Abstract Objectives The provisional criteria of the American College of Rheumatology (ACR) 2010 and the 2011 self-report modification for survey and clinical research are widely used for fibromyalgia ...diagnosis. To determine the validity, usefulness, potential problems, and modifications required for the criteria, we assessed multiple research reports published in 2010–2016 in order to provide a 2016 update to the criteria. Methods We reviewed 14 validation studies that compared 2010/2011 criteria with ACR 1990 classification and clinical criteria, as well as epidemiology, clinical, and databank studies that addressed important criteria-level variables. Based on definitional differences between 1990 and 2010/2011 criteria, we interpreted 85% sensitivity and 90% specificity as excellent agreement. Results Against 1990 and clinical criteria, the median sensitivity and specificity of the 2010/2011 criteria were 86% and 90%, respectively. The 2010/2011 criteria led to misclassification when applied to regional pain syndromes, but when a modified widespread pain criterion (the “generalized pain criterion”) was added misclassification was eliminated. Based on the above data and clinic usage data, we developed a (2016) revision to the 2010/2011 fibromyalgia criteria. Fibromyalgia may now be diagnosed in adults when all of the following criteria are met: (1) Generalized pain, defined as pain in at least 4 of 5 regions, is present. (2) Symptoms have been present at a similar level for at least 3 months. (3) Widespread pain index (WPI) ≥ 7 and symptom severity scale (SSS) score ≥ 5 OR WPI of 4–6 and SSS score ≥ 9. (4) A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses. Conclusions The fibromyalgia criteria have good sensitivity and specificity. This revision combines physician and questionnaire criteria, minimizes misclassification of regional pain disorders, and eliminates the previously confusing recommendation regarding diagnostic exclusions. The physician-based criteria are valid for individual patient diagnosis. The self-report version of the criteria is not valid for clinical diagnosis in individual patients but is valid for research studies. These changes allow the criteria to function as diagnostic criteria, while still being useful for classification.
Neonatal deaths now account for 47% of all deaths in children younger than 5 years globally. More than a third of newborn deaths are due to preterm birth complications, which is the leading cause of ...death. Understanding the causes and factors contributing to neonatal deaths is needed to identify interventions that will reduce mortality. We aimed to establish the major causes of preterm mortality in preterm infants in the first 28 days of life in Ethiopia.
We did a prospective, cross-sectional, observational study in five hospitals in Ethiopia. Study participants were preterm infants born in the study hospitals at younger than 37 gestational weeks. Infants whose gestational age could not be reliably estimated and those born as a result of induced abortion were excluded from the study. Data were collected on maternal and obstetric history, clinical maternal and neonatal conditions, and laboratory investigations. For neonates who died of those enrolled, consent was requested from parents for post-mortem examinations (both complete diagnostic autopsy and minimally invasive tissue sampling). An independent panel of experts established the primary and contributory causes of preterm mortality with available data.
Between July 1, 2016, to May 31, 2018, 4919 preterm infants were enrolled in the study and 3852 were admitted to neonatal intensive care units. By 28 days of post-natal age, 1109 (29%) of those admitted to the neonatal intensive care unit died. Complete diagnostic autopsy was done in 441 (40%) and minimally invasive tissue sampling in 126 (11%) of the neonatal intensive care unit deaths. The main primary causes of death in the 1109 infants were established as respiratory distress syndrome (502 45%); sepsis, pneumonia and meningitis (combined as neonatal infections; 331 30%), and asphyxia (151 14%). Hypothermia was the most common contributory cause of preterm mortality (770 69%). The highest mortality occurred in infants younger than 28 weeks of gestation (89 86% of 104), followed by infants aged 28–31 weeks (512 54% of 952), 32–34 weeks (349 18% of 1975), and 35–36 weeks (159 8% of 1888).
Three conditions accounted for 89% of all deaths among preterm infants in Ethiopia. Scale-up interventions are needed to prevent or treat these conditions. Further research is required to develop effective and affordable interventions to prevent and treat the major causes of preterm death.
Bill & Melinda Gates Foundation.
The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy.
A systematic literature review using ...PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed.
Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation.
Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review.
