Trends, patterns, and maternal characteristics of opioid prescribing during pregnancy in a large population-based cohort study.

BACKGROUND: Opioid use during pregnancy has been associated with adverse maternal and infant health outcomes. Prescription drug monitoring programs (PDMP) provide a population-based source of prescription data. We linked statewide PDMP and birth certificate data in Tennessee (TN) to determine patterns of prescription opioid and benzodiazepine use during pregnancy. METHODS: We constructed a cohort of 311,217 live singleton births from 2013 to 2016 with prescription history from 90 days before pregnancy to birth. Descriptive statistics were used to describe opioid prescription patterns during pregnancy overall, by maternal characteristics and by year. Multivariable logistic regression models estimated adjusted odds ratios and 95% confidence intervals for factors associated with prescription use. RESULTS: The prevalence of prescription use during pregnancy was 14.1% for opioid analgesics, 1.6% buprenorphine for medication-assisted treatment, and 2.6% for benzodiazepines. The prevalence of opioid analgesic use decreased from 16.6% (2013) to 11.8% (2016) (ptrend< 0.001). About 25% used for > 7 and 9.7% for > 30 days' supply. The most common types were hydrocodone (9.3%), codeine (3.4%), and oxycodone (2.9%). In adjusted models, lower education, lower income, pre-pregnancy obesity and smoking during pregnancy were associated with increased odds of any opioid and opioid analgesic use. CONCLUSION(S): Despite the encouraging trend of decreasing use of prescription opioid analgesics, the overall prevalence remained close to 12% with many women using for long durations. Use was associated with lower socioeconomic status, obesity, and prenatal smoking. Findings highlight the need for maternal education and resources, and provider support for implementation of evidence-based care.

Prescription Opioid Characteristics and Nonfatal Overdose Among Patients Discharged from Tennessee Emergency Departments.

BACKGROUND: Despite increasing trends of nonfatal opioid overdoses in emergency departments (EDs), population-based studies comparing prescription opioid dosing patterns before and after nonfatal opioid overdoses are limited. OBJECTIVES: To evaluate characteristics of prescribing behaviors before and after nonfatal overdoses, with a focus on opioid dosage. METHODS: Included were 5,395 adult residents of Tennessee discharged from hospital EDs after a first nonfatal opioid overdose (2016-2017). Patients were linked to eligible prescription records in the Tennessee Controlled Substance Monitoring Database. We estimated odds ratios (OR) and 95% confidence intervals (CI) to evaluate characteristics associated with filling opioid prescriptions 90 days before overdose and with high daily dose (≥ 90 morphine milligram equivalents) 90 days after overdose. RESULTS: Among patients who filled a prescription both before and after an overdose, the percentage filling a low, medium, and high dose was 33.7%, 31.9%, and 34.4%, respectively, after an opioid overdose (n = 1,516). Most high-dose users before an overdose (>70%) remained high-dose users with the same prescriber after the overdose. Male gender, ages ≥ 35 years, and medium metro residence were associated with increased odds of high-dose filling after an opioid overdose. Patients filling overlapping opioid-benzodiazepine prescriptions and with > 7 days' supply had increased odds of filling high dose after an opioid overdose (OR 1.4, 95% CI 1.08-1.70 and OR 3.7, 95% CI 2.28-5.84, respectively). CONCLUSIONS: In Tennessee, many patients treated in the ED for an overdose are still prescribed high-dose opioid analgesics after an overdose, highlighting a missed opportunity for intervention and coordination of care between ED and non-ED providers.

Characteristics of fatal opioid overdoses with stimulant involvement in Tennessee: A descriptive study using 2018 State Unintentional Drug Overdose Reporting System Data.

PURPOSE: Opioid overdose deaths involving stimulants are on the rise. Demographic characteristics for these deaths to be used in prevention efforts have not been established. METHODS: We conducted a statewide retrospective study to evaluate the characteristics of fatal opioid overdoses with stimulant involvement using 2018 Tennessee State Unintentional Drug Overdose Reporting System data. Data sources included death certificates, autopsy reports, toxicology, and prescription drug monitoring program data. Frequencies were generated to compare demographics, circumstances, opioid history, death scene information, bystander intervention, and toxicology between fatal opioid overdoses with and without stimulant involvement. RESULTS: A total of 1183 SUDORS opioid overdose deaths occurred in Tennessee in 2018 of which 434 (36.7%) involved a stimulant. Fatal opioid overdoses involving stimulants had higher frequencies of illicit drugs on toxicology specifically marijuana, fentanyl, and heroin compared to fatal opioid overdoses without stimulants. Fatal opioid overdoses involving stimulants had higher frequencies of scene indications of injection drug use compared to fatal opioid overdoses without stimulant involvement. CONCLUSIONS: Fatal overdoses are shifting from mainly opioid to multidrug involvement and over one-third include use of stimulants. This analysis can help public health practitioners understand the circumstances around fatal opioid overdoses involving stimulants to inform tailored prevention strategies.

