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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.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).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.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.

Rickets is typically characterized by bone deformities due to defective bone mineralization and chondrocyte maturation in growing bones. However, infantile rickets often goes unrecognized, because the skeletal abnormalities are more subtle and often can only be detected radiologically. Nutritional rickets is a major public health concern in several regions worldwide. It is most commonly caused by vitamin D and/or calcium deficiency.We provide an overview of historical perspective, epidemiology, and pathophysiology of nutritional rickets. Additionally, we outline diagnostic approaches and highlight challenges in radiographic diagnosis of rickets. Finally, we present strategies for prevention and treatment of rickets.Despite the evidence from clinical databases that rickets is a rare disease, it is likely that rickets is clinically underdiagnosed as studies designed to screen healthy children for radiographic evidence of rickets reported surprisingly much higher prevalence. It has been reported that some of the radiologic features of rickets can be misinterpreted as fractures. To prevent nutritional rickets, most if not all infants and young children, should receive vitamin D from formulas and foods that are fortified with vitamin D or supplementation to achieve a serum 25-hydroxyvitamin D of at least 20 ng/mL as recommended by the Institute of Medicine. It has been recommended by the Endocrine Society that to achieve maximum bone health for children and adults, a serum concentration of 25-hydroxyvitamin D should be at least 30 ng/mL and preferably 40-60 ng/mL. Pregnant women who are unable to obtain an adequate amount of vitamin D from sunlight exposure and natural and fortified diets should take a vitamin D supplement of 1500-2000 IUs daily as recommended by the Endocrine Society since it has been demonstrated that 600 IUs daily will not maintain a circulating 25-hydroxyvitamin D of at least 20 ng/mL and most pregnant women. If lactating women take approximately 6400 IUs of vitamin D daily, they provide enough vitamin D in their milk to satisfy their infant's requirement thereby preventing rickets.

Objective: This study was conducted to determine the association between gastroesophageal reflux disease (GERD) and rheumatoid arthritis (RA) by pooling the evidence from all available studies Methods: Potentially eligible studies were identified from MEDLINE and EMBASE database from inception to April 2021 employing a search strategy that consisted of terms for “Rheumatoid Arthritis” and “Gastroesophageal Reflux Disease”. Eligible studies for the meta-analysis were recruited with conditions of being cohort studies that included rheumatoid arthritis and without rheumatoid arthritis individuals. Together with this, prevalence of GERD in both groups and the odds ratio (OR) comparing the prevalence of GERD between the two cohorts have been reported. The retrieved point estimates with standard errors from each study were pooled into the final result by the random-effect model and generic inverse variance method as described by DerSimonian and Laird. Results: A total of 3,646 articles were identified. After two rounds of independent review by two investigators, five cohort studies were included in the meta-analysis as they met the eligibility criteria. The pooled analysis demonstrated a significant association between RA and GERD with the pooled odds ratio of 1.98 (95% CI, 1.49 - 2.65). High statistical heterogeneity with I2 of 83% was observed. The funnel plot was symmetric and publication bias was not observed. Conclusion: This systematic review and meta-analysis found a significant association between GERD and RA

Objective: This study was conducted in order to determine the association between psoriatic arthritis and the risk of vertebral fracture by pooling the evidence from previous studies. Methods: Potentially eligible studies were identified from MEDLINE and EMBASE databases from inception to March 2020 using a search strategy that comprised of terms “Psoriatic Arthritis” and “Vertebral Fracture”. Studies were eligible for the meta-analysis if they were cohort studies that included psoriatic arthritis and individuals without psoriasis and followed them for incident vertebral fracture. Studies were also required to report standardized incidence ration, hazard risk ratio or relative risk with related 95% confidence intervals (CI) comparing the incidence of vertebral fracture 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 and generic inverse variance method. Results: A total of 26,090 articles were identified. After two rounds of independent review by three investigators, we included five cohort studies that met the eligibility criteria in the meta-analysis. PsA is significantly associated with VF with a pooled odds ratio of 2.09 (95% CI, 1.11 – 3.96; I2 70%). The funnel plot was fairly asymmetric, thus the publication bias in favor of studies may present. Conclusions: This systematic review and meta-analysis indicates that psoriatic arthritis patients have a significantly elevated risk of developing a vertebral fracture.

