UNASSIGNED: The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD).
UNASSIGNED: This systematic review and meta-analysis included searches of MEDLINE ALL, Embase, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of loss of ambulation in DMD. Search terms included \"Duchenne muscular dystrophy\" as a Medical Subject Heading or free text term, in combination with variations of the term \"predictor\". Risk of bias was assessed using the Newcastle-Ottawa Scale. We performed meta-analysis pooling of hazard ratios of the effects of glucocorticoids (vs. no glucocorticoid therapy) by fitting a common-effect inverse-variance model.
UNASSIGNED: The bibliographic searches resulted in the inclusion of 45 studies of children and adults with DMD from 17 countries across Europe, Asia, and North America. Glucocorticoid therapy was associated with delayed loss of ambulation (overall meta-analysis HR deflazacort/prednisone/prednisolone: 0.44 [95% CI: 0.40-0.48]) (n = 25 studies). Earlier onset of first signs or symptoms, earlier loss of developmental milestones, lower baseline 6MWT (i.e.,<350 vs. ≥350 metres and <330 vs. ≥330 metres), and lower baseline NSAA were associated with earlier loss of ambulation (n = 5 studies). Deletion of exons 3-7, proximal mutations (upstream intron 44), single exon 45 deletions, and mutations amenable of skipping exon 8, exon 44, and exon 53, were associated with prolonged ambulation; distal mutations (intron 44 and downstream), deletion of exons 49-50, and mutations amenable of skipping exon 45, and exon 51 were associated with earlier loss of ambulation (n = 13 studies). Specific single-nucleotide polymorphisms in CD40 gene rs1883832, LTBP4 gene rs10880, SPP1 gene rs2835709 and rs11730582, and TCTEX1D1 gene rs1060575 (n = 7 studies), as well as race/ethnicity and level of family/patient deprivation (n = 3 studies), were associated with loss of ambulation. Treatment with ataluren (n = 2 studies) and eteplirsen (n = 3 studies) were associated with prolonged ambulation. Magnetic resonance biomarkers (MRI and MRS) were identified as significant predictors of loss of ambulation (n = 6 studies). In total, 33% of studies exhibited some risk of bias.
UNASSIGNED: Our synthesis of predictors of loss of ambulation in DMD contributes to the understanding the natural history of disease and informs the design of new trials of novel therapies targeting this heavily burdened patient population.

BACKGROUND: This study examines the associations between asthma and nitric oxide (NO) synthase (NOS) gene polymorphisms.
METHODS: After a systematic literature search in electronic databases, studies were selected based on eligibility criteria. Data were extracted from research articles and were synthesized and tabulated. Where a particular polymorphism data were reported by multiple studies, meta-analyses of odds ratios were performed, or odds ratios reported by individual studies were pooled.
RESULTS: Twenty studies (4450 asthma patients and 5306 non-asthmatic individuals) were identified. Many studies did not find any association between CCTTT repeat polymorphism in NOS2 gene and asthma. However, a study reported that pretreatment mean exhaled NO levels in asthmatics were found to be significantly higher in genotypes with higher number of CCTTT repeats. Also, alleles with <11 CCTTT repeats were associated with poor asthma treatment outcomes. A single nucleotide polymorphism, G894T, in NOS3 gene was not found to be significantly associated with asthma by at least four studies. However, a T allele at this locus was associated with lower NO levels. Also, G894T frequency was significantly higher in asthmatic children who responded to inhaled corticosteroids along with long-lasting beta2-agonists. A T allele of NOS3 786C/T polymorphism increased the probability of bronchial asthma with comorbid essential hypertension in asthma patients. Asthma severity also differed for different Ser608Leu exon 16 variants of NOS2 gene.
CONCLUSIONS: Several polymorph NOS gene variants are identified, some of which appear to have influence on asthma prevalence or outcomes. However, data are varying depending on the nature of variant, ethnicity, study design, and disease parameters.

