Association between cancer and dementia risk in the UK Biobank: evidence of diagnostic bias.

Epidemiological studies have identified an inverse association between cancer and dementia. Underlying methodological biases have been postulated, yet no studies have systematically investigated the potential for each source of bias within a single dataset. We used the UK Biobank to compare estimates for the cancer-dementia association using different analytical specifications designed to sequentially address multiple sources of bias, including competing risk of death, selective survival, confounding bias, and diagnostic bias. We included 140,959 UK Biobank participants aged ≥ 55 without dementia before enrollment and with linked primary care data. We used cancer registry data to identify cancer cases prevalent before UK Biobank enrollment and incident cancer diagnosed after enrollment. We used Cox models to evaluate associations of prevalent and incident cancer with all-cause dementia, Alzheimer's disease (AD), and vascular dementia. We used time-varying models to evaluate diagnostic bias. Over a median follow-up of 12.3 years, 3,310 dementia cases were diagnosed. All-site incident cancer was positively associated with all-cause dementia incidence (hazard ratio [HR] = 1.14, 95% CI: 1.02-1.29), but prevalent cancer was not (HR = 1.04, 95% CI: 0.92-1.17). Results were similar for vascular dementia. AD was not associated with prevalent or incident cancer. Dementia diagnosis was substantially elevated in the first year after cancer diagnosis (HR = 1.83, 95% CI: 1.42-2.36), after which the association attenuated to null, suggesting diagnostic bias. Following a cancer diagnosis, health care utilization or cognitive consequences of diagnosis or treatment may increase chance of receiving a dementia diagnosis, creating potential diagnostic bias in electronic health records-based studies.

Association of Genetic Variants Linked to Late-Onset Alzheimer Disease With Cognitive Test Performance by Midlife.

Importance: Identifying the youngest age when Alzheimer disease (AD) influences cognition and the earliest affected cognitive domains will improve understanding of the natural history of AD and approaches to early diagnosis. Objective: To evaluate the age at which cognitive differences between individuals with higher compared with lower genetic risk of AD are first apparent and which cognitive assessments show the earliest difference. Design, Setting, and Participants: This cross-sectional study used data from UK Biobank participants of European genetic ancestry, aged 40 years or older, who contributed genotypic and cognitive test data from January 1, 2006, to December 31, 2015. Data analysis was performed from March 10, 2020, to January 4, 2022. Exposure: The AD genetic risk score (GRS), which is a weighted sum of 23 single-nucleotide variations. Main Outcomes and Measures: Seven cognitive tests were administered via touchscreen at in-person visits or online. Cognitive domains assessed included fluid intelligence, episodic memory, processing speed, executive functioning, and prospective memory. Multiple cognitive measures were derived from some tests, yielding 32 separate measures. Interactions between age and AD-GRS for each of the 32 cognitive measures were tested with linear regression using a Bonferroni-corrected P value threshold. For cognitive measures with significant evidence of age by AD-GRS interaction, the youngest age of interaction was assessed with new regression models, with nonlinear specification of age terms. Models with youngest age of interaction from 40 to 70 years, in 1-year increments, were compared, and the best-fitting model for each cognitive measure was chosen. Results across cognitive measures were compared to determine which cognitive indicators showed earliest AD-related change. Results: A total of 405 050 participants (mean [SD] age, 57.1 [7.9] years; 54.1% female) were included. Sample sizes differed across cognitive tests (from 12 455 to 404 682 participants). The AD-GRS significantly modified the association with age on 13 measures derived from the pairs matching (range in difference in mean cognition per decade increase in age for 1-SD higher AD-GRS, 2.5%-11.5%), symbol digit substitution (range in difference in mean cognition per decade increase in age for 1-SD higher AD-GRS, 2.0%-5.8%), and numeric memory tests (difference in mean cognition per decade increase in age for 1-SD higher AD-GRS, 8.8%) (P = 1.56 × 10-3). Best-fitting models suggested that cognitive scores of individuals with a high vs low AD-GRS began to diverge by 56 years of age for all 13 measures and by 47 years of age for 9 measures. Conclusions and Relevance: In this cross-sectional study, by early midlife, subtle differences in memory and attention were detectable among individuals with higher genetic risk of AD.

Incidence and predictors of preterm neonatal mortality at Mbarara Regional Referral Hospital in South Western Uganda.