Rare heterozygous loss-of-function mutations of the MAX gene are associated with autosomal dominant hereditary pheochromocytoma-paraganglioma syndrome. In addition, evidence suggests that pathogenic MAX mutation may predispose to the development of other tumors, including endocrine and nonendocrine tumors, although the number of reported cases is small. We report a 67-year-old man with bilateral pheochromocytoma, primary hyperparathyroidism, prostate cancer, neurofibroma, and abdominal wall lipoma who tested positive for a heterozygous pathogenic germline MAX mutation. The patient has a history of bilateral norepinephrine-producing pheochromocytomas, for which he underwent left and right adrenalectomy in his 20s and 30s, respectively. His long-standing primary hyperparathyroidism was first documented when he was 40 years old and complicated by recurrent bilateral calcium oxalate nephrolithiasis and early-onset osteoporosis. Genetic testing revealed a heterozygous pathogenic deletional frameshift mutation of the exon 4 of the MAX gene (c.183_195del; p.Gln62Lysfs*104). This report, together with 3 previously reported cases, suggests that germline MAX mutation may contribute to the development of primary hyperparathyroidism and may be considered in suspected genetic forms of this disease.

BACKGROUND Obese and malabsorptive patients have difficulty increasing serum 25-hydroxyvitamin D [25(OH)D] after taking vitamin D supplementation. Since 25(OH)D is more hydrophilic than vitamin D, we hypothesized that oral 25(OH)D supplementation is more effective in increasing serum 25(OH)D concentrations in these patients. OBJECTIVES We aimed to investigate the pharmacokinetics of oral 25-hydroxyvitamin D3 [25(OH)D3] and oral vitamin D3 in healthy participants with differing BMI and malabsorptive patients. METHODS A randomized, double-blind crossover trial was performed in 6 malabsorptive patients and 10 healthy participants who were given 900 µg of either vitamin D3 or 25(OH)D3 orally followed by a pharmacokinetic study (PKS). After ≥28 d from the first dosing, each participant returned to receive the other form of vitamin D and undergo another PKS. For each PKS, serum vitamin D3 and 25(OH)D3 were measured at baseline and at 2, 4, 6, 8, and 12 h and days 1, 2, 3, 7, and 14. Pharmacokinetic parameters were calculated. RESULTS Data were expressed as means ± SEMs. The PKS of 900 µg vitamin D3 revealed that malabsorptive patients had 64% lower AUC than healthy participants (1177 ± 425 vs. 3258 ± 496 ng · h/mL; P

Background: Studies have demonstrated the link between vitamin D-related genetic variations and non-skeletal outcomes. We aimed to identify all available data on the association of vitamin D-related genetic variations with non-alcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using search strategy that comprised terms for “Vitamin D” and “NAFLD”. Eligible study must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study. Results: A total of 3,495 articles were identified. After systematic review, twelve studies were in-cluded. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of GC (rs222054, rs222020, rs10011000, rs7041), VDR (rs2228570, rs11168287, rs10783219, rs4752), CYP24A1 (rs3787557, rs6068816, rs2296241, rs2248359) and CYP27B1 (rs4646536). Severity of NAFLD was associated with variations of GC (rs4588), VDR (rs2228570, rs4334089), CYP2R1 (rs10741657), DHCR7 (rs1544410, rs3829251, rs12785878) and CYP24A1 (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of VDR (rs10735810). Conclusions: Multiple vitamin D-related genetic variations were associated with NAFLD, indi-cating the role of vitamin D in the pathogenesis of NAFLD.

Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases. In this review, we examine 25 selected hereditary metabolic bone diseases and recognized genetic variations of 78 genes that represent each of the three groups, including sclerosing bone disorders, disorders of defective bone mineralization and disorder of bone matrix and cartilage formation. We also review pathophysiology, manifestation and treatment for each disease. Advances in molecular genetics and basic sciences has led to accurate genetic diagnosis and novel effective therapeutic strategies for some diseases. For other diseases, the genetic basis and pathophysiology remain unclear. Further researches are therefore crucial to innovate ways to overcome diagnostic challenges and develop effective treatment options for these orphan diseases.

