-
Nutrients Jul 2023Vitamin D has been shown to have multiple pleiotropic effects beyond bone and mineral metabolism, with purported roles in cardiovascular disease, cancer, and host... (Review)
Review
Vitamin D has been shown to have multiple pleiotropic effects beyond bone and mineral metabolism, with purported roles in cardiovascular disease, cancer, and host immunity. Vitamin D deficiency is common in patients with end-stage kidney disease (ESKD); however, current clinical practice has favored the use of the active hormone. Whether vitamin D deficiency should be corrected in patients with ESKD remains unclear, as few randomized trials have been conducted. In this systematic review, we summarize the current evidence examining whether vitamin D supplementation improves outcomes, beyond mineral metabolism, in patients with ESKD. Data from randomized controlled trials of adults with ESKD were obtained by searching Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection from inception to February 2023. Twenty-three trials composed of 2489 participants were identified for inclusion. Data were synthesized by two independent reviewers and summarized in tables organized by outcome. Outcomes included measures of mortality, cardiovascular disease, inflammation, muscle strength/function, nutrition, patient well-being, and outcomes specific to ESKD including erythropoietin usage, pruritus, and dialysis access maturation. The Cochrane risk of Bias Tool (RoB 2, 2019) was used to assess study quality. Overall, our findings indicate a minimal and varied benefit of native vitamin D supplementation. From the largest studies included, we determine that vitamin D has no demonstrated effect on patient-reported measures of well-being or utilization of erythropoietin, nor does it change levels of the inflammation biomarker -reactive protein. Included trials were heterogeneous with regards to outcomes, and the majority studied small participant populations with a relatively short follow-up. We conclude that vitamin D supplementation corrects vitamin D deficiency and is safe and well-tolerated in humans with ESKD. However, it is not clear from clinical trials conducted to date that a causal pathway exists between 25(OH)D and pleiotropic effects that is responsive to vitamin D treatment.
Topics: Adult; Humans; Vitamin D; Cardiovascular Diseases; Renal Dialysis; Randomized Controlled Trials as Topic; Vitamins; Kidney Failure, Chronic; Vitamin D Deficiency; Dietary Supplements; Erythropoietin; Minerals
PubMed: 37447398
DOI: 10.3390/nu15133072 -
The Journal of Craniofacial Surgery Oct 2023The purpose of this study was to examine and compare surgical and speech outcomes of the posterior pharyngeal flap and sphincter pharyngoplasty following surgical... (Meta-Analysis)
Meta-Analysis
Pharyngeal Flap Versus Sphincter Pharyngoplasty for the Treatment of Velopharyngeal Insufficiency in 22q11.2 Deletion Syndrome: Preliminary Findings From a Systematic Review.
The purpose of this study was to examine and compare surgical and speech outcomes of the posterior pharyngeal flap and sphincter pharyngoplasty following surgical management of velopharyngeal insufficiency in patients with 22q11.2 deletion syndrome (22q11.2DS). This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses checklist and guidelines. Selected studies were chosen using a 3-step screening process. The 2 primary outcomes of interest were speech improvement and surgical complications. Preliminary findings based on included studies suggest a slightly higher rate of postoperative complications with the posterior pharyngeal flap in patients with 22q11.2DS but a lower percentage of patients needing additional surgery compared with the sphincter pharyngoplasty group. The most reported postoperative complication was obstructive sleep apnea. Results from this study provide some insight into speech and surgical outcomes following pharyngeal flap and sphincter pharyngoplasty in patients with 22q11.2DS. However, these results should be interpreted with caution due to inconsistencies in speech methodology and lack of detail regarding surgical technique in the current literature. There is a significant need for standardization of speech assessments and outcomes to help optimize surgical management of velopharyngeal insufficiency in individuals with 22q11.2DS.
