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1.
Proc Natl Acad Sci U S A ; 121(28): e2310992121, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38968105

ABSTRACT

Tissue buckling is an increasingly appreciated mode of morphogenesis in the embryo, but it is often unclear how geometric and material parameters are molecularly determined in native developmental contexts to generate diverse functional patterns. Here, we study the link between differential mechanical properties and the morphogenesis of distinct anteroposterior compartments in the intestinal tract-the esophagus, small intestine, and large intestine. These regions originate from a simple, common tube but adopt unique forms. Using measured data from the developing chick gut coupled with a minimal theory and simulations of differential growth, we investigate divergent lumen morphologies along the entire early gut and demonstrate that spatiotemporal geometries, moduli, and growth rates control the segment-specific patterns of mucosal buckling. Primary buckling into wrinkles, folds, and creases along the gut, as well as secondary buckling phenomena, including period-doubling in the foregut and multiscale creasing-wrinkling in the hindgut, are captured and well explained by mechanical models. This study advances our existing knowledge of how identity leads to form in these regions, laying the foundation for future work uncovering the relationship between molecules and mechanics in gut morphological regionalization.


Subject(s)
Morphogenesis , Animals , Chick Embryo , Morphogenesis/physiology , Biomechanical Phenomena , Chickens , Gastrointestinal Tract/physiology , Gastrointestinal Tract/anatomy & histology , Models, Biological , Intestines/physiology , Intestines/embryology
3.
BMC Public Health ; 20(1): 1282, 2020 Aug 26.
Article in English | MEDLINE | ID: mdl-32842997

ABSTRACT

BACKGROUND: Men who have sex with men (MSM) and transgender women (TGW) are disproportionately impacted by HIV and may face barriers to HIV status disclosure with negative ramifications for HIV prevention and care. We evaluated HIV status disclosure to sexual partners, HIV treatment outcomes, and stigma patterns of MSM and TGW in Abuja and Lagos, Nigeria. METHODS: Previously-diagnosed MSM and TGW living with HIV who enrolled in the TRUST/RV368 cohort from March 2013 to August 2018 were asked, "Have you told your (male/female) sexual partners (MSP/FSP) that you are living with HIV?" In separate analyses, robust Poisson regression models were used to estimate risk ratios (RRs) and 95% confidence intervals (95% CIs) for characteristics associated with HIV status disclosure to MSP and FSP. Self-reported stigma indicators were compared between groups. RESULTS: Of 493 participants living with HIV, 153 (31.0%) had disclosed their HIV status to some or all MSP since being diagnosed. Among 222 with FSP, 34 (15.3%) had disclosed to some or all FSP. Factors independently associated with disclosure to MSP included living in Lagos (RR 1.58 [95% CI 1.14-2.20]) and having viral load < 50 copies/mL (RR 1.67 [95% CI 1.24-2.25]). Disclosure to FSP was more common among participants who were working in entertainment industries (RR 6.25 [95% CI 1.06-36.84]) or as drivers/laborers (RR 6.66 [95% CI 1.10-40.36], as compared to unemployed) and also among those married/cohabiting (RR 3.95 [95% CI 1.97-7.91], as compared to single) and prescribed ART (RR 2.27 [95% CI 1.07-4.83]). No differences in self-reported stigma indicators were observed by disclosure status to MSP but disclosure to FSP was associated with a lower likelihood of ever having been assaulted (26.5% versus 45.2%, p = 0.042). CONCLUSIONS: HIV status disclosure to sexual partners was uncommon among Nigerian MSM and TGW living with HIV but was associated with improved HIV care outcomes. Disclosure was not associated with substantially increased experiences of stigma. Strategies to encourage HIV status disclosure may improve HIV management outcomes in these highly-marginalized populations with a high burden of HIV infection.


Subject(s)
Disclosure/statistics & numerical data , HIV Infections/psychology , Homosexuality, Male/psychology , Homosexuality, Male/statistics & numerical data , Sexual and Gender Minorities/statistics & numerical data , Transgender Persons/psychology , Transgender Persons/statistics & numerical data , Adolescent , Adult , Cohort Studies , Cross-Sectional Studies , Female , HIV Infections/epidemiology , Humans , Male , Middle Aged , Nigeria/epidemiology , Sexual and Gender Minorities/psychology , Young Adult
4.
Pediatr Blood Cancer ; 66(12): e27978, 2019 12.
Article in English | MEDLINE | ID: mdl-31486593

