Corrigendum: A randomized synbiotic trial to prevent sepsis among infants in rural India.

This corrects the article DOI: 10.1038/nature23480.

A randomized synbiotic trial to prevent sepsis among infants in rural India.

Sepsis in early infancy results in one million annual deaths worldwide, most of them in developing countries. No efficient means of prevention is currently available. Here we report on a randomized, double-blind, placebo-controlled trial of an oral synbiotic preparation (Lactobacillus plantarum plus fructooligosaccharide) in rural Indian newborns. We enrolled 4,556 infants that were at least 2,000 g at birth, at least 35 weeks of gestation, and with no signs of sepsis or other morbidity, and monitored them for 60 days. We show a significant reduction in the primary outcome (combination of sepsis and death) in the treatment arm (risk ratio 0.60, 95% confidence interval 0.48-0.74), with few deaths (4 placebo, 6 synbiotic). Significant reductions were also observed for culture-positive and culture-negative sepsis and lower respiratory tract infections. These findings suggest that a large proportion of neonatal sepsis in developing countries could be effectively prevented using a synbiotic containing L. plantarum ATCC-202195.

A multicenter study on the relative effectiveness of a 12-week physical training program for adults with an oncologic diagnosis.

PURPOSE: The purpose of this study was to examine the association between cancer survivors' socio-demographic and clinical characteristics and aerobic fitness changes following a physical training program. METHODS: We assessed the association between participant's characteristics and aerobic fitness in the six-min walk test (6MWT) after a 12-week LIVESTRONG® at Young Men's Christian Association (YMCA) exercise program for adults with an oncologic diagnosis using linear mixed effects models. RESULTS: Fifty-one percent of participants had a breast cancer diagnosis and 22 % had received treatment within 1 year of enrollment. At baseline, participants who reported good/excellent health status performed better in the 6MWT than those who reported poor/fair health status (384.2 vs. 345.0 m, p = 0.035). After 12 weeks, all participants increased their average 6MWT performance by 54.2 m. After adjustment for age, gender, physical activity level, and smoking status, participants who were 60 years old or younger had a greater increase in the 6MWT score than participants older than 60 years (63.2 vs. 43.9 m, p = 0.041) while those who had never been YMCA members had a greater increase in the 6MWT compared to those who had ever been a YMCA member (62.2 vs. 40.3 m, p = 0.041). CONCLUSION: Overall, aerobic fitness among adults with an oncologic diagnosis increased after a 12-week exercise program, particularly among participants who were 60 years old or younger or were not YMCA members at enrollment. Participants with poorer health had lower aerobic fitness at baseline, though they had a similar positive response to the program as healthier participants. Future study designs may include randomization and an additional untreated arm.

Quality of life changes in patients undergoing treatment for hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. One of the primary treatment goals for incurable advanced cases is to prolong quality of life (QoL). Thus, to determine which HCC therapies may be linked to a more favorable QoL, we assessed the association between QoL changes and different treatments in HCC patients. METHODS: We analyzed a non-randomized multicenter longitudinal study, which included 171 patients treated with surgery (n = 53), ablation (n = 53) or embolization (n = 65) from seven centers: four Asian and three European sites. All participants completed the EORTC QLQ-C30 and QLQ-HCC18 questionnaires before and after treatment. Propensity scores were calculated and used in addition to race for adjustment in the logistic regression model to account for the confounding effects of patient characteristics including age, gender, race, employment, living with family, at least one comorbid condition, years since diagnosis, prior treatment history, BCLC stage, Child-Pugh grade, cirrhosis, bilirubin levels and QoL score before treatment. RESULTS: After adjustment for confounders, patients tended to have higher odds of QoL deterioration when treated with ablation versus embolization (dyspnea: p = 0.019; appetite loss: p = 0.018; body image: p = 0.035) or ablation versus surgery (dyspnea: p = 0.099; appetite loss: p = 0.100; body image: p = 0.038). CONCLUSIONS: There were significant differences in QoL deterioration across different treatment groups. This information may assist patients and providers when selecting patient-centered treatment approaches for HCC.