INTRODUCTION: Preterm neonatal mortality contributes substantially to the high neonatal mortality globally. In Uganda, preterm neonatal mortality accounts for 31% of all neonatal deaths. Previous studies have shown variability in mortality rates by healthcare setting. Also, different predictors influence the risk of neonatal mortality in different populations. Understanding the predictors of preterm neonatal mortality in the low-resource setting where we conducted our study could guide the development of interventions to improve outcomes for preterm neonates. We thus aimed to determine the incidence and predictors of mortality among preterm neonates born at Mbarara Regional Referral Hospital (MRRH) in South Western Uganda. METHODS: We prospectively enrolled 538 live preterm neonates born at MRRH from October 2019 to September 2020. The neonates were followed up until death or 28 days, whichever occurred first. We used Kaplan Meier survival analysis to describe preterm neonatal mortality and Cox proportional hazards regression to assess predictors of preterm neonatal mortality over a maximum of 28 days of follow up. RESULTS: The cumulative incidence of preterm neonatal mortality was 19.8% (95% C.I: 16.7-23.5) at 28 days from birth. Birth asphyxia (adjusted hazard ratio [aHR], 14.80; 95% CI: 5.21 to 42.02), not receiving kangaroo mother care (aHR, 9.50; 95% CI: 5.37 to 16.78), delayed initiation of breastfeeding (aHR, 9.49; 95% CI: 2.84 to 31.68), late antenatal care (ANC) booking (aHR, 1.81 to 2.52; 95% CI: 1.11 to 7.11) and no ANC attendance (aHR, 3.56; 95% CI: 1.51 to 8.43), vaginal breech delivery (aHR, 3.04; 95% CI: 1.37 to 5.18), very preterm births (aHR, 3.17; 95% CI: 1.24 to 8.13), respiratory distress syndrome (RDS) (aHR, 2.50; 95% CI: 1.11 to 5.64) and hypothermia at the time of admission to the neonatal unit (aHR, 1.98; 95% CI: 1.18 to 3.33) increased the risk of preterm neonatal mortality. Attending more than 4 ANC visits (aHR, 0.35; 95% CI: 0.12 to 0.96) reduced the risk of preterm neonatal mortality. CONCLUSIONS: We observed a high cumulative incidence of mortality among preterm neonates born at a low-resource regional referral hospital in Uganda. The predictors of mortality among preterm neonates were largely modifiable factors occurring in the prenatal, natal and postnatal period (lack of ANC attendance, late ANC booking, vaginal breech delivery, birth asphyxia, respiratory distress syndrome, and hypothermia at the time of admission to the neonatal unit, not receiving kangaroo mother care and delayed initiation of breastfeeding). These findings suggest that investment in and enhancement of ANC attendance, intrapartum care, and the feasible essential newborn care interventions by providing the warm chain through kangaroo mother care, encouraging early initiation of breastfeeding, timely resuscitation for neonates when indicated and therapies reducing the incidence and severity of RDS could improve outcomes among preterm neonates in this setting.

Cognitive differences associated with HIV serostatus and antiretroviral therapy use in a population-based sample of older adults in South Africa.

Previous clinical studies have reported adverse cognitive outcomes for people living with HIV (PLWH), but there are no population-based studies comparing cognitive function between older PLWH and comparators without HIV in sub-Saharan Africa. We analyzed baseline data of 40 + years-old participants in "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa" (HAALSI) cohort. We measured cognition using a battery of conventional instruments assessing orientation, immediate- and delayed-recall, and numeracy (N = 4560), and the Oxford Cognitive Screen [OCS]-Plus, a novel instrument for low-literacy populations, assessing memory, language, visual-spatial ability, and executive functioning (N = 1997). Linear regression models comparing cognitive scores between participants with and without HIV were adjusted for sex, education, age, country of birth, father's occupation, ever-consumed alcohol, and asset index. PLWH scored on average 0.06 (95% CI 0.01-0.12) standard deviation (SD) units higher on the conventional cognitive function measure and 0.02 (95% CI - 0.07 to 0.04) SD units lower on the OCS-Plus measure than HIV-negative participants. We found higher cognitive function scores for PLWH compared to people without HIV when using a conventional measure of cognitive function but not when using a novel instrument for low-literacy settings.

HIV Status and Antiretroviral Therapy as Predictors of Disability among Older South Africans: Overall Association and Moderation by Body Mass Index.