ABSTRACT

BACKGROUND: Pediatric hematology/oncology (PHO) patients receiving therapy or undergoing hematopoietic stem cell transplantation (HSCT) often require a central line and are at risk for bloodstream infections (BSI). There are limited data describing outcomes of BSI in PHO and HSCT patients. METHODS: This is a multicenter (n = 17) retrospective analysis of outcomes of patients who developed a BSI. Centers involved participated in a quality improvement collaborative referred to as the Childhood Cancer and Blood Disorder Network within the Children's Hospital Association. The main outcome measures were all-cause mortality at 3, 10, and 30 days after positive culture date; transfer to the intensive care unit (ICU) within 48 hours of positive culture; and central line removal within seven days of the positive blood culture. RESULTS: Nine hundred fifty-seven BSI were included in the analysis. Three hundred fifty-four BSI (37%) were associated with at least one adverse outcome. All-cause mortality was 1% (n = 9), 3% (n = 26), and 6% (n = 57) at 3, 10, and 30 days after BSI, respectively. In the 165 BSI (17%) associated with admission to the ICU, the median ICU stay was four days (IQR 2-10). Twenty-one percent of all infections (n = 203) were associated with central line removal within seven days of positive blood culture. CONCLUSIONS: BSI in PHO and HSCT patients are associated with adverse outcomes. These data will assist in defining the impact of BSI in this population and demonstrate the need for quality improvement and research efforts to decrease them.


Subject(s)
Bacteremia/mortality , Catheter-Related Infections/mortality , Catheterization, Central Venous/mortality , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/mortality , Hospitalization/statistics & numerical data , Infections/mortality , Adolescent , Bacteremia/blood , Bacteremia/etiology , Catheter-Related Infections/blood , Catheter-Related Infections/etiology , Catheterization, Central Venous/adverse effects , Child , Child, Preschool , Female , Follow-Up Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Infections/blood , Infections/etiology , Male , Prognosis , Retrospective Studies , Survival Rate
5.
Pediatr Nephrol ; 33(6): 1029-1035, 2018 06.
Article in English | MEDLINE | ID: mdl-29480421

ABSTRACT

BACKGROUND: The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative is a quality improvement initiative to reduce dialysis-associated infections. The frequency of peritoneal dialysis (PD) catheter exit site infection (ESI) and variables influencing its development and end result are unclear. We sought to determine ESI rates, to elucidate the epidemiology, risk factors, and outcomes for ESI, and to assess for association between provider compliance with care bundles and ESI risk. METHODS: We reviewed demographic, dialysis and ESI data, and care bundle adherence and outcomes for SCOPE enrollees from October 2011 to September 2014. ESI involved only the exit site, only the subcutaneous catheter tunnel, or both. RESULTS: A total of 857 catheter insertions occurred in 734 children over 10,110 cumulative months of PD provided to these children. During this period 207 ESIs arose in 124 children or 0.25 ESIs per dialysis year. Median time to ESI was 392 days, with 69% of ESIs involving exit site only, 23% involving the tunnel only, and 8% involving both sites. Peritonitis developed in 6%. ESI incidence was associated with age (p = 0.003), being the lowest in children aged < 2 years and highest in those aged 6-12 years, and with no documented review of site care or an exit site score of > 0 at prior month's visit (p < 0.001). Gender, race, end stage renal disease etiology, exit site orientation, catheter cuff number or mobilization, and presence of G-tube, stoma, or vesicostomy were unassociated with ESI incidence. Of the ESIs reported, 71% resolved with treatment, 24% required hospitalization, and 9% required catheter removal, generally secondary to tunnel infection. CONCLUSIONS: Exit site infections occur at an annualized rate of 0.25, typically well into the dialysis course. Younger patient age and documented review of site care are associated with lower ESI rates. Although most ESIs resolve, hospitalization is frequent, and tunnel involvement/catheter loss complicate outcomes.


Subject(s)
Catheter-Related Infections/epidemiology , Catheters, Indwelling/adverse effects , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/adverse effects , Adolescent , Catheter-Related Infections/etiology , Catheter-Related Infections/therapy , Child , Child, Preschool , Female , Follow-Up Studies , Guideline Adherence/statistics & numerical data , Humans , Incidence , Infant , Male , Quality Improvement , Risk Factors , Standard of Care , United States , Young Adult
6.
Pediatr Nephrol ; 33(4): 713-722, 2018 04.
Article in English | MEDLINE | ID: mdl-29150711

ABSTRACT

BACKGROUND: Maintenance peritoneal dialysis (PD) is the dialysis modality of choice for infants and young children. However, there are limited outcome data for those who undergo PD catheter insertion and initiate maintenance PD within the first year of life. METHODS: Using data from the Children's Hospital Association's Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (ESRD) Collaborative (SCOPE), we examined peritonitis rates and patient survival in 156 infants from 29 North American pediatric dialysis centers who had a chronic PD catheter placed prior to their first birthday. RESULTS: In-hospital and overall annualized rates of peritonitis were 1.73 and 0.76 episodes per patient-year, respectively. Polycystic kidney disease was the most frequent renal diagnosis and pulmonary hypoplasia the most common co-morbidity in infants with peritonitis. Multivariable regression models demonstrated that nephrectomy at or prior to PD catheter placement and G-tube insertion after catheter placement were associated with a nearly sixfold and nearly threefold increased risk of peritonitis, respectively. Infants with peritonitis had longer initial hospital stays and lower overall survival (86.3 vs. 95.6%, respectively; P < 0.02) than those without an episode of peritonitis. CONCLUSIONS: In this large cohort of infants with ESRD, the frequency of peritonitis was high and several risk factors associated with the development of peritonitis were identified. Given that peritonitis was associated with a longer duration of initial hospitalization and increased mortality, increased attention to the potentially modifiable risk factors for infection is needed.


