요통 및 신장결석에 대한 위험도 예측 모형

학위논문(박사)--서울대학교 대학원 :보건대학원 보건학과(보건학전공),2020. 2. Joohon Sung.배경 복합 만성 질환은 다양한 병적 상태를 포함하는 질환으로 지역사회나 가정간호 등을 포함한 다양한 헬스케어 및 관련 기관들이 주의를 기울여야 한다. 하나의 만성적인 상태 혹은 복합적 질환의 예방과 완화를 위해서는 개선된 측정 방법과 예방법이 필요하다. 선진국에서는 만성 질환의 유병률이 급격한 고령화와 수명의 연장으로 인하여 증가하고 있고, 이러한 역학적 변화로 인해 퇴행성 질환과 생활 습관 관련 질환들은 선진국에서 감염성 질환보다 발병률 및 치사율이 더 높게 나타나고 있다. 이러한 건강 상태들은 개인과 사회 모두에게 상당한 부담을 야기하는데 지속적인 헬스케어가 필요하고, 질환으로 인한 장애가 평생 동안 지속되기 때문이다. 따라서 연령 관련 집단의 건강 상태를 관리하기 위하여 관련 전략을 세워야 하는데 고령화 인구와 이와 연관된 건강 관리 지출의 증가에 대한 고려가 필요하다. 2013년에 한국의 질병 부담 중 장애보정생존연수(DALY)의 가장 중요한 요인 중 하나는 요통이었고, 신장 결석은 지난 20년 동안 한국에서 꾸준히 질병부담이 증가해온 질환이다. 본 연구는 요통과 신장결석의 두 질환을 중점으로 위험도를 추정하고 질병을 예방하는 방법을 제안하고자 한다. 배경: 요통은 사회에 상당한 경제적 부담을 주는 신체적 질환으로, 국내 총 보험금액의 10% 이상을 차지하고 있다. 요통은 약 60-80%의 사람들이 일생에 시작될 가능성이 있고, 잠재적으로 유소년기에 나타날 수 있으며 약 6-10%의 급성 LBP 환자들 중 만성 요통이 발생하거나 반복적인 요통 증상을 경험하는 것으로 추정된다. 요통 시작 및 재발과 관련된 위험 요인에 대한 견해 차이가 존재한다. 최근엔 지질 수치, 동맥경화증, 고혈압, 당뇨병 그리고 낮은 요통과의 관계를 평가하기 위한 종적 연구가 권장된다. McIntosh 등의 2018년 체계적 문헌고찰에 따르면 만성 요통에 대한 검증된 예측 모델이 없는 것으로 나타났다. 본 연구는 일반적인 진료 데이터를 사용하여 요통 발병의 미래 위험, 재발 및 만성 위험을 추정하기 위한 예측 모델과 위험 평가 점수를 도출하고 검증하려고 시도하였다. 이 연구는 또한 대사 증후군 위험요인과 요통 사이의 연관성을 평가하는 것을 목표로 한다. 방법: 한국의 일반적인 의료 관행에서 수집된 데이터를 사용하는 인구 기반 전향적 코호트 연구로 연구 참여자는 2002년부터 2010년까지 NHIS-NSC(National Health Insurance Service-National Sample Cohort)에 등록된 502,342 명으로 설정하였다. Cox 비례 위험 모델과 프렌티스, 윌리엄, 피터슨 갭타임 모델이 분석에 사용되었다. 결과: 8.4년의 (범위:1.49 ~ 8.99)의 추적 관찰 중위수 기간 동안 요통이 없었던 참가자 438,713명과 만성 요통이 없었던 455,619명 중 처음으로 요통과 만성 요통을 경험한 환자는138,217명(31.5%)과 60,204명(13.2%)였다. 503,482명의 참가자들로부터, 170,279명의 요통환자들의 코호트가 구성되었고, 49,462(29.0%), 106,927명(62.8%)이 요통의 재발을 12개월 추적 및 5년의 추적 기간동안 경험하였다. 대사성 질환 요인과 질병 발생 전의 상태는 예측된 요통과 연관되었고 단변량 분석과 다변량 분석 시 각각 연관성의 방향이 다른 부분이 있었다. (요통의 초발에 대한 예측식) 에서는 연령, 성별, 소득 등급, 알코올 소비, 흡연 상태, 신체 운동, 체질량 지수, 총 콜레스테롤 및 질병 병력을 변수로 포함하였고, 요통 재발 예측 모델에는 연령, 성별, 소득 등급, 체질량 지수, 총콜레스테롤, 수축기 혈압, 요통 치료일수, 질병의 기왕력을 포함하였다. 5년 내 요통의 재발에대한 예측식에서는 연령, 성별, 소득 수준, 흡연여부, 알코올 소비, BMI, 총콜레스테롤, 고혈압, 신체활동력, 요통 치료 기간, 질병 기왕력 등을 포함하였다. 검증 코호트에서 Harrell의 C-통계량은 각각 요통 초발 시 0.804 (95% CI, 0.796-0.812), 만성 요통0.643 (95% CI, 0.629-0.656) 및 5년 내 재발된 요통 0.857 (95% CI, 0.847-0.866), 12개월 내 재발된 요통 0.759 (95% CI, 0.745-0.774) 였다. 간소화된 수치의 위험도, 연령, 퇴행성 디스크, 성별이 요통의 발병의 가장 큰 위험 요인으로 생각되었고 연령, 처방 일수 및 퇴행성 디스크가 5년 내 재발의 가장 큰 위험 요인으로 나타났다. 결론: 이 연구는 요통이 예측 가능하고, 예방 가능하고, 첫 진단의 효과적인 치료가 재발 위험을 줄일 수 있다는 것을 암시한다. 이 연구는 또한 대사 증후군 구성 요소가 요통의 발병과 관련되어 있다는 것을 밝혀냈고, 발병 전 단계의 상태가 향후 요통 발병과 만성도, 재발을 예측할 수 있게 하였다. 특히, 고혈압과 요통 사이에는 반비례 (역상관관계)가 있다. 그러나 발병, 재발, 만성의 예측요인에는 차이가 있는데 본 연구에서는 요통 발생 위험을 추정할 수 있는 예측 모델 5개가 일반 진료 데이터를 사용하여 전국 샘플 코호트에서 개발 및 검증하였다. 예측식이 전문가를 대신하지는 못하지만 임상적 결정의 정확도를 높이는데 사용될 수 있다. 개인의 건강 상태를 신장 결석의 위험도 부분과 함께 예측하고 전문가의 의견과 함께 진단 시 사용하는 경우 더 정확도를 높일 수 있다. 또한 이 연구는 다른 위험 예측 변수를 다른 설정에 통합하여 모델을 외부 검증하거나 업데이트할 수 있는 기회를 제공한다. 신장결석 배경: 신장결석은 요로와 신장에 결석이 있는 상태를 의미하는데 염분의 용해도와 침전도의 균형이 깨졌을 때 발생한다. 신장결석은 복잡한 병인을 가진 다인성 질환으로 서구권에서 약 10%의 유병률을 보이고 있다. Romero 등에 따르면 한국에서는 약 5.0%의 신장결석 유병률을 보이며 질병부담은 점차 증가하는 것으로 나타났지만 최근까지도 신장결석에 대한 인구 특이적 위험예측모델이 한국에서 개발되고 검증되지 않은 것으로 보인다. 신장 결석은 대사 증후군과 관련이 있지만 이에 대한 결론은 도출되지 않았다. 정교히 검증된 위험 예측 모델은 개인별 질병 위험도를 판별하는 데 도움을 줄 수 있고 예방법을 찾는 데 도움을 준다. 신장결석에 대한 많은 역학연구에도 불구하고, 일상적으로 수집되는 의료 데이터를 이용하여 신장결석 모델을 검증하고자 하는 종단연구는 시도되지 않았다. 본 연구는 개인과 의료진이 파악하고자 하는 위험 예측 요인으로부터 신장결석 예측 수식을 개발하고 검증하고자 한다. 이에 더하여, 본 연구는 대사증후군, 질병이 걸리기 전의 건강 상태와 신장결석에 대한 관계를 평가하고자 한다. 방법: 한국의 전향적 인구 기반 코호트 연구로 2002년부터 2010년까지 NHIS-NSC(National Health Insurance Service-National Sample Cohort, 국민건강보험공단 – 국가 표본 코호트)의 502,342명을 대상으로 하였다. 분석에는 Cox 비례 위험 모델을 사용하였다. 