Association between low maternal serum aflatoxin B1 exposure and adverse pregnancy outcomes in Mombasa, Kenya, 2017-2019: A nested matched case-control study.

We examined the association between serum aflatoxin B1-lysine adduct (AFB1-lys) levels in pregnant women and adverse pregnancy outcomes (low birthweight, miscarriage and stillbirth) through a nested matched case-control study of pregnant women enroled at ≤28 weeks' gestation in Mombasa, Kenya, from 2017 to 2019. Cases comprised women with an adverse birth outcome, defined as either delivery of a singleton infant weighing <2500 g, or a miscarriage, or a stillbirth, while controls were women who delivered a singleton live infant with a birthweight of ≥2500 g. Cases were matched to controls at a ratio of 1:2 based on maternal age at enrolment, gestational age at enrolment and study site. The primary exposure was serum AFB1-lys. The study included 125 cases and 250 controls. The median gestation age when serum samples were collected was 23.0 weeks (interquartile range [IQR]: 18.1-26.0) and 23.5 (IQR: 18.1-26.5) among cases and controls, respectively. Of the 375 tested sera, 145 (38.7%) had detectable serum AFB1-lys: 36.0% in cases and 40.0% in controls. AFB1-lys adduct levels were not associated with adverse birth outcomes on multivariable analysis. Mid-upper arm circumference was associated with a 6% lower odds of adverse birth outcome for every unit increase (p = 0.023). Two-fifths of pregnant women had detectable levels of aflatoxin midway through pregnancy. However, we did not detect an association with adverse pregnancy outcomes, likely because of low serum AFB1-lys levels and low power, restricting meaningful comparison. More research is needed to understand the public health risk of aflatoxin in pregnant women to unborn children.

The effect of COVID-19 pandemic on healthcare seeking in an urban informal settlement in Nairobi and a rural setting in western Kenya.

The COVID-19 pandemic caused widespread changes and disruptions to healthcare seeking behavior. There are limited studies on the effect of the COVID-19 pandemic on healthcare seeking patterns in low-and middle-income countries (LMICs), especially in settings with inequitable access to healthcare in rural and urban informal settlements. We investigated the effect of the COVID-19 pandemic on reported healthcare seeking at health facilities and chemists using morbidity data from participants in an ongoing population-based infectious disease surveillance platform in Asembo in Siaya County, a rural setting in western Kenya and Kibera, an urban informal settlement in Nairobi County. We described healthcare seeking patterns before (from 1st January 2016 to 12th March 2020) and during the pandemic (from 13th March 2020 to 31st August 2022) by gender and age for any reported illness and select clinical syndromes using frequencies and percentages. We used a generalized estimating equation with an exchangeable correlation structure to assess the effect of the pandemic on healthcare seeking adjusting for gender and age. Overall, there was a 19% (adjusted odds ratio, aOR: 0.81; 95% Confidence Interval, CI: 0.79-0.83) decline in odds of seeking healthcare at health facilities for any illness in Asembo during the pandemic, and a 30% (aOR: 0.70; 95% CI: 0.67-0.73) decline in Kibera. Similarly, there was a decline in seeking healthcare by clinical syndromes, e.g., for ARI, aOR: 0.76; 95% CI:0.73-0.79 in Asembo, and aOR: 0.68; 95% CI:0.64-0.72 in Kibera. The pandemic resulted in increased healthcare seeking at chemists (aOR: 1.23; 95% CI: 1.20-1.27 in Asembo, and aOR: 1.40; 95% CI: 1.35-1.46 in Kibera). This study highlights interruptions to healthcare seeking in resource-limited settings due to the COVID-19 pandemic. The pandemic resulted in a substantial decline in seeking care at health facilities, and an increase of the same at chemists.

Seroconversion and seroprevalence of TORCH infections in a pregnant women cohort study, Mombasa, Kenya, 2017-2019.