Objectives: Among older people living with HIV (PLWH) and comparable individuals without HIV, we evaluated whether associations of HIV and antiretroviral therapy (ART) with disability depend on body mass index (BMI). Methods: We analyzed 4552 participants in the "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa." (HAALSI) We compared prevalence of disability (≥1 impairment in basic activities of daily living) by HIV status, ART use, and BMI category, adjusting for age, sex, education, father's occupation, country of origin, lifetime alcohol use, and primary health-care utilization. Results: Among PLWH, those underweight had 9.8% points (95% confidence interval (CI): 1.2 to 18.4) higher prevalence of disability than those with normal BMI. Among ART users, those underweight had 11.9% points (95% CI: 2.2 to 21.6) higher prevalence of disability than those with normal BMI. Conclusions: We found no evidence that weight improvement associated with ART use is likely to increase disability.

Vital Signs Data and Probability of Hospitalization, Transfer to Another Facility, or Emergency Department Death Among Adults Presenting for Medical Illnesses to the Emergency Department at a Large Urban Hospital in the United States.

BACKGROUND: Vital signs are routinely measured from patients presenting to the emergency department (ED), but how they predict clinical outcomes like hospitalization is unclear. OBJECTIVES: To evaluate how pulse, respiratory rate, temperature, and mean arterial pressure (MAP) at ED presentation predicted probability of hospitalization, transfer to another center, or death in the ED (as a composite outcome) vs. other ED dispositions (discharged, eloped, and sent to observation or labor and delivery), and to assess the performance of different modeling strategies, specifically, models including flexible forms of vital signs (as restricted cubic splines) vs. linear forms (untransformed numeric variables) vs. binary transformations (vital signs values categorized simply as normal or abnormal). METHODS: We analyzed the data of 12,660 adults presenting for medical illnesses to the ED at the University of California, San Francisco Medical Center, San Francisco, California, throughout 2014. We used flexible forms of vital signs data at presentation (pulse, temperature, respiratory rate, and MAP) to predict ED disposition (admitted, transferred, or died, vs. other ED dispositions) and to guide binary transformation of vital signs. We compared performance of models including vital signs as flexible terms, binary transformations, or linear terms. RESULTS: A model including flexible forms of vital signs and age to predict the outcome had good calibration and moderate discrimination (C-statistic = 71.2, 95% confidence interval [CI] 70.0-72.4). Binary transformation of vital signs had minimal impact on performance (C-statistic = 71.3, 95% CI 70.2-72.5). A model with linear forms was less calibrated and had slightly reduced discrimination (C-statistic = 70.3, 95% CI 69.1-71.5). CONCLUSIONS: Findings suggest that flexible modeling of vital signs may better reflect their association with clinical outcomes. Future studies to evaluate how vital signs could assist clinical decision-making in acute care settings are suggested.

A comparison of the Full Outline of Unresponsiveness (FOUR) and Glasgow Coma Scale (GCS) Scores in Predicting Mortality Among Patients with Reduced Level of Consciousness in Uganda.

BACKGROUND: Reduced level of consciousness (LOC) is a common cause of presentation among acutely ill adults in sub-Saharan Africa and is associated with high rates of mortality. Although the Full Outline of Unresponsiveness (FOUR) score is often used in clinical practice, its utility in predicting mortality has not been assessed in the region. METHODS: We prospectively enrolled adults presenting with reduced LOC to Mbarara Regional Referral Hospital in Uganda. We recorded clinical and laboratory data and performed the FOUR and Glasgow Coma Scale (GCS) scores at admission. We used survival analysis, fit Cox proportional hazards regression models to assess the predictive properties of the two scores, and compared their performance using area under the receiver operating characteristic curve (AUROC). RESULTS: We enrolled 359 patients, mean (SD) age was 51 (22.2) years, and 58% (210/359) were male. The median (interquartile range) admission FOUR and GCS scores were 13.0 (3.0-16.0) and 10.0 (3.0-14.0), respectively. Subjects with the FOUR score of 0-11 had a 2.6-fold higher hazard of 30-day mortality (HR 2.6, 95% CI 1.9-3.6, p < 0.001) compared to those with the score of 12-16. Those with the GCS score of 3-8 had a 2.7-fold higher hazard of 30-day mortality (HR 2.7, 95% CI 2.0-3.8, p < 0.001) compared to those with the score of 9-15. The AUROC (95% CI) for the FOUR score and GCS score was 0.68 (0.62-0.73) and 0.67 (0.62-0.73), respectively (p = 0.825). CONCLUSIONS: The FOUR score is comparable to the GCS score in predicting mortality in Uganda. Our findings support the introduction of the FOUR score in guiding the management of patients with reduced LOC in sub-Saharan Africa.