결과: 중위수 8.5년(범위=2.0-8.9)의 추적관찰 기간 동안, 496,971명의 대상자 중 18,205명이 신장 결석 기록이 있었으며 단변량 분석과 다변량 분석 시 각각 연관성의 방향이 다른 부분이 있지만 대사 증후군 관련 성분과 발병 전의 건강 상태는 예측된 신장 결석과 연관이 있었다. 절약 모형의 새로 진단된 신장결석의 위험 예측 변수로는 연령, 성별, 소득 수준, 흡연 상태, 알코올 소비량, 체질량 지수, 병력, 통풍 과거력, 부갑상선 항진증, 염증성 장질환 등이 포함되었다. 과적합 보정 Harrell의 C-statistics를 적용하였을 때 derivation cohort 와 validation cohort의 예측력은 각각 0.820 (95% CI, 0.806-0.834), 0.819 (95% CI, 0.798-0.838)였다. 검증 코호트의 모델의 민감도와 특이도는 각각 0.821 (95% CI, 0.760-0.888), 0.513 (95% CI, 0.390-0.656)였다. 고위험자를 정의하기 위한 Youden의 최적 기준에 따르면 모델의 민감도와 특이도는 66%, 77.5%로 나타났다. 신장결석 위험 점수를 기반으로 한 간소화된 점수를 토대로 하였을 때 연령, 성별, BMI가 새로 진단된 신장 결석의 가장 큰 위험 점수를 차지하였고 총 처방 일수, 성별, 연령이 5년 내 신장결석의 재발에 가장 큰 위험요인이 되는 것으로 나타났다. 추적 기간의 중간 기간 동안 7,086 (30.1%) 건의 신장 결석 재발이 23,576 명의 참가자들로부터 발생하였다. 신장결석의 재발에 대한 누적 위험도는 2004년에 19.8 (95% CI, 19.3 to 20.4) 에서 37.6 (95% CI, 36.8 to 38.3) 로 추적기간의 마지막 연도에 증가하였다 (8.5년). 신장 결석의 재발은 성별, 연령, BMI, 및 처방전의 총일 요인에 의해 예측되었고 Harrells C-통계에 따르면 해석 코호트와 검증 코호트에서 각각 0.926 (95% CI, 0.907-0.945), 0.909 (95% CI, 0.879-0.935) 이었다. 결론: 이 연구는 신장결석이 예측 가능한 건강상태이고, 연구에 사용된 모델은 위험군을 스크리닝하는 데 사용될 수 있음을 시사한다. 고안된 예측 방정식은 일반 인구에 웹 기반 계산기의 형태로 적용하거나 의료진들이 건강한 사람을 상대로 신장결석의 위험을 예측하는 데 적용할 수 있다. 또한 최근에 신장결석을 진단받은 사람의 예후를 예측할 수 있다. 개인의 건강 상태를 신장 결석의 위험도 부분과 함께 예측하고 전문가의 의견과 함께 진단 시 사용하는 경우 더 정확도를 높일 수 있으며 개발된 모델의 변수는 실제 임상 현장에서 적용할 수 있고 사용이 편리하다. 이 연구를 통해 정밀의료의 시대에서 또한 외적 타당도를 높이고 다른 환경에서 다른 위험인자를 포함함으로써 모델을 개선할 수 있을 것으로 보인다.Background A Complex Chronic Disease is a condition that involves multiple morbidities requiring the attention of multiple health care and facilities including community or home-based care. Prevention and mitigation of the effect of a single chronic condition, or constellation of conditions, requires improved measurement, and prediction. In developed nations, the prevalence of chronic diseases is increasing due to rapid aging of the population and the greater longevity of people with chronic conditions. Due to epidemiological transition, degenerative and life-style-related diseases have superseded infectious diseases in terms of morbidity and mortality in developed countries. These conditions have resulted into considerable cost both to individuals and to society through substantial health care needs and life-long disability. Thus, there is need to develop strategies to deal with age-related conditions, especially considering the rapidly ageing population and the associated increase in health care expenditure. Low back pain was one of the most important contributors to the Korean DALYs in 2013, while the prevalence of nephrolithiasis and burden of disease has increased in Korea over the past 20 years. This study focused on two complex diseases; low back pain and nephrolithiasis, attempting to provide means of estimating risks and preventing these conditions. Low Back Pain Introduction: Low back pain is a common debilitating condition with a considerable economic burden to society, and accounting for over 10% of total insurance claims in Korea. Low back pain occurs in approximately 60–80% of people at some points in their lives, with a potential childhood onset, and an estimated 6-10% of acute low back pain patients developing chronic low back pain or experiencing repeated fluctuating pain episodes. There is still a knowledge gap regarding risk factors associated with onset of low back pain and its recurrence. Recently, longitudinal studies recommended assessing lipid profiles, atherosclerosis, hypertension, diabetes mellitus, and their relationship with low back pain. A 2018 systematic review by McIntosh et al., reported absence of validated prediction models for chronic low back pain. This study aimed at derivation and