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International Journal of Molecular... May 2024The published data on the vitamin status of patients with phenylketonuria (PKU) is contradictory; therefore, this systematic review and meta-analysis evaluated the... (Meta-Analysis)
Meta-Analysis Review
The published data on the vitamin status of patients with phenylketonuria (PKU) is contradictory; therefore, this systematic review and meta-analysis evaluated the vitamin status of PKU patients. A comprehensive search of multiple databases (PubMed, Web of Sciences, Cochrane, and Scopus) was finished in March 2024. The included studies compared vitamin levels between individuals diagnosed with early-treated PKU and healthy controls while excluding pregnant and lactating women, untreated PKU or hyperphenylalaninemia cases, control groups receiving vitamin supplementation, PKU patients receiving tetrahydrobiopterin or pegvaliase, and conference abstracts. The risk of bias in the included studies was assessed by the Newcastle-Ottawa scale. The effect sizes were expressed as standardised mean differences. The calculation of effect sizes with 95% CI using fixed-effects models and random-effects models was performed. A -value < 0.05 was considered statistically significant. The study protocol was registered in the PROSPERO database (CRD42024519589). Out of the initially identified 11,086 articles, 24 met the criteria. The total number of participants comprised 770 individuals with PKU and 2387 healthy controls. The meta-analyses of cross-sectional and case-control studies were conducted for vitamin B12, D, A, E, B6 and folate levels. PKU patients demonstrated significantly higher folate levels (random-effects model, SMD: 1.378, 95% CI: 0.436, 2.320, = 0.004) and 1,25-dihydroxyvitamin D concentrations (random-effects model, SMD: 2.059, 95% CI: 0.250, 3.868, = 0.026) compared to the controls. There were no significant differences in vitamin A, E, B6, B12 or 25-dihydroxyvitamin D levels. The main limitations of the evidence include a limited number of studies and their heterogeneity and variability in patients' compliance. Our findings suggest that individuals with PKU under nutritional guidance can achieve a vitamin status comparable to that of healthy subjects. Our study provides valuable insights into the nutritional status of PKU patients, but further research is required to confirm these findings and explore additional factors influencing vitamin status in PKU.
Topics: Phenylketonurias; Humans; Vitamins; Vitamin D; Folic Acid; Vitamin B 12; Vitamin A
PubMed: 38791104
DOI: 10.3390/ijms25105065 -
Aesthetic Plastic Surgery May 2024Different combinations of excision and adjuvant therapies have been applied to improve outcomes for earlobe keloids, though evidence in this field is still lacking.
BACKGROUND
Different combinations of excision and adjuvant therapies have been applied to improve outcomes for earlobe keloids, though evidence in this field is still lacking.
OBJECTIVES
This study sought to systematically investigate efficacy and safety of these treatments.
METHODS
We conducted a systematic search on PubMed, Embase, Web of Science, and Cochrane Library to find all relevant studies. Meta-analysis of recurrence rates (RRs) and adverse event rates with 95% confidence intervals, and individual participants data (IPD) were calculated for each intervention when possible. Otherwise, narrative syntheses were performed.
RESULTS
A total of 85 articles, covering 23 treatments for earlobe keloids, were included, indicating a preference for multiple combination therapy. The estimated RRs for 6 interventions (i.e., excision monotherapy, combinations of excision with imiquimod, pressure therapy, radiotherapy, steroids, and steroids with pressure therapy) appeared to be comparable. Electron radiotherapy was found to have potential advantages over X-ray treatment, contributing to the observed heterogeneity. Further meta-analysis using IPD revealed that both combination therapies of excision plus steroid therapy (p=0.003) and excision plus radiotherapy (p=0.003) yielded better recurrence-free survival compared to excision alone. The median recurrence-free interval for combination therapy was 10 months. Adverse event rates were similar among different intervention groups.