Subject(s)
Catheter-Related Infections/epidemiology , Catheters, Indwelling/adverse effects , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/adverse effects , Peritonitis/epidemiology , Catheter-Related Infections/mortality , Female , Humans , Infant , Infant, Newborn , Length of Stay/statistics & numerical data , Male , Peritonitis/etiology , Peritonitis/mortality , Risk Factors , Survival Rate
7.
Med Care ; 55(9): 810-816, 2017 09.
Article in English | MEDLINE | ID: mdl-28671930

ABSTRACT

BACKGROUND: Social determinants of health (SDH) data collected in health care settings could have important applications for clinical decision-making, population health strategies, and the design of performance-based incentives and penalties. One source for cataloging SDH data is the International Statistical Classification of Diseases and Related Health Problems (ICD). OBJECTIVE: To explore how SDH are captured with ICD Ninth revision SDH V codes in a national inpatient discharge database. MATERIALS AND METHODS: Data come from the 2013 Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample, a national stratified sample of discharges from 4363 hospitals from 44 US states. We estimate the rate of ICD-9 SDH V code utilization overall and by patient demographics and payer categories. We additionally estimate the rate of SDH V code utilization for: (a) the 5 most common reasons for hospitalization; and (b) the 5 conditions with the highest rates of SDH V code utilization. RESULTS: Fewer than 2% of overall discharges in the National Inpatient Sample were assigned an SDH V code. There were statistically significant differences in the rate of overall SDH V code utilization by age categories, race/ethnicity, sex, and payer (all P<0.001). Nevertheless, SDH V codes were assigned to <7% of discharges in any demographic or payer subgroup. SDH V code utilization was highest for major diagnostic categories related to mental health and alcohol/substance use-related discharges. CONCLUSIONS: SDH V codes are infrequently utilized in inpatient settings for discharges other than those related to mental health and alcohol/substance use. Utilization incentives will likely need to be developed to realize the potential benefits of cataloging SDH information.


Subject(s)
International Classification of Diseases/statistics & numerical data , Needs Assessment/statistics & numerical data , Patient Discharge/statistics & numerical data , Social Determinants of Health/statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Mental Health , Middle Aged , Racial Groups , Sex Distribution , Socioeconomic Factors , Substance-Related Disorders/diagnosis , Substance-Related Disorders/epidemiology , United States , Vulnerable Populations , Young Adult
8.
Kidney Int ; 89(6): 1346-54, 2016 06.
Article in English | MEDLINE | ID: mdl-27165827

ABSTRACT

The Standardizing Care to improve Outcomes in Pediatric End stage renal disease (SCOPE) Collaborative aims to reduce peritonitis rates in pediatric chronic peritoneal dialysis patients by increasing implementation of standardized care practices. To assess this, monthly care bundle compliance and annualized monthly peritonitis rates were evaluated from 24 SCOPE centers that were participating at collaborative launch and that provided peritonitis rates for the 13 months prior to launch. Changes in bundle compliance were assessed using either a logistic regression model or a generalized linear mixed model. Changes in average annualized peritonitis rates over time were illustrated using the latter model. In the first 36 months of the collaborative, 644 patients with 7977 follow-up encounters were included. The likelihood of compliance with follow-up care practices increased significantly (odds ratio 1.15, 95% confidence interval 1.10, 1.19). Mean monthly peritonitis rates significantly decreased from 0.63 episodes per patient year (95% confidence interval 0.43, 0.92) prelaunch to 0.42 (95% confidence interval 0.31, 0.57) at 36 months postlaunch. A sensitivity analysis confirmed that as mean follow-up compliance increased, peritonitis rates decreased, reaching statistical significance at 80% at which point the prelaunch rate was 42% higher than the rate in the months following achievement of 80% compliance. In its first 3 years, the SCOPE Collaborative has increased the implementation of standardized follow-up care and demonstrated a significant reduction in average monthly peritonitis rates.