Integrated delivery of antiretroviral treatment and pre-exposure prophylaxis to HIV-1 serodiscordant couples in East Africa: a qualitative evaluation study in Uganda.

INTRODUCTION: Serodiscordant couples are a priority population for delivery of new HIV prevention interventions in Africa. An integrated strategy of delivering time-limited, oral pre-exposure prophylaxis (PrEP) to uninfected partners in serodiscordant couples as a bridge to long-term antiretroviral treatment (ART) for infected partners has been implemented in East Africa, nearly eliminating new infections. We conducted a qualitative evaluation of the integrated strategy in Uganda, to better understand its success. METHODS: Data collection consisted of 274 in-depth interviews with 93 participating couples, and 55 observations of clinical encounters between couples and healthcare providers. An inductive content analytic approach aimed at understanding and interpreting couples' experiences of the integrated strategy was used to examine the data. Analysis sought to characterize: (1) key aspects of services provided; (2) what the services meant to recipients; and (3) how couples managed the integrated strategy. Themes were identified in each domain, and represented as descriptive categories. Categories were grouped inductively into more general propositions based on shared content. Propositions were linked and interpreted to explain "why the integrated strategy worked." RESULTS: Couples found "couples-focused" services provided through the integrated strategy strengthened partnered relationships threatened by the discovery of serodiscordance. They saw in services hope for "getting help" to stay together, turned joint visits to clinic into opportunities for mutual support, and experienced counselling as bringing them closer together. Couples adopted a "couples orientation" to the integrated strategy, considering the health of partners as they made decisions about initiating ART or accepting PrEP, and devising joint approaches to adherence. A couples orientation to services, grounded in strengthened partnerships, may have translated to greater success in using antiretrovirals to prevent HIV transmission. CONCLUSIONS: Various strategies for delivering antiretrovirals for HIV prevention are being evaluated. Understanding how and why these strategies work will improve evaluation processes and strengthen implementation platforms. We highlight the role of service organization in shaping couples' experiences of and responses to ART and PrEP in the context of the integrated strategy. Organizing services to promote positive care experiences will strengthen delivery and contribute to positive outcomes as antiretrovirals for prevention are rolled out.

Alcohol Types and HIV Disease Progression Among HIV-Infected Drinkers Not Yet on Antiretroviral Therapy in Russia and Uganda.

In HIV-infected drinkers, alcohol types more likely to cause inflammation could plausibly increase the risk of HIV disease progression. We therefore assessed the association between alcohol type and plasma HIV RNA level (HIV viral load) among HIV-infected drinkers not on antiretroviral therapy (ART) in Russia and Uganda. We analyzed the data of participants from cohorts in Russia and Uganda and assessed their HIV viral load at enrollment by the alcohol type predominantly consumed. We defined predominant alcohol type as the alcohol type contributing >50% of total alcohol consumption in the 1 month (Russia) or 3 months (Uganda) prior to enrollment. Using multiple linear regression, we compared log10 HIV viral load by predominant alcohol type, controlling for age, gender, socioeconomic status, total number of standard drinks, frequency of drinking ≥6 drinks/occasion, and in Russia, history of injection drug use. Most participants (99.2% of 261 in Russia and 98.9% of 352 in Uganda) predominantly drank one alcohol type. In Russia, we did not find evidence for differences in viral load levels between drinkers of fortified wine (n = 5) or hard liquor (n = 49), compared to drinkers of beer/low-ethanol-content cocktails (n = 163); however, wine/high-ethanol-content cocktail drinkers (n = 42) had higher mean log10 viral load than beer/low-ethanol-content cocktail drinkers (ß = 0.38, 95% CI 0.07-0.69; p = 0.02). In Uganda, we did not find evidence for differences in viral load levels between drinkers of locally-brewed beer (n = 41), commercially-distilled spirits (n = 38), or locally-distilled spirits (n = 43), compared to drinkers of commercially-made beer (n = 218); however, wine drinkers (n = 8) had lower mean log10 HIV viral load (ß = -0.65, 95% CI -1.36 to 0.07, p = 0.08), although this did not reach statistical significance. Among HIV-infected drinkers not yet on ART in Russia and Uganda, we observed an association between the alcohol type predominantly consumed and the HIV viral load level in the Russia sample. These exploratory results suggest that, in addition to total number of drinks and drinking patterns, alcohol type might be a dimension of alcohol use that merits examination in studies of HIV and alcohol related outcomes.

