years to three years (RR 1.08; 95% CI: 0.67 to 1.75; 40 participants).  All five RCTs examined mean IOP, but at different time points. Very-low-certainty evidence showed that anti-VEGFs were effective in reducing mean IOP by 6.37 mmHg (95% CI: -10.09 to -2.65; 3 RCTs; 173 participants) at four to six weeks when compared with no anti-VEGFs.  Anti-VEGFs may reduce mean IOP at three months (MD -4.25; 95% CI -12.05 to 3.54; 2 studies; 75 participants), six months (MD -5.93; 95% CI -18.13 to 6.26; 2 studies; 75 participants), one year (MD -5.36; 95% CI -18.50 to 7.77; 2 studies; 75 participants), and more than one year (MD -7.05; 95% CI -16.61 to 2.51; 2 studies; 75 participants) when compared with no anti-VEGFs, but such effects remain uncertain. Two RCTs reported the proportion of participants who achieved an improvement in visual acuity with specified time points. Participants receiving anti-VEGFs had a 2.6 times (95% CI 1.60 to 4.08; 1 study; 93 participants) higher chance of improving visual acuity when compared with those not receiving anti-VEGFs at one month (very low certainty of evidence). Likewise, another RCT found a similar result at 18 months (RR 4.00, 95% CI 1.33 to 12.05; 1 study; 40 participants).  Two RCTs reported the outcome, complete regression of new iris vessels, at our time points of interest. Low-certainty evidence showed that anti-VEGFs had a nearly three times higher chance of complete regression of new iris vessels when compared with no anti-VEGFs (RR 2.63, 95% CI 1.65 to 4.18; 1 study; 93 participants). A similar finding was observed at more than one year in another RCT (RR 3.20, 95% CI 1.45 to 7.05; 1 study; 40 participants).  Regarding adverse events, there was no evidence that the risks of hypotony and tractional retinal detachment were different between the two groups (RR 0.67; 95% CI: 0.12 to 3.57 and RR 0.33; 95% CI: 0.01 to 7.72, respectively; 1 study; 40 participants). No RCTs reported incidents of endophthalmitis, vitreous hemorrhage, no light perception, and serious adverse events. Evidence for the adverse events of anti-VEGFs was low due to limitations in the study design due to insufficient information to permit judgments and imprecision of results due to the small sample size. No trial reported the proportion of participants with relief of pain and resolution of redness at any time point., Authors' Conclusions: Anti-VEGFs as an adjunct to conventional treatment could help reduce IOP in NVG in the short term (four to six weeks), but there is no evidence that this is likely in the longer term. Currently available evidence regarding the short- and long-term effectiveness and safety of anti-VEGFs in achieving control of IOP, visual acuity, and complete regression of new iris vessels in NVG is insufficient. More research is needed to investigate the effect of these medications compared with, or in addition to, conventional surgical or medical treatment in achieving these outcomes in NVG., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Glaucoma is an optic neuropathy that leads to visual field defects and vision loss. It is the second leading cause of irreversible blindness in the world. Treatment for glaucoma aims to reduce intraocular pressure (IOP) to slow or prevent further vision loss. IOP can be lowered with medications, laser, or incisional surgery. Trabeculectomy is a surgical approach which lowers IOP by shunting aqueous humor to a subconjunctival bleb. Device-modified trabeculectomy techniques are intended to improve the durability and safety of this bleb-forming surgery. Trabeculectomy-modifying devices include the Ex-PRESS, the XEN Gel Stent, the PreserFlo MicroShunt, as well as antifibrotic materials such as Ologen, amniotic membrane, expanded polytetrafluoroethylene (ePTFE) membrane, Gelfilm and others. However, the comparative effectiveness and safety of these devices are uncertain., Objectives: To evaluate the benefits and harms of different devices as adjuncts to trabeculectomy on IOP control in eyes with glaucoma compared to standard trabeculectomy., Search Methods: We used standard, extensive Cochrane search methods. The latest search was August 2021., Selection Criteria: We included randomized controlled trials in participants with glaucoma comparing device-modified trabeculectomy techniques with standard trabeculectomy. We included studies that used antimetabolites in either or both treatment groups., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were 1. change in IOP and 2. mean postoperative IOP at one year. Our secondary outcomes were 3. mean change in IOP from baseline, 4. mean postoperative IOP at any time point, 5. mean best-corrected visual acuity (BCVA), 6. visual field change, 7. quality of life, 8. proportion of participants who are drop-free at one year, 9. mean number of IOP lowering medications at one year, and 10. proportion of participants with complications., Main Results: Eight studies met our inclusion criteria, of which seven were full-length journal articles and one was a conference abstract. The eight studies included 961 participants with glaucoma, and compared two types of devices implanted during trabeculectomy versus standard trabeculectomy. Seven studies (462 eyes, 434 participants) used the Ex-PRESS, and one study (527 eyes, 527 participants) used the PreserFlo MicroShunt. No studies using the XEN Gel Stent implantation met our criteria. The studies were conducted in North America, Europe, and Africa. Planned follow-up periods ranged from six months to five years. The studies were reported poorly, which limited our ability to judge risk of bias for many domains. None of the studies explicitly masked outcome assessment. We rated seven studies at high risk of detection bias. Low-certainty of evidence from five studies showed that using the Ex-PRESS plus trabeculectomy compared with standard trabeculectomy may be associated with a slightly lower IOP at one year (mean difference (MD) -1.76 mmHg, 95% confidence interval (CI) -2.81 to -0.70; 213 eyes). Moderate-certainty of evidence from one study showed that using the PreserFlo MicroShunt may be associated with a slightly higher IOP than standard trabeculectomy at one year (MD 3.20 mmHg, 95% CI 2.29 to 4.11). Participants who received standard trabeculectomy may have a higher risk of hypotony compared with those who received device-modified trabeculectomy, but the evidence is uncertain (RR 0.73, 95% CI 0.46 to 1.17; I² = 38%; P = 0.14). In the subgroup of participants who received the PreserFlo MicroShunt, there was a lower risk of developing hypotony or shallow anterior chamber compared with those receiving standard trabeculectomy (RR 0.44, 95% CI 0.25 to 0.79; 526 eyes). Device-modified trabeculectomy may lead to less subsequent cataract surgery within one year (RR 0.46, 95% CI 0.27 to 0.80; I² = 0%)., Authors' Conclusions: Use of an Ex-PRESS plus trabeculectomy may produce greater IOP reduction at one-year follow-up than standard trabeculectomy; however, due to potential biases and imprecision in effect estimates, the certainty of evidence is low. PreserFlo MicroShunt may be inferior to standard trabeculectomy in lowering IOP. However, PreserFlo MicroShunt may prevent postoperative hypotony and bleb leakage. Overall, device-modified