Women infected during pregnancy with TORCH (Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes simplex viruses) pathogens have a higher risk of adverse birth outcomes including stillbirth / miscarriage because of mother-to-child transmission. To investigate these risks in pregnant women in Kenya, we analyzed serum specimens from a pregnancy cohort study at three healthcare facilities. A sample of 481 participants was selected for TORCH pathogen antibody testing to determine seroprevalence. A random selection of 285 from the 481 participants was selected to measure seroconversion. These sera were tested using an IgG enzyme-linked immunosorbent assay against 10 TORCH pathogens. We found that the seroprevalence of all but three of the 10 TORCH pathogens at enrollment was >30%, except for Bordetella pertussis (3.8%), Treponema pallidum (11.4%), and varicella zoster virus (0.5%). Conversely, very few participants seroconverted during their pregnancy and were herpes simplex virus type 2 (n = 24, 11.2%), parvovirus B19 (n = 14, 6.2%), and rubella (n = 12, 5.1%). For birth outcomes, 88% of the participant had live births and 12% had stillbirths or miscarriage. Cytomegalovirus positivity at enrolment had a statistically significant positive association with a live birth outcome (p = 0.0394). Of the 10 TORCH pathogens tested, none had an association with adverse pregnancy outcome.

Heterogenous transmission and seroprevalence of SARS-CoV-2 in two demographically diverse populations with low vaccination uptake in Kenya, March and June 2021.

Background: SARS-CoV-2 has extensively spread in cities and rural communities, and studies are needed to quantify exposure in the population. We report seroprevalence of SARS-CoV-2 in two well-characterized populations in Kenya at two time points. These data inform the design and delivery of public health mitigation measures. Methods: Leveraging on existing population based infectious disease surveillance (PBIDS) in two demographically diverse settings, a rural site in western Kenya in Asembo, Siaya County, and an urban informal settlement in Kibera, Nairobi County, we set up a longitudinal cohort of randomly selected households with serial sampling of all consenting household members in March and June/July 2021. Both sites included 1,794 and 1,638 participants in the March and June/July 2021, respectively. Individual seroprevalence of SARS-CoV-2 antibodies was expressed as a percentage of the seropositive among the individuals tested, accounting for household clustering and weighted by the PBIDS age and sex distribution. Results: Overall weighted individual seroprevalence increased from 56.2% (95%CI: 52.1, 60.2%) in March 2021 to 63.9% (95%CI: 59.5, 68.0%) in June 2021 in Kibera. For Asembo, the seroprevalence almost doubled from 26.0% (95%CI: 22.4, 30.0%) in March 2021 to 48.7% (95%CI: 44.3, 53.2%) in July 2021. Seroprevalence was highly heterogeneous by age and geography in these populations-higher seroprevalence was observed in the urban informal settlement (compared to the rural setting), and children aged <10 years had the lowest seroprevalence in both sites. Only 1.2% and 1.6% of the study participants reported receipt of at least one dose of the COVID-19 vaccine by the second round of serosurvey-none by the first round. Conclusions: In these two populations, SARS-CoV-2 seroprevalence increased in the first 16 months of the COVID-19 pandemic in Kenya. It is important to prioritize additional mitigation measures, such as vaccine distribution, in crowded and low socioeconomic settings.

Correcting for measurement error in assessing gestational age in a low-resource setting: a regression calibration approach.

Introduction: Measurement error in gestational age (GA) may bias the association of GA with a health outcome. Ultrasound-based GA is considered the gold standard and is not readily available in low-resource settings. We corrected for measurement error in GA based on fundal height (FH) and date of last menstrual period (LMP) using ultrasound from the sub-cohort and adjusted for the bias in associating GA with neonatal mortality and low birth weight (< 2,500 grams, LBW). Methods: We used data collected from 01/2015 to 09/2019 from pregnant women enrolled at two public hospitals in Siaya county, Kenya (N = 2,750). We used regression calibration to correct for measurement error in FH- and LMP-based GA accounting for maternal and child characteristics. We applied logistic regression to associate GA with neonatal mortality and low birth weight, with and without calibrating FH- and LMP-based GA. Results: Calibration improved the precision of LMP (correlation coefficient, ρ from 0.48 to 0.57) and FH-based GA (ρ from 0.82 to 0.83). Calibrating FH/LMP-based GA eliminated the bias in the mean GA estimates. The log odds ratio that quantifies the association of GA with neonatal mortality increased by 29% (from -0.159 to -0.205) by calibrating FH-based GA and by more than twofold (from -0.158 to -0.471) by calibrating LMP-based GA. Conclusion: Calibrating FH/LMP-based GA improved the accuracy and precision of GA estimates and strengthened the association of GA with neonatal mortality/LBW. When assessing GA, neonatal public health and clinical interventions may benefit from calibration modeling in settings where ultrasound may not be fully available.