Factors influencing use of long-acting versus short-acting contraceptive methods among reproductive-age women in a resource-limited setting.

BACKGROUND: Unplanned pregnancy remains a common problem in many resource-limited settings, mostly due to limited access to modern family planning (FP) services. In particular, use of the more effective long-acting reversible contraceptive (LARC) methods (i.e., intrauterine devices and hormonal implants) remains low compared to the short-acting methods (i.e., condoms, hormonal pills, injectable hormones, and spermicides). Among reproductive-age women attending FP and antenatal care clinics in Uganda, we assessed perceptions and practices regarding the use of modern contraceptive methods. We specifically aimed to evaluate factors influencing method selection. METHODS: We performed a mixed-methods cross-sectional study, in which we administered structured interviews to 180 clients, and conducted 4 focus group discussions (FGDs) with 36 clients and 8 in-depth personal qualitative interviews with health service providers. We summarized quantitative data and performed latent content analysis on transcripts from the FGDs and qualitative interviews. RESULTS: The prevalence of ever use for LARC methods was 23%. Method characteristics (e.g., client control) appeared to drive method selection more often than structural factors (such as method availability) or individual client characteristics (such as knowledge and perceptions). The most common reasons for choosing LARC methods were: longer protection; better child-spacing; and effectiveness. The most common reasons for not choosing LARC methods included requiring a client-controlled method and desiring to conceive in the near future. The most common reasons for choosing short-acting methods were ease of access; lower cost; privacy; perceived fewer side effects; and freedom to stop using a method without involving the health provider. The personal characteristics of clients, which appeared to be important were client knowledge and number of children. The structural factor which appeared to be important was method availability. CONCLUSIONS: Our results suggest that interventions to improve uptake of LARC among reproductive age women in this setting should consider: incorporating desired method-characteristics into LARC methods; targeted promotion and supply of LARC; and increased counselling, sensitization, and education.

D-Dimer Levels and Traditional Risk Factors Are Associated With Incident Hypertension Among HIV-Infected Individuals Initiating Antiretroviral Therapy in Uganda.

OBJECTIVES: We sought to describe blood pressure (BP) changes after antiretroviral therapy (ART) initiation and evaluate the association of markers of inflammation with incident hypertension in a cohort of HIV-infected individuals in Uganda. METHODS: We used mixed effects linear regression to model changes in systolic BP over time among a cohort of HIV-infected individuals initiating ART in Uganda. After exclusion of participants with preexisting hypertension, we identified participants with normal BP throughout follow-up (controls) and those with elevated BP on ≥3 consecutive visits (cases). Before ART initiation, participants had testing for interleukin 6, kynurenine/tryptophan ratio, lipopolysaccharide, soluble CD14, soluble CD163, and D-dimer and those with viral suppression at 6 months during ART had repeat tests. We fit logistic regression models to estimate associations between biomarkers and risk of incident hypertension. RESULTS: In the entire cohort, systolic BP increased by 9.6 mm Hg/yr (95% CI: 7.3 to 11.8) in the first 6 months of ART, then plateaued. Traditional factors: male gender (adjusted odds ratio (AOR) 2.76, 95% CI: 1.34 to 5.68), age (AOR 1.09, 95% CI: 1.04 to 1.13), overweight (AOR 4.48, 95% CI: 1.83 to 10.97), and a CD4 count <100 cells (AOR 3.08, 95% CI: 1.07 to 8.89) were associated with incident hypertension. After adjusting for these, D-dimer levels at month 6 were inversely associated with incident hypertension (AOR 0.61, 95% CI: 0.37 to 0.99). Although not significant, similar associations were seen with sCD14 and kynurenine/tryptophan ratio. CONCLUSION: BP increases early after ART initiation in Ugandans. Traditional risk factors, rather than immune activation, were associated with incident hypertension in this population.

Alcohol Consumption in Ugandan HIV-Infected Household-Brewers Versus Non-Brewers.