trabeculectomy appears associated with a lower risk of cataract surgery within five years compared with standard trabeculectomy. Due to various limitations in the design and conduct of the included studies, the applicability of this evidence synthesis to other populations or settings is uncertain. Further research is needed to determine the effectiveness and safety of other devices in subgroup populations, such as people with different types of glaucoma, of various races and ethnicity, and with different lens types (e.g. phakic, pseudophakic)., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Low vision affects over 300 million people worldwide and can compromise both activities of daily living and quality of life. Rehabilitative training and vision assistive equipment (VAE) may help, but some visually impaired people have limited resources to attend in-person visits to rehabilitation clinics to be trained to learn to use VAE. These people may be able to overcome barriers to care through access to remote, internet-based consultation (telerehabilitation)., Objectives: To compare the effects of telerehabilitation with face-to-face (e.g. in-office or inpatient) vision rehabilitation services for improving vision-related quality of life and near reading ability in people with visual function loss due to any ocular condition. Secondary objectives were to evaluate compliance with scheduled rehabilitation sessions, abandonment rates for VAE devices, and patient satisfaction ratings., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 9); Ovid MEDLINE; Embase.com; PubMed; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any language restriction or study design filter in the electronic searches; however, we restricted the searches from 1980 onwards because the internet was not introduced to the public until 1982. We last searched CENTRAL, MEDLINE Ovid, Embase, and PubMed on 14 September 2021, and the trial registries on 16 March 2022., Selection Criteria: We included randomized controlled trials (RCTs) or controlled clinical trials (CCTs) in which participants diagnosed with low vision had received vision rehabilitation services remotely from a human provider using internet, web-based technology compared with an approach involving in-person consultations., Data Collection and Analysis: Two review authors independently screened titles and abstracts retrieved by the searches of the electronic databases and then full-text articles for eligible studies. Two review authors independently abstracted data from the included studies. Any discrepancies were resolved by discussion., Main Results: We identified one RCT/CCT that indirectly met our inclusion criteria, and two ongoing trials that met our inclusion criteria. The included trial had an overall high risk of bias. We did not conduct a quantitative analysis since multiple controlled trials were not identified.  The single included trial of 57 participants utilized a parallel-group design. It compared 30 hours of either personalized low vision training through telerehabilitation with a low vision therapist (the experimental group) with the self-training standard provided by eSight using the eSkills User Guide that was self-administered by the participants at home for one hour per day for 30 days (the comparison group). The trial investigators found a similar direction of effects for both groups for vision-related quality of life and satisfaction at two weeks, three months, and six months. A greater proportion of participants in the comparison group had abandoned or discontinued use of the eSight Eyewear at two weeks than those in the telerehabilitation group, but discontinuance rates were similar between groups at one month and three months. We rated the certainty of the evidence for all outcomes as very low due to high risk of bias in randomization processes and missing outcome data and imprecision.   AUTHORS' CONCLUSIONS: The included trial found similar efficacy between telerehabilitation with a therapist and an active control intervention of self-guided training in mostly younger to middle-aged adults with low vision who received a new wearable electronic aid. Given the disease burden and the growing interest in telemedicine, the two ongoing studies, when completed, may provide further evidence of the potential for telerehabilitation as a platform for providing services to people with low vision., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: Little is known about the normative values of trabecular bone score (TBS) in Thailand. We aimed to provide reference values of dual-energy x-ray absorptiometry (DXA)-derived lumbar spine TBS in Thai community-dwelling adults of varying ages., Methodology: Bone density studies of participants aged 20-90 years who underwent bone mineral density (BMD) testing at Srinagarind Hospital, Kohn Kaen, Thailand were reviewed. DXA studies were performed using a narrow fan-beam bone densitometer. Lumbar spine TBS for each of the L1-L4 vertebra was obtained using the iNsight software. Mean TBS (L1-L4 TBS) was calculated. This study was approved by the institutional research ethics committee (HE581241)., Results: A total of 1372 participants were included. The mean ± SD age was 57.25 ± 17.35 years and 799 (58.2%) were female. There were 476 (34.7%) and 243 (17.7%) participants with osteopenia (T-score -1.0 to -2.5) and osteoporosis (T-score ≤-2.5) of the lumbar spine. Age and sex stratified analysis of L1-L4 TBS revealed peak TBS among females aged 30-49 years (mean ± SD: 1.42 ± 0.08) and males aged 30-59 years (mean ± SD: 1.42 ± 0.09). The rate of L1-L4 TBS reduction from ages 30 to 90 year is 13.4% (0.27%/year) for females and 5.6% (0.11%/year) for males., Conclusion: This is the first study reporting a normative database for DXA derived TBS in Thai community-dwelling population. We found that TBS decreased with age at the rate of approximately 0.27%/year for females and 0.11%/year for males., Competing Interests: Declaration of Competing Interest Chatlert Pongchaiyakul, Daris Theerakulpisut, Nipith Charoenngam, Thanitsara Rittiphairoj, Dueanchonnee Sribenjalak declare no conflicts of interest, (Copyright © 2022 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies of type 1 diabetes in childhood and adolescence have found large variations in reported incidence around the world. However, it is unclear whether these reported incidence levels are impacted by differences in country health systems and possible underdiagnosis and if so, to what degree. The aim of this study was to estimate both the total and diagnosed incidence of type 1 diabetes globally and to project childhood type 1 diabetes incidence indicators from 1990 to 2050 for each country., Methods: We developed the type 1 diabetes global microsimulation model to simulate the natural history and diagnosis of type 1 diabetes for children and adolescents (aged 0-19 years) in 200 countries and territories, accounting for variability in underlying incidence and health system performance. The model follows an open population of children and adolescents in monthly intervals and simulates type 1 diabetes incidence and progression, as well as health system factors which influence diagnosis. We calibrated the model to