Systematic reviews and meta-analyses pool data from individual studies to generate a higher level of evidence to be evaluated by guidelines. These reviews ultimately guide clinicians and stakeholders in health-related decisions. However, the informativeness and quality of evidence synthesis inherently depend on the quality of what has been pooled into meta-research projects. Moreover, beyond the quality of included individual studies, only a methodologically correct process, in relation to systematic reviews and meta-analyses themselves, can produce a reliable and valid evidence synthesis. Hence, quality of meta-research projects also affects evidence synthesis reliability. In this overview, the authors provide a synthesis of advantages and disadvantages and main characteristics of some of the most frequently used tools to assess quality of individual studies, systematic reviews, and meta-analyses. Specifically, the tools considered in this work are the Newcastle-Ottawa scale (NOS) and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) for observational studies, the Consolidated Standards of Reporting Trials (CONSORT), the Jadad scale, the Cochrane risk of bias tool 2 (RoB2) for randomized controlled trials, the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and the Assessment of Multiple Systematic Reviews 2 (AMSTAR2), and AMSTAR-PLUS for meta-analyses. WHAT IS ALREADY KNOWN?: The informativeness and quality of evidence synthesis inherently depend on the quality of what has been pooled into meta-research projects. Beyond the quality of included individual studies, only a methodologically correct process, in relation to systematic reviews and meta-analyses themselves, can produce a reliable and valid evidence synthesis. WHAT IS NEW?: In this overview, the authors provide a synthesis of advantages and disadvantages and main characteristics of some of the most frequently used tools to assess quality of individual studies, systematic reviews, and meta-analyses. POTENTIAL IMPACT: This overview serves as a starting point and a brief guide to identify and understand the main and most frequently used tools for assessing the quality of studies included in meta-research. The authors here share their experience in publishing several meta-research-related articles covering different areas of medical sciences.

Ovarian steroid cell tumors NOS are rare sex cord-stromal tumors. They account for less than 0.1% of ovarian tumors. We present a case of a 17-year-old girl with the complaint of amenorrhea. The serum testosterone level was 11.55 nmol/L (reference value, 0.35-2.6 nmol/L) and the serum value of dehydroepiandrosterone-sulfate (DHEA-S) was 5.9 μmol/L (reference value, 0.49-8.71 μmol/L). A computed tomography (CT) pelvic scan identified a solid, right ovarian tumor and detected no adrenal gland enlargement or additional tumors. We took a surgical excision and a wedge resection of the normal contralateral ovary. The histopathologic examination on microscopy confirmed it was a benign ovarian steroid cell tumor NOS. Four days postoperative, her sex hormones were declined to normal levels and her serum testosterone level was 2.37 nmol/L (reference value, 0.35-2.6 nmol/L) a month after surgery. Her serum testosterone level was in the normal range and there was no evidence of recurrence 6 months after surgery.

Evidence suggests that cesarean section is likely associated with a reduced placental transfusion and poor hematological status in neonates. However, clinical studies have reported somewhat inconsistent results. We conducted a systematic review and meta-analysis to examine whether cesarean section affects placental transfusion and iron-related hematological indices. Pubmed, Web of Science, ScienceDirect, and Ovid Databases were searched for relevant studies published before April 9, 2013. Mean differences between cesarean section and vaginal delivery in outcomes of interests (placental residual blood volume; hematocrit level, hemoglobin concentration, and erythrocyte count in cord/peripheral blood) were extracted and pooled using a random effects model. We identified 15 studies (n = 8477) eligible for the meta-analysis. Compared with neonates born vaginally, those born by cesarean section had a higher placental residual blood volume [weighted mean difference (WMD), 8.87 ml; 95% confidence interval (CI), 2.32 ml-15.43 ml]; a lower level of hematocrit (WMD, -2.91%; 95% CI, -4.16% to -1.65%), hemoglobin (WMD, -0.51 g/dL; 95% CI, -0.74 g/dL to -0.27 g/dL) and erythrocyte (WMD, -0.16 × 10(12)/L; 95% CI, -0.30 × 10(12)/L to -0.01 × 10(12)/L). Subgroup analysis showed that the WMD for hematocrit in neonate\'s peripheral blood (-6.94%; 95% CI, -9.15% to -4.73%) was substantially lower than that in cord blood (-1.75%; 95% CI, -2.82%, -0.68%) (P value for testing subgroup differences <0.001). In conclusion, cesarean section compared with vaginal delivery is associated with a reduced placental transfusion and poor iron-related hematologic indices in both cord and peripheral blood, indicating that neonates delivered by cesarean section might be more likely affected by iron-deficiency anemia in infancy.