Impact of benzodiazepines and polysubstance status on repeat non-fatal drug overdoses.

Research has shown that benzodiazepines and mental health disorders can increase the likelihood of repeat overdose, but researchers have not explored this association in Tennessee (TN). We examined benzodiazepines, polysubstance overdose status with/without benzodiazepines, and mental health comorbidities with repeat overdose using statewide data in TN. This study analyzed TN hospital discharge data on nonfatal overdoses for patients ages 18-64 from 2012 to 2016 for 21,066 patients with an initial inpatient visit and 36,244 patients with an initial outpatient visit. The study assessed each patient at one year after initial overdose to determine likelihood of repeat overdose. We used a Cox proportional hazards model to compute hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the factors associated with repeat nonfatal overdose. Repeat overdose rates, by one year after index overdose, were 12.9% of the sample for inpatients and 13.9% of the sample for outpatients. The visit factors (overdose characteristics and comorbidities determined from the initial visit) that the study found to be independently associated with repeat overdoses among inpatients were polysubstance status (HR: 0.88, 95% CI 0.78-0.99), benzodiazepine/polysubstance interaction (HR: 1.29, 95% CI 1.02-1.64), and presence of any mental health disorder (HR: 1.28, 95% CI: 1.18-1.39). For outpatients, the benzodiazepine/polysubstance interaction (HR: 1.21, 95% CI 1.01-1.44) was significant without adjusting for demographic factors. We found evidence that benzodiazepine/polysubstance status and mental health disorders were associated with repeat overdose for inpatients, and that benzodiazepine/polysubstance status was associated with repeat overdose for outpatients. Findings support the need to include polysubstance status and mental health in overdose prevention efforts.

Utility of RSV rapid diagnostic assays in hospitalized children in Amman, Jordan.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections in children worldwide and a frequent cause of hospitalization. Rapid diagnostic assays (RDAs) are available for RSV and they help guide management; however, they are underutilized in developing countries. We compared molecular diagnostics to RSV RDA in hospitalized children in Amman, Jordan. MATERIALS AND METHODS: Children under 2 years of age, admitted with fever and/or respiratory symptoms were enrolled prospectively from March 2010 to 2012. Demographic and clinical data were collected through parent/guardian interviews and medical chart abstraction. RSV RDAs were performed, and nasal/throat swabs were tested for RSV using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: RSV RDA and PCR were performed on specimens from 1271 subjects. RSV RDA had a sensitivity of 26% and a specificity of 99%, with positive and negative predictive values of 98.6% and 43%, respectively. RDA-positive patients had fewer days of symptoms at presentation and were more likely to have a history of prematurity, lower birth weight, require supplemental oxygen, and a longer hospitalization as compared with subjects with negative RDA. Multivariate analysis showed only lower birth weight, lack of cyanosis on examination, and lower cycle threshold to be independently associated with positive RDA (p ≤ .001). CONCLUSION: RSV RDAs had high specificity, but low sensitivity as compared with qRT-PCR. Positive RDA was associated with patients with a more severe disease, as indicated by oxygen use, longer length of stay, and higher viral load. Implementation of RDAs in developing countries could be an inexpensive and expedient method for predicting RSV disease severity and guiding management.

Uncovering Outcome Disparities of ß2 Adrenergic Agonists in Blacks: A Systematic Review.