validation of prediction models and simplified risk scores to estimate future risk of developing low back pain, its recurrence, and chronicity using data from general medical practice. The study also aimed to assess the association between risk factors for metabolic syndrome components and low back pain. Methods: A population based prospective cohort study using routinely collected data from general medical practice in Korea. A total of 502,342 participants from National Health Insurance Service–National Sample Cohort (NHIS-NSC) enrolled from 2002 to 2010. Cox proportional hazards model and Prentice, Williams and Peterson Gap Time models were used in the analysis. Results: During a median follow-up of 8.4 years (Range:1.49 to 8.99), there were 138,217 (31.5%) and 60,204 (13.2%) participants who experienced first onset of low back pain and chronic low back pain among 438,713 and 455,619 participants who were free of low back pain and chronic low back pain at baseline. From 503,482 participants, a consecutive cohort of 170,279 (33.8%) low back pain patients was constituted, and 49,462 (29.0%) and 106,927 (62.8%) patients experienced recurrent low back pain episodes within twelve (12) months and five (5) years of follow up, respectively. Metabolic syndrome components and premorbid conditions were associated with and predicted low back pain, although the direction of associations varied in univariate and multivariate analyses. The prediction equations of first onset of low back pain comprised of age, sex, and income grade, alcohol consumption, smoking status, physical exercise, body mass index, total cholesterol, fasting blood glucose, blood pressure and medical history of diseases. The prediction equations for 5-year low back pain recurrence comprised of age, sex, income grade, smoking status, alcohol consumption, body mass index, total cholesterol, hypertension, physical activity, number of days of low back pain treatment and medical history of diseases. The Harrells C-statistics for the prediction equations in the validation cohorts were 0.804 (95% CI, 0.796-0.812), 0.643 (95% CI, 0.629-0.656), 0.857 (95% CI, 0.847-0.866) and 0.759 (95% CI, 0.745-0.774) for first onset of low back pain, chronic low back pain, 5-year recurrent low back pain and 12-months low back pain recurrence, respectively. Based on simplified points based risk scores, age, disc degeneration, and sex conferred highest risk points for low back pain onset, whereas age, total days of prescription and disc degeneration conferred highest risk for 5-year recurrence. Conclusion: This study implies low back pain is predictable, preventable and treatment of initial episode can effectively reduce risk of recurrence. The study also provides evidence that metabolic syndrome components are associated with low back pain outcomes and premorbid conditions are predictive of future low back pain, chronicity and its recurrence. Of particular interest, there was an inverse association between hypertension and chronic low back pain. However, there are some differences in predictors of onset, predictors of recurrence and chronicity of low back pain. Five low back pain prediction models that can estimate individuals risk of developing and experiencing recurrent episodes have been developed and validated in a nationwide sample cohort using data from general practice. However, the derived equations cannot substitute the clinical expertise, but rather augment precision in clinical decision-making. Knowledge of the overall health status of a patient with respect to low back pain risk and expert knowledge from clinical