IMPORTANCE: Growing evidence suggests an association between sleep-disordered breathing (SDB) and cognitive decline in elderly persons. However, results from population-based studies have been ...conflicting, possibly owing to different methods to assess SDB or cognitive domains, making it difficult to draw conclusions on this association. OBJECTIVE: To provide a quantitative synthesis of population-based studies on the relationship between SDB and risk of cognitive impairment. DATA SOURCES: PubMed, EMBASE, and PsychINFO were systematically searched to identify peer-reviewed articles published in English before January 2017 that reported on the association between SDB and cognitive function. STUDY SELECTION: We included cross-sectional and prospective studies with at least 200 participants with a mean participant age of 40 years or older. DATA EXTRACTION AND SYNTHESIS: Data were extracted independently by 2 investigators. We extracted and pooled adjusted risk ratios from prospective studies and standard mean differences from cross-sectional studies, using random-effect models. This meta-analysis followed the PRISMA guidelines and also adhered to the MOOSE guidelines. MAIN OUTCOMES AND MEASURES: Cognitive outcomes were based on standard tests or diagnosis of cognitive impairment. Sleep-disordered breathing was ascertained by apnea-hypopnea index or clinical diagnosis. RESULTS: We included 14 studies, 6 of which were prospective, covering a total of 4 288 419 men and women. Pooled analysis of the 6 prospective studies indicated that those with SDB were 26% (risk ratio, 1.26; 95% CI, 1.05-1.50) more likely to develop cognitive impairment, with no evidence of publication bias but significant heterogeneity between studies. After removing 1 study that introduced significant heterogeneity, the pooled risk ratio was 1.35 (95% CI, 1.11-1.65). Pooled analysis of the 7 cross-sectional studies suggested that those with SDB had slightly worse executive function (standard mean difference, −0.05; 95% CI, −0.09 to 0.00), with no evidence of heterogeneity or publication bias. Sleep-disordered breathing was not associated with global cognition or memory. CONCLUSIONS AND RELEVANCE: Sleep-disordered breathing is associated with an increased risk of cognitive impairment and a small worsening in executive function. Further studies are required to determine the mechanisms linking these common conditions and whether treatment of SDB might reduce risk of cognitive impairment.
68Ga-PSMA-11 PET is used to stage patients with prostate cancer. We performed an updated metaanalysis that separates imaging at the time of diagnosis and at the time of biochemical recurrence and ...focuses on pathology correlation in both populations. Methods: We searched the MEDLINE and EMBASE databases using the PRISMA statement. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool 2. In total, 1,811 studies were screened, 58 were analyzed, 41 were included for qualitative synthesis, and 29 were included for quantitative analysis. A random-effect model and a hierarchical summary receiver-operating-characteristic model were used to summarize the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy for pelvic lymph nodes in initial staging compared with pathology at prostatectomy and the PPV for lesions with pathologic correlation in those with biochemical recurrence. We also summarized the detection rate of 68Ga-PSMA-11 in those with biochemical recurrence stratified by prostate-specific antigen (PSA) at the time of imaging. Results: The metaanalysis of 68Ga-PSMA-11 at initial staging demonstrated a sensitivity and specificity of 0.74 (95% confidence interval 95% CI, 0.51–0.89) and 0.96 (95% CI, 0.85–0.99), respectively, using nodal pathology at prostatectomy as a gold standard. At biochemical recurrence, the PPV was 0.99 (95% CI, 0.96–1.00). The detection rate was 0.63 (95% CI, 0.55–0.70), with a PSA of less than 2.0 and 0.94 (95% CI, 0.91–0.96) with a PSA of more than 2.0. Conclusion: 68Ga-PSMA-11 performed well for the localization of metastatic prostate cancer at initial staging and at the time of biochemical recurrence.
Diabetes is associated with increased fracture risk but we do not know what affects this risk. We investigated the risk of hip and non-vertebral fractures in diabetes and whether this risk was ...affected by age, gender, body mass index, diabetes type and duration, insulin use and diabetic complications.
We selected a previously published review to be updated. MEDLINE, Embase and Cochrane databases were searched up to March 2020. We included observational studies with age and gender-adjusted risk of fractures in adults with diabetes compared to adults without diabetes. We extracted data from published reports that we summarised using random effects model.