PURPOSE: Outcome differences driven by variation in Blacks' biologic response to treatment may contribute to persistent racial disparities in asthma morbidity and mortality. This review assessed systematic variation in ß2 agonist treatment outcomes among Blacks compared to other groups. METHODS: We conducted a systematic review of studies reporting differential response to ß2 agonists among Blacks, including studies identifying pharmacogenetic variants. RESULTS: Of 3158 papers, 20 compared safety or efficacy of ß2 agonists among Blacks as compared with other subgroups. Six papers evaluating efficacy of short-acting ß2 agonists (SABA) found similar or improved results among Blacks compared with other groups, while one small study found reduced response to SABA therapy among Blacks. Reports of safety and efficacy of long-acting ß2 agonists (LABA) indicated similar results among Blacks in four papers, while four reports found reduced safety among Blacks, as compared with other groups. Four papers assessed genomic variation and relative treatment response in Blacks, with two finding significant effects of the p.Arg16Gly variant in ADRB2 on ß2 agonist response and one finding significant gene-gene IL6/IL6R interaction effects on albuterol response. CONCLUSIONS: Evidence suggests the potential for differences in ß2 agonist outcomes among Blacks compared with other groups. This literature, however, remains small and significantly underpowered for substantive conclusions. There are notable opportunities for adequately-powered investigations exploring safety and efficacy of ß2 agonists among Blacks, including pharmacogenomic modifiers of response.

Exploring Biologic Predictors Response Disparities to Atypical Antipsychotics among Blacks: A Quasi-Systematic Review.

Purpose: Management of schizophrenia among Blacks in the United States is affected by persistent disparities. This review explored response to atypical antipsychotics among Blacks compared with other groups to assess systematic variation that may contribute to disparities. Methods: We conducted a quasi-systematic review of studies reporting response to atypical antipsychotics among Blacks compared with other groups, including effects of genetic variation. Results: Of 48 identified research articles, 29 assessed differences in outcomes without inclusion of genetic variation and 20 explored effects of genetic variation; of note: one article included both types of data. Analysis of the 29 papers with clinical outcomes only suggests that while data on efficacy and risk of movement disorders were heterogeneous, findings indicate increased risk of metabolic effects and neutropenia among Blacks. Of the 20 articles exploring effects of genetic variation, allelic or genotypic variations involving several genes were associated with altered efficacy or safety among Blacks but not Whites, including risk of decreased response involving variation in DRD4 and DRD1, and improved efficacy associated with variants in DRD2, COMT, and RGS4. Others showed significant improvement in treatment response only among Whites, including variation in DTNBP1, DRD4, and GNB3. Conclusions: The current analysis can help tailor management among Blacks using an atypical antipsychotic. Heterogeneity in genetic variation effects and response allele frequency suggests that pharmacogenetics approaches for atypical antipsychotics will need to explicitly incorporate race and ethnicity.

Record Linkage Approaches Using Prescription Drug Monitoring Program and Mortality Data for Public Health Analyses and Epidemiologic Studies.

BACKGROUND: The use of Prescription Drug Monitoring Program (PDMP) data has greatly increased in recent years as these data have accumulated as part of the response to the opioid epidemic in the United States. We evaluated the accuracy of record linkage approaches using the Controlled Substance Monitoring Database (Tennessee's [TN] PDMP, 2012-2016) and mortality data on all drug overdose decedents in Tennessee (2013-2016). METHODS: We compared total, missed, and false positive (FP) matches (with manual verification of all FPs) across approaches that included a variety of data cleaning and matching methods (probabilistic/fuzzy vs. deterministic) for patient and death linkages, and prescription history. We evaluated the influence of linkage approaches on key prescription measures used in public health analyses. We evaluated characteristics (e.g., age, education, sex) of missed matches and incorrect matches to consider potential bias. RESULTS: The most accurate probabilistic/fuzzy matching approach identified 4,714 overdose deaths (vs. the deterministic approach, n = 4,572), with a low FP linkage error (<1%) and high correct match proportion (95% vs. 92% and ~90% for probabilistic approaches not using comprehensive data cleaning). Estimation of all prescription measures improved (vs. deterministic approach). For example, frequency (%) of decedents filling an oxycodone prescription in the last 60 days (n = 1,371 [32%] vs. n = 1,443 [33%]). Missed overdose decedents were more likely to be younger, male, nonwhite, and of higher education. CONCLUSION: Implications of study findings include underreporting, prescribing and outcome misclassification, and reduced generalizability to population risk groups, information of importance to epidemiologists and researchers using PDMP data.

Prescribing patterns before and after a non-fatal drug overdose using Tennessee's controlled substance monitoring database linked to hospital discharge data.