Dynamic Incidence of Typhoid Fever over a 10-Year Period (2010-2019) in Kibera, an Urban Informal Settlement in Nairobi, Kenya.

Typhoid fever burden can vary over time. Long-term data can inform prevention strategies; however, such data are lacking in many African settings. We reexamined typhoid fever incidence and antimicrobial resistance (AMR) over a 10-year period in Kibera, a densely populated urban informal settlement where a high burden has been previously described. We used data from the Population Based Infectious Diseases Surveillance platform to estimate crude and adjusted incidence rates and prevalence of AMR in nearly 26,000 individuals of all ages. Demographic and healthcare-seeking information was collected through household visits. Blood cultures were processed for patients with acute fever or lower respiratory infection. Between 2010 and 2019, 16,437 participants were eligible for blood culture and 11,848 (72.1%) had a culture performed. Among 11,417 noncontaminated cultures (96.4%), 237 grew Salmonella enterica serovar Typhi (2.1%). Overall crude and adjusted incidences were 95 and 188 cases per 100,000 person-years of observation (pyo), respectively. Annual crude incidence varied from 144 to 233 between 2010 and 2012 and from 9 to 55 between 2013 and 2018 and reached 130 per 100,000 pyo in 2019. Children 5-9 years old had the highest overall incidence (crude, 208; adjusted, 359 per 100,000 pyo). Among isolates tested, 156 of 217 were multidrug resistant (resistant to chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole [71.9%]) and 6 of 223 were resistant to ciprofloxacin (2.7%). Typhoid fever incidence resurged in 2019 after a prolonged period of low rates, with the highest incidence among children. Typhoid fever control measures, including vaccines, could reduce morbidity in this setting.

Associations of Midlife Dietary Patterns with Incident Dementia and Brain Structure: Findings from the UK Biobank Study.

BACKGROUND: At present, the results on the associations between dietary patterns and risk of dementia are inconsistent, and studies on the associations between dietary patterns and brain structures are limited. OBJECTIVES: We aimed to investigate the associations of midlife dietary patterns with incident dementia and brain structures. METHODS: On the basis of the UK Biobank Study, we investigated the 1) prospective associations of 4 healthy dietary pattern indices [healthy plant-based diet index (hPDI), Mediterranean diet score (MDS), recommended food score (RFS), and Mediterranean-DASH Intervention for Neurodegenerative Delay Diet (MIND)] with incident dementia (identified using linked hospital data; N = 114,684; mean age, 56.8 y; 55.5% females) using Cox proportional-hazards regressions and the 2) cross-sectional associations of these dietary pattern indices with brain structures (estimated using magnetic resonance imaging; N = 18,214; mean age, 55.9 y; 53.1% females) using linear regressions. A series of covariates were adjusted, and several sensitivity analyses were conducted. RESULTS: A total of 481 (0.42%) participants developed dementia during the average 9.4-y follow-up. Although the associations were not statistically significant, all dietary patterns exerted protective effects against incident dementia (all HRs < 1). Furthermore, higher dietary pattern indices were significantly associated with larger regional brain volumes, including volumes of gray matter in the parietal and temporal cortices and volumes of the hippocampus and thalamus. The main results were confirmed via sensitivity analyses. CONCLUSIONS: Greater adherence to hPDI, MDS, RFS, and MIND was individually associated with larger brain volumes in specific regions. This study shows a comprehensive picture of the consistent associations of midlife dietary patterns with risk of dementia and brain health, underscoring the potential benefits of a healthy diet in the prevention of dementia.

A multivariate joint model to adjust for random measurement error while handling skewness and correlation in dietary data in an epidemiologic study of mortality.

PURPOSE: A substantial proportion of global deaths is attributed to unhealthy diets, which can be assessed at baseline or longitudinally. We demonstrated how to simultaneously correct for random measurement error, correlations, and skewness in the estimation of associations between dietary intake and all-cause mortality. METHODS: We applied a multivariate joint model (MJM) that simultaneously corrected for random measurement error, skewness, and correlation among longitudinally measured intake levels of cholesterol, total fat, dietary fiber, and energy with all-cause mortality using US National Health and Nutrition Examination Survey linked to the National Death Index mortality data. We compared MJM with the mean method that assessed intake levels as the mean of a person's intake. RESULTS: The estimates from MJM were larger than those from the mean method. For instance, the logarithm of hazard ratio for dietary fiber intake increased by 14 times (from -0.04 to -0.60) with the MJM method. This translated into a relative hazard of death of 0.55 (95% credible interval: 0.45, 0.65) with the MJM and 0.96 (95% credible interval: 0.95, 0.97) with the mean method. CONCLUSIONS: MJM adjusts for random measurement error and flexibly addresses correlations and skewness among longitudinal measures of dietary intake when estimating their associations with death.