CONCLUSIONS
This study suggests that combining excision with radiotherapy or perioperative steroid therapy has the potential to improve prognosis of earlobe keloids without increasing the risk of adverse events. Overall evaluation of patients' conditions and further studies with sufficient follow-up are warranted for clinical practice.
LEVEL OF EVIDENCE IV
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
PubMed: 38789810
DOI: 10.1007/s00266-024-04092-0 -
Archives of Endocrinology and Metabolism May 2024Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We... (Comparative Study)
Comparative Study
Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: -1.46, 95% confidence interval [CI]: -1.76 to -1.17, < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.
Topics: Humans; Familial Hypophosphatemic Rickets; Antibodies, Monoclonal, Humanized; Fibroblast Growth Factor-23; Treatment Outcome; Calcitriol; Antibodies, Monoclonal; Phosphorus
PubMed: 38788147
DOI: 10.20945/2359-4292-2023-0242 -
PloS One 2024Acute respiratory infections (ARIs) have a substantial impact on morbidity, healthcare utilization, and functional decline among older adults. Therefore, we... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute respiratory infections (ARIs) have a substantial impact on morbidity, healthcare utilization, and functional decline among older adults. Therefore, we systematically reviewed evidence from randomized controlled trials (RCTs) to evaluate the efficacy and safety of vitamin D supplementation in preventing ARIs in older adults.
METHODS
PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched until 1 February 2024. RCTs evaluating the use of vitamin D supplements to protect older adults from ARIs were included. Two reviewers independently screened papers, extracted the data and assessed the risk of bias. Data were summarised as relative risks (RRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Random effects meta-analyses were used to synthesise the results. GRADE was used to evaluate the quality of evidence. All the analysis were performed with Stata version 17.
RESULTS
Twelve trials (41552 participants) were included in the meta-analysis. It showed that vitamin D supplementation probably does not reduce the incidence of ARIs (RR, 0.99; 95% CI, 0.97-1.02, I2 = 0%; moderate certainty). No significant effect of vitamin D supplementation on the risk of ARI was observed for any of the subgroups defined by baseline 25(OH)D concentration, control treatments, dose frequency, study duration, and participants' condition. However, there was a possibility, although not statistically significant, that vitamin D may reduce the risk of ARI in patients with a baseline 25(OH)D concentration <50 nmol/L (OR, 0.90; 95% CI, 0.79-1.04, I2 = 14.7%). Additionally, vitamin D supplements might result in little to no difference in death due to any cause, any adverse event, hypercalcinemia, and kidney stones.
CONCLUSIONS
Vitamin D supplementation among older adults probably results in little to no difference in the incidence of ARIs. However, further evidence is needed, particularly for individuals with vitamin D deficiency and populations residing in low and middle income countries.
TRIAL REGISTRATION
This study was registered on PROSPERO (CRD42023451265).
Topics: Humans; Vitamin D; Respiratory Tract Infections; Dietary Supplements; Aged; Acute Disease; Randomized Controlled Trials as Topic
PubMed: 38787821
DOI: 10.1371/journal.pone.0303495 -
Journal of Gastrointestinal Cancer May 2024Pembrolizumab is associated with the development of gastritis, but its clinical features have not been characterized. To explore the clinical features of pembrolizumab...
BACKGROUND
Pembrolizumab is associated with the development of gastritis, but its clinical features have not been characterized. To explore the clinical features of pembrolizumab induced gastritis and provide reference for the prevention and treatment of gastritis.
METHODS
Case reports and case series related to pembrolizumab induced gastritis were retrospectively analyzed by searching the database from inception to September 30, 2023.
RESULTS
Thirty-nine patients with gastritis entered the study with a median age of 63 years (range 34, 81). The median time to gastritis was 11.1 months (range 0.3, 60) and 7 cycles (range 1, 27) after administration. Epigastric pain (24 cases, 61.5%), nausea (17 cases, 43.6%), and vomiting (16 cases, 41.0%) were the most frequently complained symptoms. Esophagogastroduodenoscopy mainly showed erythematous (16 cases, 41.0%), hemorrhage (14 cases, 35.9%) and erosions (11 cases, 28.2%). Gastric mucosal biopsy shows chronic active gastritis with lymphocytic infiltration. These patients' symptoms and gastric mucosa improved or recovered after receiving systemic steroid and proton pump inhibitor therapy regardless of whether pembrolizumab was discontinued. These patients' symptoms and gastric mucosa improved or recovered after treatment with systemic steroids, proton pump inhibitors, and biological agents.