OBJECTIVE: To conduct a systematic review and meta-analysis to establish the association between pain and falls in community-dwelling older adults.
METHODS: Electronic databases from inception until March 1, 2013, including Cochrane Library, CINAHL, EBSCO, EMBASE, PubMed, and PsycINFO.
METHODS: Two reviewers independently conducted the searches and completed methodological assessment of all included studies. Studies were included that (1) focused on adults older than 60 years; (2) recorded falls over 6 or more months; and (3) identified a group with and without pain. Studies were excluded that included (1) participants with dementia or a neurologic condition (eg, stroke); (2) participants whose pain was caused by a previous fall; or (3) individuals with surgery/fractures in the past 6 months.
METHODS: One author extracted all data, and this was independently validated by another author.
RESULTS: A total of 1334 articles were screened, and 21 studies met the eligibility criteria. Over 12 months, 50.5% of older adults with pain reported 1 or more falls compared with 25.7% of controls (P<.001). A global meta-analysis with 14 studies (n=17,926) demonstrated that pain was associated with an increased odds of falling (odds ratio [OR]=1.56; 95% confidence interval [CI], 1.36-1.79; I(2)=53%). A subgroup meta-analysis incorporating studies that monitored falls prospectively established that the odds of falling were significantly higher in those with pain (n=4674; OR=1.71; 95% CI, 1.48-1.98; I(2)=0%). Foot pain was strongly associated with falls (n=691; OR=2.38; 95% CI, 1.62-3.48; I(2)=8%) as was chronic pain (n= 5367; OR=1.80; 95% CI, 1.56-2.09; I(2)=0%).
CONCLUSIONS: Community-dwelling older adults with pain were more likely to have fallen in the past 12 months and to fall again in the future. Foot and chronic pain were particularly strong risk factors for falls, and clinicians should routinely inquire about these when completing falls risk assessments.

OBJECTIVE: Screening of persons with newly diagnosed colorectal cancer for Lynch syndrome can yield substantial benefits at acceptable costs, presuming sufficient uptake of genetic testing by first-degree relatives of Lynch syndrome probands. We performed a systematic review of the literature to determine the frequency of and factors associated with genetic testing of first-degree relatives of Lynch syndrome probands.
METHODS: We searched 4 databases (CINAHL, PsycInfo, PUBMED, and SCOPUS) for articles published through May 2011 reporting uptake of genetic testing by relatives of Lynch syndrome probands. Two investigators independently screened articles to determine whether they met inclusion criteria; data were collected on study population, genetic counseling, and genetic testing. A narrative, qualitative systematic review was performed.
RESULTS: We identified 1258 potentially relevant articles; 533 underwent full-text review, and 8 were included in the final analysis. Of first-degree relatives of Lynch syndrome probands, 52% or less received genetic testing. For each proband, 3.6 or fewer relatives underwent genetic testing. Demographic factors (age <50 years, female sex, parenthood, level of education, employment, participation in medical studies), psychological factors (lack of depressive symptoms), and possibly family history (greater number of relatives with cancer) were associated with uptake of genetic testing.
CONCLUSIONS: Genetic testing appears to be underutilized by first-degree relatives of patients with Lynch syndrome. The clinical benefit and economic feasibility of screening persons with colorectal cancer for Lynch syndrome depend on optimizing family-wide uptake of genetic testing. Future research and clinical efforts should focus on ways to overcome barriers to genetic testing.