The brewing of alcohol in Ugandan households is common, yet little is known about its relationship with alcohol consumption in HIV-infected individuals. We performed a cross-sectional analysis to assess the association between household brewing and unhealthy alcohol consumption among 387 HIV-infected adults in a prospective study examining the association between alcohol consumption and HIV-disease progression. Household brewing was defined as participants reporting that they or a household member home-brewed alcohol. Logistic regression was used to assess the association between household brewing and unhealthy alcohol consumption, defined as phosphatidylethanol (PEth) level ≥50 ng/ml or AUDIT-C (modified to measure the prior 3 months) positive. Sixty-six (17.0 %) participants reported household brewing. Household brewers had higher odds of unhealthy alcohol consumption (AOR 2.27, 95 % CI 1.26-4.12). Among HIV-infected individuals, household brewing was associated with unhealthy alcohol consumption. Interventions to reduce alcohol consumption in this population could target household brewers.

Predictors of dropout from care among HIV-infected patients initiating antiretroviral therapy at a public sector HIV treatment clinic in sub-Saharan Africa.

BACKGROUND: In sub-Saharan Africa (SSA), antiretroviral therapy (ART) can prolong life for HIV-infected patients. However, patients initiating ART, especially in routine treatment programs, commonly dropout from care either due to death or loss to follow-up. METHODS: In a cohort of HIV-infected patients initiating ART at a public sector clinic in Uganda, we assessed predictors of dropout from care (a composite outcome combining death and loss to follow-up). From a large set of socio-demographic, clinical, and laboratory variables routinely collected at ART initiation, we selected those predicting dropout at P <0.1 in unadjusted analyses for inclusion into a multivariable proportional hazards regression model. We then used a stepwise backward selection procedure to identify variables which independently predicted dropout at P <0.05. RESULTS: Data from 5,057 patients were analyzed. The median age was 33 years (IQR 28 to 40) and 27.4% had CD4+ T-cell counts <100 cells/µL at ART initiation. The median duration of follow-up was 24 months (IQR = 14 to 42, maximum follow-up = 64 months). Overall dropout was 26.9% (established cumulative mortality = 2.3%, loss to follow-up = 24.6%), 5.6% were transferred to other service providers, and 67.5% were retained in care. A diagnosis of Kaposi's sarcoma (hazard ratio (HR) = 3.3, 95% CI 2.5 to 4.5); HIV-associated dementia (HR = 2.6, 95% CI 1.5 to 4.6); history of cryptococcosis (HR = 2.2, 95% CI 1.4 to 3.3); and reduced hemoglobin concentration (<11 g/dl versus ≥13.8 g/dl (HR = 1.9, 95% CI 1.6 to 2.2) were strong predictors of dropout. Other independent predictors of dropout were: year of ART initiation; weight loss ≥10%; reduced total lymphocyte count; chronic diarrhea; male sex; young age (≤28 years); and marital status. CONCLUSIONS: Among HIV-infected patients initiating ART at a public sector clinic in SSA, biological factors that usually predict death were especially predictive of dropout. As most of the dropouts were lost to follow-up, this observation suggests that many losses to follow-up may have died. Future studies are needed to identify appropriate interventions that may improve both individual-level patient outcomes and outcome ascertainment among HIV-infected ART initiators in this setting.

Simplifications of the mini nutritional assessment short-form are predictive of mortality among hospitalized young and middle-aged adults.

OBJECTIVE: Measuring malnutrition in hospitalized patients is difficult in all settings. I evaluated associations of items in the mini nutritional assessment short-form (MNA-sf), a nutritional-risk screening tool previously validated in the elderly, with malnutrition among hospitalized patients in Uganda. I used results to construct two simplifications of this tool that may be applicable to young and middle-aged adults. METHODS: I assessed the association of each MNA-sf item with the mid-upper arm circumference (MUAC), a specific measure of malnutrition at appropriate cut-offs. I incorporated only malnutrition-specific items into the proposed simplifications scoring each item according to its association with malnutrition. I assessed numbers classified to different score-levels by the simplifications and, via proportional hazards regression, how the simplifications predicted in-hospital mortality. RESULTS: I analyzed 318 patients (median age 37, interquartile range 27 to 56). Variables making it into the simplifications were: reduced food intake, weight loss, mobility, and either BMI in kg/m(2) (categorized as <16, 16 to 16.9, and ≥17) or MUAC in centimeters (categorized as <16 or <17, 16 to 18.9 or 17 to 19.9, and ≥19 or ≥20 for females and males respectively). Compared to the traditional MNA-sf, the simplifications classified fewer patients as malnourished, yet remained strongly predictive of in-hospital mortality. In the MUAC-incorporating simplification, malnourished patients had 3.8-fold (95% CI 1.9 to 7.8) higher risk of in-hospital death than those not malnourished; adjusting for age, sex, and HIV status. CONCLUSION: The MNA-sf simplifications described may provide an improved measure of malnutrition in hospitalized young and middle-aged adults.