Subject(s)
Aftercare/standards , Guideline Adherence/standards , Kidney Failure, Chronic/therapy , Patient Care Bundles/standards , Peritoneal Dialysis/standards , Peritonitis/epidemiology , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Guidelines as Topic , Humans , Infant , Infant, Newborn , Male , Odds Ratio , Patient Compliance , Peritoneal Dialysis/adverse effects , Peritonitis/etiology , Quality Improvement/standards
9.
Pediatr Blood Cancer ; 63(9): 1603-7, 2016 09.
Article in English | MEDLINE | ID: mdl-27198806

ABSTRACT

BACKGROUND: Central line associated bloodstream infections (CLABSIs) are a significant cause of morbidity and mortality in pediatric hematology/oncology (PHO) patients. Understanding the differences in CLABSI rates by central line (CL) type is important to inform clinical decisions. PROCEDURE: CLABSI, using similar definitions, noted with three commonly used CL types (totally implanted catheter [port], tunneled externalized catheter [TEC], peripherally inserted central catheter [PICC]) and CL-specific line days were prospectively tracked across 15 US PHO centers from May 2012 until April 2015 and CLABSI rates (CLABSI per 1,000 CL-specific line days) were calculated. Host and organism characterstics associated with the CLABSI events were analyzed. RESULTS: Over the course of 2.8 million line days, 1,113 CLABSI events (397 in inpatients and 716 in ambulatory patients) were noted. The inpatient CLABSI rate was higher than the ambulatory CLABSI rate for each of the CL types: 1.48 versus 0.16 for ports, 3.51 versus 1.38 for TECs, and 3.07 versus 1.16 for PICCs, respectively. TECs and PICCs were associated with higher CLABSI rates than ports, inpatient and ambulatory. CONCLUSIONS: We found that CLABSI rates were significantly higher for inpatients compared to ambulatory PHO patients for all CL types. Among ambulatory patients, TECs had the highest CLABSI rate and ports the lowest. Among inpatients, TECs and PICCs had higher CLABSI rates than ports but were not statistically different from one another. Cognizant that host and underlying disease attributes may contribute to these differences, these results can still inform CL choice in clinical practice.


Subject(s)
Bacteremia/epidemiology , Catheter-Related Infections/epidemiology , Catheterization, Central Venous/adverse effects , Neoplasms/complications , Child , Female , Humans , Male , Prospective Studies
10.
Pediatr Nephrol ; 29(9): 1477-84, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25055994

ABSTRACT

The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative is a North American multi-center quality transformation effort whose primary aim is to minimize exit-site infection and peritonitis rates among pediatric chronic peritoneal dialysis patients. The project, developed by the quality improvement faculty and staff at the Children's Hospital Association's Quality Transformation Network (QTN) and content experts in pediatric nephrology and pediatric infectious diseases, is modeled after the QTN's highly successful Pediatric Intensive Care Unit and Hematology-Oncology central line-associated blood-stream infection (CLABSI) Collaboratives. Like the Association's other QTN efforts, the SCOPE Collaborative is part of a broader effort to assist pediatric nephrology teams in learning about and using quality improvement methods to develop and implement evidence-based practices. In addition, the design of this project allows for targeted research that builds on high-quality, ongoing data collection. Finally, the project, while focused on reducing peritoneal dialysis catheter-associated infections, will also serve as a model for future pediatric nephrology projects that could further improve the quality of care provided to children with end stage renal disease.


Subject(s)
Catheter-Related Infections/prevention & control , Pediatrics/standards , Peritoneal Dialysis/adverse effects , Quality Improvement/standards , Child , Cooperative Behavior , Humans , Kidney Failure, Chronic/therapy
11.
Dev Cell ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39116876

ABSTRACT

Hox transcription factors play crucial roles in organizing developmental patterning across metazoa, but how these factors trigger regional morphogenesis has largely remained a mystery. In the developing gut, Hox genes help demarcate identities of intestinal subregions early in embryogenesis, which ultimately leads to their specialization in both form and function. Although the midgut forms villi, the hindgut develops sulci that resolve into heterogeneous outgrowths. Combining mechanical measurements of the embryonic chick intestine and mathematical modeling, we demonstrate that the posterior Hox gene HOXD13 regulates biophysical phenomena that shape the hindgut lumen. We further show that HOXD13 acts through the transforming growth factor ß (TGF-ß) pathway to thicken, stiffen, and promote isotropic growth of the subepithelial mesenchyme-together, these features lead to hindgut-specific surface buckling. TGF-ß, in turn, promotes collagen deposition to affect mesenchymal geometry and growth. We thus identify a cascade of events downstream of positional identity that direct posterior intestinal morphogenesis.