PurposeThis study aimed to investigate the association between asthma and risk of myasthenia gravis (MG) using the method of systematic review and meta-analysis.MethodsPotentially eligible studies were identified from Medline and EMBASE databases from inception to … using search strategy that comprised of terms for “Asthma” and “Myasthenia Gravis”. Eligible cohort study must consist of one cohort of individuals with asthma and another cohort of individuals without asthma. Then, the study must report relative risk (RR) with 95% confidence intervals (95% CIs) of incident MG between the groups. Eligible case-control studies must include cases with MG and controls without MG. Then, the study must explore their history of asthma. Odds ratio (OR) with 95% CIs of the association between asthma status and MG must be reported. Point estimates with standard errors were retrieved from each study and were combined together using the generic inverse variance method.ResultsA total of 6,835 articles were identified. After two rounds of independent review by five investigators, two cohort studies and three case-control studies met the eligibility criteria and were included into the meta-analysis. Pooled analysis showed that asthma was significantly associated with risk of MG with the pooled risk ratio of 1.38 (95%CI, 1.02 – 1.86). Funnel plot was symmetric.Conclusion The current study found a significant association between asthma and increased risk of MG.

Objective To determine the association between vitamin D status and morbidity and mortality in adult hospitalized coronavirus disease 2019 (COVID-19) patients Methods We performed a retrospective chart review study in COVID-19 patients aged ≥18 year hospitalized at Boston University Medical Center between March 1 and August 4, 2020. All studied patients tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D (25[OH]D) results measured within 1 year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and was analyzed to determine the association between vitamin D status and hospital morbidity and mortality. Results Among the 287 patients, 100 (36%) were vitamin D sufficient (25[OH]D >30 ng/mL) and 41 (14%) died during hospitalization. Multivariate analysis in patients aged ≥65 years revealed that vitamin D sufficiency (25[OH]D ≥30 ng/mL) was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95% CI, 0.12-0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95% CI, 0.05-0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95% CI, 0.08-0.88), after adjustment for potential confounders. Among patients with body mass index Conclusion We revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.

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.

Evidence on vitamin D and parathyroid hormone (PTH) status in patients with early kidney impairment is limited. We aimed to determine the associations among kidney function, vitamin D, and PTH status in community-dwelling elderly patients with mild-to-moderate kidney impairment. Community-dwelling elderly patients were enrolled in this Institutional Review Board approved cross-sectional study. The eligibility criteria were as follows: age > 60 years, no recent hospitalization within the past 12 months, no conditions that affect vitamin D status including vitamin D supplementation, and eGFR > 30 mL/min/1.73 m2. Serum 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) levels were assessed. A total of 226 patients were enrolled. Data were expressed as mean ± SD. The mean serum 25(OH)D was 26.61 ± 10.44 ng/mL and the mean serum PTH was 50.67 ± 22.67 pg/mL. The prevalence of vitamin D deficiency [25(OH)D 65 pg/mL] were 25.3% and 18.1%, respectively. Patients with eGFR 30−

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; I2 75%). Conclusion This systematic review and meta-analysis found a significant association between DPP4i use and a lower risk of incident RA.

Atrial fibrillation (AF) is more likely found in patients with premature ventricular complexes (PVCs). Nonetheless, the outcomes of previous investigations remain inconclusive. To evaluate the link between PVCs and the risk of AF, we did a systematic review and meta-analysis.Potentially eligible studies were found by searching for published publications indexed in the MEDLINE and EMBASE databases from inception to April 13, 2021, looking for studies that assessed the risk of AF in patients with PVCs vs those who did not have PVCs. Dersimonian and Laird's random-effect, generic inverse variance technique was used to calculate the pooled risk ratio (RR) and 95 % confidence interval (CI).The meta-analysis includes 6 cohort studies (1 prospective and 5 retrospective cohort studies) with a total of 9,662,088 individuals. We found that patients with PVCs have a significantly higher risk of AF than individuals without PVCs with the pooled RR of 1.90 (95% CI, 1.51-2.39, I2 = 83%).PVCs are significantly related with a 1.90-fold higher incidence of AF, according to the present systematic review and meta-analysis. Nonetheless, further research is needed to determine how this connection should be treated in clinical practice if it is causal.

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).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.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; IThe 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.