published data on type 1 diabetes incidence, autoantibody profiles, and proportion of cases diagnosed with diabetic ketoacidosis from 1990 to 2020 and assessed the predictive accuracy using a randomly sampled test set of data withheld from calibration., Findings: We estimate that in 2021 there were 355 900 (95% UI 334 200-377 300) total new cases of type 1 diabetes globally among children and adolescents, of which 56% (200 400 cases, 95% UI 180 600-219 500) were diagnosed. Estimated underdiagnosis varies substantially by region, with over 95% of new cases diagnosed in Australia and New Zealand, western and northern Europe, and North America, but less than 35% of new cases diagnosed in west Africa, south and southeastern Asia, and Melanesia. The total number of incident childhood cases of type 1 diabetes is projected to increase to 476 700 (95% UI 449 500-504 300) in 2050., Interpretation: Our research indicates that the total global incidence of childhood and adolescent type 1 diabetes is larger than previously estimated, with nearly one-in-two children currently undiagnosed. Policymakers should plan for adequate diagnostic and medical capacity to improve timely type 1 diabetes detection and treatment, particularly as incidence is projected to increase worldwide, with highest numbers of new cases in Africa., Funding: Novo Nordisk., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Importance: Dry eye is a common clinical manifestation, a leading cause of eye clinic visits, and a significant societal and personal economic burden in the United States. Meibomian gland dysfunction (MGD) is a major cause of evaporative dry eye., Objective: To conduct a systematic review and meta-analysis to obtain updated estimates of the prevalence and incidence of dry eye and MGD in the United States., Data Sources: Ovid MEDLINE and Embase., Study Selection: A search conducted on August 16, 2021, identified studies published between January 1, 2010, and August 16, 2021, with no restrictions regarding participant age or language of publication. Case reports, case series, case-control studies, and interventional studies were excluded., Data Extraction and Synthesis: The conduct of review followed a protocol registered on PROSPERO (CRD42021256934). PRISMA guidelines were followed for reporting. Joanna Briggs Institute and Newcastle Ottawa Scale tools were used to assess risk of bias. Data extraction was conducted by 1 reviewer and verified by another for accuracy. Prevalence of dry eye and MGD were combined in separate meta-analyses using random-effects models., Main Outcomes and Measures: Prevalence and incidence of dry eye and MGD in the United States. Summary estimates from meta-analysis of dry eye and MGD prevalence with 95% CI and 95% prediction intervals (95% PI)., Results: Thirteen studies were included in the systematic review. Dry eye prevalence was reported by 10 studies, dry eye incidence by 2 studies, and MGD prevalence by 3 studies. Meta-analysis estimated a dry eye prevalence of 8.1% (95% CI, 4.9%-13.1%; 95% PI, 0%-98.9%; 3 studies; 9 808 758 participants) and MGD prevalence of 21.2% (95% CI, 7.2%-48.3%; 95% PI, 0%-100%; 3 studies; 19 648 participants). Dry eye incidence was 3.5% in a population 18 years and older and 7.8% in a population aged 68 years and older. No studies reported MGD incidence., Conclusions and Relevance: This systematic review and meta-analysis demonstrated uncertainty about the prevalence and incidence of dry eye and MGD in the United States. Population-based epidemiological studies that use consistent and validated definitions of dry eye and MGD are needed for higher-certainty estimates of dry eye and MGD prevalence and incidence in the United States.

Background: Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks)., Objectives: To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 8); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The date of the last search was 20 August 2021., Selection Criteria: We included randomized controlled trials (RCTs) in which topical corticosteroids, alone or in combination with tobramycin, were compared with no treatment, artificial tears (AT), vehicles, AT plus tobramycin, or cyclosporine A (CsA)., Data Collection and Analysis: We applied standard Cochrane methodology., Main Results: We identified 22 RCTs conducted in the USA, Italy, Spain, China, South Korea, and India. These RCTs reported outcome data from a total of 4169 participants with DED.  Study characteristics and risk of bias All trials recruited adults aged 18 years or older, except one trial that enrolled children and adolescents aged between 3 and 14 years. Half of these trials involved predominantly female participants (median 79%, interquartile range [IQR] 76% to 80%). On average, each trial enrolled 86 participants (IQR 40 to 158). The treatment duration of topical steroids ranged between one week and three months; trial duration lasted between one week and six months. Eight trials were sponsored exclusively by industry, and four trials were co-sponsored by industry and institutional or governmental funds. We assessed the risk of bias of both subjective and objective outcomes using RoB 2, finding nearly half of the trials to be at high risk of bias associated with selective outcome reporting. Findings Of the 22 trials, 16 evaluated effects of topical steroids, alone or in combination with tobramycin, as compared with lubricants (AT, vehicle), AT plus tobramycin, or no treatment. Corticosteroids probably have a small to moderate effect on improving patient-reported symptoms by 0.29 standardized mean difference (SMD) (95% confidence interval [CI] 0.16 to 0.42) as compared with lubricants (moderate certainty evidence). Topical steroids also likely have a small to moderate effect on lowering corneal staining scores by 0.4 SMDs (95% CI 0.18 to 0.62) (moderate certainty evidence). However, steroids may increase tear film break-up time (TBUT) slightly (mean difference [MD] 0.70 s, 95% CI 0.06 to 1.34; low certainty evidence) but not tear osmolarity (MD 1.60 mOsm/kg, 95% CI -10.47 to 13.67; very low certainty evidence).  Six trials examined topical steroids, either alone or in combination with CsA, against CsA alone. Low certainty evidence indicates that steroid-based interventions may have a small to moderate effect on improving participants' symptoms (SMD -0.33, 95% CI -0.51 to -0.15), but little to no effect on corneal staining scores (SMD 0.05, 95% CI -0.25 to 0.35) as compared with CsA. The effect of topical steroids compared to CsA alone on TBUT (MD 0.37 s, 95% CI -0.13 to 0.87) or tear osmolarity (MD 5.80 mOsm/kg, 95% CI -0.94 to 12.54; loteprednol etabonate alone) is uncertain because the certainty of the evidence is low or very low. None of the included trials reported on quality of life scores. Adverse effects The evidence for adverse ocular effects of topical corticosteroids is very uncertain. Topical corticosteroids may increase participants' risk of intraocular pressure (IOP) elevation (risk ratio [RR] 5.96, 95% CI 1.30 to 27.38) as compared with lubricants. However, when compared with CsA, steroids alone or combined with CsA may decrease or increase IOP elevation (RR 1.45, 95% CI 0.25 to 8.33). It is also uncertain whether topical steroids may increase risk of cataract formation when compared with lubricants (RR 0.34, 95% CI 0.01 to 8.22), given the short-term use and study duration (four weeks or less) to observe longer-term adverse effects.  