Abstract Purpose Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of antihyperglycemic agents available on the market. Regulator warnings and concerns regarding the risk of ...developing diabetic ketoacidosis (DKA), however, have dampened enthusiasm for the class despite the combined glycemic, blood pressure, and occasional weight benefits of SGLT2 inhibitors. With the goal of improving patient safety, a cross-Canada expert panel and writing group were convened to review the evidence to-date on reported SGLT2 inhibitor–related DKA incidents and to offer recommendations for preventing and recognizing patients with SGLT2 inhibitor–associated DKA. Methods Reports covering DKA events in subjects taking SGLT2 inhibitors that were published in PubMed, presented at professional conferences, or in the public domain from January 2013 to mid-August 2016 were reviewed by the group independently and collectively. Practical recommendations for diagnosis and prevention were established by the panel. Findings DKA is rarely associated with SGLT2 inhibitor therapy. Patients with SGLT2 inhibitor–associated DKA may be euglycemic (plasma glucose level <14 mmol/L). DKA is more likely in patients with insulin-deficient diabetes, including those with type 2 diabetes, and is typically precipitated by insulin omission or dose reduction, severe acute illness, dehydration, extensive exercise, surgery, low-carbohydrate diets, or excessive alcohol intake. SGLT2 inhibitor–associated DKA may be prevented by withholding SGLT2 inhibitors when precipitants develop, avoiding insulin omission or inappropriate insulin dose reduction, and by following sick day protocols as recommended. Implications Preventive strategies should help avoid SGLT2 inhibitor–associated DKA. All SGLT2 inhibitor–treated patients presenting with signs or symptoms of DKA should be suspected to have DKA and be investigated for DKA, especially euglycemic patients. If DKA is diagnosed, SGLT2 inhibitor treatment should be stopped, and the DKA should be treated with a traditional treatment protocol.
Abstract Objectives This study sought to examine whether imaging of the atrioventricular (AV) membranous septum (MS) by computed tomography (CT) can be used to identify patient-specific anatomic risk ...of high-degree AV block and permanent pacemaker (PPM) implantation before transcatheter aortic valve implantation (TAVI) with self-expandable valves. Background MS length represents an anatomic surrogate of the distance between the aortic annulus and the bundle of His and may therefore be inversely related to the risk of conduction system abnormalities after TAVI. Methods Seventy-three consecutive patients with severe aortic stenosis underwent contrast-enhanced CT before TAVI. The aortic annulus, aortic valve, and AV junction were assessed, and MS length was measured in the coronal view. Results In 13 patients (18%), high-degree AV block developed, and 21 patients (29%) received a PPM. Multivariable logistic regression analysis revealed MS length as the most powerful pre -procedural independent predictor of high-degree AV block (odds ratio OR: 1.35, 95% confidence interval CI: 1.1 to 1.7, p = 0.01) and PPM implantation (OR: 1.43, 95% CI: 1.1 to 1.8, p = 0.002). When taking into account pre- and post -procedural parameters, the difference between MS length and implantation depth emerged as the most powerful independent predictor of high-degree AV block (OR: 1.4, 95% CI: 1.2 to 1.7, p < 0.001), whereas the difference between MS length and implantation depth and calcification in the basal septum were the most powerful independent predictors of PPM implantation (OR: 1.39, 95% CI: 1.2 to 1.7, p < 0.001 and OR: 4.9, 95% CI: 1.2 to 20.5, p = 0.03; respectively). Conclusions Short MS, insufficient difference between MS length and implantation depth, and the presence of calcification in the basal septum, factors that may all facilitate mechanical compression of the conduction tissue by the implanted valve, predict conduction abnormalities after TAVI with self-expandable valves. CT assessment of membranous septal anatomy provides unique pre-procedural information about the patient-specific propensity for the risk of AV block.