practitioners will create a much clearer picture than either one alone. These variables in the models can easily be obtained in clinical practice and the points system is simple to use. This study also offers an opportunity for external validation or updating the models by incorporating other risk predictors in other settings especially in this era of precision medicine. Nephrolithiasis Introduction: Nephrolithiasis is the presence of renal calculi in the urinary tract and kidneys caused by disruptions in the balance between solubility and precipitation of salts. Nephrolithiasis is a multifactorial disorder with complex aetiology and with a prevalence approximating 10% in Western countries. A study by Romero et al. reported a 5.0% prevalence of nephrolithiasis in South Korea and the disease burden has been increasing but to date no population specific nephrolithiasis risk prediction models have been developed and validated in Korea. Nephrolithiasis has been linked to metabolic syndrome, although conclusions have not been drawn. Well-validated risk prediction models help to identify individuals at high risk of diseases and to take preventive measures. Despite the abundant epidemiologic research on nephrolithiasis, longitudinal studies have not attempted to develop and validate nephrolithiasis risk prediction models using routinely collected medical data. This study aimed to develop and validate nephrolithiasis prediction equations and simplified risk scores from risk predictors that individuals and clinicians are likely to know. In addition, the study aimed to assess the relationship between metabolic syndrome risk factors, premorbid conditions, and nephrolithiasis. Methods: A prospective population based cohort study in Korea. A total of 502,342 participants from the National Health Insurance Service–National Sample Cohort (NHIS-NSC) enrolled from 2002 to 2010. Cox proportional hazard model was used in the analysis. Results: During a median follow-up of 8.5 years (Range=2.0-8.9) and among 496,971 participants, there were 18,205 (3.7%) cases of nephrolithiasis. Metabolic syndrome components and premorbid conditions were associated with and predicted nephrolithiasis, although the strength of associations varied in univariate and multivariate analyses. The risk predictors in the parsimonious model for newly diagnosed nephrolithiasis included age, sex, income grade, alcohol consumption, body mass index, total cholesterol, fasting blood glucose, history of diagnosed gout, hyperparathyroidism and inflammatory bowel disease. The Harrells C-statistic was 0.820 (95% CI, 0.806-0.834) and 0.819 (95% CI, 0.798-0.838) in the derivation and validation cohorts, respectively. Using the optimal threshold determined by Youdens index to define high-risk individuals, the models sensitivity and specificity in the validation cohort were 76.5% (95% CI, 75.4% to 77.5%) and 62.0% (95% CI, 61.8% to 62.3%), respectively. During the median follow-up period, there were 7,086 (30.1%) recurrent cases of nephrolithiasis in the consecutive cohort of 23,576 patients. The cumulative risk of nephrolithiasis recurrence increased from 19.8 (95% CI, 19.3 to 20.4) to 37.6 (95% CI, 36.8 to 38.3) during a 5-year follow up period. The parsimonious model for 5-year nephrolithiasis recurrence comprised of sex, age, body mass index, and total number of days of prescription. The Harrells C-statistic was 0.926 (95% CI, 0.907-0.945) and 0.909 (95% CI, 0.879-0.935) for derivation and validation cohorts, respectively. Using the optimal threshold determined by Youdens index to define high-risk individuals, the