We performed a statewide evaluation of prescribing patterns of controlled substances (CS) before and after an overdose, using Tennessee's Hospital Discharge Data System and the Controlled Substance Monitoring Database (CSMD). Adults' first non-fatal overdose discharges either from the emergency department (ED) or inpatient (IP) stay occurring between 2013 and 2016 were linked to prescriptions in the CSMD. The difference in the proportion of patients filling a prescription before versus after an overdose was calculated. Included were 49,398 patients with an overdose and a prescription record; most (60.5%) were treated in the ED. Among any drug type overdose the percentage of patients who filled a CS prescription within a year of experiencing an overdose was as follows: opioid analgesics: 59.1%, benzodiazepines: 37.3%, stimulants: 5.0%, muscle relaxants: 3.4%, concurrent opioid-benzodiazepines: 24.0% with the percent difference from before to after similar in both settings. Among patients treated for an opioid overdose, this represented a decrease in opioid analgesics filled by 9.7% (95%CI: -11.2, -8.3) among those treated in the ED, and by 7.1% (95% CI: -8.3, -5.9) among treated inpatients. Among patients treated for a heroin overdose, 12.2% (95%CI: -15.2, -9.3) fewer of those treated in the ED and 8.8% (95%CI: -15.0, -2.7%) fewer of treated inpatients filled a CS prescription in that year. The most common opioid analgesics included hydrocodone and oxycodone. The number of patients filling buprenorphine for treatment increased in the year after overdoses associated with any drug or opioids but decreased among those treated for a heroin overdose.

Prevalence and Risk Factors Associated With Long-term Opioid Use After Injury Among Previously Opioid-Free Workers.

Importance: Using opioids for acute pain can lead to long-term use and associated morbidity and mortality. Injury has been documented as a gateway to long-term opioid use in some populations, but data are limited for injured workers. Objective: To evaluate the prevalence and risk factors of long-term opioid use after injury among workers in Tennessee who were opioid free at the time of injury. Design, Setting, and Participants: This cohort study identified injured workers aged 15 to 99 years who reported only 1 injury to the Tennessee Bureau of Workers' Compensation from March 2013 to December 2015 and had no opioid prescription in the 60 days before injury. Participants were matched to their prescription history in Tennessee's prescription drug monitoring program. Analysis was conducted from November 2017 to March 2018. Logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% CIs for associations of demographic, injury, and opioid use variables with long-term use. Main Outcomes and Measures: The primary outcome was long-term opioid use, defined as having an opioid supplied for 45 or more days in the 90 days after injury. Results: Among 58 278 injured workers who received opioids after injury (18 977 [32.5%] aged 15-34 years, 27 514 [47.2%] aged 35-54 years, and 11 787 [20.2%] aged 55-99 years; 32 607 [56.0%] men), 46 399 (79.6%) were opioid free at the time of injury. Among opioid-free injured workers, 1843 (4.0%) began long-term opioid use. After controlling for covariates, long-term use was associated with receiving 20 or more days' supply in the initial opioid prescription compared with receiving less than 5 days' supply (OR, 28.94; 95% CI, 23.44-35.72) and visiting 3 or more prescribers in the 90 days after injury compared with visiting 1 prescriber (OR, 14.91; 95% CI, 12.15-18.29). However, even just 5 days' to 9 days' supply was associated with an increase in the odds of long-term use compared with less than 5 days' supply (OR, 1.83; 95% CI, 1.56-2.14). Conclusions and Relevance: In this study of injured workers, injury was associated with long-term opioid use. The number of days' supply of the initial opioid prescription was the strongest risk factor of developing long-term use, highlighting the importance of careful prescribing for initial opioid prescriptions.

Prescription opioid use by injured workers in Tennessee: a descriptive study using linked statewide databases.

PURPOSE: This is the first study in Tennessee to measure opioid use in injured workers and among the first nationally to use a prescription drug monitoring program to do so. We conducted a retrospective cohort study to evaluate the prevalence of opioid use after injury and associated characteristics among workers reporting one injury to Tennessee Workers' Compensation. METHODS: Injured workers identified in Workers' Compensation records 2013-2015 were linked to their prescription history in Tennessee's prescription drug monitoring database. RESULTS: Among 172,256 injured workers, the prevalence of receiving an opioid after injury was 22.8% in 1 week, 29.7% in 1 month, and 33.3% in 6 months. Receiving an opioid was associated with having a fracture (odds ratio, 4.9; 95% confidence interval, 4.64-5.11 vs. other injuries). Hydrocodone short-acting was the most commonly received opioid (69.5% of injured workers), and the mean of each worker's maximum dose was 42.8 morphine milligram equivalents (SD 39.26). Ten percent of injured workers who received opioids also received a benzodiazepine. CONCLUSIONS: Injured workers have a high prevalence of opioid use after injury, but prescribing patterns generally tend to follow Tennessee prescribing guidelines.