12.
bioRxiv ; 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37645918

ABSTRACT

Correct intestinal morphogenesis depends on the early embryonic process of gut rotation, an evolutionarily conserved program in which a straight gut tube elongates and forms into its first loops. However, the gut tube requires guidance to loop in a reproducible manner. The dorsal mesentery (DM) connects the gut tube to the body and directs the lengthening gut into stereotypical loops via left-right (LR) asymmetric cellular and extracellular behavior. The LR asymmetry of the DM also governs blood and lymphatic vessel formation for the digestive tract, which is essential for prenatal organ development and postnatal vital functions including nutrient absorption. Although the genetic LR asymmetry of the DM has been extensively studied, a divider between the left and right DM has yet to be identified. Setting up LR asymmetry for the entire body requires a Lefty1+ midline barrier to separate the two sides of the embryo-without it, embryos have lethal or congenital LR patterning defects. Individual organs including the brain, heart, and gut also have LR asymmetry, and while the consequences of left and right signals mixing are severe or even lethal, organ-specific mechanisms for separating these signals are not well understood. Here, we uncover a midline structure composed of a transient double basement membrane, which separates the left and right halves of the embryonic chick DM during the establishment of intestinal and vascular asymmetries. Unlike other basement membranes of the DM, the midline is resistant to disruption by intercalation of Netrin4 (Ntn4). We propose that this atypical midline forms the boundary between left and right sides and functions as a barrier necessary to establish and protect organ asymmetry.

13.
PLoS One ; 16(3): e0249259, 2021.
Article in English | MEDLINE | ID: mdl-33784358

ABSTRACT

BACKGROUND: Clinical laboratory reference intervals (RIs) are essential for diagnosing and managing patients in routine clinical care as well as establishing eligibility criteria and defining adverse events in clinical trials, but may vary by age, gender, genetics, nutrition and geographic location. It is, therefore, critical to establish region-specific reference values in order to inform clinical decision-making. METHODS: We analyzed data from a prospective observational HIV incidence cohort study in Kombewa, Kenya. Study participants were healthy males and females, aged 18-35 years, without HIV. Median and 95% reference values (2.5th percentile to 97.5th percentile) were calculated for laboratory parameters including hematology, chemistry studies, and CD4 T cell count. Standard Deviation Ratios (SDR) and Bias Ratios (BR) are presented as measures of effect magnitude. Findings were compared with those from the United States and other Kenyan studies. RESULTS: A total of 299 participants were analyzed with a median age of 24 years (interquartile range: 21-28). Ratio of males to females was 0.9:1. Hemoglobin range (2.5th-97.5th percentiles) was 12.0-17.9 g/dL and 9.5-15.3 g/dL in men and women respectively. In the cohort, MCV range was 59-95fL, WBC 3.7-9.2×103/µL, and platelet 154-401×103/µL. Chemistry values were higher in males; the creatinine RI was 59-103 µmol/L in males vs. 46-76 µmol/L in females (BRUL>.3); and the alanine transferase range was 8.8-45.3 U/L in males vs. 7.5-36.8 U/L in females (SDR>.3). The overall CD4 T cell count RI was 491-1381 cells/µL. Some parameters including hemoglobin, neutrophil, creatinine and ALT varied with that from prior studies in Kenya and the US. CONCLUSION: This study not only provides clinical reference intervals for a population in Kisumu County but also highlights the variations in comparable settings, accentuating the requirement for region-specific reference values to improve patient care, scientific validity, and quality of clinical trials in Africa.


Subject(s)
CD4 Lymphocyte Count/standards , Hematology/standards , Laboratories , Adolescent , Adult , Cohort Studies , Female , Humans , Kenya , Male , Middle Aged , Reference Values , Young Adult
14.
PLoS One ; 15(4): e0232018, 2020.
Article in English | MEDLINE | ID: mdl-32352972

ABSTRACT

INTRODUCTION: In many African countries, laboratory reference values are not established for the local healthy adult population. In Mozambique, reference values are known for young adults (18-24yo) but not yet established for a wider age range. Our study aimed to establish hematological, biochemical and immunological reference values for vaccine trials in Mozambican healthy adults with high-risk for HIV acquisition. METHODS: A longitudinal cohort and site development study in Mozambique between November 2013 and 2014 enrolled 505 participants between 18 to 35 years old. Samples from these healthy participants, were analyzed to determine reference values. All volunteers included in the analysis were clinically healthy and human immunodeficiency virus (HIV), hepatitis B and C virus, and syphilis negative. Median and reference ranges were calculated for the hematological, biochemical and immunological parameters. Ranges were compared with other African countries, the USA and the US National Institute of Health (NIH) Division of AIDS (DAIDS) toxicity tables. RESULTS: A total of 505 participant samples were analyzed. Of these, 419 participants were HIV, hepatitis B and C virus and syphilis negative including 203 (48.5%) females and 216 (51.5%) males, with a mean age of 21 years. In the hematological parameters, we found significant differences between sex for erythrocytes, hemoglobin, hematocrit, MCV, MCH and MCHC as well as white blood cells, neutrophils and platelets: males had higher values than females. There were also significant differences in CD4+T cell values, 803 cells/µL in men versus 926 cells/µL in women. In biochemical parameters, men presented higher values than women for the metabolic, enzymatic and renal parameters: total and direct bilirubin, ALT and creatinine. CONCLUSION: This study has established reference values for healthy adults with high-risk for HIV acquisition in Mozambique. These data are helpful in the context of future clinical research and patient care and treatment for the general adult population in the Mozambique and underline the importance of region-specific clinical reference ranges.