Funding Acknowledgements Type of funding sources: None. Background/objectives: Recent studies have suggested that patients with premature ventricular complexes (PVCs) may have a higher risk of ischemic stroke. However, the data are limited and inconclusive. We conducted a systematic review and meta-analysis to investigate the association between PVCs and the risk of ischemic stroke. Methods A comprehensive literature review was conducted by searching for published articles indexed in MEDLINE and EMBASE databases from inception through September 25, 2020, to identify studies that compared the risk of ischemic stroke between patients with PVCs and individuals without PVCs. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of Dersimonian and Laird. Results A total of four observational studies (2 prospective and 2 retrospective cohort studies) with 42,677 participants met the eligibility criteria and were included in the meta-analysis. We found that patients with PVCs have a significantly higher risk of ischemic stroke than individuals without PVCs with the pooled RR of 1.31 (95% CI, 1.07-1.60, I2 = 43%). Conclusions: From our systematic review and meta-analysis, we found that PVCs are associated with a higher risk of ischemic stroke. Whether this association is causal and how it should be addressed in clinical practice require further investigations. Table 1Ofoma et al.Agarwal et al.Lin et al.Im et al.Year of publication2012201520152018Country of originUnited StatesUnited StatesTaiwanKoreaStudy designProspective cohort studyProspective cohort studyRetrospective cohort studyRetrospective cohort studyStudy subjectsCases: Cases were patients with PVCs who were diagnosed based on 2-minute ECG. Cases were identified from the 1987 to 1989 ARIC study. Comparators: Comparators were the rest of the patients in the study who did not carry a diagnosis of PVCs. The average follow-up time was 13 years. Patients with a history of stroke, CAD, SAH, and ICH were excluded from the analysis.Cases: Cases were patients with PVCs who were diagnosed based on routine ECG. Cases were identified from the 2003 to 2007 REGARDS study. Comparators: Comparators were the rest of the patients in the study who did not carry a diagnosis of PVCs. An average (SD) follow-up time was 6 (2) years. Patients with a history of stroke or TIA and hemorrhagic stroke were excluded from the analysis.Cases: Cases were patients with PVCs ( 720 beats/day were excluded from the analysis.Cases: Cases were patients with PVCs (>10%) who were diagnosed based on standard ECG or 24-hour ECG monitoring. Cases were identified from the 2013 to 2015 Kosin University database. Comparators: Comparators were the rest of the patients in the database who did not carry a diagnosis of PVCs. The average follow-up time was 4 years. Patients with a history of cardiomyopathy, VHD, CHD, hepatic or renal disease, and acute cardiovascular or cerebrovascular event within 3 months, any trauma or surgery within 3 months, hyperthyroidism, uncontrolled HT, malignancy, CTD, IHD, and any acute or chronic inflammatory disease were excluded from the analysis.Number of subjectsCases: 793Comparators: 13,700Cases: 1,415Comparators: 23,045Cases: 1,074 (Uniform PVCs), 1,166 (Multiform PVCs)Comparators: 1,111Cases: 203Comparators: 170Baseline characteristics of subjectsMean age, year: Cases: 55.97Comparators: 53.85 Mean BMI, kg/m2:Cases: 28.47Comparators: 27.61 Mean TC, mg/dL: Cases: 211.85Comparators: 214.69 Female: Case: 50.82%Comparators: 57.06% White: Case: 68.1%Comparators: 73.38% HT:Cases: 44.54 %Comparators: 32.80 % Diabetes:Cases: 13.98%Comparators: 10.76% Smoking:Cases: 25.73%Comparators: 25.83% Mean age, year: Cases: 68.3 ± 9.2 Comparators: 64.3 ± 9.3 Mean BMI, kg/m2:Cases: 29.2 ± 6.1Comparators: 29.3 ± 6.2 Mean SBP, mmHg:Cases: 130.1 ± 16.9 Comparators: 126.9 ± 16.4 Female:Cases: 45.4%Comparators: 59% Black: Cases: 41.9%Comparators: 39.9% EducationNo high