CONCLUSIONS
Gastritis is an extremely rare adverse effect of pembrolizumab. When patients receiving pembrolizumab complain of abdominal symptoms, endoscopy, tissue biopsy, and immunohistochemical staining should be actively performed for early identification and diagnosis of gastritis.
PubMed: 38787493
DOI: 10.1007/s12029-024-01067-x -
British Journal of Anaesthesia Jul 2024The efficacy of perineural vs intravenous dexamethasone as a local anaesthetic adjunct to increase duration of analgesia could be particular to specific peripheral nerve... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Intravenous versus perineural dexamethasone to prolong analgesia after interscalene brachial plexus block: a systematic review with meta-analysis and trial sequential analysis.
BACKGROUND
The efficacy of perineural vs intravenous dexamethasone as a local anaesthetic adjunct to increase duration of analgesia could be particular to specific peripheral nerve blocks because of differences in systemic absorption depending on the injection site. Given this uncertainty, we performed a systematic review with meta-analysis and trial sequential analysis comparing dexamethasone administered perineurally or intravenously combined with local anaesthetic for interscalene brachial plexus block.
METHODS
Following a search of various electronic databases, we included 11 trials (1145 patients). The primary outcome was the duration of analgesia defined as the time between peripheral nerve block or onset of sensory blockade and the time to first analgesic request or initial report of pain.
RESULTS
The primary outcome, duration of analgesia, was greater in the perineural dexamethasone group, with a mean difference (95% confidence interval) of 122 (62-183) min, I=73%, P<0.0001. Trial sequential analysis indicated that firm evidence had been reached. The quality of evidence was downgraded to low, mainly because of moderate inconsistency and serious publication bias. No significant differences were present for any of the secondary outcomes, except for onset time of sensory and motor blockade and resting pain score at 12 h, but the magnitude of differences was not clinically relevant.
CONCLUSIONS
There is low-quality evidence that perineural administration of dexamethasone as a local anaesthetic adjunct increases duration of analgesia by an average of 2 h compared with intravenous injection for interscalene brachial plexus block. Given the limited clinical relevance of this difference, the off-label use of perineural administration, and the risk of drug crystallisation, we recommend intravenous dexamethasone administration.
SYSTEMATIC REVIEW PROTOCOL
PROSPERO (CRD42023466147).
Topics: Humans; Dexamethasone; Brachial Plexus Block; Analgesia; Pain, Postoperative; Administration, Intravenous; Anesthetics, Local; Brachial Plexus
PubMed: 38782616
DOI: 10.1016/j.bja.2024.03.042 -
BMJ Paediatrics Open May 2024To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment. (Review)
Review
OBJECTIVE
To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment.
METHODS
A systematic literature review using Cochrane guidance was carried out by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Eosinophilic Oesophagitis (EoE) Working Group (WG) and research leads to determine the evidence base for preparation, dosing and duration of use of swallowed topical steroid (STS) formulations in EoE. Seven themes relating to pEoE were reviewed by the WG, alongside the Cochrane review this formed the evidence base for consensus recommendations for pEoE in the UK. We provide an overview of practical considerations including treatment regimen and dosing. Oral viscous budesonide (OVB) and, if agreed by local regulatory committees, orodispersible budesonide (budesonide 1 mg tablets) were selected for ease of use and with most improvement in histology. A practical 'how to prepare and use' OVB appendix is included. Side effects identified included candidiasis and adrenal gland suppression. The use of oral systemic steroids in strictures is discussed briefly.
