Complications, Symptoms, Presurgical Predictors in Patients With Chronic Hypoparathyroidism: A Systematic Review.

The complications and symptoms of hypoparathyroidism remain incompletely defined. Measuring serum parathyroid hormone (PTH) and calcium levels early after total thyroidectomy may predict the development of chronic hypoparathyroidism. The study aimed (i) to identify symptoms and complications associated with chronic hypoparathyroidism and determine the prevalence of those symptoms and complications (Part I), and (ii) to examine the utility of early postoperative measurements of PTH and calcium in predicting chronic hypoparathyroidism (Part II). We searched Medline, Medline In-Process, EMBASE, and Cochrane CENTRAL to identify complications and symptoms associated with chronic hypoparathyroidism. We used two predefined criteria (at least three studies reported the complication and symptom and had statistically significantly greater pooled relative estimates). To estimate prevalence, we used the median and interquartile range (IQR) of the studies reporting complications and symptoms. For testing the predictive values of early postoperative measurements of PTH and calcium, we used a bivariate model to perform diagnostic test meta-analysis. In Part I, the 93 eligible studies enrolled a total of 18,973 patients and reported on 170 complications and symptoms. We identified nine most common complications or symptoms probably associated with chronic hypoparathyroidism. The complications or symptoms and the prevalence are as follows: nephrocalcinosis/nephrolithiasis (median prevalence among all studies 15%), renal insufficiency (12%), cataract (17%), seizures (11%), arrhythmia (7%), ischemic heart disease (7%), depression (9%), infection (11%), and all-cause mortality (6%). In Part II, 18 studies with 4325 patients proved eligible. For PTH measurement, regarding the posttest probability, PTH values above 10 pg/mL 12-24 hours postsurgery virtually exclude chronic hypoparathyroidism irrespective of pretest probability (100%). When PTH values are below 10 pg/mL, posttest probabilities range from 3% to 64%. Nine complications and symptoms are probably associated with chronic hypoparathyroidism. A PTH value above a threshold of 10 pg/mL 12-24 hours after total thyroidectomy is a strong predictor that the patients will not develop chronic hypoparathyroidism. Patients with PTH values below the threshold need careful monitoring as some will develop chronic hypoparathyroidism. © 2022 American Society for Bone and Mineral Research (ASBMR).

Parathyroid Hormone Therapy for Managing Chronic Hypoparathyroidism: A Systematic Review and Meta-Analysis.

The efficacy and safety of parathyroid hormone (PTH) therapy for managing long-term hypoparathyroidism is being evaluated in ongoing clinical trials. We undertook a systematic review and meta-analysis of currently available randomized controlled trials to investigate the benefits and harms of PTH therapy and conventional therapy in the management of patients with chronic hypoparathyroidism. To identify eligible studies, published in English, we searched Embase, PubMed, and Cochrane CENTRAL from inception to May 2022. Two reviewers independently extracted data and assessed the risk of bias. We defined patients' important outcomes and used grading of recommendations, assessment, development, and evaluation (GRADE) to provide the structure for quantifying absolute effects and rating the quality of evidence. Seven randomized trials of 12 publications that enrolled a total of 386 patients proved eligible. The follow-up duration ranged from 1 to 36 months. Compared with conventional therapy, PTH therapy probably achieves a small improvement in physical health-related quality of life (mean difference [MD] 3.4, 95% confidence interval [CI] 1.5-5.3, minimally important difference 3.0, moderate certainty). PTH therapy results in more patients reaching 50% or greater reduction in the dose of active vitamin D and calcium (relative risk [RR] = 6.5, 95% CI 2.5-16.4, 385 more per 1000 patients, high certainty). PTH therapy may increase hypercalcemia (RR =2.4, 95% CI 1.2-5.04, low certainty). The findings may support the use of PTH therapy in patients with chronic hypoparathyroidism. Because of limitations of short duration and small sample size, evidence from randomized trials is limited regarding important benefits of PTH therapy compared with conventional therapy. Establishing such benefits will require further studies. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Effects of Medium Cut-Off Versus High-Flux Hemodialysis Membranes on Biomarkers: A Systematic Review and Meta-Analysis.