Validation of anamnestic diagnostic criteria for recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is characterized by painful recurrent oral ulcers and is typically diagnosed via history and clinical examination. Our aim was to validate a set of anamnestic diagnostic criteria (RASDX) to increase the accuracy of RAS diagnosis, particularly when a clinical examination is not feasible. METHODS: Participants were enrolled during an unmatched case-control study. RASDX consisted of an initial phone screening using standardized questionnaires and recognition of RAS photographs in the clinic. The proportion of agreement with an examination by an oral medicine expert was calculated. RESULTS: A total of 115 participants were scheduled for a clinical diagnostic visit and 11 were withdrawn. The remaining 104 participants were aged 18-50 years, 54% women, 64% White and 20% Hispanic. Of these, all 49 controls with negative RASDX had no clinical ulcers. Of the 54 cases diagnosed with RAS by RASDX, 53 were clinically confirmed to have RAS lesions (99% agreement; exact one-sided 95% CI = 95-100%). CONCLUSIONS: RASDX, based on a combination of history and photograph recognition, was highly accurate compared with a diagnosis that employed an oral examination.

Effect of stressful life events on the onset and duration of recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common and painful oral mucosal disease. Possible etiologies include genetics, vitamin deficiencies, trauma, immune dysfunction, and stress. The goal of this study was to examine the relationship between the occurrence, type, and magnitude of stressful events and the onset and duration of RAS episodes. METHODS: One hundred and sixty subjects with a history of RAS completed a weekly phone survey for up to 1 year, providing data on the occurrence of RAS episodes and details of any stressful events they experienced during the previous week. During RAS episodes, subjects also completed daily paper diaries that recorded incidence and duration of the RAS episode. Stressful events were quantified using the validated Recent Life Changes Questionnaire (RLCQ) and were classified as mental or physical stressors. RESULTS: Stressful life events were significantly associated with the onset of RAS episodes (P < 0.001), however, not with the duration of the RAS episodes. Experiencing a stressful life event increased the odds of an RAS episode by almost three times (OR = 2.72; 95% CI = 2.04-3.62). When controlled for each other, mental stressors had a larger effect (OR = 3.46, 95% CI = 2.54-4.72) than physical stressors (OR = 1.44; 95% CI = 1.04-1.99) on the occurrence of RAS episodes. RAS episodes did not occur more frequently or last longer with increasing stress severity. CONCLUSIONS: In patients with a history of RAS, stressful events may mediate changes involved in the initiation of new RAS episodes. Mental stressors are more strongly associated with RAS episodes than physical stressors.

Factors Associated with Musculoskeletal Discomfort in Farmers and Ranchers in the U.S. Central States.

Agricultural work involves ergonomic and psychosocial strain, which contribute to musculoskeletal conditions. The aim of this study was to assess if specific ergonomic, psychosocial, and preventive factors are linked to musculoskeletal pain or discomfort symptoms (MSS) in farmers and ranchers. We analyzed data from the Central States Center for Agricultural Safety and Health survey that was conducted in 2018 in a seven-state region of the central United States. MSS were assessed with questions from the Standardized Nordic Questionnaire. The survey included questions on demographic, ergonomic, psychosocial and preventive factors. Farm production variables were added from the Farm Market iD database. We analyzed the data using Generalized Estimating Equations. The overall prevalence of MSS for all body sites combined was 59% among 4,354 farmers and ranchers who responded (19% response rate). After controlling for age, sex, and operator status, three factors (high stress level, sleep deprivation, and exhaustion/fatigue) showed the strongest associations with MSS in any body site, with adjusted odds ratios (OR) ranging from 4.8 to 5.6. Forceful exertions, repetitive tasks, awkward postures, frequent manual labor, and vibration were also significantly associated with MSS, with adjusted ORs ranging from 1.8 to 3.3. Recommended preventive techniques were not protective for MSS. New effective strategies are needed to reduce the high burden of musculoskeletal outcomes among farmers and agricultural workers.

Prevalence and Risk Factors for Pulmonary Conditions among Farmers and Ranchers in the Central United States.