Subject(s)
Blood Cells/chemistry , HIV Infections/prevention & control , Hematologic Tests/standards , Adult , Blood Platelets/chemistry , Cohort Studies , Female , HIV Infections/blood , Hematocrit/standards , Hemoglobins/analysis , Humans , Leukocyte Count/standards , Leukocytes/chemistry , Longitudinal Studies , Male , Middle Aged , Mozambique/epidemiology , Reference Values , Risk Factors
15.
Antivir Ther ; 24(8): 595-601, 2019.
Article in English | MEDLINE | ID: mdl-32125280

ABSTRACT

BACKGROUND: Across sub-Saharan Africa, men who have sex with men (MSM) and transgender women (TGW) have disproportionately poor HIV treatment outcomes. Stigma and criminalization create barriers to health-care engagement and adherence to antiretroviral therapy (ART), potentially promoting the development of HIV drug resistance (HIVDR). We evaluated transmitted, pre-treatment and acquired HIVDR among MSM and TGW in Lagos and Abuja, Nigeria. METHODS: Adults with HIV RNA ≥1,000 copies/ml in the TRUST/RV368 cohort, including incident cases diagnosed via 3-monthly screening, underwent HIVDR testing using the Sanger sequencing method. Major mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were identified from the 2017 IAS-USA list. World Health Organization surveillance drug resistance mutations (SDRMs) were identified in ART-naive participants. RESULTS: From March 2013 to June 2017, 415 participants with median age 24 (interquartile range [IQR] 21-27) years, CD4+ T-cell count 370 (IQR 272-502) cells/mm3, and HIV RNA 4.73 (IQR 4.26-5.15) log10 copies/ml underwent HIVDR testing. SDRMs were observed in 36 of 373 ART-naive participants (9.7%, 95% confidence interval [95% CI 6.8, 13.1%]), including 8 of 39 incident cases (20.5%, [95% CI] 9.3, 36.5%). Among 42 ART-experienced participants, NNRTI resistance was detected in 18 (42.9%, 95% CI 27.7, 59.0%) and NRTI resistance in 10 (23.8%, 95% CI 12.0, 39.4%). No PI resistance was detected. CONCLUSIONS: The high prevalence of transmitted and acquired drug resistance among Nigerian MSM and TGW living with HIV suggests the need for programmatic solutions to improve uninterrupted access to ART and timely switch to second-line regimens in cases of viral failure.


Subject(s)
Anti-HIV Agents/pharmacology , Drug Resistance, Viral , HIV Infections/virology , Homosexuality, Male , Transgender Persons , Adult , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV-1/drug effects , HIV-1/genetics , Humans , Male , Mutation , Nigeria/epidemiology , Young Adult
16.
J Hosp Med ; 13(7): 445-452, 2018 07.
Article in English | MEDLINE | ID: mdl-29964274

ABSTRACT

OBJECTIVE: Mental health conditions (MHCs) are prevalent among hospitalized children and could influence the success of hospital discharge. We assessed the relationship between MHCs and 30-day readmissions. METHODS: This retrospective, cross-sectional study of the 2013 Nationwide Readmissions Database included 512,997 hospitalizations of patients ages 3 to 21 years for the 10 medical and 10 procedure conditions with the highest number of 30-day readmissions. MHCs were identified by using the International Classification of Diseases, 9th Revision-Clinical Modification codes. We derived logistic regression models to measure the associations between MHC and 30-day, all-cause, unplanned readmissions, adjusting for demographic, clinical, and hospital characteristics. RESULTS: An MHC was present in 17.5% of medical and 13.1% of procedure index hospitalizations. Readmission rates were 17.0% and 6.2% for medical and procedure hospitalizations, respectively. In the multivariable analysis, compared with hospitalizations with no MHC, hospitalizations with MHCs had higher odds of readmission for medical admissions (adjusted odds ratio [AOR], 1.23; 95% confidence interval [CI], 1.19-1.26] and procedure admissions (AOR, 1.24; 95% CI, 1.15-1.33). Three types of MHCs were associated with higher odds of readmission for both medical and procedure hospitalizations: depression (medical AOR, 1.57; 95% CI, 1.49-1.66; procedure AOR, 1.39; 95% CI, 1.17-1.65), substance abuse (medical AOR, 1.24; 95% CI, 1.18-1.30; procedure AOR, 1.26; 95% CI, 1.11-1.43), and multiple MHCs (medical AOR, 1.43; 95% CI, 1.37-1.50; procedure AOR, 1.26; 95% CI, 1.11-1.44). CONCLUSIONS: MHCs are associated with a higher likelihood of hospital readmission in children admitted for medical conditions and procedures. Understanding the influence of MHCs on readmissions could guide strategic planning to reduce unplanned readmissions for children with cooccurring physical and mental health conditions.