Background The Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network previously demonstrated an association between stillbirth and ...maternal marijuana use as defined by the presence of tetrahydrocannabinol in the umbilical cord homogenate. However, the relationship between marijuana use and perinatal complications in live births is uncertain. Objective Our aim was to examine if maternal marijuana use is associated with increased odds of adverse pregnancy outcomes and neonatal morbidity among live-born controls in the Stillbirth Collaborative Research Network cohort. Study Design We conducted secondary analysis of singleton, live-born controls in the Stillbirth Collaborative Research Network data set. Marijuana use was measured by self-report and/or the presence of tetrahydrocannabinol in umbilical cord homogenate. Tobacco use was measured by self-report and/or presence of any cotinine in maternal serum. Adverse pregnancy outcome was a composite of small for gestational age, spontaneous preterm birth resulting from preterm labor with or without intact membranes, and hypertensive disorders of pregnancy. Neonatal morbidity included neonatal intensive care unit admission and composite neonatal morbidity (pulmonary morbidity, necrotizing enterocolitis, seizures, retinopathy of prematurity, infection morbidity, anemia requiring blood transfusion, neonatal surgery, hyperbilirubinemia, neurological morbidity, or death prior to hospital discharge). Effect of maternal marijuana use on the probability of an adverse outcome was estimated using weighted methodology to account for oversampling in the original study. tetrahydrocannabinol cord homogenate analysis was performed in the subset of women for whom biospecimens were available. Comparisons using logistic modeling, χ2 , and t tests were weighted to account for oversampling of preterm births and non-Hispanic blacks. Results are reported as weighted percent and unweighted frequencies. Results Maternal marijuana use was identified in 2.7% (unweighted frequency 48/1610) of live births. Use was self-reported by 1.6% (34/1610) and detected by tetrahydrocannabinol in cord homogenate for 1.9% (17/897), n = 3 overlapping. Rate of tobacco use was 12.9% (217/1610), with 10.7% (167/1607) by self-report and 9.5% (141/1313) by serum cotinine. The composite adverse pregnancy outcome was not significantly increased in women with marijuana use compared to nonusers (31.2% vs 21.2%; P = .14). After adjustment for tobacco, clinical, and socioeconomic factors, marijuana use was not associated with the composite adverse pregnancy outcome (adjusted odds ratio, 1.29; 95% confidence interval, 0.56–2.96). Similarly, among women with umbilical cord homogenate and serum cotinine data (n = 765), marijuana use was not associated with adverse pregnancy outcomes (adjusted odds ratio, 1.02; 95% confidence interval, 0.18–5.66). Neonatal intensive care unit admission rates were not statistically different between groups (16.9% users vs 9.5% nonusers, P = .12). Composite neonatal morbidity or death was more frequent among neonates of mothers with marijuana use compared to nonusers (14.1% vs 4.5%; P = .002). In univariate comparisons, the components of the composite outcome that were more frequent in neonates of marijuana users were infection morbidity (9.8% vs 2.4%; P < .001) and neurologic morbidity (1.4% vs 0.3%; P = .002). After adjustment for tobacco, race, and other illicit drug use, marijuana use was still associated with composite neonatal morbidity or death (adjusted odds ratio, 3.11; 95% confidence interval, 1.40–6.91). Conclusion Maternal marijuana use was not associated with a composite of small for gestational age, spontaneous preterm birth, or hypertensive disorders of pregnancy. However, it was associated with an increased risk of neonatal morbidity.
Objective To determine incidence and clinical characteristics of hospital-associated venous thromboembolism (VTE) in pediatric patients. Study design A retrospective analysis of patients with ...hospital-associated VTE at the Johns Hopkins Hospital from 1994 to 2009 was performed. Clinical characteristics of patients aged 21 years and younger who developed VTE symptoms after 2 days of hospitalization or <90 days after hospital discharge were examined. International Classification of Diseases, Ninth Revision codes were used to categorize patients with complex chronic medical conditions and trauma. Results There were 270 episodes of hospital-associated VTE in 90 485 admissions (rate 30 per 10 000 admissions). Young adults (18-21 years) and adolescents (14-17 years) had significantly increased rates of VTE compared with children (2-9 years) (incidence rate ratio IRR 7.7, 95% CI 5.1-12.0; IRR 4.3, 95% CI 2.7-6.8, respectively). A central venous catheter (CVC) was present in 50% of patients, and a surgical procedure was performed in 45% of patients before VTE diagnosis. For patients without a CVC, trauma was the most common admitting diagnosis. CVC-related VTE was diagnosed most frequently in infants (<1 year old) and in patients with malignancy. Renal and cardiac diseases were associated with the highest rates of VTE (51 and 48 per 10 000, respectively). Rates were significantly higher among those with ≥4 medical conditions compared with those with 1 medical condition (IRR 4.0, 95% CI 1.4-8.9). Conclusion Older age and multiple medical conditions were associated with increased rates of hospital-associated VTE. These data can contribute to the design of future clinical trials to prevent hospital-associated VTE in high-risk children.