Predictors of Intravenous Immunoglobulin Nonresponse and Racial Disparities in Kawasaki Disease.

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in American children. Intravenous immunoglobulin (IVIG) nonresponse is a known risk factor for cardiac sequelae. Previously reported risk factors for nonresponse include age, male sex and laboratory abnormalities. We set out to identify additional risk factors for IVIG nonresponse in a racially diverse KD population. METHODS: We conducted a retrospective chart review at a referral center in the Southeastern United States of children meeting ICD-9 (International Statistical Classification of Disease and Related Health Problems) criteria for KD and being treated with IVIG. RESULTS: Four-hundred and fifty-nine children met inclusion criteria, 67 were excluded for subsequent rheumatologic diagnosis, unknown race, or failure to meet the American Heart Association guideline criteria. Our final cohort consisted of 392 subjects, with median age of 2.7 years, 65.1% male, 66.1% White, 24.2% Black, 4.9% Asian and 82.9% responded to a single dose of IVIG. Coronary ectasia or aneurysm developed in 27%; 7.4% developed aneurysms and 2.3% giant coronary aneurysms. Nonresponders were more likely to be Black, have higher white blood cell, erythrocyte sedimentation rate and C-reactive protein, lower hemoglobin, develop ectasia or aneurysm and require critical care and hospital readmission. Responders achieved echocardiographic normalization more often compared with nonresponders (81.3% vs. 60.9%, P = 0.002) and coronary artery pseudonormalization (87.2% vs. 69.7%, P = 0.03) at 1 year. Black nonresponders had the slowest normalization at 1 year (52.9%, P = 0.02). CONCLUSIONS: Nonresponders have higher rates and greater severity of coronary involvement than responders. Our study uniquely demonstrates Black race as a risk factor for nonresponse and for delayed normalization of cardiac involvement at 1-year follow-up.

Effect of gender and adiposity on in vivo vascular function in young African Americans.

The relationship between obesity and high blood pressure is not as strong among African Americans (AA) as compared to Caucasians. We designed the current study to determine the effect of adiposity on vascular endothelial function (a harbinger of hypertension) among young healthy AA without additional cardiovascular disease risk factors. A total of 108 AA subjects (46 women) between the ages of 18 and 45 years were recruited. All the subjects were normotensive, nonsmokers, and normoglycemic. Anthropometric and cardiovascular disease risk factor measurements (lipid, insulin resistance, and inflammatory markers) were obtained. Vascular endothelial function was measured by brachial artery flow-mediated dilation (FMD). Adiposity distribution was measured by using magnetic resonance imaging scan. There were no gender differences in age and levels of blood pressure, lipids, insulin resistance, and inflammatory markers. Women had higher total body fat percentage and higher peripheral adiposity compared to men. We observed that total and central adiposity did not correlate significantly with brachial artery FMD in women (r = -0.12 and r = 0.23, respectively; P = NS). However, in men, waist circumference was positively associated with FMD (r = 0.3, P ≤ .05). Hyperemic flow was negatively correlated significantly with total and central adiposity in men (r = -0.34 and r = -0.48, respectively; P < .05), but not in women (r = -0.26 and r = 0.03, respectively; P = NS). Our study suggests that increased adiposity may pose greater risk to AA men compared to AA women by adversely affecting resistance vessel function (as measured by hyperemic flow). Larger studies are necessary to validate these findings.

Postoperative Bleeding and Associated Utilization following Tonsillectomy in Children.