Subject(s)
Databases, Factual/statistics & numerical data , Mental Disorders/therapy , Patient Readmission/statistics & numerical data , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , Female , Hospitalization , Humans , Male , Patient Discharge/statistics & numerical data , Retrospective Studies , Risk Factors , Time Factors , Young Adult
17.
Infect Control Hosp Epidemiol ; 38(6): 690-696, 2017 06.
Article in English | MEDLINE | ID: mdl-28399945

ABSTRACT

OBJECTIVE To assess the burden of bloodstream infections (BSIs) among pediatric hematology-oncology (PHO) inpatients, to propose a comprehensive, all-BSI tracking approach, and to discuss how such an approach helps better inform within-center and across-center differences in CLABSI rate DESIGN Prospective cohort study SETTING US multicenter, quality-improvement, BSI prevention network PARTICIPANTS PHO centers across the United States who agreed to follow a standardized central-line-maintenance care bundle and track all BSI events and central-line days every month. METHODS Infections were categorized as CLABSI (stratified by mucosal barrier injury-related, laboratory-confirmed BSI [MBI-LCBI] versus non-MBI-LCBI) and secondary BSI, using National Healthcare Safety Network (NHSN) definitions. Single positive blood cultures (SPBCs) with NHSN defined common commensals were also tracked. RESULTS Between 2013 and 2015, 34 PHO centers reported 1,110 BSIs. Among them, 708 (63.8%) were CLABSIs, 170 (15.3%) were secondary BSIs, and 232 (20.9%) were SPBCs. Most SPBCs (75%) occurred in patients with profound neutropenia; 22% of SPBCs were viridans group streptococci. Among the CLABSIs, 51% were MBI-LCBI. Excluding SPBCs, CLABSI rates were higher (88% vs 77%) and secondary BSI rates were lower (12% vs 23%) after the NHSN updated the definition of secondary BSI (P<.001). Preliminary analyses showed across-center differences in CLABSI versus secondary BSI and between SPBC and CLABSI versus non-CLABSI rates. CONCLUSIONS Tracking all BSIs, not just CLABSIs in PHO patients, is a patient-centered, clinically relevant approach that could help better assess across-center and within-center differences in infection rates, including CLABSI. This approach enables informed decision making by healthcare providers, payors, and the public. Infect Control Hosp Epidemiol 2017;38:690-696.


Subject(s)
Catheter-Related Infections/epidemiology , Catheterization, Central Venous/adverse effects , Cross Infection/epidemiology , Hematologic Neoplasms/complications , Population Surveillance/methods , Sepsis/epidemiology , Blood Culture , Hematology/statistics & numerical data , Holistic Health , Hospital Units/statistics & numerical data , Hospitals, Pediatric/statistics & numerical data , Humans , Neutropenia/complications , Patient Care Bundles , Prospective Studies , Quality Improvement , Terminology as Topic , United States
18.
Am J Public Health ; 96(10): 1772-8, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17008572

ABSTRACT

OBJECTIVES: We assessed the extent to which borderline mental retardation and mental retardation at preschool ages are related to emotional and behavioral problems in young adulthood. We also explored early risk factors for having mental health problems as a young adult that might be related to preschool differences in cognitive ability. METHODS: We used data from a cohort of births studied in the Johns Hopkins Collaborative Perinatal Study and followed up in the Pathways to Adulthood Study. Preschool cognitive functioning was assessed at 4 years of age. Individual characteristics, psychosocial factors, and mental problems were prospectively evaluated from birth through young adulthood. RESULTS: Children with subaverage cognitive abilities were more likely to develop mental health problems than their counterparts with IQs above 80. Inadequate family interactions were shown to increase 2- to 4-fold the risk of emotional or behavioral problems among children with borderline mental retardation. CONCLUSIONS: Subaverage cognitive functioning in early life increases later risk of mental health problems. Future research may help to delineate possible impediments faced at different developmental stages and guide changes in supportive services to better address the needs of children with borderline mental retardation.


Subject(s)
Cognition Disorders/physiopathology , Mental Disorders/epidemiology , Adult , Baltimore/epidemiology , Child , Child, Preschool , Cognition , Cohort Studies , Female , Follow-Up Studies , Humans , Intelligence , Male , Mental Health , Racial Groups , Risk Factors , Socioeconomic Factors
19.
Clin J Am Soc Nephrol ; 11(9): 1590-1596, 2016 09 07.
Article in English | MEDLINE | ID: mdl-27340282