school:Cases: 15.5%Comparators: 11.1% High school/no college:Cases: 26.3%Comparators: 25.6% College or professional: Cases: 58.2%Comparators: 63.3% Geographic regionNon-Belt:Cases: 47.2%Comparators: 43.9% Belt:Cases: 33.9%Comparators: 34.8% Buckle:Cases: 19.0%Comparators: 21.3% Previous heart disease: Cases: 25.4%Comparators: 12.2% HT:Cases: 64.7%Comparators: 56.2% DM: Cases: 21.8%Comparators: 19.1% AF: Cases: 9.7%Comparators: 7.8% LVH: Cases: 11.2%Comparators: 9.4% Current smoking:Cases: 13.0%Comparators: 14.0% Use of warfarin: Case: 3.5%Comparators: 2.7% Use of aspirin: Case: 48.1%Comparators: 40.9%Mean age, year: Cases: 58.7 ± 19.3 (Uniform PVCs), 65.7 ± 16.9 (Multiform PVCs)Comparators: 50.7 ± 20.1 Female:Cases: 44.9% (Uniform PVCs), 31.4% (Multiform PVCs)Comparators: 53.4% DM: Cases: 7.4% (Uniform PVCs), 9.4% (Multiform PVCs)Comparators: 5.6% HT: Cases: 31.2% (Uniform PVCs), 38.0% (Multiform PVCs)Comparators: 21.6% Hyperlipidemia: Cases: 7.4% (Uniform PVCs), 5.8% (Multiform PVCs)Comparators: 5.5% CKD: Cases: 1.4% (Uniform PVCs), 1.4% (Multiform PVCs)Comparators: 0.3% Cirrhosis: Cases: 0.8% (Uniform PVCs),0.8% (Multiform PVCs)Comparators: 0.5% AF: Cases: 6.7 % (Uniform PVCs), 6.8 % (Multiform PVCs)Comparators: 6.7% CLD: Cases: 2.6% (Uniform PVCs), 2.8% (Multiform PVCs)Comparators: 2.0% Use of AAD: Cases: 0.2% (Uniform PVCs), 0.5% (Multiform PVCs)Comparators: 0.5% Use of anti-HT: Cases: 16.4% (Uniform PVCs), 20.8 % (Multiform PVCs)Comparators: 12.2% Use of statin: Cases: 7.2 % (Uniform PVCs), 5.7% (Multiform PVCs)Comparators: 5.1% Mean age, year:Cases: 61.0 ± 15.2Comparators: 57.6 ± 16.4 Female: Cases: 56.7 %Comparators: 52.7% DM:Cases: 17.5 %Comparators: 20.0% HT:Cases: 28.4%Comparators: 30.6% CAD: Cases: 11.3%Comparators: 12.4% MedicationAmiodarone: Cases: 7.7%Comparators: 0% Propafenone: Cases: 1.0%Comparators: 0% Digoxin: Cases: 5.2%Comparators: 4.8% Beta-blocker:Cases: 53.6%Comparators: 8.2% CCB: Cases: 21.6%Comparators: 20% ARB & ACEI: Cases: 17.0%Comparators: 16.4% Statin: Cases: 39.4%Comparators: 37.6% Aspirin: Cases: 24.6%Comparators: 25.3% Clopidogrel: Cases: 13.4%Comparators: 12.0% VKA: Cases: 9.8%Comparators: 11.2%Diagnosis of PVCsPVCs were detected by 2-minute ECG.PVCs were detected by routine ECG. PVCs were detected by 24-hour Holter monitoring.PVCs were detected by standard ECG or 24-hour Holter monitoring.Diagnosis of strokeThe diagnosis of ischemic stroke was supported by annual telephone follow-up and a community surveillance system. Stroke was diagnosed by agreement of computer and reviewer classification. Disagreements were adjudicated by a second physician-reviewer.The diagnosis of ischemic stroke was supported by telephone follow-up every 6 months. Stroke events were defined following the WHO definition. The stroke was diagnosed and confirmed by an adjudication committee.Ischemic stroke was diagnosed by physicians and also confirmed by brain imaging.Ischemic stroke was determined by a neurologist if the patient felt painless, weakness, sudden numbness or dead feeling on one side of the body, sudden painless loss of vision, and sudden loss of ability to understand what people were saying and also confirmed by brain MRI in all patients.Confounder adjusted in the multivariate analysisAge, race, gender, BMI, HT, diabetes, smoking, TC levelsAge, sex, race, geographic region, education level, previous heart disease, SBP, use of antihypertensive medication, LVH, AF, DM, current smoking, use of warfarin and aspirinAge, sex, HT, DM, CKD, use of hypertensive medicationAge, AF, HT, LVH, E/E’, MR grade, NT-proBNPNewcastle-Ottawa scoreSelection: 4 stars Comparability: 2 stars Outcome: 3 starsSelection: 4 stars Comparability: 2 stars Outcome: 3 starsSelection: 3 stars Comparability: 1 star Outcome: 3 starsSelection: 4 stars Comparability: 2 stars Outcome: 3 starsBaseline characteristics of studies included in the meta-analysisAbstract Figure. Forest plot of the meta-analysis