This study was conducted to evaluate the prevalence and risk factors for work-related respiratory conditions (asthma, farmer's lung, sinusitis, rhinitis, and environmental allergies, diagnosed by a physician) among farm and ranch operators in the central US. A survey was conducted by the Central States Center for Agricultural Safety and Health (CS-CASH) in 2018, focusing on work-related injuries, illnesses, exposures, and preventive measures in a seven-state region (Iowa, Kansas, Minnesota, Missouri, Nebraska, North Dakota, and South Dakota). Farms and ranches (n = 16,818) with an email address and annual sales exceeding $5,000 were randomly selected for the survey. Agricultural production and weather data were merged with survey responses. The relationship between exposures and respiratory conditions was analyzed using generalized estimating equations. We received responses from 3,268 agricultural operations (19% response rate) containing information on 4,064 individual operators. The life-time prevalence of (any) respiratory conditions among farm/ranch operators was 18%. Risk factors for respiratory conditions included exposures to grain/hay/feed dust (OR 2.41), animal confinement dust (OR 1.57), field/road dust (OR 2.11), manure/silage gasses (OR 1.66), anhydrous ammonia (OR 1.51), fuels/solvents/paints (OR 1.92), older age group >70 vs. <43 (OR 1.40), female gender (OR 1.82), and being primary vs. third operator (OR 1.61). Farmers and ranchers have a high prevalence of respiratory conditions associated with dust and gas exposures at work. More effective protective measures are needed using the hierarchy of controls, including improved use of respiratory protection.

Patient-specific risk factors contributing to blood culture contamination.

Objective: Contaminated blood cultures result in extended hospital stays and unnecessary antibiotic therapy. Patient-specific factors associated with blood culture contamination remain largely unexplored. Identifying patients at higher risk of blood culture contamination could alert healthcare providers to take extra precautionary measures to limit contamination in these patients, and thereby prevent associated adverse outcomes. We sought to identify patient-related factors that contribute to blood culture contamination in hospitalized patients. Design and setting: We conducted a secondary data analysis of a retrospective cohort study at an academic medical center. Patients: Study participants included 19,255 adult patients who had blood culture(s) performed during a hospital admission between June 2014 and December 2016. Methods: Data were analyzed to evaluate risk factors for blood culture contamination using logistic regression. Results: Among adult patients, we identified 464 contaminated episodes and 11,010 negative blood-culture episodes. Chronic obstructive pulmonary disease (adjusted odds ratio [AOR], 1.67; 95% confidence interval [CI], 1.20-2.34) and stay in an intensive care unit (ICU) during an admission (AOR, 1.41; 95% CI, 1.14-1.74) were associated with blood culture contamination. Other risk factors included race, body mass index, and admission from the emergency department. Subgroup analyses of patients admitted from the emergency department showed similar results. Conclusions: We identified patient-specific factors that increase the odds of false-positive blood cultures. By introducing mitigation strategies to limit contamination in patients with these risk factors, it may be possible to reduce the adverse clinical impact of blood culture contamination.

An assessment of factors associated with neurocognitive decline in people living with HIV.

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) remains a health concern. However, limited research has been done to identify factors associated with neurocognitive decline. We assessed risk factors associated with neurocognitive decline in people living with HIV using a definition of decline that is statistically easy to adopt, is based on a commonly used neuropsychological cut-off and may be clinically relevant. Cox proportional hazards modeling was performed using the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study database. 581 participants were followed for up to 12 years. Neurocognitive decline was defined as the first observed drop in global T-scores of at least 2.67. Lifetime methamphetamine use had the strongest association with neurocognitive decline (adjusted Hazard Ratio; aHR = 1.48; 95% CI = 0.92-2.39) followed by no current antiretroviral medication use (aHR = 1.32; 95% CI = 0.91-1.92). Other risk factors included Hispanic ethnicity, lifetime history of major depressive disorder, lifetime cannabis use, hepatitis-C infection, and difficulty eating, dressing, bathing, or using the toilet. Results indicate that consistent use of ART may be of high significance to preserving neurocognition. Furthermore, Hispanic patients, those with a history of depression and substance use, and those having difficulty in essential activities of daily living may require vigilant follow-up.