Topics: Humans; Velopharyngeal Insufficiency; DiGeorge Syndrome; Pharynx; Plastic Surgery Procedures; Speech; Postoperative Complications; Treatment Outcome; Retrospective Studies; Cleft Palate
PubMed: 37431935
DOI: 10.1097/SCS.0000000000009531 -
Cureus Jun 2023Major depressive disorder (MDD) is a common neuropsychiatry manifestation that is more prevalent lately. Many contributing factors are present (for example,... (Review)
Review
Major depressive disorder (MDD) is a common neuropsychiatry manifestation that is more prevalent lately. Many contributing factors are present (for example, neurochemical, physiological, pathophysiological, and endocrinological factors). Patients with increased serum parathyroid levels are usually linked to psychosis symptoms but not to depressive symptoms. We conducted this systematic review to explore a correlation between depressive disorder and increased serum parathyroid levels, a major endocrinological pathology, and help establish mental wellness in patients suffering from hyperparathyroidism. We conducted a thorough literature search using five major databases, MEDLINE, PubMed, PubMed Central (PMC), ScienceDirect, and Google Scholar, using three keywords-MDD, depression, and hyperparathyroidism. We included mixed method studies, including observational studies, non-randomized controlled trials, case reports, and review articles published in the last ten years, focusing on the adult and geriatric population (>18 years) and on depressive and anxiety symptoms associated with patients with hyperparathyroidism. We included 11 articles (seven observational studies + four case reports) for qualitative synthesis after screening the literature. The reviewed studies showed an association between high serum parathyroid level, high serum calcium level, high serum alkaline phosphatase level, low serum phosphorous level, and increased depressive neurocognitive symptoms. After a patient with hyperparathyroidism is treated for hypercalcemia or undergoes parathyroidectomy and the serum parathyroid levels are lowered, a decrease in severe depressive symptoms is noted. The qualitative analysis of the reviewed literature showed an association between major depressive disorder and hyperparathyroidism. This paper can guide clinicians to assess patients with increased serum parathyroid levels for depressive neuropsychiatric symptoms and plan treatment, as treatment of their hyperparathyroidism can significantly lower their depressive symptoms. More randomized controlled trials should be conducted to find the treatment effectiveness of depression in patients with hyperparathyroidism.
PubMed: 37425517
DOI: 10.7759/cureus.40150 -
American Journal of Kidney Diseases :... Nov 2023Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality,...
RATIONALE & OBJECTIVE
Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality, cardiovascular, bone, and kidney outcomes in adults with CKD.
STUDY DESIGN
Systematic review of randomized controlled trials (RCT) with highly sensitive searching of MEDLINE, Embase, and CENTRAL, through February 25, 2023.
SETTING & STUDY POPULATIONS
Adults with stage 3, 4, or 5 CKD, including kidney failure treated with dialysis. Recipients of a kidney transplant were excluded.
SELECTION CRITERIA FOR STUDIES
RCTs with≥3 months of follow-up evaluating a vitamin D compound.
DATA EXTRACTION
Data were extracted independently by three investigators.
ANALYTICAL APPROACH
Treatment estimates were summarized using random effects meta-analysis. Primary review endpoints were all-cause death, cardiovascular death, and fracture. Secondary outcomes were major adverse cardiovascular events, hospitalization, bone mineral density, parathyroidectomy, progression to kidney failure, proteinuria, estimated glomerular filtration rate, hypercalcemia, hyperphosphatemia, biochemical markers of CKD-MBD, and various intermediate outcome measures of cardiovascular disease. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2 tool. Evidence certainty was adjudicated using GRADE.
RESULTS
Overall, 128 studies involving 11,270 participants were included. Compared with placebo, vitamin D therapy probably had no effect on all-cause death (relative risk [RR], 1.04; 95% CI, 0.84-1.24); and uncertain effects on fracture (RR, 0.68; 95% CI, 0.37-1.23) and cardiovascular death (RR, 0.73; 95% CI, 0.31-1.71). Compared with placebo, vitamin D therapy lowered serum parathyroid hormone and alkaline phosphatase, but increased serum calcium.
LIMITATIONS
Data were limited by trials with short-term follow-up periods, small sample size, and the suboptimal quality.