Weight change across adulthood and accelerated biological aging in middle-aged and older adults.

BACKGROUND: Little is known regarding the association between weight change and accelerated aging. OBJECTIVES: This study aimed to estimate the influence of weight change across adulthood on biological aging acceleration in middle-aged and older adults in the United States. METHODS: We used data of 5553 adults (40-84 y) from the National Health and Nutrition Examination Survey 1999-2010. Weight change patterns (i.e., stable normal, maximal overweight, obese to nonobese, nonobese to obese, and stable obese) and absolute weight change groups across adulthood (i.e., from young to middle adulthood, young to late adulthood, and middle to late adulthood) were defined. A biological aging measure (i.e., phenotypic age acceleration [PhenoAgeAccel]) at late adulthood was calculated. Survey analysis procedures with the survey weights were performed. RESULTS: Across adulthood, maximal overweight, nonobese to obese, and stable obesity were consistently associated with higher PhenoAgeAccel. For instance, from young to middle adulthood, compared with participants who had stable normal weight, participants experiencing maximal overweight, moving from the nonobese to obese, and maintaining obesity had 1.71 (standard error [SE], 0.21; P < 0.001), 3.62 (SE, 0.28; P < 0.001), and 6.61 (SE, 0.58; P < 0.001) higher PhenoAgeAccel values, respectively. From young to middle adulthood, relative to absolute weight loss or gain of <2.5 kg, weight loss of ≥2.5 kg was marginally associated with lower PhenoAgeAccel (P = 0.054), whereas an obese to nonobese pattern from middle to late adulthood was associated with higher PhenoAgeAccel (P < 0.001). CONCLUSIONS: Maximal overweight, nonobese to obese, and stable obesity across adulthood, as well as an obese to nonobese pattern from middle to late adulthood, were associated with accelerated biological aging. In contrast, weight loss from young to middle adulthood was associated with decelerated biological aging. The findings highlight the potential role of weight management across adulthood for aging. Monitoring weight fluctuation may help identify the population at high risk of accelerated aging.

The impact of facility characteristics on Merkel cell carcinoma outcomes: A retrospective cohort study.

BACKGROUND: Previous work has suggested that facility-level characteristics, such as case volume and academic affiliation, are associated with patient survival for rare malignancies. Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with high mortality and rising incidence. The effect of facility characteristics on MCC outcomes is not yet established. OBJECTIVE: We aimed to investigate whether facility academic affiliation or case volume was associated with MCC patient survival. METHODS: We conducted a retrospective cohort analysis of US adult MCC cases diagnosed during 2004-2014 in the National Cancer Database. RESULTS: Both facility academic affiliation (P < .001) and case volume (P < .001) were significantly associated with patient survival. The 5-year survival of patients treated at academic facilities was 63.0% (standard error [SE] 1.7) and that of a propensity score- matched cohort of patients treated at nonacademic facilities was 53.4% (SE 1.9). The 5-year survival of patients treated at high-case volume facilities was 67.4% (SE 2.1) and that of a propensity score-matched cohort of patients treated at low- and intermediate-case volume facilities was 58.6% (SE 2.0). LIMITATIONS: Disease-specific survival and local recurrence data were not available. CONCLUSION: Treatment of MCC at academic and high-volume centers is associated with significantly improved patient survival. Further studies evaluating comorbidities and disease-specific survival are needed to establish whether experienced centers have improved outcomes in MCC treatment.

A three-part regression calibration to handle excess zeroes, skewness and heteroscedasticity in adjusting for measurement error in dietary intake data.