AUTHORS' CONCLUSIONS: Overall, the evidence for the specified review outcomes was of moderate to very low certainty, mostly due to high risk of bias associated with selective results reporting. For dry eye patients whose symptoms require anti-inflammatory control, topical corticosteroids probably provide small to moderate degrees of symptom relief beyond lubricants, and may provide small to moderate degrees of symptom relief beyond CsA. However, the current evidence is less certain about the effects of steroids on improved tear film quality or quantity. The available evidence is also very uncertain regarding the adverse effects of topical corticosteroids on IOP elevation or cataract formation or progression. Future trials should generate high certainty evidence to inform physicians and patients of the optimal treatment strategies with topical corticosteroids in terms of regimen (types, formulations, dosages), duration, and its time-dependent adverse profile., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: To summarize all available data using systematic review and meta-analysis to estimate the 1-year mortality risk after atypical femoral fracture (AFF) and risk ratio of mortality after AFF versus typical femoral fracture (TFF)., Methods: Potentially eligible studies were identified from MEDLINE and Embase databases from inception to February 2022 using a search strategy that comprised the terms for "atypical femoral fracture" and "mortality." An eligible study must consist of a cohort of patients with AFF. Then, the study must report the 1-year mortality rate after the AFF or report effect estimates with 95% confidence intervals, comparing the incident mortality between patients with AFF and TFF. Point estimates with standard errors were retrieved from each study and combined using the generic inverse variance method., Results: A total of 8967 articles were identified. After 2 rounds of independent review by 3 investigators, we identified 7 studies reporting the 1-year mortality rate of AFFs and 3 studies comparing the mortality rate of AFF with that of TFF. Pooled analysis revealed a pooled 1-year mortality rate after an AFF of 0.10 (95% confidence interval, 0.05-0.16; I 2  = 93.3%). Two studies compared the mortality risks of AFF with those of TFF and revealed conflicting results., Conclusion: The 1-year mortality rate after an AFF was approximately 10%. However, evidence is insufficient to conclude whether there was a difference in mortality risk between AFF and TFF., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies., (© 2022. The Author(s).)

Objective: We compared methods used with current recommendations for synthesizing harms in systematic reviews and meta-analyses (SRMAs) of gabapentin., Study Design & Setting: We followed recommended systematic review practices. We selected reliable SRMAs of gabapentin (i.e., met a pre-defined list of methodological criteria) that assessed at least one harm. We extracted and compared methods in four areas: pre-specification, searching, analysis, and reporting. Whereas our focus in this paper is on the methods used, Part 2 examines the results for harms across reviews., Results: We screened 4320 records and identified 157 SRMAs of gabapentin, 70 of which were reliable. Most reliable reviews (51/70; 73%) reported following a general guideline for SRMA conduct or reporting, but none reported following recommendations specifically for synthesizing harms. Across all domains assessed, review methods were designed to address questions of benefit and rarely included the additional methods that are recommended for evaluating harms., Conclusion: Approaches to assessing harms in SRMAs we examined are tokenistic and unlikely to produce valid summaries of harms to guide decisions. A paradigm shift is needed. At a minimal, reviewers should describe any limitations to their assessment of harms and provide clearer descriptions of methods for synthesizing harms., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: In this methodologic study (Part 2 of 2), we examined the overlap in sources of evidence and the corresponding results for harms in systematic reviews for gabapentin., Study Design & Setting: We extracted all citations referenced as sources of evidence for harms of gabapentin from 70 systematic reviews, as well as the harms assessed and numerical results. We assessed consistency of harms between pairs of reviews with a high degree of overlap in sources of evidence (>50%) as determined by corrected covered area (CCA)., Results: We found 514 reports cited across 70 included reviews. Most reports (244/514, 48%) were not cited in more than one review. Among 18 pairs of reviews, we found reviews had differences in which harms were assessed and their choice to meta-analyze estimates or present descriptive summaries. When a specific harm was meta-analyzed in a pair of reviews, we found similar effect estimates., Conclusion: Differences in harms results across reviews can occur because the choice of harms is driven by reviewer preferences, rather than standardized approaches to selecting harms for assessment. A paradigm shift is needed in the current approach to synthesizing harms., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is a lack of published studies on incidence of type 1 diabetes (T1D) and diabetic ketoacidosis (DKA) in Thailand. We aimed to estimate the national prevalence and incidence of T1D and DKA., Methods: Using Thailand's nationwide population-based longitudinal data covering 69 million individuals, we included the entire children and adolescents recorded in the database. Diseases were identified using ICD-10 codes. We investigated the prevalence of T1D and cumulative incidence of T1D, T1D referral, DKA, and mortality risk of DKA in five years from 2015 to 2020. T1D and DKA annual incidence were also estimated. We present findings for the total population and by sex, age, and urban-rural residencies., Findings: A total of 19,784,781 individuals aged less than 20 years were identified in 2015. The crude T1D prevalence in 2015 was 17·6 per 100,000 and crude T1D incidence rate was 5·0 per 100,000. T1D prevalence and cumulative incidence were significantly higher in older children ( p  < 0·001) and females ( p  < 0·001) than their counterparts. Among those with T1D, cumulative incidence of T1D referral was 42·4%. It was highest amongst children aged 5-14 years and was significantly higher among females (all p  < 0·05). The crude DKA incidence rate at any point after diagnosis was 10·8%. The cumulative incidence of DKA was significantly higher in females and peaked in individuals aged 5-14 years (all p  < 0·001). The DKA mortality risk was 258·2 per 100,000., Interpretation: Older children and females had higher T1D prevalence. The DKA cumulative incidence and mortality risk were relatively low, and such incidence was peak in individuals aged 5-14 years., Funding: Harvard University., Competing Interests: The authors declare that they have no competing interests., (© 2022 The Author(s).)