Objective To assess posttonsillectomy hemorrhage (PTH), associated nonoperative readmissions/revisits, and reoperations in children. Data Sources MEDLINE, EMBASE, and the Cochrane Library. Review Methods Two investigators independently screened studies against predetermined criteria and extracted key data. Investigators independently assessed study risk of bias and the strength of the evidence of the body of literature. We calculated unadjusted pooled estimates of PTH frequency and conducted a Bayesian meta-analysis to estimate frequency of primary and secondary PTH and PTH-associated reoperation and revisits/readmissions by partial and total tonsillectomy and surgical approach. Results In meta-analysis, the frequency of primary and secondary PTH associated with total and partial tonsillectomy was <4% for any technique and with overlapping confidence bounds. Pooled frequencies of PTH were also <5% overall (4.2% for total tonsillectomy, 1.5% for partial tonsillectomy) in comparative studies. Fewer PTH episodes occurred with tonsillectomy for obstructive sleep-disordered breathing than for throat infection. In meta-analysis, frequency of PTH-associated nonoperative revisits/readmission or reoperation ranged from 0.2% to 5.7% for total tonsillectomy and from 0.1% to 3.7% for partial tonsillectomy. At least 4 deaths were reported in case series including 1,778,342 children. Conclusions PTH occurred in roughly 4% of tonsillectomies in studies included in this review. Although studies typically did not report bleeding severity or amount, relatively few episodes of PTH necessitated reoperation for hemostasis. Nonetheless, tonsillectomy is not without risk of harm. Frequency of PTH across techniques was similar; thus, we cannot conclude that a given technique is superior.

Adverse family experiences during childhood and adolescent obesity.

OBJECTIVE: To evaluate the association between adverse family experiences (AFEs) during childhood and adolescent obesity and to determine populations at highest risk for AFEs. METHODS: A cross-sectional analysis was performed of the 2011-2012 National Survey of Children's Health, including children aged 10-17 years. Weighted estimates of 31,258,575 children were based on interviews with 42,239 caregivers. Caregiver reports of nine psychosocial risk factors measured AFEs during childhood. Adolescent overweight and obesity were derived by caregiver-reported child height and weight. RESULTS: Nearly one-third (30.5%) of children had experienced ≥2 AFEs, with geographic variation by state. The prevalence of obesity among children experiencing ≥2 AFEs was 20.4%, when compared with 12.5% among children with 0 AFEs. Adjusted survey regression models were controlled for child, parent, household, and neighborhood characteristics. Children with ≥2 AFEs in childhood were more likely to have obesity (AOR = 1.8; 95% CI = 1.47-2.17; P < 0.001) than those with no AFEs, with Non-Hispanic, White children most affected. CONCLUSIONS: Adolescents in this national sample who were exposed to greater numbers of AFEs in childhood also had higher rates of overweight and obesity. Geographic variation and differential associations based on race/ethnicity identified children at greatest risk.

Pharmacologic Agents That Promote Airway Clearance in Hospitalized Subjects: A Systematic Review.

Pharmacologic agents to promote mucus clearance may reduce the sequelae of obstructive secretions. We systematically reviewed comparative studies of pharmacologic agents for mucus clearance in hospitalized or postoperative subjects without cystic fibrosis and over 12 months of age. We searched MEDLINE and other databases from January 1970 to July 2014 to identify relevant literature. Two reviewers independently assessed each study against predetermined inclusion/exclusion criteria. Two reviewers also independently extracted data regarding subject and intervention characteristics and outcomes and assigned overall quality ratings. The 9 studies meeting review criteria included 5 randomized controlled trials, 3 crossover randomized controlled trials, and one retrospective cohort study. Studies were small and together included a total of 379 subjects (mean of 42 subjects per study). N-acetylcysteine, heparin plus N-acetylcysteine, albuterol, ipratropium bromide, and saline were assessed. Studies reported no benefit of studied agents on expectoration, pulmonary function, and atelectasis and little effect on changes in sputum volume, weight, or viscosity. Adverse effects of agents were not consistently reported. Nausea was reported in 2 studies of N-acetylcysteine (one paper reported 2 experiments and did not clearly identify in which experiment adverse effects occurred), 3 studies reported that there were no adverse events, and 3 studies did not address adverse effects at all. Further research with clearly characterized populations and interventions is needed to understand the potential benefits and adverse effects of mucoactive agents.

Treatment of ankyloglossia and breastfeeding outcomes: a systematic review.