From the 3140 records identified, 49 were included, 42 in the hip fracture analysis, reporting data from 17,571,738 participants with 319,652 fractures and 17 in the non-vertebral fracture review, reporting data from 2,978,487 participants with 181,228 fractures. We found an increase in the risk of fracture in diabetes both for hip (RR 4.93, 3.06–7.95, in type 1 diabetes and RR1.33, 1.19–1.49, in type 2 diabetes) and for non-vertebral fractures (RR 1.92, 0.92–3.99, in type 1 and RR 1.19, 1,11–1.28 in type 2). At the hip, the risk was higher in the younger population in both type 1 and type 2 diabetes. In those with type 2 diabetes, longer diabetes duration and insulin use was associated with an increased risk. We did not investigate the effect of bone density, falls, anti-diabetic drugs and hypoglycemia.
Diabetes is associated with an increase in both hip and non-vertebral fracture risk.
•The risk of hip fractures was greater in T1D than T2D.•Hip fracture risk is higher in people younger than 65 years for both type 1 and type 2 diabetes.•In type 2 diabetes, insulin use and longer diabetes duration is associated with greater risk of hip fractures.
IMPORTANCE: Previous studies have reported that drug treatments, particularly treatment with bisphosphonates, is associated with reduced overall mortality rates in addition to decreased fracture ...risk. If so, drug treatments should be recommended for this reason alone, regardless of a patient’s risk of fracture. OBJECTIVE: To assess whether randomized clinical trials demonstrate that treatment with bisphosphonates, particularly zoledronate, is associated with reduced mortality rates. DATA SOURCES: Science Direct, MEDLINE, Embase, and the Cochrane Library were searched for randomized placebo-controlled clinical trials of drug treatments for osteoporosis published after 2009 and published or in press before April 19, 2019. Conference abstracts from annual osteoporosis society meetings were also included in the search. STUDY SELECTION: Included studies were clinical trials that (1) were randomized and placebo-controlled; (2) studied drug treatments with proven antifracture efficacy; (3) used agents at the approved dose for treatment of osteoporosis; and (4) had a duration of 1 year or more. Abstracts from the literature searches were reviewed for inclusion and exclusion criteria, and mortality rate data were abstracted from the article by 1 researcher and validated by a second. A total of 2045 records were screened; 38 (1.8%) were included in the meta-analyses. DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist was followed for abstracting data and assessing data quality and validity. Data were pooled using random-effects models, and between-study variability was assessed using the I2 index. The risk of bias for each study was assessed, and funnel plots and Egger and Begg statistics were used to evaluate publication bias. MAIN OUTCOMES AND MEASURES: Associations of all drug treatments, particularly bisphosphonate and zoledronate treatments, with overall mortality. RESULTS: Of 38 clinical trials that included 101 642 unique participants, 38 were included in the meta-analyses of all drug treatments (45 594 participants randomized to placebo; 56 048 to treatment); 21 clinical trials, of bisphosphonate treatments (20 244 participants randomized to placebo; 22 623 to treatment); and 6 clinical trials, of zoledronate treatments (6944 participants randomized to placebo; 6926 to treatment). No significant association was found between all drug treatments for osteoporosis and overall mortality rate (risk ratio RR, 0.98; 95% CI, 0.91-1.05; I2 = 0%). Clinical trials of bisphosphonate treatment (RR, 0.95; 95% CI, 0.86-1.04) showed no significant association with overall mortality. Also, clinical trials of zoledronate treatment (RR, 0.88; 95% CI, 0.68-1.13) showed no association with overall mortality rate; however, evidence existed for heterogeneity of the results (I2 = 48.2%). CONCLUSIONS AND RELEVANCE: Results of this meta-analysis suggest that bisphosphonate treatment may not be associated with reduced overall mortality rates in addition to decreased fracture risk and should only be recommended to reduce fracture risk. Additional trials are needed to clarify whether treatment with zoledronate reduces mortality rates.