Background: Chronic hepatitis C virus (HCV) infection is associated with increased risk of hepatobiliary tract cancer. However, whether chronic HCV infection is also associated with elevated risk of other types of cancer is still unknown. This systematic review and meta-analysis was conducted in order to investigate whether chronic HCV infection is positively associated with esophageal cancer., Methods: A systematic review was conducted using Embase and MEDLINE databases from inception to November 2019, with a search strategy that comprised the terms for "hepatitis C virus" and "cancer." Eligible studies were cohort studies consisting of patients with chronic HCV infection and comparators without HCV infection, and followed them for incident esophageal cancer. Hazard risk ratio, incidence rate ratio, relative risk or standardized incidence ratio of this association were extracted from each eligible study along with their 95% confidence intervals and were combined to calculate the pooled effect estimate using the random effect, generic inverse variance method., Results: A total of 20,459 articles were identified using this search strategy. After 2 rounds of independent review, 7 studies satisfied the inclusion criteria and were included in the meta-analysis. Chronic HCV infection was significantly associated with a higher incidence of esophageal cancer with the pooled relative risk of 1.61 (95% confidence interval: 1.19-2.17; I2=39%). The funnel plot was relatively symmetric which was not suggestive of publication bias., Conclusion: This systematic review and meta-analysis demonstrated that there is a modest association between chronic HCV and incident esophageal cancer. However, more studies are needed to investigate the causality of this association., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Multiple observational studies have reported high prevalence of fracture in patients with thalassemia. However, most of these studies have included limited number of patients, and only few of them have reported prevalence of fracture among patients with different types and severity of thalassemia., Objective: This systematic review and meta-analysis was conducted to summarize all available data of fracture prevalence among patients with thalassemia., Methods: A systematic review was conducted using EMBASE and MEDLINE databases from inception to June 2021 to determine studies that reported prevalence of fracture in thalassemia patients. The pooled prevalence with 95% confidence interval (95%CI) of fracture across studies was determined using a random-effect, generic inverse variance method., Results: After two rounds of systematic review, a total of 25 studies with 4934 patients were included in the meta-analysis. The pooled prevalence of fracture among patients with thalassemia was 16% (95%CI, 15-17%, I 2 = 94.3%). The subgroup analyses showed that the pooled prevalence of fracture was 4% (95%CI, 2-6%; I 2 = 70.4%) among patients with alpha thalassemia, 17% (95%CI, 16-19%; I 2 = 93.2%) among patients with beta thalassemia, 18% (95%CI, 16-19%; I 2 = 89.0%) among patients with transfusion-dependent thalassemia, and 7% (95%CI, 4-10%; I 2 = 94.2%) among patients with non-transfusion-dependent thalassemia., Conclusion: Fracture is common in patients with thalassemia, and may be more prevalent in beta thalassemia and transfusion-dependent thalassemia than in alpha thalassemia and non-transfusion-dependent thalassemia., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Background: It is still unclear whether patients with atopic dermatitis (AD) have an increased risk of developing rheumatoid arthritis (RA)., Objective: We aimed to investigate the association between AD and risk of RA using systematic review and meta-analysis., Methods: We searched Medline and EMBASE up to April 2021 using search strategy, including terms for "atopic dermatitis" and "rheumatoid arthritis." Eligible cohort study must compare the incidence of RA between patients with AD and comparators without AD. Eligible case-control study must recruit cases with RA and controls without RA. Then, the study must compare the prevalence of AD between the groups. Point estimates with standard errors from each study were combined using the generic inverse variance method., Results: The meta-analysis found that AD patients had a significantly higher risk of incident RA than individuals without AD with a pooled odds ratio (OR) of 1.30 (95% confidence interval [CI], 1.17-1.44; I2, 48%). Subgroup analysis revealed a significantly higher risk of RA in cohort study subgroup (pooled OR, 1.37; 95% CI, 1.25-1.50; I2, 63%) but not case-control study subgroup (pooled OR, 0.99; 95% CI, 0.77-1.28; I2, 10%)., Conclusions: This study found a significantly higher risk of incident RA among AD patients., Competing Interests: The authors have no funding or conflicts of interest to declare., (Copyright © 2021 American Contact Dermatitis Society. All Rights Reserved.)