Comparison of Traditional and Novel Self-Report Measures to an Alcohol Biomarker for Quantifying Alcohol Consumption Among HIV-Infected Adults in Sub-Saharan Africa.

BACKGROUND: In Sub-Saharan Africa (SSA), HIV-infected patients may underreport alcohol consumption. We compared self-reports of drinking to phosphatidylethanol (PEth), an alcohol biomarker. In particular, we assessed beverage-type-adjusted fractional graduated frequency (FGF) and quantity frequency (QF) measures of grams of alcohol, novel nonvolume measures, and the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). METHODS: We analyzed cohort entry data from the Biomarker Research of Ethanol Among Those with HIV cohort study (2011 to 2013). Participants were HIV-infected past-year drinkers, newly enrolled into care. Self-report measures included FGF and QF grams of alcohol, the AUDIT-C, number of drinking days, and novel adaptations of FGF and QF methods to expenditures on alcohol, time spent drinking, and symptoms of intoxication. PEth levels were measured from dried blood spots. We calculated Spearman's rank correlation coefficients of self-reports with PEth and bias-corrected bootstrap 95% confidence intervals (CIs) for pairwise differences between coefficients. RESULTS: A total of 209 subjects (57% men) were included. Median age was 30; interquartile range (IQR) 25 to 38. FGF grams of alcohol over the past 90 days (median 592, IQR 43 to 2,137) were higher than QF grams (375, IQR 33 to 1,776), p < 0.001. However, both measures were moderately correlated with PEth: ρ = 0.58, 95% CI 0.47 to 0.66 for FGF grams and 0.54, 95% CI 0.43 to 0.63 for QF grams (95% CI for difference -0.017 to 0.099, not statistically significant). AUDIT-C, time drinking, and a scale of symptoms of intoxication were similarly correlated with PEth (ρ = 0.35 to 0.57). CONCLUSIONS: HIV-infected drinkers in SSA likely underreport both any alcohol consumption and amounts consumed, suggesting the need to use more objective measures like biomarkers when measuring drinking in this population. Although the FGF method may more accurately estimate drinking than QF methods, the AUDIT-C and other nonvolume measures may provide simpler alternatives.

A simple prognostic index based on admission vital signs data among patients with sepsis in a resource-limited setting.

INTRODUCTION: In sub-Saharan Africa, vital signs are a feasible option for monitoring critically ill patients. We assessed how admission vital signs data predict in-hospital mortality among patients with sepsis. In particular, we assessed whether vital signs data can be incorporated into a prognostic index with reduced segmentation in the values of included variables. METHODS: Subjects were patients with sepsis hospitalized in Uganda, who participated in two cohort studies. Using restricted cubic splines of admission vital signs data, we predicted probability of in-hospital death in the development cohort and used this information to construct a simple prognostic index. We assessed the performance of the index in a validation cohort and compared its performance to that of the Modified Early Warning Score (MEWS). RESULTS: We included 317 patients (167 in the development cohort and 150 in the validation cohort). Based on how vital signs predicted mortality, we created a prognostic index giving a score of 1 for: respiratory rates ≥30 cycles/minute; pulse rates ≥100 beats/minute; mean arterial pressures ≥110/<70 mmHg; temperatures ≥38.6/<35.6°C; and presence of altered mental state defined as Glasgow coma score ≤14; 0 for all other values. The proposed index (maximum score = 5) predicted mortality comparably to MEWS. Patients scoring ≥3 on the index were 3.4-fold (95% confidence interval (CI) 1.6 to 7.3, P = 0.001) and 2.3-fold (95% CI 1.1 to 4.7, P = 0.031) as likely to die in hospital as those scoring 0 to 2 in the development and validation cohorts respectively; those scoring ≥5 on MEWS were 2.5-fold (95% CI 1.2 to 5.3, P = 0.017) and 1.8-fold (95% CI 0.74 to 4.2, P = 0.204) as likely to die as those scoring 0 to 4 in the development and validation cohorts respectively. CONCLUSION: Among patients with sepsis, a prognostic index incorporating admission vital signs data with reduced segmentation in the values of included variables adequately predicted mortality. Such an index may be more easily implemented when triaging acutely-ill patients. Future studies using a similar approach may develop indexes that can be used to monitor treatment among acutely-ill patients, especially in resource-limited settings.