Sickle cell disease (SCD) is characterized by deoxygenation-induced polymerization of hemoglobin in red blood cells, leading to hemolytic anemia, vaso-occlusion, and the development of multiple ...clinical complications. To characterize the clinical burden associated with differences in hemoglobin concentration and hemolysis measures, a systematic literature review of MEDLINE, EMBASE, and related meta-analyses was undertaken. For quantitative analyses related to hemoglobin concentration, pooled results were analyzed using random effects models to control for within-and between-study variability. To derive risk ratios associated with hemoglobin concentration change, we combined ratios of means from select studies, which reported hazard and odds ratios in meta-analyses for hemoglobin concentration-related outcomes and changes between groups. Forty-one studies were identified for inclusion based on relating hemoglobin concentration to clinical outcomes. Meta-analyses demonstrated that mean hemoglobin concentration was significantly lower in patients with cerebrovascular disease (0.4 g/dL), increased transcranial Doppler velocity in cerebral arteries (0.6 g/dL), albuminuria (0.6 g/dL), elevated estimated pulmonary artery systolic pressure (0.9 g/dL), and in patients that subsequently died (0.6 g/dL). In a risk reduction meta-analysis, modeled increased hemoglobin concentrations of 1 g/dL or greater resulted in decreased risk of negative clinical outcomes of 41% to 64%. In conclusion, chronic anemia is associated with worse clinical outcomes in individuals with SCD and even modest increases in hemoglobin concentration may be beneficial in this patient population. This systematic review has been registered on Prospero (Registration number CRD42018096860; https://www.crd.york.ac.uk/prospero/).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Unnecessary diagnostic imaging leads to higher costs, longer emergency department stays, and increased patient exposure to ionizing radiation. We sought to prospectively derive and validate two ...decision instruments (DIs) for selective chest computed tomography (CT) in adult blunt trauma patients.
From September 2011 to May 2014, we prospectively enrolled blunt trauma patients over 14 y of age presenting to eight US, urban level 1 trauma centers in this observational study. During the derivation phase, physicians recorded the presence or absence of 14 clinical criteria before viewing chest imaging results. We determined injury outcomes by CT radiology readings and categorized injuries as major or minor according to an expert-panel-derived clinical classification scheme. We then employed recursive partitioning to derive two DIs: Chest CT-All maximized sensitivity for all injuries, and Chest CT-Major maximized sensitivity for only major thoracic injuries (while increasing specificity). In the validation phase, we employed similar methodology to prospectively test the performance of both DIs. We enrolled 11,477 patients-6,002 patients in the derivation phase and 5,475 patients in the validation phase. The derived Chest CT-All DI consisted of (1) abnormal chest X-ray, (2) rapid deceleration mechanism, (3) distracting injury, (4) chest wall tenderness, (5) sternal tenderness, (6) thoracic spine tenderness, and (7) scapular tenderness. The Chest CT-Major DI had the same criteria without rapid deceleration mechanism. In the validation phase, Chest CT-All had a sensitivity of 99.2% (95% CI 95.4%-100%), a specificity of 20.8% (95% CI 19.2%-22.4%), and a negative predictive value (NPV) of 99.8% (95% CI 98.9%-100%) for major injury, and a sensitivity of 95.4% (95% CI 93.6%-96.9%), a specificity of 25.5% (95% CI 23.5%-27.5%), and a NPV of 93.9% (95% CI 91.5%-95.8%) for either major or minor injury. Chest CT-Major had a sensitivity of 99.2% (95% CI 95.4%-100%), a specificity of 31.7% (95% CI 29.9%-33.5%), and a NPV of 99.9% (95% CI 99.3%-100%) for major injury and a sensitivity of 90.7% (95% CI 88.3%-92.8%), a specificity of 37.9% (95% CI 35.8%-40.1%), and a NPV of 91.8% (95% CI 89.7%-93.6%) for either major or minor injury. Regarding the limitations of our work, some clinicians may disagree with our injury classification and sensitivity thresholds for injury detection.
We prospectively derived and validated two DIs (Chest CT-All and Chest CT-Major) that identify blunt trauma patients with clinically significant thoracic injuries with high sensitivity, allowing for a safe reduction of approximately 25%-37% of unnecessary chest CTs. Trauma evaluation protocols that incorporate these DIs may decrease unnecessary costs and radiation exposure in the disproportionately young trauma population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
To explore the context in which older men navigate treatment for stress urinary incontinence (SUI) following prostate surgery by characterizing lived experience of men with symptomatic ...SUI.