This systematic review aimed to evaluate the effectiveness and safety of probiotics for glycemic control in adults with impaired glucose control, including prediabetes and type 2 diabetes mellitus (T2DM). We searched PubMed, Embase, and Cochrane databases, and trial registries up to February 2019. We included randomized controlled trials (RCTs) of participants with prediabetes or T2DM. Eligible trials compared probiotics versus either placebo, no intervention, or comparison probiotics, or compared synbiotics versus prebiotics. Primary outcomes were mean change in fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) from baseline to short term (<12 wk) and long term (≥12 wk). We performed meta-analyses using the random-effects model. We included 28 RCTs (1947 participants). Overall, probiotics reduced FBG more than the placebo/no intervention group with a mean difference (MD) of -12.99 mg/dL (95% CI: -23.55, -2.42; P value: 0.016) over the short term; and -2.99 mg/dL (95% CI: -5.84, -0.13; P value: 0.040) over the long term. There was also some evidence for reduced HbA1c in the probiotics group at both short term (MD: -0.17; 95% CI: -0.37, 0.02; P value: 0.084) and long term (MD: -0.14; 95% CI: -0.34, 0.06; P value: 0.172), however, these did not reach statistical significance possibly because only a few trials reported HbA1c as an outcome. Subgroup analyses showed a greater reduction in HbA1c in participants not receiving insulin therapy than those receiving insulin therapy. Furthermore, the effect of probiotics on the reduction of FBG was more pronounced in participants with FBG >130 mg/dL and those not receiving insulin therapy than their counterparts. Probiotics were also effective in lowering serum cholesterol over the short and long term. In conclusion, we found that probiotics may have a glucose-lowering effect in T2DM participants. The effect appeared to be stronger in participants with poorly controlled diabetes and those not on insulin therapy. Systematic review registration: CRD42019121682., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Patients with psoriasis may have a higher risk of dementia because of the higher inflammatory burden, although results from previous epidemiological studies have been inconsistent., Aims: To determine the association between psoriasis and risk of dementia by pooling the evidence from previous studies., Methods: Potentially eligible studies were identified from Medline and EMBASE databases from inception to July 2019 using a search that comprised terms for "psoriasis" and "dementia." Studies were eligible for the meta-analysis if they were cohort studies that included psoriatic patients and individuals without psoriasis and followed them for incident dementia. Studies were also required to report standardized incidence ratio, hazard risk ratio or relative risk with related 95% confidence intervals (CI) comparing the incidence of dementia between the two cohorts. The retrieved point estimates with standard errors from each study were pooled into the final result by the random-effect model, generic inverse variance method., Results: A total of 8,861 articles were identified. After two rounds of independent review by three investigators, we included six cohort studies that met the eligibility criteria in the meta-analysis. The risk of dementia was significantly higher among psoriatic patients than in those without psoriasis with a pooled risk ratio of 1.16 (95% CI, 1.04-1.30; I2 95%). A funnel plot was relatively symmetric and was not suggestive of the presence of publication bias., Limitations: Limited accuracy of diagnosis of psoriasis and dementia as four included studies were coding-based studies, and high statistical heterogeneity among studies., Conclusion: This systematic review and meta-analysis indicates that psoriatic patients have a significantly elevated risk of developing dementia.

Objective: To investigate the association between allergic rhinitis (AR) and the risk of rheumatoid arthritis (RA)., Methods: Potentially eligible studies were identified from MEDLINE and EMBASE databases from inception to November 2019. Eligible cohort study must report relative risk with 95% confidence intervals (95% CIs) of incident RA between AR patients and comparators. Eligible case-control studies must include cases with RA and controls without RA, and must explore their history of AR. Odds ratio with 95% CIs of the association between AR and RA must be reported. Point estimates with standard errors from each study were combined using the generic inverse variance method., Results: A total of 21,824 articles were identified. After two rounds of the independent review by three investigators, two cohort studies and 10 case-control studies met the eligibility criteria. The pooled analysis showed no association between AR and risk of RA (RR = 0.94; 95% CI, 0.73 to 1.20; I 2   = 84%). However, when we conducted a sensitivity analysis including only studies with acceptable quality, defined as Newcastle-Ottawa score of seven or higher, we found that patients with AR had a significantly higher risk of RA (RR = 1.36; 95% CI, 1.12 to 1.65; I 2  = 45%)., Conclusions: The current systematic review and meta-analysis could not reveal a significant association between AR and RA. However, when only studies with acceptable quality were included, a significantly higher risk of RA among patients with AR than individuals without AR was observed., (© 2020 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Background and Aims: Case reports have described occurrence of rheumatoid arthritis (RA) after initiation of Dipeptidyl Peptidase-4 Inhibitors (DPP4i), suggesting a possible adverse effect of the medications. However, the findings from subsequent cohort studies suggest the opposite as they indicate that T2DM patients who used DPP4i tended to have a lower risk of RA. We aimed to investigate the association between use of DPP4i and incident RA in patients with type 2 diabetes mellitus (T2DM) using systematic review and meta-analysis., Methods: Potentially eligible studies were identified from Medline and EMBASE databases from inception to May 2020 using search strategy that comprised of terms for "Dipeptidyl peptidase-4 inhibitor" and "Rheumatoid arthritis". Eligible study must be cohort study consisting of one cohort of patients with T2DM who were DPP4i users and another cohort of comparators with T2DM who did not receive DPP4i. Then, the study must report effect estimates with 95% confidence intervals (95% CIs) comparing incident RA between DPP4i users versus comparators. Point estimates with standard errors retrieved from each study were combined together using the generic inverse variance method., Results: A total of 709 articles were identified. After systematic review, four retrospective cohort studies met the eligibility criteria and were included into the meta-analysis. DPP4i users had a significantly lower risk of incident RA compared with comparators with the pooled hazard ratio of 0.72 (95% CI, 0.54-0.96; I 2 75%)., Conclusion: This systematic review and meta-analysis found a significant association between DPP4i use and a lower risk of incident RA., Competing Interests: Declaration of competing interest We declare that there is no financial or nonfinancial potential conflict of interest., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: Diabetic macular edema (DME) is secondary to leakage from diseased retinal capillaries with thickening of central retina, and is an important cause of poor central visual acuity in people with diabetic retinopathy. Intravitreal steroids have been used to reduce