BACKGROUND: Medium cut-off (MCO) membranes enhance large middle-molecule clearance while selectively retaining molecules >45 000 Da. OBJECTIVES: We undertook a systematic review and meta-analysis comparing the effects of MCO versus high-flux membranes on biomarkers. METHODS: We searched MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science from January 2015 to July 2020, and gray literature sources from 2017. We included randomized (RS) and nonrandomized studies (NRS) comparing MCO and high-flux membranes in adults (>18 years) receiving maintenance hemodialysis. We performed study selection, data extraction, and quality appraisals in duplicate and used the Grading of Recommendations Assessment, Development, and Evaluation framework. Outcomes included solute removal (plasma clearance or dialysate quantitation), reduction ratios, and predialysis serum concentrations for a range of prespecified large middle molecules. RESULTS: We identified 26 eligible studies (10 RS and 16 NRS; N = 1883 patients; patient-years = 1366.3). The mean difference (MD) for albumin removal was 2.31 g per session (95% confidence interval [CI], 2.79 to 1.83; high certainty), with a reduction in predialysis albumin of -0.12 g/dl (95% CI, -0.16 to -0.07; I 2 = 0%; high certainty) in the first 24 weeks, returning to normal (MD = -0.02 g/dl, 95% CI, -0.07 to -0.03; I 2 = 56%; high certainty) after 24 weeks. We also found with high certainty that MCO dialysis resulted in a large increase (standardized mean difference [SMD]> 2.0 for all) in ß2-microglobulin, κ- and λ-free light chains, and myoglobin removal, resulting in moderate (SMD > 0.5) to large (SMD > 0.8) reductions in predialysis concentrations for all of these solutes. Medium cut-off dialysis increased the reduction ratio for tumor necrosis factor-alpha (TNF-α) by 7.7% (95% CI, 4.7 to 10.6; moderate certainty), and reduced predialysis TNF-α by SMD -0.48 (95% CI, -0.91 to -0.04; moderate certainty). We found with moderate certainty that MCO dialysis had little to no effect on predialysis interleukin-6 (IL-6) plasma concentrations. Medium cut-off dialysis reduced mRNA expression of TNF-α and IL-6 in peripheral leukocytes by MD -15% (95% CI, -19.6 to -10.4; moderate certainty) and -8.8% (95% CI, -10.2 to -7.4; moderate certainty), respectively. CONCLUSION: Medium cut-off dialysis increases the clearance of a wide range of large middle molecules and likely reduces inflammatory mediators with a concomitant transient reduction in serum albumin concentration. The net effect of MCO dialysis on large middle molecules could translate into important clinical effects.

CONTEXTE: Les membranes MCO (Medium cut-off) améliorent la clairance des moyennes molécules de masse moléculaire élevée tout en retenant sélectivement les molécules de plus de 45 000 Da. OBJECTIFS: Nous avons entrepris une revue systématique et une méta-analyse comparant les effets des membranes MCO et des membranes à perméabilité élevée sur certains biomarqueurs. MÉTHODOLOGIE: Nous avons effectué des recherches dans MEDLINE, EMBASE, CINAHL, Cochrane Library et Web of Science entre janvier 2015 et juillet 2020, et dans des sources de littérature grise de 2017. Nous avons inclus les études randomisées (ÉR) et non randomisées (ÉNR) comparant les membranes MCO et les membranes à perméabilité élevée chez les adultes recevant une hémodialyse d'entretien. Nous avons procédé à la sélection des études, à l'extraction des données et à l'évaluation de la qualité en duplicata, puis nous avons utilisé la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation). Les résultats comprenaient l'élimination du soluté (clairance plasmatique ou quantification du dialysat), les rapports de réduction et les concentrations sériques prédialyse pour une gamme de moyennes molécules à masse moléculaire élevée prédéterminées. RÉSULTATS: Nous avons répertorié 26 études admissibles (10 ÉR, 16 ÉNR; n = 1 883 patients; 1 366,3 années-patients). La différence moyenne (DM) pour l'élimination de l'albumine était de 2,31 g par séance (IC 95 % : 2,79 à 1,83; haute certitude), avec une réduction de l'albumine prédialyse de -0,12 g/dl (IC 95 % : -0,16 à -0,07; I 2 = 0 %; haute certitude) au cours des 24 premières semaines, et un retour à la normale (DM = -0,02 g/dl; IC 95 % : -0,07 à -0,03; I 2 = 56 %; haute certitude) après 24 semaines. Nous avons constaté, avec une grande certitude, que la dialyse MCO entraînait une élimination importante de ß2-microglobuline, chaînes légères κ- et λ- et de myoglobine (différence moyenne standardisée [DMS] > 2,0 pour toutes), ce qui s'est traduit par des réductions modérées (DMS > 0,5) à importantes (DMS > 0,8) des concentrations prédialyse pour tous ces solutés. La dialyse MCO a haussé le taux de réduction du TNF-α de 7,7 % (IC 95 % : 4,7 à 10,6; certitude modérée) et réduit le TNF-α prédialyse (DMS = -0,48; IC 95 % : -0,91 à -0,04; certitude modérée). Nous avons constaté, avec une certitude modérée, que la dialyse MCO n'a que peu ou pas d'effet sur les concentrations plasmatiques d'IL-6 prédialyse. La dialyse MCO a réduit l'expression de l'ARNm du TNF-α et d'IL-6 dans les leucocytes périphériques avec une DM de -15 % (IC 95 % : -19,6 à -10,4; certitude modérée) et de -8,8 % (IC 95 % : -10,2 à -7,4; certitude modérée) respectivement. CONCLUSION: La dialyse MCO augmente la clairance d'une vaste gamme de moyennes molécules de haute masse moléculaire et semble réduire les médiateurs inflammatoires avec une réduction transitoire concomitante de la concentration en albumine sérique. L'effet net de la dialyse MCO sur les moyennes molécules de haute masse moléculaire pourrait se traduire par des effets cliniques importants.