models sensitivity and specificity in the validation cohort were 66.0% (95% CI, 64.1% to 68.0%) and 77.5% (95% CI, 76.4% to 78.6%), respectively. Based on the simplified points based nephrolithiasis risk scores, age, sex, and body mass index conferred highest risk points for newly diagnosed nephrolithiasis, whereas total days of prescription, sex, and age conferred highest risk for 5-year nephrolithiasis recurrence. Conclusion This study implies nephrolithiasis might be a predictable condition, and the models might be used to screen a high-risk group. The derived prediction equations can be availed to general population in form of web-based calculator or used by medical practitioners to assess nephrolithiasis risk among health individuals and prognosis among patients who have recently developed nephrolithiasis. Knowledge of the overall health status of a patient with respect to nephrolithiasis risk and expert knowledge from clinical practitioners will create a much clearer picture than either one alone. These variables in the derived models can easily be obtained in clinical practice and the points system is simple to use. This study also offers an opportunity for external validation or updating the model by incorporating other risk predictors in other settings especially in this era of precision medicine.I. Introduction 1 1.1 Background 2 1.2 Low Back Pain 4 1.3 Nephrolithiasis 9 II. Literature Review 14 2.1 Literature Review: Low Back Pain 15 2.2 Risk factors and pathogenesis of low back pain 17 2.3 Association between lifestyle risk factors and low back pain 20 2.4. Association between anthropometric measures and low back pain. 22 2.5. Metabolic syndrome components and risk factors 24 2.6 Comorbidity, premorbid diseases, psychosocial and hereditary risk factors 29 2.7 Literature Review: Nephrolithiasis 36 2.8 Association between demographic factors and nephrolithiasis 39 2.9 Association between lifestyle risk factors and nephrolithiasis 40 2.10 Association between anthropometric measures and nephrolithiasis. 42 2.11 Association between metabolic syndrome and nephrolithiasis 44 2.12 Association between diseases, medication, genetics, and nephrolithiasis 47 III. Methods and Materials 52 3.1 Study design, setting and cohort description 53 3.2 Data extraction and choice of risk predictors 54 3.3 Assessment and measurement of covariates 55 3.4 Case definition, prospective ascertainment, and exclusion criteria 57 3.5 Statistical analysis 60 3.6 Validation and performance evaluation of risk prediction models 63 3.7 Measures of discrimination and predictive accuracy 73 3.8 Calculation of personalized risk based on models and simplified risk scores 90 IV. Results 95 4.1 Prediction of first onset of low back pain. 96 4.2 Prediction of chronic low back pain 124 4.3 Prediction of five (5-year) low back pain recurrence risk 154 4.4 Prediction of low back pain recurrence within twelve (12) months 183 4.5 Modelling low back pain using Prentice, Williams and Peterson models 212 4.6 Prediction of nephrolithiasis Risk 229 4.7 Prediction of 5-year nephrolithiasis recurrence risk 255 4.8 Sensitivity analysis for models based on selected subgroups 281 V. Discussion 284 5.1 Newly diagnosed low back pain 285 5.2 Chronic low back pain 290 5.3 Low back pain recurrence within five (5) years 294 5.4 Low back pain recurrence within twelve (12) months 299 5.5 Multiple episodic low back pain 303 5.6 Newly diagnosed nephrolithiasis 306 5.7 Nephrolithiasis recurrence within five (5) years 312 VI. Summaries and conclusions 316 6.1 Low Back Pain 317 6.2 Nephrolithiasis 320 References 324 Korean Abstract (국문 초록) 354Docto