retinal thickness and improve vision in people with DME., Objectives: To assess the effectiveness and safety of intravitreal steroid therapy compared with other treatments for DME., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase on 15 May, 2019. We also searched reference lists, Science Citation Index, conference proceedings, and relevant trial registers. We conducted a top up search on 21 October, 2020., Selection Criteria: We included randomized controlled trials that evaluated any type of intravitreal steroids as monotherapy against any other intervention (e.g. observation, laser photocoagulation, anti-vascular endothelial growth factor (antiVEGF) for DME., Data Collection and Analysis: Two review authors independently assessed study eligibility and risk of bias and extracted data. Where appropriate, we performed meta-analyses., Main Results: We included 10 trials (4348 participants, 4505 eyes). These trials compared intravitreal steroid therapies versus other treatments, including intravitreal antiVEGF therapy, laser photocoagulation, and sham injection. Most trials had an overall unclear or high risk of bias. One trial (701 eyes ) compared intravitreal dexamethasone implant 0.7mg with sham. We found moderate-certainty evidence that dexamethasone leads to slightly more improvement of visual acuity than sham at 12 months (mean difference [MD] -0.08 logMAR, 95% confidence interval [CI] -0.12 to -0.05 logMAR). Regarding improvement of three or more lines of visual acuity, there was moderate-certainty evidence in favor of dexamethasone at 12 months, but the CI covered the null value (risk ratio (RR) 1.39, 95% CI 0.91 to 2.12). Regarding adverse events, dexamethasone increased by about four times the risk of cataract progression and the risk of using intraocular pressure (IOP)-lowering medications compared to sham (RR 3.89, 95% CI 2.75 to 5.50 and RR 4.54, 95% CI 3.19 to 6.46, respectively; moderate-certainty evidence); about 4 in 10 participants treated with dexamethasone needed IOP-lowering medications. Two trials (451 eyes) compared intravitreal dexamethasone implant 0.7mg with intravitreal antiVEGF (bevacizumab and ranibizumab). There was moderate-certainty evidence that visual acuity improved slightly less with dexamethasone compared with antiVEGF at 12 months (MD 0.07 logMAR, 95% CI 0.04 to 0.09 logMAR; 2 trials; 451 participants/eyes; I 2 = 0%). The RR of gain of three or more lines of visual acuity was inconsistent between trials, with one trial finding no evidence of a difference between dexamethasone and bevacizumab at 12 months (RR 0.99, 95% CI 0.70 to 1.40; 1 trial; 88 eyes), and the other, larger trial finding the chances of vision gain were half with dexamethasone compared with ranibizumab (RR 0.50, 95% CI 0.32 to 0.79; 1 trial; 432 participants). The certainty of evidence was low. Cataract progression and the need for IOP-lowering medications increased more than 4 times with dexamethasone implant compared to antiVEGF (moderate-certainty evidence). One trial (560 eyes) compared intravitreal fluocinolone implant 0.19mg with sham. There was moderate-certainty evidence that visual acuity improved slightly more with fluocinolone at 12 months (MD -0.04 logMAR, 95% CI -0.06 to -0.01 logMAR). There was moderate-certainty evidence that an improvement in visual acuity of three or more lines was more common with fluocinolone than with sham at 12 months (RR 1.79, 95% CI 1.16 to 2.78). Fluocinolone also increased the risk of cataract progression (RR 1.63, 95% CI 1.35 to 1.97; participants = 335; moderate-certainty evidence), which occurred in about 8 in 10 participants, and the use of IOP-lowering medications (RR 2.72, 95% CI 1.87 to 3.98; participants = 558; moderate-certainty evidence), which were needed in 2 to 3 out of 10 participants. One small trial with 43 participants (69 eyes) compared intravitreal triamcinolone acetonide injection 4 mg with sham. There may be a benefit in visual acuity at 24 months (MD -0.11 logMAR, 95% CI -0.20 to -0.03 logMAR), but the certainty of evidence is low. Differences in adverse effects were poorly reported in this trial. Two trials (615 eyes) compared intravitreal triamcinolone acetonide injection 4mg with laser photocoagulation and reached discordant results. The smaller trial (31 eyes followed up to 9 months) found more visual acuity improvement with triamcinolone (MD -0.18 logMAR, 95% CI -0.29 to -0.07 logMAR), but a larger, multicenter trial (584 eyes, 12-month follow-up) found no evidence of a difference regarding change in visual acuity (MD 0.02 logMAR, 95% CI -0.03 to 0.07 logMAR) or gain of three or more lines of visual acuity (RR 0.85, 95% CI 0.55 to 1.30) (overall low-certainty evidence). Cataract progression was about three times more likely (RR 2.68, 95% CI 2.21 to 3.24; moderate-certainty evidence) and the use of IOP-lowering medications was about four times more likely (RR 3.92, 95% CI 2.59 to 5.96; participants = 627; studies = 2; I 2 = 0%; moderate-certainty evidence) with triamcinolone. About 1 in 3 participants needed IOP-lowering medication. One small trial (30 eyes) compared intravitreal triamcinolone acetonide injection 4mg with intravitreal antiVEGF (bevacizumab or ranibizumab). Visual acuity may be worse with triamcinolone at 12 months (MD 0.18 logMAR, 95% CI 0.10 to 0.26 logMAR); the certainty of evidence is low. Adverse effects were poorly reported in this trial. Four trials reported data on pseudophakic participants, for whom cataract is not a concern. These trials found no decrease in visual acuity in the second treatment year due to cataract progression., Authors' Conclusions: Intravitreal steroids may improve vision in people with DME compared to sham or control. Effects were small, about one line of vision or less in most comparisons. More evidence is available for dexamethasone or fluocinolone implants when compared to sham, and the evidence is limited and inconsistent for the comparison of dexamethasone with antiVEGF treatment. Any benefits should be weighed against IOP elevation, the use of IOP-lowering medication and, in phakic patients, the progression of cataract. The need for glaucoma surgery is also increased, but remains rare., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objectives: To investigate the relationship between ankylosing spondylitis (AS) and risk of dementia., Methods: Potentially eligible studies that compared the risk of developing dementia between patients with AS and individuals without AS were identified from MEDLINE and EMBASE databases from inception to May 2019 using a search strategy that comprised terms for "dementia" and "ankylosing spondylitis". Eligible studies could be either cohort studies or case-control studies. For cohort design, eligible studies included patients with AS and comparators without AS and followed them for incident dementia. For case-control design, eligible studies included cases with dementia and controls without dementia and explored prior history of AS in both groups. Effect estimate and standard error from each study were extracted and combined together using the random effect, generic inverse variance. Funnel plot was used to assess for publication bias., Results: A total of 7091 articles were identified using the aforementioned search strategy. After 2 rounds of independent review by 3 investigators, 4 studies fulfilled the inclusion criteria and were included into the meta-analysis. The risk of developing dementia was significantly higher among patients with AS than individuals without AS with the pooled relative risk of 1.19 (95% CI 1.01-1.41; I 2  = 76%). The funnel plot was relatively