Clinical Outcomes With Medium Cut-Off Versus High-Flux Hemodialysis Membranes: A Systematic Review and Meta-Analysis.

BACKGROUND: A novel medium cut-off (MCO) dialyzer (Theranova, Baxter Healthcare, Deerfield, IL, USA) enhances large middle molecule clearance while retaining selectivity for molecules >45 000 Da. OBJECTIVE: We undertook a systematic review and meta-analysis evaluating clinical outcomes with MCO vs high-flux membranes. METHODS: We searched MEDLINE, EMBASE, CINAHL, Cochrane Library, and Web of Science through July 2020, and gray literature sources from 2017. We included randomized (RS) and nonrandomized studies (NRS) comparing MCO and high-flux membranes in adults receiving maintenance hemodialysis. Pairs of reviewers performed study selection, data extraction, and risk of bias assessment in duplicate. We conducted random-effects pairwise meta-analyses to pool results across studies and used the Grading of Recommendations Assessment, Development and Evaluation approach to assess evidence certainty. RESULTS: We identified 22 eligible studies (6 RS, 16 NRS; N = 1811 patients; patient-years = 1546). The MCO dialyzer improved (estimate; 95% confidence interval [CI]; certainty rating) quality of life (mean difference [MD] = 16.7/100 points; 6.9 to 26.4; moderate), Kidney Disease Quality of Life Instrument (KDQOL) subscales-burden (MD = 4.0; 1.1 to 6.9; moderate) and effects (MD = 5.4; 3.2 to 7.6; moderate), pruritus (MD = -4.4; -7.1 to -1.7; moderate), recovery time (MD = -420 minutes; -541 to -299; high), and restless legs syndrome (odds ratio = 0.39; 0.29 to 0.53; moderate). There was little to no difference in all-cause mortality (risk difference = -0.4%; -2.8 to 2.1; moderate) and serious adverse events (rate ratio = 0.63; 0.38 to 1.04; low). MCO dialysis reduced hospitalization (rate ratio = 0.48; 0.27 to 0.84; low), infection (rate ratio = 0.38; 0.17 to 0.85; moderate), hospitalization days (MD = -1.5 days; 95% CI, -2.22 to -0.78; moderate), erythropoiesis resistance index (MD = -2.92 U/kg/week/g/L; 95% CI, -4.25 to -1.6; moderate) and cumulative iron use over 12 weeks (MD = -293 mg; 95% CI, -368 to -218; moderate). We found with low certainty that MCO dialysis had little to no effect on KDQOL symptoms/problem list, pain, and physical health and moderate certainty that MCO dialysis likely has no effect on the KDQOL mental health composite. CONCLUSIONS: We found with predominantly moderate certainty that the MCO dialyzer improves several patient-important outcomes with no apparent risks or harms. More definitive studies are needed to better quantify the effects of MCO membranes on mortality, hospitalization, and other rare events.