Redesigning Delivery: Boosting Adoption of Coffee Management Practices in Uganda. The climate smart investment pathway approach and the farmer segmentation tool

Coffee is an important crop for the Ugandan economy, as it earns the country US$415 million in foreign export revenues and supports 1.7 million smallholder farmers (UCDA, 2016). Nevertheless, coffee yields have stagnated for over a decade, despite concerted efforts to improve productivity. Climate change is increasing the pressure on the sector, and the effects are already being felt. Climate smart agricultural (CSA) practices are being promoted as a means to help farmers cope with climate change. The CSA training package focuses on planning good agricultural practices in a way that the changing climate is taken into consideration. The training package for coffee consists of a large number of practices (soil and water conservation, tree management, quality of coffee, among others), and is currently provided all in one go as a complete package. This approach is cumbersome and not aligned to pertinent needs of coffee farmers, as coffee is a perennial crop and needs continuous care throughout the year. To address the need for better targeting of practices, this Info Note presents two complementary approaches: the climate smart investment pathways (CSIPs) and farmer segmentation. The CSIPs break down the full training package of CSA practices into more manageable subsets of practices. These smaller packages are aimed at being more aligned with the structural (resource endowments) and functional (entrepreneurship) characteristics of different types of farmers. CSIPs build up a sequential and incremental approach to implementing the practices. The farmer segmentation tool differentiates the coffee farmers into different groups, based on their assets and entrepreneurial characteristics. These segmentations will help advise the relevant stakeholders that support farmers on how to best engage with and train farmers in the most relevant practices (based on the CSIP) by taking their capacity and willingness to implement the practices into consideration. This Info Note will first go through the development process of the CSIPs, based on the results from a study on Robusta coffee systems in Luweero and Nakasongola. Then it will move onto the process and results of the farmer segmentation work done in the Greater Luweero region (which encompasses Luweero and Nakasongola). The implications of this work will be discussed and recommendations will be made for further work and use of these methods

Estimating the costs of induced abortion in Uganda: A model-based analysis

<p>Abstract</p> <p>Background</p> <p>The demand for induced abortions in Uganda is high despite legal and moral proscriptions. Abortion seekers usually go to illegal, hidden clinics where procedures are performed in unhygienic environments by under-trained practitioners. These abortions, which are usually unsafe, lead to a high rate of severe complications and use of substantial, scarce healthcare resources. This study was performed to estimate the costs associated with induced abortions in Uganda.</p> <p>Methods</p> <p>A decision tree was developed to represent the consequences of induced abortion and estimate the costs of an average case. Data were obtained from a primary chart abstraction study, an on-going prospective study, and the published literature. Societal costs, direct medical costs, direct non-medical costs, indirect (productivity) costs, costs to patients, and costs to the government were estimated. Monte Carlo simulation was used to account for uncertainty.