symmetric and was not suggestive of presence of publication bias., Conclusion: A significantly 1.2 fold higher risk of developing dementia among patients with AS was demonstrated by this systematic review and meta-analysis., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: This study aimed to investigate whether patients with asthma have a higher risk of incident rheumatoid arthritis (RA) using systematic review and meta-analysis technique., Methods: Potentially eligible studies were identified from Medline and EMBASE databases from inception to May 2020 using search strategy that comprised of terms for "Asthma" and "Rheumatoid arthritis". Eligible cohort study must consist of one cohort of patients with asthma and another cohort of individuals without asthma. Then, the study must effect estimates with 95% confidence intervals (95% CIs) comparing incident RA between the groups. Eligible case-control studies must include cases with RA and controls without RA. Then, the study must explore their history of asthma. Odds ratio (OR) with 95% CIs of the association between asthma status and RA must be reported. Point estimates with standard errors were retrieved from each study and were combined together using the generic inverse variance method., Results: A total of 22,442 articles were identified. After two rounds of independent review by three investigators, six cohort studies and fourteen case-control studies met the eligibility criteria and were included into the meta-analysis. Meta-analysis of cohort studies found that patients with asthma had a significantly higher risk of RA compared with individuals without asthma with the pooled hazard ratio of 1.42 (95% CI, 1.18 - 1.70). Meta-analysis of case-control studies revealed that patients with asthma had a higher risk of RA compared with individuals without asthma with the pooled odds ratio of 1.33 (95%CI, 0.97 - 1.83). Funnel plot for the meta-analysis of case-control studies was asymmetric, suggesting the presence of publication bias., Conclusions: This systematic review and meta-analysis found a significant association between asthma and higher risk of incident RA., Competing Interests: Declaration of Competing Interests We do not have any financial or non-financial potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Chronic hepatitis C virus (HCV) infection is associated with increased risk of hepatocellular carcinoma. However, whether HCV infection also increases the risk of extra-hepatic cancer is still not well-established. This systematic review and meta-analysis was conducted in order to investigate the relationship between chronic HCV infection and lung cancer., Materials and Methods: A systematic review was performed using MEDLINE and EMBASE databases from inception to November 2019 with search strategy that included the terms for "hepatitis C virus" and "cancer". Eligible studies must be cohort studies that included patients with chronic HCV infection and comparators without HCV infection, then followed them for incident lung cancer. Relative risk, incidence rate ratio, standardized incidence ratio or hazard risk ratio of this association along with associated 95% confidence interval (CI) were extracted from each eligible study and combined for the calculation of the pooled effect estimate using the random effect, generic inverse variance method., Results: A total of 20,459 articles were identified using the aforementioned search strategy. After two rounds of review, eight studies fulfilled the inclusion criteria and were included into the meta-analysis. Chronic HCV infection was significantly associated with an increased risk of lung cancer with the pooled relative risk of 1.94 (95% CI 1.56-2.42; I 2  = 87%). Funnel plot was fairly symmetric and not suggestive of presence of publication bias., Conclusions: The current study demonstrated that chronic HCV infection is significantly associated with a 1.94-fold increased risk of developing lung cancer. However, further studies are still needed to investigate if this association is causative.

Background: Studies on receipt of statins and risk of multiple myeloma (MM) yielded conflicting results. This systematic review and meta-analysis was conducted in order to comprehensively investigate the relationship between receipt of statins and risk of MM., Patients and Methods: Potentially eligible studies that compared the risk of MM between statin recipients and those who did not receive statins were identified from Medline and Embase databases from inception to August 2019 using a search strategy that comprised terms for "statin" and "multiple myeloma." To be eligible, cohort studies must have recruited 2 groups of participants, statin recipients and nonrecipients, and followed their participants for incident MM. Eligible case-control studies must have recruited cases of MM and controls without MM, and must have explored the history of receipt of statins. Relative risk, hazard risk ratio, standardized incidence ratio, or odds ratio (OR) of this association must be reported. Relative risk and standard error from each study were extracted and combined using random-effect generic inverse variance. Relative risk of cohort study was used as an estimate for OR to calculate the pooled effect estimate along with the OR of the case-control studies., Results: A total of 1744 articles were identified using the search strategy, and 10 studies were included in the meta-analysis. The odds of MM were significantly lower among statin recipients than nonrecipients, with a pooled OR of 0.80 (95% confidence interval, 0.68-0.93; I 2 72%). The funnel plot was relatively symmetrical and did not suggest publication bias., Conclusion: Receipt of statins is associated with a significant 20% reduction in the odds of MM., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Type 2 diabetes mellitus (T2DM) is a major public health problem worldwide. It is characterized by the increased concentration of glucose in the blood and leads to damage of the body system, especially blood vessels and nerves. Lifestyle modification is often combined with anti-diabetic therapy as the standard of care for T2DM to maintain the proper blood glucose and to prevent long-term diabetic complications. The role of probiotics in improving glycemic control has been investigated in several randomized controlled trials (RCTs). Previous systematic reviews and meta-analyses, including different sets of trials have concluded an overall beneficial effect of probiotics in patients with T2DM. At least two RCTs with a longer treatment duration have been published since the publication of existing reviews., Methods: We will conduct a systematic review of RCTs that evaluated the effectiveness and safety of probiotics for glycemic control in T2DM patients. Primary outcomes are fasting blood glucose and glycosylated hemoglobin (A1c). Secondary outcomes are plasma insulin, blood lipid profile, adverse events, and cost associated with the intervention and hospital visits. We will search PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, and trial registries. Two reviewers will independently screen titles and abstracts, review full texts, extract information, and assess the risk of bias. We will summarize the results both qualitatively and statistically. We will use random-effects model for meta-analysis., Discussion: This systematic review aims to examine whether probiotics are effective and safe for glycemic control in T2DM patients. Evidence generated from this review will inform clinical and public health practice and future research., Systematic Review Registration: CRD42019121682.