Variability in preventive care practices among US adults with diabetes mellitus.

INTRODUCTION: Patients with diabetes are advised to follow standard medical care including daily blood glucose and foot checks, eye examinations with pupil dilation, and cholesterol checks to prevent diabetes-related complications. It is unclear how these practices currently vary across different US population subgroups. The objective of this study was to assess variation in overall and individual diabetes care practices and identify specific factors associated with differences in these practices in a representative sample of US diabetic adults. RESEARCH DESIGN AND METHODS: Cross-sectional data were from the 2017 Behavioral Risk Factor Surveillance System. Survey logistic regression was used to account for the complex sampling design. RESULTS: Among 30 780 eligible participants, 8957 (equivalent to 28% of the target population) followed all four diabetes care practices. Insulin-dependent participants had higher adjusted odds (adjusted OR=2.95; 95% CI 2.62 to 3.31) of following all four diabetic care practices compared with those who did not. Cost-related variables (having healthcare coverage and/or a personal doctor) were positively associated with diabetes care practices, with the strongest association observed for adherence to more costly practices (annual eye examination and cholesterol check) versus less costly ones (daily blood glucose check, daily foot check). CONCLUSIONS: Our findings suggest the need for diabetes care practice-specific and population subgroup-specific public health interventions to encourage early adherence to diabetic care practices and reduce complications.

US adults with diabetes mellitus: Variability in oral healthcare utilization.

BACKGROUND: Diabetic patients are advised to have at least one dental examination per year. It is unclear to what extent different subgroups of US diabetic adults closely follow this recommendation. Thus, we assessed dental care utilization and related factors in a representative sample of US diabetic adults from rural and urban counties. METHODS: Cross-sectional data were from the 2018 Behavioral Risk Factor Surveillance System (BRFSS). Survey logistic regression was used to account for the complex sampling design. RESULTS: Among 40,585 eligible participants, 24,887 (60% of the population) had at least one dental visit for any reason within the past year. The lowest compliance was observed among edentulous participants (27%, adjusted OR = 0.26, 95% CI = 0.22-0.31 vs. fully dentate). Dental compliance was also negatively associated with having a lower income or education, ever being a smoker, or having barriers to access to care. Rural residents had lower dental compliance compared to urban residents, particularly those without healthcare coverage. CONCLUSIONS: Dental compliance among US adult diabetic individuals was low, particularly among rural residents, and as compared to other recommended diabetic care practices. Future public health interventions may target rural individuals without healthcare coverage, smokers and edentulous individuals. There is a need to integrate dental and medical care to facilitate cross-talks among different health professionals, so that educational preventive messages are reinforced at every healthcare visit.

Neurocognitive impairment and health-related quality of life among people living with Human Immunodeficiency Virus (HIV).

The association between HIV-associated neurocognitive impairment (NCI) and health-related quality of life (HRQoL) is not well known. We investigated this association among the CNS (Central Nervous System) HIV Antiretroviral Therapy Effects Research (CHARTER) study participants. We performed factor analysis to distinguish physical and mental HRQoL, followed by general linear models. We analyzed 1,340 HIV participants, including 35.6% with NCI, 77.2% males, 70.5% unemployed, and 42.2% with depression. Impaired participants had lower (worse) mental and physical HRQoL mean scores compared to unimpaired participants. NCI was negatively associated with mental HRQoL in crude (mean difference: -4.38; 95% CI: -6.70 to -2.06) and adjusted analysis (-2.56, -4.83 to -0.30). NCI was also negatively associated with physical HRQoL in unadjusted analysis (-4.62, -7.45 to -1.78), though the association weakened in the adjusted analysis (-2.20, -4.81 to 0.40). The association between NCI and HRQoL was confounded mainly by employment and was partially mediated by depression. These findings suggest that future strategies aimed at improving HRQoL among HIV-infected patients with NCI might benefit from concurrent management of depression.