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.

Purpose of review The goal of this review is to give an overview of diagnosis and up-to-date management of major pediatric metabolic bone diseases that are associated with bone fragility, including nutritional rickets, hypophosphatemic rickets, osteogenesis imperfecta, Ehlers--Danlos syndrome, Marfan's syndrome, hypophosphatasia, osteopetrosis and skeletal fluorosis. Recent findings During the past decade, a number of advanced treatment options have been introduced and shown to be an effective treatment in many metabolic bone disorders, such as burosumab for hypophosphatemic rickets and asfotase alfa for hypophosphatasia. On the other hand, other disorders, such as nutritional rickets and skeletal fluorosis continue to be underrecognized in many regions of the world. Genetic disorders of collagen-elastin, such as osteogenesis imperfecta, Ehlers--Danlos syndrome and Marfan's syndrome are also associated with skeletal fragility, which can be misdiagnosed as caused by non-accidental trauma/child abuse. Summary It is essential to provide early and accurate diagnosis and treatment for pediatric patients with metabolic bone disorders in order to maintain growth and development as well as prevent fractures and metabolic complications.

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; I2 = 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.

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; I2 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.

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. 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. 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; I2 = 87%). Funnel plot was fairly symmetric and not suggestive of presence of publication bias. 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.

This study aimed to investigate the association between circulating soluble Klotho level and risk of all-cause mortality in chronic kidney disease (CKD) patients using systematic review and meta-analysis technique. Potentially eligible studies were identified from Medline and EMBASE databases from inception to March 2020 using a search strategy that consisted of terms for “Klotho” and “Mortality”. Eligible study must be a cohort study that consists of one cohort of CKD patients with higher circulating soluble Klotho level and another cohort of CKD patients with lower circulating soluble Klotho level. The study must also report relative risk (RR), incidence rate ratio, hazard risk ratio or standardized incidence ratio with 95% confidence intervals (95% CIs) comparing all-cause mortality between CKD patients with lower circulating soluble Klotho level versus CKD patients with higher circulating soluble Klotho level. If the study divides patients (per circulating soluble Klotho level) into more than two groups, a comparison between the highest and the lowest group would be extracted. Point estimates with standard errors were retrieved from each study and were combined together using the generic inverse variance method. A total of 2964 articles were retrieved. After two rounds of an independent review by two investigators, six prospective cohort studies met the eligibility criteria and were included into the meta-analysis. CKD patients with lower circulating soluble Klotho level had a significantly increased risk of all-cause mortality with the pooled risk ratio of 1.88 (95% CI 1.29–2.74; I2 0%). The funnel plot was fairly symmetric and did not reveal any suggestive evidence of publication bias. The current study found a significant association between lower circulating soluble Klotho level and increased risk of all-cause mortality in CKD patients. However, this meta-analysis carries some limitations, including relatively small sample size, lack of adjustment for potential confounders and between-study heterogeneity in baseline characteristics of the patients and cut-off values used to categorize patients into higher and lower circulating serum Klotho level group.

Background Increased risk of coronary heart disease has been observed in several chronic inflammatory disorders, including chronic infection. However, data on the association between tuberculosis and risk of coronary heart diseases are limited. Methodology This systematic review and meta-analysis identified all cohort studies that compared the risk of coronary heart disease among patients with tuberculosis versus individuals without tuberculosis and summarized their results together. Literature search was independently conducted by two investigators using MEDLINE and EMBASE database up to August 2019. Point estimates and standard errors from each study were pooled together using the generic inverse variance method of DerSimonian and Laird. Results A total of four cohort studies met the eligibility criteria and were included into the meta-analysis. The pooled analysis found that patients with tuberculosis have an increased risk of developing coronary heart disease with the pooled risk ratio of 1.76 (95% CI, 1.05-2.95; I2 of 97%). Conclusion A significantly increased risk of coronary heart diseases among patients with tuberculosis was demonstrated by the current study.