CONCLUSIONS
Vitamin D therapy did not reduce the risk of all-cause death in people with CKD. Effects on fracture and cardiovascular and kidney outcomes were uncertain.
TRIAL REGISTRATION
Registered at PROSPERO with study number CRD42017057691.
PLAIN-LANGUAGE SUMMARY
Chronic kidney disease (CKD) is associated with increased risk of death, cardiovascular disease, and fractures. This excess risk is thought to be related to changes in bone and mineral metabolism, leading to the development of CKD-mineral and bone disorder (CKD-MBD) which is characterized by vascular calcification and reduced bone quality. Vitamin D is commonly used in the treatment of this condition. We reviewed randomized controlled trials examining the effect of vitamin D therapy in CKD. We found that vitamin D therapy affects serum biomarkers, including an increase in serum calcium. However, it probably has no effect on risk of all-cause death in CKD, and the effects on other clinical bone, cardiovascular, and kidney outcomes are uncertain.
PubMed: 37356648
DOI: 10.1053/j.ajkd.2023.04.003 -
Medicine Jun 2023Correction of calcium, phosphorus, and parathyroid hormone disorders is the standard of treatment in nondialysis patients with chronic kidney disease-mineral and bone... (Meta-Analysis)
Meta-Analysis
A meta-analysis of randomized controlled trials of tonifying kidney and strengthen bone therapy on nondialysis patients with chronic kidney disease-mineral and bone disorder.
BACKGROUND
Correction of calcium, phosphorus, and parathyroid hormone disorders is the standard of treatment in nondialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). However, the side effects and adverse reactions are still the main problems. Moreover, the lack of protection of kidney function in the treatment dramatically affects patients' health. Although Traditional Chinese Medicine, specifically tonifying kidney and strengthen bone (TKSB) therapy, is wildly applied to patients with CKD-MBD in China, the evidence of TKSB therapy in the treatment of CKD-MBD is limited. Thus, we conducted this meta-analysis to evaluate the efficacy and safety of TKSB therapy combined with Western medicine (WM) for nondialysis patients with CKD-MBD.
METHODS
Two investigators conducted systematic research of randomized controlled trials of TKSB therapy for CKD-MBD from 7 electronic databases. Methodological quality evaluations were performed using the Cochrane collaboration tool, and data analysis was conducted by RevMan v5.3 software and STATA v15.0.
RESULTS
In total, 8 randomized controlled trials involving 310 patients met the criteria of meta-analysis. The complete results showed that compared with WM alone, TKSB treatment could improve the clinical efficacy rate (risk ratio = 4.49, 95% confidence interval [CI]: [2.64, 7.61], P .00001), calcium (weighted mean difference [WMD] = 0.11, 95% CI: [0.08, 0.14], P < .00001), serum creatinine (WMD = 45.58, 95% CI: [32.35, 58.8], P < .00001) phosphorus (WMD = 0.11, 95% CI: [0.08, 0.13], P < .00001), parathyroid hormone (WMD = 16.72, 95% CI: [12.89, 20.55], P < .00001), blood urea nitrogen levels (WMD = 0.95, 95% CI: [0.26, 1.64], P = .007) on nondialysis patients with CKD-MBD, which was beneficial to improve the patients' bone metabolic state and renal function. In addition, evidence shows that, compared with WM alone, TKSB treatment is safe and does not increase side effects.
CONCLUSION
The systematic review found that TKSB therapy combined with WM has a positive effect on improving renal function and correcting bone metabolism disorder in nondialysis patients with CKD-MBD, which shows that Traditional Chinese Medicine is effective and safe in treating CKD-MBD. However, more high-quality, large-sample, multicenter clinical trials should be conducted to assess the safety and efficacy of TKSB therapy in treating nondialysis patients with CKD-MBD.Systematic review registration: INPLASY2020120086.