Bedside measures of malnutrition and association with mortality in hospitalized adults.

BACKGROUND & AIMS: The impact of malnutrition on the outcomes of hospitalized adults in resource-limited settings such as sub-Saharan Africa (SSA) is not fully described. We aimed to determine the association between malnutrition and mortality in adults admitted to hospital in the resource-limited setting of Southwestern Uganda. METHODS: We performed a cohort study of adults admitted to the medical ward of Mbarara Regional Referral Hospital. Measures of nutritional status included: 1) body mass index (BMI), 2) the mini-nutritional assessment short form (MNA-sf), and 3) mid-upper arm circumference (MUAC). Subjects were followed until death or 30 days from admission. We used proportional hazards regression to assess associations between malnutrition and in-hospital and 30-day mortality. RESULTS: We enrolled 318 subjects. The prevalence of malnutrition was 25-59% depending on the measure used. In-hospital and 30-day mortality were 18% and 37% respectively. In the adjusted analysis, subjects with MNA-sf score 0-7 had a 2.7-fold higher risk of in-hospital mortality (95% CI: 1.3-5.9, p = 0.011) than those with a score of 8-14, and subjects with malnutrition determined by MUAC (<20 cm for males, and <19 cm for females) had a 1.8-fold higher risk of in-hospital mortality (95% CI: 0.98-3.4, p = 0.06) than those normally nourished. MNA-sf (HR 1.6, 95% CI: 1.02-2.6, p = 0.039) and MUAC (HR 1.6, 95% CI: 1.0-2.3, p = 0.048) were independently predictive of 30-day mortality. BMI <18.5 was not associated with in-hospital or 30-day mortality. CONCLUSIONS: Malnutrition was common and simple measures of nutritional status predicted in-hospital and 30-day mortality. Further research is needed to understand the pathophysiology of malnutrition during acute illness and mitigate its effects.

Frequency of vital signs monitoring and its association with mortality among adults with severe sepsis admitted to a general medical ward in Uganda.

INTRODUCTION: Optimal vital signs monitoring of patients with severe sepsis in resource-limited settings may improve outcomes. The objective of this study was to determine the frequency of vital signs monitoring of patients with severe sepsis and its association with mortality in a regional referral hospital in Uganda. METHODS: We reviewed medical records of patients admitted to Mbarara Regional Referral Hospital in Southwestern Uganda with severe sepsis defined by the presence of infection plus ≥ 2 of the systemic inflammatory response syndrome criteria, and ≥ 1 organ dysfunction (altered mental state, hypotension, jaundice, or thrombocytopenia). We recorded frequency of vital signs monitoring in addition to socio-demographic, clinical, and outcome data. We analyzed the data using logistic regression. RESULTS: We identified 202 patients with severe sepsis. The median age was 35 years (IQR, 25-47) and 98 (48%) were female. HIV infection and anemia was present in 115 (57%) and 83 (41%) patients respectively. There were 67 (33%) in-hospital deaths. The median monitoring frequency per day was 1.1 (IQR 0.9-1.5) for blood pressure, 1.0 (IQR, 0.8-1.3) for temperature and pulse, and 0.5 (IQR, 0.3-1.0) for respiratory rate. The frequency of vital signs monitoring decreased during the course of hospitalization. Patients who died had a higher frequency of vital signs monitoring (p<0.05). The admission respiratory rate was associated with both frequency of monitoring (coefficient of linear regression 0.6, 95% CI 0.5-0.8, p<0.001) and mortality (AOR 2.5, 95% CI 1.3-5.3, p = 0.01). Other predictors of mortality included severity of illness, HIV infection, and anemia (p<0.05). CONCLUSIONS: More research is needed to determine the optimal frequency of vital signs monitoring for severely septic patients in resource-limited settings such as Uganda.