RESULTS
2638 citations were identified and 18 randomised controlled trials were included. Evidence exists for the use of STS for induction and maintenance therapy in EoE, especially regarding histological improvement. Using the Appraisal of Guidelines, Research and Evaluation criteria, dosing of steroids by age (0.5 mg two times per day <10 years and 1 mg two times per day ≥10 years) for induction of at least 3 months was suggested based on evidence and practical consideration. Once histological remission is achieved, maintenance dosing of steroids appears to reduce the frequency and severity of relapse, as such a maintenance weaning regimen is proposed.
CONCLUSION
A practical, evidence-based flow chart and guidance recommendations with consensus from the EoE WG and education and research representatives of BSPGHAN were developed with detailed practical considerations for use in the UK.
Topics: Humans; Eosinophilic Esophagitis; Child; Budesonide; Administration, Topical; Evidence-Based Medicine; Glucocorticoids; United Kingdom; Administration, Oral
PubMed: 38782481
DOI: 10.1136/bmjpo-2023-002467 -
Breast Cancer Research and Treatment Jul 2024Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum...
PURPOSE
Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum oestrogen levels as a surrogate marker of safety, but methods vary. We sought to summarise the data on serum oestrogen measurement in women with breast cancer using vaginal oestrogens to better understand the methods, levels and reliability.
METHODS
We searched Medline, Embase, CENTRAL, SCOPUS and CINAHL from inception to October 2023 for clinical studies where serum oestrogen was measured in women with a history of early breast cancer using vaginal oestrogens. Studies with a reported testing methodology were included.
RESULTS
Nine studies met the inclusion criteria for this systematic review. Methods used to measure oestradiol and oestriol in selected studies included mass spectrometry and immunoassays; several studies used more than one with variable concordance. Mass spectrometry detected oestradiol levels down to a lower limit between 1.0 pg/mL and 3.0 pg/mL. Immunoassays such as ELISA (enzyme-linked immunosorbent assay), ECLIA (enhanced chemiluminiscence immunoassay) and RIA (radioimmunoassay) had lower detection limits ranging between 0.8 pg/mL and 10 pg/mL. Studies were heterogeneous in testing techniques used, timing of testing, and the population including with subsequent varying results in the effect on oestrogens reported.
CONCLUSIONS
Adopting consistent and standardised methods of measuring oestrogens in clinical trials involving women with early breast cancer on vaginal oestrogens is critical. Serum oestrogens are used as a surrogate marker of safety in this population, and good-quality data are necessary to enable clinicians and patients to feel confident in prescribing and taking vaginal oestrogens. Mass spectrometry, although more expensive, gives more reliable results when dealing with very low levels of oestrogens often found in women on aromatase inhibitors, compared to immunoassays.
Topics: Female; Humans; Administration, Intravaginal; Breast Neoplasms; Cancer Survivors; Estradiol; Estriol; Estrogens; Vagina
PubMed: 38780887
DOI: 10.1007/s10549-024-07364-0 -
Headache Jun 2024Hemicrania continua is a primary unilateral headache characterized by ipsilateral parasympathetic and sympathetic autonomic features. A key diagnostic criterion is its... (Review)
Review
BACKGROUND
Hemicrania continua is a primary unilateral headache characterized by ipsilateral parasympathetic and sympathetic autonomic features. A key diagnostic criterion is its dramatic response to indomethacin treatment; however, various vascular or structural abnormalities have been reported to cause secondary hemicrania continua, presenting with clinical features similar to those of the primary headache presentation.
OBJECTIVE
We reviewed the literature to compile secondary hemicrania continua cases, highlighting the importance of imaging during the evaluation. Additionally, we also contributed our three cases to the existing studies.
METHODS
We conducted a review of articles from the PubMed and EMBASE databases that described reported cases of secondary hemicrania continua, covering the period from 1993 to 2021. Our review included detailed patient information, signs, and symptoms of hemicrania continua, as well as information on indomethacin usage and headache resolution (if pertinent).