Exposure measurement error (ME) biases exposure-outcome associations. Calibration dietary intake data used in the regression calibration (RC) response to adjust for ME are usually right-skewed, heteroscedastic and with excess zeroes. We proposed three-part RC models to handle these distributional complexities simultaneously, while correcting for ME in fish intake. We applied data from the National Health and Nutrition Examination Survey (NHANES), where long-term intake was measured with food frequency questionnaire (FFQ) in the main study and short-term intake with 24-hour recall (24HR) in the calibration study. In the three-part RC models, never consumers were modelled using two approaches: a zero distribution (Three-part RC-het-det), and logistic distribution (Three-part RC-het-prob); heteroscedasticity using an exponential distribution and right-skewness using generalized gamma distribution. The proposed models were compared with two-part RC model that ignores never consumers, and with methods that estimate intakes using FFQ and 24HR. The models were evaluated in a simulation study. With NHANES data, mean increase in the mercury level (in µ g / L ) was 1.20 using FFQ-method, 0.4 using 24HR-method, 1.87 using two-part RC and 2.02 using three-part RC-het-prob method. The three-part RC estimated the association with the least bias in the simulation study.

Modeling of correlated cognitive function and functional disability outcomes with bounded and missing data in a longitudinal aging study.

Longitudinal studies of correlated cognitive and disability outcomes among older adults are characterized by missing data due to death or loss to follow-up from deteriorating health conditions. The Mini-Mental State Examination (MMSE) score for assessing cognitive function ranges from a minimum of 0 (floor) to a maximum of 30 (ceiling). To study the risk factors of cognitive function and functional disability, we propose a shared parameter model to handle missingness, correlation between outcomes, and the floor and ceiling effects of the MMSE measurements. The shared random effects in the proposed model handle missingness (either missing at random or missing not at random) and correlation between these outcomes, while the Tobit distribution handles the floor and ceiling effects of the MMSE measurements. We used data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) and a simulation study. By ignoring the MMSE floor and ceiling effects in the analyses of the CLHLS, the association of systolic blood pressure with cognitive function was not significant and the association of age with cognitive function was lower by 16.6% (from -6.237 to -5.201). By ignoring the MMSE floor and ceiling effects in the simulation study, the relative bias in the estimated association of female gender with cognitive function was 43 times higher (from -0.01 to -0.44). The estimated associations obtained with data missing at random were smaller than those with data missing not at random, demonstrating how the missing data mechanism affects the analytic results. Our work underscores the importance of proper model specification in longitudinal analysis of correlated outcomes subject to missingness and bounded values.

Persons with dementia and informal caregivers prioritizing care: A mixed-methods study.

INTRODUCTION: More persons with dementia are residing in the community as many countries shift from residential care to home and community care. Although there are many forms of care and support available to avoid crisis situations and prolong community living, it remains unclear how these are valued by community-dwelling persons with dementia and their informal caregivers. Understanding perspectives of persons with dementia and informal caregivers on care characteristics is a vital step in valuing care services. This study aims to prioritize care characteristics for community-dwelling persons with dementia and informal caregivers with the use of an innovative mixed-methods approach. METHODS: Six mixed focus groups were conducted in The Netherlands with persons with dementia (n = 23) and informal caregivers (n = 20), including a quantitative ranking exercise that prioritized seven care and support characteristics from "most important" to "least important," followed by a group discussion about the prioritization. Audio recordings were transcribed and analyzed using thematic analysis. RESULTS: The ranking exercise and discussion showed that persons with dementia favored in-home care, help with daily activities, and social activities, whereas informal caregivers favored social activities, information about dementia, navigating the health care system, and emotional support. DISCUSSION: Persons with dementia prioritized day-to-day activities, whereas informal caregivers preferred assistance with organizing care and coping with caregiving. This study created a method to capture the care preferences of persons with dementia and informal caregivers.