Recent studies have suggested that irritable bowel syndrome (IBS) could be a risk factor for osteoporosis although the evidence is still limited. The current study aimed to comprehensively examine the risk of osteoporosis among patients with IBS using systematic review and meta-analysis technique. Literature search was independently conducted by two investigators using MEDLINE, EMBASE, and Google Scholar database up to October 2019. Eligible study must evaluate whether patients with IBS have a higher risk of osteoporosis and/or osteoporotic fracture. It could be either cross-sectional study, case-control study, or cohort study. Point estimates and standard errors from each eligible study were combined together using the generic inverse variance method of DerSimonian and Laird. Of the 320 articles identified from the three databases, four cohort and one cross-sectional study with 526,633 participants met the eligibility criteria and were included into the meta-analysis. All five studies investigated the risk of osteoporosis among patients with IBS, and the pooled analysis found that patients with IBS had a significantly higher risk of osteoporosis than individuals without IBS with the pooled risk ratio of 1.95 (95% CI, 1.04–3.64; I2 100%). Sensitivity analysis including only cohort studies found a lower RR (pooled RR 1.55; 95% CI, 1.39–1.72) with a lower I2 (59%). Three studies investigated the risk of osteoporotic fracture, and the pooled analysis found that patients with IBS also had a higher risk of osteoporotic fracture than individuals without IBS with the pooled risk ratio of 1.58 although statistical significance was not reached (95% CI, 0.95–2.62; I2 99%). Sensitivity analysis including only cohort studies found a lower RR (pooled RR 1.27; 95% CI, 1.20–1.39) with a dramatically lower I2 (0%). Limitations included high heterogeneity and reliance on diagnostic codes. A significantly increased risk of osteoporosis among IBS patients was observed in this study. Early intervention to prevent the development of osteoporosis, such as weight-bearing exercise, adequate intake of vitamin D and calcium, and early screening for osteoporosis, may be beneficial to these patients although further studies are still required to confirm the efficacy and cost-effectiveness of this approach.

Background Matched donor (MD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the preferred choice of treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients who have achieved complete remission. This systematic review and meta-analysis was conducted to investigate the effects of allo-HSCTs from different donor types for Ph+ ALL patients who received tyrosine kinase inhibitors (TKIs). Methods Studies in EMBASE and MEDLINE between inception and December 2020 were identified using search terms related to "Ph+ ALL" and "HSCT." Eligible studies were studies with Ph+ ALL patients who received a TKI and allo-HSCT. The primary outcomes of interest-the overall survival (OS) or relapse-free survival (RFS)-needed to be reported. The Mantel-Haenszel method was used to combine the effect estimates and associated 95% confidence intervals (CIs) of each donor type. Results Fourteen cohort studies were identified for the meta-analysis. Haploidentical (HID)-HSCT for Ph+ ALL patients resulted in a superior RFS to MD-HSCT, with a pooled odds ratio (OR) of 1.57 (95% CI, 1.05-2.32; I2 = 0%). However, HID-HSCT and MD-HSCT had comparable OS. Furthermore, HID-HSCT group had a significantly lower relapse rate than MD-HSCT group. On the other hand, the risks of graft-versus-host disease (GvHD) were higher for HID-HSCT and pooled OR of chronic GvHD rate. The OS and RFS of matched sibling-HSCT, matched unrelated-HSCT, and cord blood-HSCT were comparable with those of HID-HSCT. Conclusion This systematic review and meta-analysis showed that HID-HSCT is as effective as MD-HSCT in Ph+ ALL patients.

Vitamin D plays an important role in maintaining a healthy mineralized skeleton. It is also considered an immunomodulatory agent that regulates innate and adaptive immune systems. The aim of this narrative review is to provide general concepts of vitamin D for the skeletal and immune health, and to summarize the mechanistic, epidemiological, and clinical evidence on the relationship between vitamin D and rheumatic diseases. Multiple observational studies have demonstrated the association between a low level of serum 25-hydroxyvitamin D [25(OH)D] and the presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies, and osteoarthritis (OA). Nevertheless, the specific benefits of vitamin D supplements for the treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for the improvement of disease activity of RA, SLE, and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently than others, as inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain a serum 25(OH)D level of at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis, and fracture, and possibly 40–60 ng/mL (100–150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.