RESULTS
Secondary hemicrania continua can result from a remarkably diverse range of structural and vascular lesions, yet clinical reports on long-term follow-up are lacking. Notably, cases may exhibit a classical response to indomethacin, emphasizing the importance of neuroimaging in excluding secondary cases. Our search yielded 41 cases meeting our criteria. We excluded six cases that were not treated with indomethacin or were unresponsive to it. Additionally, we present three cases that highlight the necessity of neuroimaging in evaluating hemicrania continua, along with short- and long-term clinical outcomes following indomethacin and lesion-directed treatments. Case 1 presented with daily right-sided headaches and cranial autonomic symptoms. Her pain completely resolved with indomethacin use. Neuroimaging of the brain revealed a laterally directed saccular aneurysm of the right internal carotid artery. Case 2 presented with continuous left-sided unilateral headaches with superimposed exacerbations. She complained of left-sided photophobia with a dull sensation in the left ear. Her symptoms decreased after 2 weeks of indomethacin use. Neuroimaging of the head indicated a benign tumor with mass effect into the left lateral medulla and inferior cerebellar peduncle. Case 3 presented with a right side-locked headache with daily, severe superimposed exacerbations. She had photophobia in the right eye and a right-sided Horner's syndrome, along with tearing during her exacerbations. Neuroimaging of the brain revealed a pituitary tumor and her pain completely resolved with indomethacin.
CONCLUSION
Hemicrania continua is a rare headache disorder that can be either primary or secondary. Importantly, response to indomethacin can still occur in secondary hemicrania continua. Thus, neuroimaging should be considered to rule out underlying structural etiology in all cases, regardless of their clinical responsiveness to indomethacin therapy.
Topics: Female; Humans; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Neuroimaging
PubMed: 38780233
DOI: 10.1111/head.14728 -
BMC Women's Health May 2024Polycystic ovary syndrome (PCOS) is an endocrine gynecological disease affecting many women of reproductive age. Clomiphene is the first-line treatment for PCOS... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Polycystic ovary syndrome (PCOS) is an endocrine gynecological disease affecting many women of reproductive age. Clomiphene is the first-line treatment for PCOS patients, but most individuals may be resistant to it. This study aims to assess the efficacy of dexamethasone and clomiphene in the treatment of PCOS patients, and to provide a theoretical basis for clinicians to study and treat PCOS.
METHODS
Chinese and English databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Medical Network, and VIP Information Chinese Journal Service Platform (VIP) were searched from the inception to January 2023. Review Manager and Stata software were used for meta- analysis. The risk of bias of eligible studies were assessed using Cochrane's risk of bias tool. Publication bias was assessed by funnel plots, Begg's and Egger's tests.
RESULTS
A total of 12 literatures were finally included, with a total of 1270 PCOS patients. Compared with the control group, dexamethasone combined with clomiphene could significantly improve pregnancy (RR = 1.71, P < 0.00001), ovulation (RR = 1.30, P < 0.00001), luteinizing hormone level (SMD = -0.94, P < 0.00001), estradiol level (SMD = 0.99, P = 0.05), progesterone level (SMD = 5.08, P = 0.002) and testosterone level (SMD = -1.59, P < 0.00001). However, there were no significant effects on ovulation-stimulating hormone level (SMD = 0.15, P = 0.37), adverse reactions (RR = 1.30, P = 0.30), dizziness (RR = 1.50, P = 0.45), and vomiting (RR = 1.67, P = 0.48).
CONCLUSION
The treatment of dexamethasone combined with clomiphene is helpful to improve the ovulation and pregnancy rate in patients with PCOS, and improve the hormone levels of patients.
Topics: Humans; Polycystic Ovary Syndrome; Clomiphene; Female; Dexamethasone; Fertility Agents, Female; Pregnancy; Drug Therapy, Combination; Treatment Outcome; Pregnancy Rate
PubMed: 38769509
DOI: 10.1186/s12905-024-03141-9