Topics: Humans; Calcium; Calcium, Dietary; Chronic Kidney Disease-Mineral and Bone Disorder; Drug-Related Side Effects and Adverse Reactions; Kidney; Multicenter Studies as Topic; Parathyroid Hormone; Randomized Controlled Trials as Topic
PubMed: 37352066
DOI: 10.1097/MD.0000000000034044 -
The Journal of Clinical Endocrinology... Oct 2023Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia, yet long-term (5- and 10-year) recurrence rates after curative surgery have been unclear. (Meta-Analysis)
Meta-Analysis
CONTEXT
Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia, yet long-term (5- and 10-year) recurrence rates after curative surgery have been unclear.
OBJECTIVE
To perform the first systematic review and meta-analysis investigating the long-term recurrence rates of sporadic PHPT after successful parathyroidectomy.
METHODS
A comprehensive search of multiple databases (including PubMed, EMBASE, Cochrane, EBSCO-CINHAL, EMBASE, Ovid, Scopus, and Google Scholar) was performed from each database's inception to January 18, 2023. Observational studies reporting at least 5 years of follow-up data after surgical resection were included. Two reviewers independently screened articles for relevance. Of 5769 articles initially identified, 242 were examined in full-text review and 34 were deemed eligible for inclusion. Two authors independently performed data extraction and study appraisal, using the National Institutes of Health study quality assessment tools.
RESULTS
Of 30 658 participants, 350 patients (1.1%) experienced recurrence after resection. A meta-analysis of proportions was performed to obtain the pooled recurrence rates. The pooled estimate for overall recurrence rate was 1.56% (95% CI 0.96-2.28%; I2 = 91%). The pooled estimates for 5- and 10-year recurrence rate after resection were 0.23% (0.04-0.53%, 19 studies; I2 = 66%) and 1.03% (0.45-1.80%, 14 studies; I2 = 89%), respectively. Sensitivity analyses did not find a statistically significant difference when adjusting for study size, diagnosis, or surgical approach.
CONCLUSION
Approximately 1.56% of sporadic PHPT patients eventually develop recurrence following parathyroidectomy. The initial diagnosis and procedure type does not influence recurrence rates. Consistent long-term follow-up is warranted to help identify recurrent disease.
Topics: Humans; Hyperparathyroidism, Primary; Hypercalcemia; Parathyroidectomy; Recurrence
PubMed: 37279502
DOI: 10.1210/clinem/dgad316 -
Hemodialysis International.... Oct 2023The effects of denosumab on bone mineral density (BMD) and metabolism in patients with end-stage renal disease (ESRD) remain controversial. Hence, we performed a... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The effects of denosumab on bone mineral density (BMD) and metabolism in patients with end-stage renal disease (ESRD) remain controversial. Hence, we performed a systematic review and meta-analysis of observational studies.
METHODS
The MEDLINE, EMBASE, and Cochrane Library databases were searched in June 2022 to identify studies that evaluated the risk of denosumab-associated hypocalcemia and changes in bone metabolism, changes in BMD from baseline to post-treatment in patients with ESRD.
FINDINGS
Twelve studies with 348 participants were included. The pooled incidence of hypocalcemia during denosumab treatment was 35.0% (95% confidence interval [CI], 25%-46%; I = 63.6%). There were no significant changes in either the serum calcium or phosphate levels from the baseline to post-treatment period; the mean differences were 0.04 mg/dL (95% CI, -0.12 to 0.20 mg/dL) and -0.39 mg/dL (95% CI, -0.89 to 0.12 mg/dL). We found significant changes in the alkaline phosphatase and parathyroid hormone levels; the standardized mean differences were -2.98 (95% CI, -5.36 to -0.59) and -3.12 (95% CI: -4.94 to -1.29), respectively. Denosumab may increase BMD, with mean differences of 9.10% (95% CI: 4.07%-14.13%) and 9.00% (95% CI: 5.93%-12.07%) for the femoral neck and lumbar spine, respectively.
DISCUSSION
Denosumab increased the BMDs of the lumbar spine and femoral neck in patients with ESRD. The onset of hypocalcemia must be carefully monitored during denosumab administration.