</p> <p>Results</p> <p>The average societal cost per induced abortion (95% credibility range) was $177 ($140-$223). This is equivalent to$64 million in annual national costs. Of this, the average direct medical cost was $65 ($49-86) and the average direct non-medical cost was $19 ($16-$23). The average indirect cost was$92 ($57-$139). Patients incurred $62 ($46-$83) on average while government incurred$14 ($10-$20) on average.</p> <p>Conclusion</p> <p>Induced abortions are associated with substantial costs in Uganda and patients incur the bulk of the healthcare costs. This reinforces the case made by other researchers--that efforts by the government to reduce unsafe abortions by increasing contraceptive coverage or providing safe, legal abortions are critical.</p

The use of personal digital assistants for data entry at the point of collection in a large household survey in southern Tanzania

Survey data are traditionally collected using pen-and-paper, with double data entry, comparison of entries and reconciliation of discrepancies before data cleaning can commence. We used Personal Digital Assistants (PDAs) for data entry at the point of collection, to save time and enhance the quality of data in a survey of over 21,000 scattered rural households in southern Tanzania. Pendragon Forms 4.0 software was used to develop a modular questionnaire designed to record information on household residents, birth histories, child health and health-seeking behaviour. The questionnaire was loaded onto Palm m130 PDAs with 8 Mb RAM. One hundred and twenty interviewers, the vast majority with no more than four years of secondary education and very few with any prior computer experience, were trained to interview using the PDAs. The 13 survey teams, each with a supervisor, laptop and a four-wheel drive vehicle, were supported by two back-up vehicles during the two months of field activities. PDAs and laptop computers were charged using solar and in-car chargers. Logical checks were performed and skip patterns taken care of at the time of data entry. Data records could not be edited after leaving each household, to ensure the integrity of the data from each interview. Data were downloaded to the laptop computers and daily summary reports produced to evaluate the completeness of data collection. Data were backed up at three levels: (i) at the end of every module, data were backed up onto storage cards in the PDA; (ii) at the end of every day, data were downloaded to laptop computers; and (iii) a compact disc (CD) was made of each team's data each day.A small group of interviewees from the community, as well as supervisors and interviewers, were asked about their attitudes to the use of PDAs. Following two weeks of training and piloting, data were collected from 21,600 households (83,346 individuals) over a seven-week period in July-August 2004. No PDA-related problems or data loss were encountered. Fieldwork ended on 26 August 2004, the full dataset was available on a CD within 24 hours and the results of initial analyses were presented to district authorities on 28 August. Data completeness was over 99%. The PDAs were well accepted by both interviewees and interviewers. The use of PDAs eliminated the usual time-consuming and error-prone process of data entry and validation. PDAs are a promising tool for field research in Africa

The Shade Tree Advice Tool