A machine-learning modified CART algorithm informs Merkel cell carcinoma prognosis.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with a high mortality rate. MCC staging is currently based on tumour primary size, clinical detectability of lymph node metastases, performance of a lymph node biopsy, and presence of distant metastases. OBJECTIVE: We aimed to use a modified classification and regression tree (CART) algorithm using available data points in the National Cancer Database (NCDB) to elucidate novel prognostic factors for MCC. METHODS: Retrospective cohort study of the NCDB and Surveillance, Epidemiology, and End Results (SEER) registries. Cases from the NCDB were randomly assigned to either the training or validation cohorts. A modified CART algorithm was created with data from the training cohort and used to identify prognostic groups that were validated in the NCDB validation and SEER cohorts. RESULTS: A modified CART algorithm using tumour variables available in the NCDB identified prognostic strata as follows: I: local disease, II: ≤3 positive nodes, III: ≥4 positive nodes, and IV: presence of distant metastases. Three-year survival for these groups in the NCDB validation cohort were 81.2% (SE: 1.7), 59.6% (SE: 3.0), 38.0% (SE: 6.0), and 20.2% (SE: 7.0), respectively. These strata were exhibited greater within-group homogeneity than AJCC groups and were more predictive of survival. CONCLUSIONS: Risk-stratified grouping of MCC patients incorporating positive lymph node count were strongly predictive of survival and demonstrated a high degree of within-group homogeneity and survival prediction. Incorporation of positive lymph node count within overall staging or sub-staging may help to improve future MCC staging criteria.

CRcoder: An Interactive Web Application and SAS Macro to Support Personalized Clinical Decisions.

INTRODUCTION: Electronic health care data offer an opportunity to improve clinical decision making through advanced statistical analyses of longitudinal observations. OBJECTIVE: To describe a Web application and SAS/STAT macro (SAS Institute Inc, Cary, NC) for computing joint models to estimate the typical and personalized risk of 2 concurrent binary outcomes. METHODS: Features of the Web application design include uploading longitudinal files formatted with constant or time-varying covariates, specification of 2 binary outcomes, specification of a propensity model for treatment, and joint and separate models of the outcomes. In addition we designed an SAS macro for conducting the analysis. Fitting of joint and separate statistical models was implemented using a model specified in the Web application, with subsequent processing by the SAS macro. To illustrate the fitting of models, a sample of older adults with comorbid hypertension and chronic obstructive pulmonary disease from the Medical Expenditure Panel Survey was created to examine the association between polypharmacy (use of ≥ 5 medication classes) and limitations in social activities and mobility. RESULTS: Relative to separate models, the joint models typically estimated attenuated associations between explanatory variables and the 2 outcomes with smaller standard errors. These joint models yielded estimates of personalized concurrent risk and typical concurrent risk. DISCUSSION: Clinical decision making based on electronic health data can be improved using joint modeling to generate an individual's probability of concurrent risk. CONCLUSION: This user-friendly software performs the advanced statistical analyses needed to estimate typical and personalized concurrent risks.

Comparison of Survival After Mohs Micrographic Surgery vs Wide Margin Excision for Early-Stage Invasive Melanoma.

IMPORTANCE: Melanoma is among the most common malignant neoplasms in the United States, with 91 270 cases estimated to be diagnosed in 2018. Since 2012, Mohs micrographic surgery (MMS) has gained popularity in the treatment of melanoma in situ. Although current guidelines for invasive melanoma without nodal metastases recommend surgery with wide margin excision (WME), use of MMS for this disease has increased as well, particularly in early stages. How the survival outcomes after each procedure compare with one another for early-stage invasive melanoma is unknown to date. OBJECTIVE: To evaluate overall survival of patients with stage I melanoma defined by the American Joint Committee on Cancer Cancer Staging Manual, 8th edition (AJCC-8) after MMS vs traditional WME. DESIGN, SETTING, AND ANALYSIS: This retrospective cohort study includes all patients with AJCC-8 stage I melanoma who underwent MMS or WME in the National Cancer Database with a diagnosis from January 1, 2004, through December 31, 2014. The National Cancer Database includes all reportable cases from Commission on Cancer-accredited facilities and represents approximately 50% of all newly diagnosed melanoma cases in the United States. Data were analyzed from November 13, 2018, through June 9, 2019. EXPOSURES: MMS vs WME. MAIN OUTCOMES AND MEASURES: Overall survival evaluated using multivariable Cox proportional hazards regression analysis. RESULTS: A total of 70 319 eligible patients (52.3% male and 47.7% female; median [SD] age, 57.0 [16.2] years) were identified, including 67 085 treated with WME and 3234 treated with MMS. Multivariable Cox proportional hazards regression survival analysis controlling for clinical and tumor factors revealed that treatment with MMS was associated with a modest improvement in overall survival relative to WME (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97). Propensity score-matched analysis of cohorts of patients treated with MMS vs WME also found modestly improved survival for those treated with MMS (HR, 0.82; 95% CI, 0.68-0.98). Academic facilities were more likely to use MMS than nonacademic facilities (odds ratio, 2.03; 95% CI, 1.88-2.18). CONCLUSIONS AND RELEVANCE: These findings suggest that Mohs surgery may provide an alternative approach to traditional WME for appropriately selected cases of AJCC-8 stage I melanoma without compromising patient survival.