CONTEXTE: Un nouveau dialyseur MCO (Medium cut-off) (Theranova, Baxter Healthcare, Deerfield, IL, É.-U.) améliore la clairance des molécules importantes de taille moyenne tout en maintenant la sélectivité des molécules de plus de 45 000 Da. OBJECTIFS: Nous avons entrepris une revue systématique et une méta-analyse évaluant les résultats cliniques des membranes MCO par rapport aux membranes à perméabilité élevée. MÉTHODOLOGIE: Nous avons effectué des recherches dans MEDLINE, embase, CINAHL, Cochrane Library et Web of Science jusqu'en juillet 2020, et dans des sources de littérature grise de 2017. Nous avons inclus les études randomisées (ÉR) et non randomisées (ÉNR) comparant les membranes MCO et les membranes à perméabilité élevée chez les adultes recevant une hémodialyse d'entretien. Des paires de réviseurs ont procédé à la sélection des études, à l'extraction des données et à l'évaluation du risque de biais en duplicata. Nous avons effectué des méta-analyses à effets aléatoires par paires pour regrouper les résultats des différentes études, puis nous avons employé la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation) pour évaluer la certitude des preuves. RÉSULTATS: Nous avons répertorié 22 études admissibles (6 ÉR, 16 ÉNR ; n=1811 patients; 1 546 années-patients). Le dialyseur MCO a amélioré (estimation; IC à 95 %; évaluation de la certitude) la qualité de vie (différence moyenne [DM] = 16,7/100 points; 6,9 à 26,4; modérée), les sous-échelles KDQOL ­ le fardeau de la maladie (DM = 4,0; 1,1 à 6,9; modérée), les effets (DM = 5,4; 3,2 à 7,6; modérée), le prurit (DM = -4,4; -7,1 à -1,7; modérée), le temps de récupération (DM = -420 minutes; -541 à -299; élevée) et le syndrome des jambes sans repos (rapport de cotes = 0,39; 0,29 à 0,53; modéré). On a noté peu ou pas de différence pour la mortalité toutes causes confondues (risque différentiel = -0,4 %; -2,8 à 2,1; modérée) et les événements indésirables graves (rapport des taux = 0,63; 0,38 à 1,04; faible). La dialyse par MCO a réduit les hospitalisations (rapport des taux = 0,48; 0,27 à 0,84; faible), les infections (rapport des taux = 0,38; 0,17 à 0,85; modérée), la durée des hospitalisations (DM = -1,5 jour; -2,22 à -0,78; modérée), l'indice de résistance à l'érythropoïèse (DM = -2,92 U/kg/semaine/g/L; -4,25 à -1,6; modérée) et l'utilisation cumulative de fer sur 12 semaines (DM = -293 mg; -368 à -218; modérée). Nous avons constaté, avec peu de certitude, que la dialyse MCO n'avait que peu ou pas d'effet sur les symptômes/problèmes liés à la KDQOL, de même que sur la douleur et la santé physique. Et nous avons constaté, avec une certitude modérée, que la dialyse MCO n'avait probablement aucun effet sur le composite de santé mentale de la KDQOL. CONCLUSION: Nous avons constaté avec une certitude principalement modérée que le dialyseur MCO améliorait plusieurs résultats importants pour le patient sans risques ou préjudices apparents. Des études plus définitives sont nécessaires afin de mieux quantifier les effets des membranes MCO sur le taux de mortalité, les hospitalisations et les autres événements rares.

Mortality at For-Profit Versus Not-For-Profit Hemodialysis Centers: A Systematic Review and Meta-analysis.

We conducted a systematic review and meta-analysis to assess differences in risk-adjusted mortality rates between for-profit (FP) and not-for-profit (NFP) hemodialysis facilities. We searched 10 databases for studies published between January 2001 to December 2019 that compared mortality at private hemodialysis facilities. We included observational studies directly comparing adjusted mortality rates between FP and NFP private hemodialysis providers in any language or country. We excluded evaluations of dialysis facilities that changed their profit status, studies with overlapping data, and studies that failed to adjust for patient age and some measure of clinical severity. Pairs of reviewers independently screened all titles and abstracts and the full text of potentially eligible studies, abstracted data, and assessed risk of bias, resolving disagreement by discussion. We included nine observational studies of hemodialysis facilities representing 1,163,144 patient-years. In pooled random-effects meta-analysis, the odds ratio of mortality in FP relative to NFP facilities was 1.07 (95% CI 1.04-1.11). Patients at FP hemodialysis facilities have 7 percent greater odds of death annually than patients with similar risk profiles at NFP facilities. Approximately 3,800 excess deaths might be averted annually if U.S. FP hemodialysis operators matched NFP mortality rates.

Impact of maternal reproductive factors on cancer risks of offspring: A systematic review and meta-analysis of cohort studies.