Topics: Humans; Bone Density; Denosumab; Hypocalcemia; Bone Density Conservation Agents; Renal Dialysis; Kidney Failure, Chronic
PubMed: 37264758
DOI: 10.1111/hdi.13098 -
The Journal of Clinical Endocrinology... Oct 2023Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid... (Meta-Analysis)
Meta-Analysis
CONTEXT
Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia.
OBJECTIVE
The objective of this analysis was to compare the efficacy and adverse effects of extended-release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on the biomarkers PTH, calcium, and phosphate in patients with non-dialysis CKD (ND-CKD).
METHODS
A systematic literature research was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting.
RESULTS
Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on 2 overlapping networks, due to nonreporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared with ERC (0.2 mg/dL increase; 95% CI, -0.37 to -0.05 mg/dL). No differences in effects on phosphate were observed.
CONCLUSION
This network meta-analysis showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well-tolerated treatment option for the management of SHPT in patients with ND-CKD.
Topics: Humans; Calcifediol; Calcium; Ergocalciferols; Hyperparathyroidism, Secondary; Network Meta-Analysis; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic
PubMed: 37235771
DOI: 10.1210/clinem/dgad289 -
Langenbeck's Archives of Surgery May 2023We have performed an updated meta-analysis of randomized controlled trials (RCT) comparing total thyroidectomy (TT) with less than total thyroidectomy (LTT) for benign... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We have performed an updated meta-analysis of randomized controlled trials (RCT) comparing total thyroidectomy (TT) with less than total thyroidectomy (LTT) for benign multinodular non-toxic goiter (BMNG).
OBJECTIVES
The objective was to evaluate the effects and outcomes of TT as compared to LTT.
METHODS
Eligibility criteria: RCTs comparing TT vs LTT.
INFORMATION SOURCES
PubMed, Embase, Cochrane Library and online registers were searched for articles comparing TT with LTT. Risk of bias: Articles were assessed for risk of bias using the Cochrane's revised tool to assess risk of bias in randomized trials (RoB 2 tool).
SYNTHESIS OF RESULTS
The main summary measures were risk difference using a random effects model.
RESULTS
Five randomized controlled trials were included in the meta-analysis. Recurrence rate was lower for TT compared to LTT. Adverse events like temporary or permanent recurrent laryngeal nerve (RLN) palsy and permanent hypoparathyroidism were similar in both groups except for the rate of temporary hypoparathyroidism which was lower in the LTT group.
DISCUSSION
All studies had unclear risk of bias for blinding of the participants and personnel and high risk of bias for certain selective reporting. This meta-analysis did not show any clear benefit or harm of either procedure (TT vs LTT) for goiter recurrence and re-operation rates (for both recurrence and incidental thyroid cancer). However, re-operation for goiter recurrence was significantly higher in the LTT group based on a single RCT. Evidence suggests increased rates of temporary hypoparathyroidism with TT but there was no difference in the rate of RLN palsy and permanent hypoparathyroidism between the two methods. The overall quality of evidence was low to moderate.
Topics: Humans; Goiter, Nodular; Thyroidectomy; Neoplasm Recurrence, Local; Hypoparathyroidism; Vocal Cord Paralysis
PubMed: 37204607
DOI: 10.1007/s00423-023-02941-1 -
BMJ (Clinical Research Ed.) May 2023To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures... (Meta-Analysis)
Meta-Analysis
Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.
OBJECTIVE
To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors.
DESIGN
Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.
DATA SOURCES
Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events.
RESULTS
The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; β=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision.
CONCLUSIONS
The evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019128391.
Topics: Humans; Female; Bone Density Conservation Agents; Network Meta-Analysis; Postmenopause; Denosumab; Receptor, Parathyroid Hormone, Type 1; Osteoporosis; Osteoporotic Fractures; Diphosphonates; Spinal Fractures; Risk Reduction Behavior; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic
PubMed: 37130601
DOI: 10.1136/bmj-2021-068033