Personalized and typical concurrent risk of limitations in social activity and mobility in older persons with multiple chronic conditions and polypharmacy.

PURPOSE: We define personalized concurrent risk (PCR) as the subject-specific probability of an index outcome within a defined interval of time, while currently at risk for a separate outcome, where the outcomes are not mutually exclusive and can be jointly modeled with a shared random intercept. We further define typical concurrent risk as the risk obtained by setting the random intercept to null. METHODS: Drawing data from the Medical Expenditure Panel Survey (cohorts 2008-2013), we jointly model limitations in social activity and mobility over two years among older community-dwelling persons with both hypertension and chronic obstructive pulmonary disease. The joint model uses inverse probability of treatment weighting based on each participant's baseline propensity of polypharmacy (≥5 classes of medication). RESULTS: Even among participants with the same covariates, older persons with multiple chronic conditions exhibit wide-ranging heterogeneity of the treatment effect from polypharmacy, a risk factor for negative health outcomes among older persons. The magnitude of the PCRs is dominated by the value of the subject-specific random effect. CONCLUSIONS: Estimates of PCR and typical concurrent risk can be calculated from national or institutional data sets and may facilitate the practice of personalized care for older patients with multiple chronic conditions.

Substance P and fibrotic diseases.

Substance P (SP) is an undecapeptide encoding the tachykinin 1 (TAC1) gene and belongs to the tachykinin family. SP is widely distributed in the central nervous system and the peripheral nervous system. SP is also produced by nonneuronal cells, such as inflammatory cells and endothelial cells. The biological activities of SP are mainly regulated through the high-affinity neurokinin 1 receptor (NK-1R). The SP/NK-1R system plays an important role in the molecular bases of many human pathophysiologic processes, such as pain, infectious and inflammatory diseases, and cancer. In addition, this system has been implicated in fibrotic diseases and processes such as wound healing, myocardial fibrosis, bowel fibrosis, myelofibrosis, renal fibrosis, and lung fibrosis. Recently, studies have shown that SP plays an important role in liver fibrosis and that NK-1R antagonists can inhibit the progression of fibrosis. NK-1R receptor antagonists could provide clinical solutions for fibrotic diseases. This review summarizes the structure and function of SP and its involvement in fibrotic diseases.

Associations of food groups and cardiometabolic and inflammatory biomarkers: does the meal matter?

Increased attention has been paid to circadian patterns and how predisposition to metabolic disorders can be affected by meal timing. Currently, it is not clear which role can be attributed to the foods selected at meals. On a cross-sectional sub-cohort study (815 adults) within the European Prospective Investigation into Cancer and Nutrition-Potsdam study, we investigated whether the same foods (vegetables, fruits, refined grains, whole grains, red and processed meats) eaten at different meals (breakfast, lunch or dinner) show different associations with biomarkers of cardiometabolic risk. Meal-specific usual intakes were calculated from multiple 24-h dietary recalls. Multivariable-adjusted linear regression models showed that intake of vegetables at breakfast was associated with lower LDL-cholesterol (-0·37 mmol/l per 50 g; 95 % CI -0·61, -0·12) and vegetables at dinner was associated with higher HDL-cholesterol (0·05 mmol/l per 50 g; 95 % CI 0, 0·10). Fruit intake at breakfast was associated with lower glycated Hb (HbA1c) (-0·06 % per 50 g; 95 % CI -0·10, -0·01) and fruits at dinner with lower C-reactive protein (CRP) (-0·21 mg/l per 50 g; 95 % CI -0·42, -0·01). Red and processed meat intake at breakfast was associated with higher HbA1c (0·25 % per 50 g; 95 % CI 0·05, 0·46) and CRP (0·76 mg/l per 50 g; 95 % CI 0·15, 1·36). Our results suggest that by preferring fruits and vegetables and avoiding red and processed meats at specific meals (i.e. breakfast and dinner), cardiometabolic profiles and ultimately chronic disease risk could be improved. Lunch seemed to be a less important meal in terms of food-biomarker associations.