BACKGROUND: A number of studies have reported on associations between reproductive factors, such as delivery methods, number of birth and breastfeeding, and incidence of cancer in children, but systematic reviews addressing this issue to date have important limitations, and no reviews have addressed the impact of reproductive factors on cancer over the full life course of offspring. METHODS: We performed a comprehensive search in MEDLINE, and Embase up to January 2020 and Web of Science up to 2018 July, including cohort studies reporting the association between maternal reproductive factors of age at birth, birth order, number of births, delivery methods, and breastfeeding duration and cancer in children. Teams of two reviewers independently extracted data and assessed risk of bias. We conducted random effects meta-analyses to estimate summary relative estimates, calculated absolute differences between those with and without risk factors, and used the GRADE approach to evaluate the certainty of evidence. RESULTS: For most exposures and most cancers, we found no suggestion of a causal relation. We found low to very low certainty evidence of the following very small possible impact: higher maternal age at birth with adult multiple myeloma and lifetime uterine cervix cancer incidence; lower maternal age at birth with childhood overall cancer mortality (RR = 1.15, 95% CI = 1.01-1.30; AR/10,000 = 1, 95% CI = 0 to 2), adult leukemia and lifetime uterine cervix cancer incidence; higher birth order with adult melanoma, cervix uteri, corpus uteri, thyroid cancer incidence, lifetime lung, corpus uteri, prostate, testis, sarcoma, thyroid cancer incidence; larger number of birth with childhood brain (RR = 1.27, 95% CI = 1.06-1.52; AR/10,000 = 1, 95% CI = 0 to 2), leukemia (RR = 2.11, 95% CI = 1.62-2.75; AR/10,000 = 9, 95% CI = 5 to 14), lymphoma (RR = 4.66, 95% CI = 1.40-15.57; AR/10,000 = 11, 95% CI = 1 to 44) incidence, adult stomach, corpus uteri cancer incidence and lung cancer mortality, lifetime stomach, lung, uterine cervix, uterine corpus, multiple myeloma, testis cancer incidence; Caesarean delivery with childhood kidney cancer incidence (RR = 1.25, 95% CI = 1.01-1.55; AR/10,000 = 0, 95% CI = 0 to 1); and breastfeeding with adult colorectal cancer incidence. CONCLUSION: Very small impacts existed between a number of reproductive factors and cancer incidence and mortality in children and the certainty of evidence was low to very low primarily due to observational design.

Hospitals safety from disasters in I.R.iran: the results from assessment of 224 hospitals.

BACKGROUND AND OBJECTIVE: Iran's hospitals have been considerably affected by disasters during last decade. To address this, health system of I.R.Iran has taken an initiative to assess disaster safety of the hospitals using an adopted version of Hospital Safety Index (HSI). This article presents the results of disaster safety assessment in 224 Iran's hospitals. METHODS: A self-assessment approach was applied to assess the disaster safety in 145 items categorized in 3 components including structural, non-structural and functional capacity. For each item, safety level was categorized to 3 levels: not safe (0), average safe (1) and high safe (2). A raw score was tallied for each safety component and its elements by a simple sum of all the corresponding scores. All scores were normalized on a 100 point scale. Hospitals were classified to three safety classes according to their normalized total score: low (≤34.0), average (34.01-66.0) and high (>66.0). RESULTS: The average score of all safety components were 32.4 out of 100 (± 12.7 SD). 122 hospitals (54.5%) were classified as low safe and 102 hospitals (45.5%) were classified as average safe. No hospital was placed in the high safe category. Average safety scores out of 100 were 27.3 (±14.2 SD) for functional capacity, 36.0 (±13.9 SD) for non-structural component and 36.0 (±19.0 SD) for structural component. Neither the safety classes nor the scores of safety components were significantly associated with types of hospitals in terms of affiliation, function and size (P>0.05). CONCLUSIONS: To enhance the hospitals safety for disaster in Iran, we recommend: 1) establishment of a national committee for hospital safety in disasters; 2) supervision on implementation of the safety standards in construction of new hospitals; 3) enhancement of functional readiness and safety of non-structural components while structural retrofitting of the existing hospitals is being taken into consideration, whenever is cost-effective; 4) considering the disaster safety status as the criteria for licensing and accreditation of the hospitals. Key words: Hospital, safety, disaster, emergency, Iran Correspondence to: Ali Ardalan MD, PhD. Tehran University of Medical Sciences, Harvard Humanitarian Initiative, Email: aardalan@tums.ac.ir, ardalan@hsph.harvard.edu.