ABSTRACT

BACKGROUND AND OBJECTIVES: The Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative is a quality improvement initiative that aims to reduce peritoneal dialysis-associated infections in pediatric patients on chronic peritoneal dialysis. Our objectives were to determine whether provider compliance with peritoneal dialysis catheter care bundles was associated with lower risk for infection at the individual patient level and describe the epidemiology, risk factors, and outcomes for peritonitis in the Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We collected peritoneal dialysis characteristics, causative organisms, compliance with care bundles, and outcomes in children with peritonitis between October of 2011 and September of 2014. Chi-squared tests, t tests, and generalized linear mixed models were used to assess risk factors for peritonitis. RESULTS: Of 734 children enrolled (54% boys; median age =9 years old; interquartile range, 1-15) from 29 centers, 391 peritonitis episodes occurred among 245 individuals over 10,130 catheter-months. The aggregate annualized peritonitis rate was 0.46 episodes per patient-year. Rates were highest among children ≤2 years old (0.62 episodes per patient-year). Gram-positive peritonitis predominated (37.8%) followed by culture-negative (24.7%), gram-negative (19.5%), and polymicrobial (10.3%) infections; fungal only peritonitis accounted for 7.7% of episodes. Compliance with the follow-up bundle was associated with a lower rate of peritonitis (rate ratio, 0.49; 95% confidence interval, 0.30 to 0.80) in the multivariable model. Upward orientation of the catheter exit site (rate ratio, 4.2; 95% confidence interval, 1.49 to 11.89) and touch contamination (rate ratio, 2.22; 95% confidence interval, 1.44 to 3.34) were also associated with a higher risk of peritonitis. Infection outcomes included resolution with antimicrobial treatment alone in 76.6%, permanent catheter removal in 12.2%, and catheter removal with return to peritoneal dialysis in 6% of episodes. CONCLUSIONS: Lower compliance with standardized practices for follow-up peritoneal dialysis catheter care in the Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative was associated with higher risk of peritonitis. Quality improvement and prevention strategies have the potential to reduce peritoneal dialysis-associated peritonitis.


Subject(s)
Catheter-Related Infections/epidemiology , Guideline Adherence/statistics & numerical data , Patient Care Bundles/standards , Peritoneal Dialysis/standards , Peritonitis/epidemiology , Adolescent , Age Factors , Anti-Infective Agents/therapeutic use , Catheter-Related Infections/microbiology , Catheterization/adverse effects , Catheterization/methods , Catheterization/standards , Catheters, Indwelling/adverse effects , Catheters, Indwelling/microbiology , Child , Child, Preschool , Device Removal , Female , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/therapy , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/therapy , Humans , Infant , Infant, Newborn , Kidney Failure, Chronic/therapy , Male , Mycoses/epidemiology , Mycoses/therapy , Peritoneal Dialysis/adverse effects , Peritonitis/microbiology , Peritonitis/therapy , Prospective Studies , Risk Factors , United States/epidemiology , Young Adult
20.
Pediatrics ; 138(6)2016 12.
Article in English | MEDLINE | ID: mdl-27940716

ABSTRACT

OBJECTIVE: Mental health conditions are prevalent among children hospitalized for medical conditions and surgical procedures, but little is known about their influence on hospital resource use. The objectives of this study were to examine how hospitalization characteristics vary by presence of a comorbid mental health condition and estimate the association of a comorbid mental health condition with hospital length of stay (LOS) and costs. METHODS: Using the 2012 Kids' Inpatient Database, we conducted a retrospective, nationally representative, cross-sectional study of 670 161 hospitalizations for 10 common medical and 10 common surgical conditions among 3- to 20-year-old patients. Associations between mental health conditions and hospital LOS were examined using adjusted generalized linear models. Costs of additional hospital days associated with mental health conditions were estimated using hospital cost-to-charge ratios. RESULTS: A comorbid mental health condition was present in 13.2% of hospitalizations. A comorbid mental health condition was associated with a LOS increase of 8.8% (from 2.5 to 2.7 days, P < .001) for medical hospitalizations and a 16.9% increase (from 3.6 to 4.2 days, P < .001) for surgical hospitalizations. For hospitalizations in this sample, comorbid mental health conditions were associated with an additional 31 729 (95% confidence interval: 29 085 to 33 492) hospital days and $90 million (95% confidence interval: $81 to $101 million) in hospital costs. CONCLUSIONS: Medical and surgical hospitalizations with comorbid mental health conditions were associated with longer hospital stay and higher hospital costs. Knowledge about the influence of mental health conditions on pediatric hospital utilization can inform clinical innovation and case-mix adjustment.


Subject(s)
Chronic Disease/epidemiology , Hospital Units/statistics & numerical data , Hospitalization/statistics & numerical data , Length of Stay/economics , Mental Disorders/epidemiology , Mental Disorders/therapy , Adolescent , Age Factors , Child , Child, Preschool , Chronic Disease/therapy , Comorbidity , Cost-Benefit Analysis , Cross-Sectional Studies , Databases, Factual , Female , General Surgery , Hospital Costs , Hospital Units/economics , Hospitals, Pediatric , Humans , Internal Medicine , Male , Mental Disorders/diagnosis , Netherlands , Retrospective Studies , Risk Assessment , Sex Factors , Treatment Outcome , Young Adult
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