Clinical consequences of contaminated blood cultures in adult hospitalized patients at an institution utilizing a rapid blood-culture identification system.

OBJECTIVE: To assess the clinical impact of contaminated blood cultures in hospitalized patients during a period when rapid diagnostic testing using a FilmArray Blood Culture Identification (BCID) panel was in use. DESIGN: Retrospective cohort study. SETTING: Single academic medical center. PARTICIPANTS: Patients who had blood culture(s) performed during an admission between June 2014 and December 2016. METHODS: Length of hospital stay and days of antibiotic therapy were assessed in relation to blood-culture contamination using generalized linear models with univariable and multivariable analyses. RESULTS: Among 11,474 patients who had blood cultures performed, the adjusted mean length of hospital stay for patients with contaminated blood-culture episodes (N = 464) was 12.3 days (95% confidence interval [CI], 11.4-13.2) compared to 11.5 days (95% CI, 11.0-11.9) for patients (N = 11,010) with negative blood-culture episodes (P = .032). The adjusted mean durations of antibiotic therapy for patients with contaminated and negative blood-culture episodes were 6.0 days (95% CI, 5.3-6.7) and 5.2 days (95% CI, 4.9-5.4), respectively (P = .011). CONCLUSIONS: Despite the use of molecular-based, rapid blood-culture identification, contamination of blood cultures continues to result in prolonged hospital stay and unnecessary antibiotic therapy in hospitalized patients.

Agricultural Injuries among Farmers and Ranchers in the Central United States during 2011-2015.

The high risk of occupational fatalities in agriculture is well documented, but information on non-fatal injuries is lacking due to challenges in injury surveillance. This surveillance study explored the frequency, characteristics, and risk factors for non-fatal injuries among farmers and ranchers in the central United States. The Central States Center for Agricultural Safety and Health (CS-CASH), in collaboration with the USDA National Agricultural Statistics Service (NASS), conducted annual surveys (n = 34,777 sent) during 2011-2015 covering a seven-state region (Iowa, Kansas, Minnesota, Missouri, North Dakota, Nebraska, and South Dakota). The average response rate was 32% in the five consecutive annual surveys. The average injury incidence rate was 7.0 injuries/100 operators per year. Most injuries (89%) occurred during agricultural work. The most frequent sources of injury were livestock (22%), machinery (13%), and hand tools (12%). Risk factors for injury included: male gender, younger age (vs. 65+ years), farming as the primary occupation, greater work time, greater land area, ranch (vs. farm), organic farming, internet access, and production of several types of crops and animals. Most injuries (56%) required a doctor visit, and 12% required hospitalization. The average medical costs were $1,936 out of pocket and $8,043 paid by insurance. The combined average costs for most serious injuries were $7,858. Most injuries (66%) resulted in some lost time from agricultural work, and 13% were serious, resulting in more than 30 days of lost work time. The non-fatal injury rate for self-employed farmers and ranchers was higher than that of hired agricultural workers reported by the Bureau of Labor Statistics. This result reaffirms farming/ranching as a dangerous occupation and emphasizes the need for efforts to prevent agricultural injuries, especially those associated with identified injury sources and risk factors.

Neurocognitive status and risk of mortality among people living with human immunodeficiency virus: an 18-year retrospective cohort study.

HIV-related neurocognitive impairment (NCI) may increase the risk of death. However, a survival disadvantage for patients with NCI has not been well studied in the post-combination antiretroviral therapy (cART) era. Specifically, limited research has been conducted considering the reversible nature and variable progression of the impairment and this area demands further evaluation. We performed multivariable Cox proportional hazards modeling to assess the association between baseline NCI (global T scores) and mortality. A joint modeling approach was then used to model the trajectory of global neurocognitive functioning over time and the association between neurocognitive trajectory and mortality. Among the National NeuroAIDS Tissue Consortium's (NNTC) HIV-infected participants, we found a strong negative association between NCI and mortality in the older age groups (e.g., at age = 55, HR = 0.79; 95% CI 0.64-0.99). Three neurocognitive sub-domains (abstraction and executive functioning, speed of information processing, and motor) had the strongest negative association with mortality. Joint modelling indicated a 33% lower hazard for every 10-unit increase in global T scores (HR = 0.67; 95% CI 0.56-0.80). The study identified older HIV-infected individuals with NCI as a group needing special attention for the longevity of life. The study has considerable prognostic utility by not only predicting mortality hazard, but also future cognitive status.