Subjects/Patients and Methods
Mixed method study using surveys and semistructured interviews to examine a cohort of men who underwent evaluation for treatment of postprostatectomy SUI.
Results
Thirty‐six men were interviewed after consultation for SUI and 31 had complete quantitative clinical data. Twenty‐six underwent surgery and 10 chose no surgical intervention. In qualitative interviews, respondents experienced substantial decline in quality of life due to incontinence citing concerns associated with use of pads and worrying about incontinence. Most patients reported “workarounds”—efforts to mitigate or manage incontinence including Kegels, physical therapy, and garments. Participants also reported lifestyle changes including less strenuous physical activity, less sexual activity, and/or fewer social gatherings. Patients then described a “breaking point” where incontinence workarounds were no longer sufficient. After seeking evaluation, men described challenges in exploring treatment for SUI, including access to care and provider knowledge of treatment options.
Conclusion
In a novel study of patients living with SUI a predictable lived experience was observed that culminated in a desire for change or “breaking point.” In all men, this led to treatment‐seeking behaviors and for many it led to SUI intervention. Despite effective treatments, patients continue to meet barriers gaining access to SUI evaluation and treatment.
Objectives To systematically review risks and summarize reported complication rates associated with the performance of endoscopic retrograde cholangiopancreatography (ERCP) in children during the ...past 2 decades. Study design A systematic literature search of MEDLINE, Embase, and Web of Science from January 1995 to January 2016 was conducted for observational studies published in English. Studies reporting ERCP complications in patients <21 years without history of liver transplant or cholecystectomy were included. A summary estimate of the proportion of children who experienced complications following ERCP was derived via a random effects meta-analysis. Results Thirty-two studies involving 2612 children and 3566 procedures were included. Subjects' ages ranged from 3 days to 21 years. Procedures were performed for biliary (54%), pancreatic (38%), and other (8%) indications; 56% of ERCPs were interventional. The pooled complication rate was 6% (95% CI 4%- 8%). Procedural complications included post-ERCP pancreatitis (166, 4.7%), bleeding (22, 0.6%), and infections (27, 0.8%). The pooled estimate of post-ERCP pancreatitis was 3% (95% CI 0.02-0.05), and other complications were 1% (95% CI 0.02-0.05). In the subgroup with neonatal cholestasis, the pooled complication rate was 3% (95% CI 0.01-0.07). Adult and pediatric gastroenterologists and surgeons performed the ERCPs. Available data limited the ability to report differences between pediatric-trained and other endoscopists. Conclusions Complications associated with pediatric ERCP range widely in severity and are reported inconsistently. Our review suggests 6% of pediatric ERCPs have complications. Further studies that use systematic and standardized methodologies are needed to determine the frequency and risk factors for ERCP-related complications.
TAR DNA-binding protein 43 (TDP-43) aggregation is the most common pathological hallmark in frontotemporal dementia (FTD) and characterizes nearly all patients with motor neuron disease (MND). The ...earliest stages of TDP-43 pathobiology are not well-characterized, and whether neurodegeneration results from TDP-43 loss-of-function or aggregation remains unclear. In the behavioral variant of FTD (bvFTD), patients undergo selective dropout of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices. Here, we examined TDP-43 pathobiology within these vulnerable neurons in the FI across a clinical spectrum including 17 patients with sporadic bvFTD, MND, or both. In an exploratory analysis based on our initial observations, we further assessed ten patients with
C9orf72
-associated bvFTD/MND. VENs and fork cells showed early, disproportionate TDP-43 aggregation that correlated with anatomical and clinical severity, including loss of emotional empathy. The presence of a TDP-43 inclusion was associated with striking nuclear and somatodendritic atrophy. An intriguing minority of neurons lacked detectable nuclear TDP-43 despite the apparent absence of a cytoplasmic TDP-43 inclusion. These cells showed neuronal atrophy comparable to inclusion-bearing neurons, suggesting that the loss of nuclear TDP-43 function promotes neurodegeneration, even when TDP-43 aggregation is inconspicuous or absent.
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