OBJECTIVE: Ankyloglossia is a congenital condition characterized by an abnormally short, thickened, or tight lingual frenulum that restricts tongue mobility. The objective of this study was to systematically review literature on surgical and nonsurgical treatments for infants with ankyloglossia. METHODS: Medline, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and Embase were searched up to August 2014. Two reviewers independently assessed studies against predetermined inclusion/exclusion criteria. Two reviewers independently extracted data regarding participant and intervention characteristics and outcomes and assigned quality and strength-of-evidence ratings. RESULTS: Twenty-nine studies reported breastfeeding effectiveness outcomes (5 randomized controlled trials [RCTs], 1 retrospective cohort, and 23 case series). Four RCTs reported improvements in breastfeeding efficacy by using either maternally reported or observer ratings, whereas 2 RCTs found no improvement with observer ratings. Although mothers consistently reported improved effectiveness after frenotomy, outcome measures were heterogeneous and short-term. Based on current literature, the strength of the evidence (confidence in the estimate of effect) for this issue is low. We included comparative studies published in English. The evidence base is limited, consisting of small studies, short-term outcomes, and little information to characterize participants adequately. No studies addressed nonsurgical interventions, longer-term breastfeeding or growth outcomes, or surgical intervention compared with other approaches to improve breastfeeding, such as lactation consultation. CONCLUSIONS: A small body of evidence suggests that frenotomy may be associated with mother-reported improvements in breastfeeding, and potentially in nipple pain, but with small, short-term studies with inconsistent methodology, strength of the evidence is low to insufficient.

Effects of simvastatin and ezetimibe in lowering low-density lipoprotein cholesterol in subjects with type 1 and type 2 diabetes mellitus.

OBJECTIVE: Statins are used to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels among patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). However, there are no studies of statin efficacy among T1DM patients. T1DM patients have higher gut cholesterol absorption than synthesis; hence cholesterol absorption inhibitors such as ezetimibe may also be effective in T1DM. Here, we compare the effects of simvastatin and ezetimibe among subjects with T1DM and T2DM. RESEARCH DESIGN AND METHODS: Subjects with T1DM (n=20, 45% female) or T2DM (n=27, 56% female) were assigned to alternating therapy with simvastatin (40 mg) or ezetimibe (10 mg) for 6 weeks in a crossover design. RESULTS: Among T2DM subjects, simvastatin lowered TC and LDL-C from the baseline (-25±4% and -40±5%, respectively, P<0.001), whereas ezetimibe was not as effective (-2±4% and -3±5%, respectively). Among T1DM subjects, both statin and ezetimibe showed significant decreases in TC and LDL-C from baseline, although ezetimibe lowered LDL-C much more than simvastatin (-32±12 (P<0.001) and -19±5% (P<0.01), respectively). Effect of simvastatin on LDL-C was much lower among T1DM subjects compared to T2DM subjects (P=0.02). CONCLUSIONS: This study shows that the cholesterol synthesis inhibitor simvastatin was less effective in lowering LDL-C in T1DM than T2DM subjects, whereas the cholesterol absorption inhibitor ezetimibe was at least as effective in lowering LDL-C as simvastatin among T1DM subjects.

Surgical intervention for feeding and nutrition difficulties in cerebral palsy: a systematic review.

AIM: The aim of the study was to systematically review surgical intervention for feeding difficulties in cerebral palsy. METHOD: We searched databases including MEDLINE from 1980 to July 2012. Two reviewers independently assessed studies and rated the overall quality and strength of the evidence. RESULTS: Thirteen publications (11 unique studies) met the inclusion criteria and addressed gastrostomy outcomes or treatment of reflux via fundoplication. In nine studies, gastrostomy-fed children gained weight. Relative to typically developing populations, baseline weight z-scores ranged from -3.56 to -0.39 and follow-up z-scores ranged from -2.63 to -0.33. Other growth measures were mixed. Two studies assessed fundoplication: in one, both Nissen fundoplication and vertical gastric plication reduced reflux (by 57% and 43% respectively), while in one case series, reflux recurred within 12 months in 30% of children. The highest rates of adverse events across studies were site infection (59%), granulation tissue (42%), and recurrent reflux (30%). Death rates ranged from 7 to 29%; however, the underlying cause was probably not surgery. INTERPRETATION: Evidence for the effectiveness of surgical interventions is insufficient to low. Studies of gastrostomy typically demonstrated significant weight gain. Results for other measures were mixed. Many children remained underweight, although, given a lack of appropriate reference standards, these results should be interpreted cautiously.