Elevated serum insulin-like growth factor 1 in recurrent aphthous stomatitis.

Over 100 million Americans experience recurrent aphthous stomatitis (RAS) at some point in life. To develop targeted drugs for RAS treatment, it is critical to identify its etiology. We determined if serum insulin-like growth factor 1 (IGF-1) and related factors are associated with RAS, because both RAS prevalence and IGF-1 are highest during puberty. We analyzed data from 1,480 Third National Health and Nutrition Examination Survey participants aged 20-40 years. Participants with a history of diabetes or lupus, cotinine levels 6 ng/ml or higher or glycemia 110 mg/dl or higher were excluded. We compared levels of IGF-1, IGFBP-3, leptin, and insulin in participants with a positive vs. negative RAS history in the prior 12 months. We used logistic regression in SAS/SUDAAN to account for the complex sampling design. The odds of a positive RAS history were 1.31 times higher for every 100 ng/ml increase in serum IGF-1. This association persisted after adjustment for age, race/ethnicity, medication intake, body mass index, insulin, leptin, glycemia, and income (adjusted OR = 1.30, 95% CI [1.06, 1.60]; p = 0.013). The odds of a positive RAS history were also higher among non-Hispanic white compared with non-Hispanic black participants (adjusted OR = 4.37, 95% CI [3.00, 6.38]). Leptin, IGFBP-3, and insulin levels did not differ by RAS status. The significantly higher IGF-1 levels in participants with a positive RAS history compared with controls suggest a possible role of the IGF-1 pathway in RAS etiology.

Qualifications and Characteristics North American Dental Deans Seek in Department Chairpersons.

The aim of this study was to determine whether deans of North American dental schools perceived that one category of department chairperson skills (leadership or management) was more important than the other for their chairpersons to be successful. A secondary purpose was to determine the professional qualifications and personal characteristics these deans perceived contributed most to the success of department chairpersons and whether those differed by the research emphasis of the school. An email survey was sent in 2016 to all 75 deans of U.S. and Canadian dental schools with graduating classes. Section one of the survey was an open response section asking deans to list the five most essential characteristics of a successful department chairperson. Section two asked deans to rank the importance of eight listed professional qualifications, and the last section asked deans to rate the importance of four leadership and four management traits that could contribute to the success of their chairpersons. Questions about characteristics of the deans and the schools were also included. A response rate of 46.7% was obtained. The most frequent characteristics listed in the open response section were in the categories of vision, academic expertise, and integrity. The three most highly ranked professional qualifications were previous teaching experience, previous administrative experience, and history of external research funding. Four of the eight professional qualifications were ranked differently by deans of high compared to moderate research-intensive schools (p<0.05). Overall, the respondents rated leadership skills more highly than management skills (p=0.002) as important for departmental chairpersons.

Geospatial, Clinical, and Social Determinants of Hospital Readmissions.

Unnecessary hospital readmissions increase patient burden, decrease health care quality and efficiency, and raise overall costs. This retrospective cohort study sought to identify high-risk patients who may serve as targets for interventions aiming at reducing hospital readmissions. The authors compared geospatial, social demographic, and clinical characteristics of patients with or without a 90-day readmission. Electronic health records of 42 330 adult patients admitted to 2 Midwestern hospitals during 2013 to 2016 were used, and logistic regression was performed to determine risk factors for readmission. The 90-day readmission percentage was 14.9%. Two main groups of patients with significantly higher odds of a 90-day readmission included those with severe conditions, particularly those with a short length of stay at incident admission, and patients with Medicare but younger than age 65. These findings expand knowledge of potential risk factors related to readmissions. Future interventions to reduce hospital readmissions may focus on the aforementioned high-risk patient groups.