Transcatheter aortic valve implantation (TAVI) is a novel treatment for high risk or inoperable patients with symptomatic severe aortic stenosis. However, significant atrioventricular (AV) conduction ...system abnormalities requiring permanent pacemaker (PPM) implantation might complicate this procedure. We used best subsets logistic regression analysis to identify the independent predictors for the development of high-degree AV block (HDAVB) among 70 patients who underwent TAVI at 3 referral centers in Israel from 2008 to 2010. The mean age of the study patients was 83 ± 4.6 years. Of the 70 patients, 28 (40%) developed AV conduction abnormalities requiring PPM implantation within 14 days (median 2) of the procedure. The indications for PPM implantation were HDAVB (n = 25), new-onset left bundle branch block with PR prolongation (n = 2), and slow atrial fibrillation (n = 1). Best subsets logistic regression analysis showed that, among the 15 prespecified clinical, electrocardiographic, and echocardiographic candidate risk factors, only right bundle branch block at baseline (odds ratio 43; p = 0.002) and deep valve implantation (<6 mm from the lower edge of the noncoronary cusp to the ventricular end of the prosthesis, odds ratio 22; p <0.001) were independently associated with the development of periprocedural HDAVB. At 3 months of follow-up, HDAVB was still present in 40% of the patients who received PPM implantation for this indication. In conclusion, 40% of the patients who undergo CoreValve TAVI require PPM implantation after the procedure, with most cases (36%) associated with the development of postprocedural HDAVB. Baseline conduction abnormalities (right bundle branch block) and deep valve implantation (>6 mm) independently predicted the development of HDAVB and the need for PPM implantation after CoreValve TAVI.
Objectives We aimed to evaluate the relationship between echocardiographic response to cardiac resynchronization therapy (CRT) and the risk of subsequent ventricular tachyarrhythmias (VTAs). ...Background Current data regarding the effect of CRT on the risk of VTA are limited and conflicting. Methods The risk of a first appropriate implantable cardioverter-defibrillator (ICD) therapy for VTA (including ventricular tachycardia, ventricular fibrillation, and ventricular flutter) was compared between high- and low-echocardiographic responders to CRT defibrillator (CRT-D) therapy (defined as ≥25% and <25% reductions, respectively, in left ventricular end-systolic volume LVESV at 1 year compared with baseline) and ICD-only patients enrolled in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy). Results The cumulative probability of a first VTA at 2 years after assessment of echocardiographic response was highest among low responders to CRT-D (28%), intermediate among ICD-only patients (21%), and lowest among high responders to CRT-D (12%), with p < 0.001 for the overall difference during follow-up. Multivariate analysis showed that high responders to CRT-D experienced a significant 55% reduction in the risk of VTA compared with ICD-only patients (p < 0.001), whereas the risk of VTA was not significantly different between low responders and ICD-only patients (hazard ratio HR: 1.26; p = 0.21). Consistently, assessment of response to CRT-D as a continuous measure showed that incremental 10% reductions in left ventricular end-systolic volume were associated with corresponding reductions in the risk of subsequent VTA (HR: 0.80; p < 0.001), VTA/death (HR: 0.79; p < 0.001), ventricular tachycardia (HR: 0.80; p < 0.001), and ventricular fibrillation/ventricular flutter (HR: 0.75; p = 0.044). Conclusions In patients with left ventricular dysfunction enrolled in the MADIT-CRT trial, reverse remodeling was associated with a significant reduction in the risk of subsequent life-threatening VTAs. (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy MADIT-CRT; NCT00180271 )
Objectives This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) ...intervals. Background Current data regarding the outcome of patients with concealed LQTS are limited. Methods Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (≤440 ms n = 469), LQTS with prolonged QTc interval (>440 ms n = 1,392), and unaffected family members (genotyped negative with ≤440 ms n = 1,525). Results The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1:LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3:LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age >13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002). Conclusions Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup.
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