Key messages: Climate change adaptation for coffee and cocoa farming requires low cost and multipurpose solutions, such as shade trees. Selecting appropriate shade trees is paramount for maximizing tree-based ecosystem services while minimizing disservices. The shade tree advice tool presented here guides coffee and cocoa farmers on choosing shade trees whose ecosystem services will best meet their needs, based on fellow coffee farmers' local knowledge in their region

Hf- and O-isotope data from detrital and granitoid zircons reveal characteristics of the Permian–Triassic magmatic belt along the Antarctic sector of Gondwana

Permian–Triassic strata in the Transantarctic Mountains and West Antarctica carry a significant detrital component derived from a contemporaneous magmatic belt along the Gondwana margin. Hf- and O-isotope characteristics were determined for near-contemporaneous (as shown by U-Pb zircon geochronology) detrital igneous zircons in Upper Permian and Triassic sandstones. Zircons from six granitoids in the contemporaneous magmatic belt were also analyzed for Hf and O isotopes in order to gain insight into the potential detrital zircon sources. Although the ages of these granitoids only loosely correspond with the depositional ages of the sandstones, the initial εHf and δ18O isotope compositions for these igneous zircon grains, in general, overlap those recorded for the detrital igneous zircon grains. Results demonstrate a range of εHf and δ18O values. Features of particular interest are the very low δ18O values in two of the granitoids, and similar low values also recorded in the detrital igneous zircons in two sandstones. The distribution of Permian–Triassic granitoids must be much greater than is apparent from the existing outcrops in the extensively ice-covered region. The Permian and one of the Triassic granitoids have Hf-isotope characteristics similar to the Cretaceous granites and Devonian–Carboniferous plutons of West Antarctica, whereas the other Triassic granite differs from both. Importantly, the zircon isotopic data from the Permian–Triassic rocks suggest that an Hf-defined Upper Mesoproterozoic lithosphere underlies much of the magmatic belt

Gender differences among patients with drug resistant tuberculosis and HIV co-infection in Uganda: a countrywide retrospective cohort study

Background Gender differences among patients with drug resistant tuberculosis (DRTB) and HIV co-infection could affect treatment outcomes. We compared characteristics and treatment outcomes of DRTB/HIV co-infected men and women in Uganda. Methods We conducted a retrospective chart review of patients with DRTB from 16 treatment sites in Uganda. Eligible patients were aged ≥ 18 years, had confirmed DRTB, HIV co-infection and a treatment outcome registered between 2013 and 2019. We compared socio-demographic and clinical characteristics and tuberculosis treatment outcomes between men and women. Potential predictors of mortality were determined by cox proportional hazard regression analysis that controlled for gender. Statistical significance was set at p < 0.05. Results Of 666 DRTB/HIV co-infected patients, 401 (60.2%) were men. The median (IQR) age of men and women was 37.0 (13.0) and 34.0 (13.0) years respectively (p < 0.001). Men were significantly more likely to be on tenofovir-based antiretroviral therapy (ART), high-dose isoniazid-containing DRTB regimen and to have history of cigarette or alcohol use. They were also more likely to have multi-drug resistant TB, isoniazid and streptomycin resistance and had higher creatinine, aspartate and gamma-glutamyl aminotransferase and total bilirubin levels. Conversely, women were more likely to be unemployed, unmarried, receive treatment from the national referral hospital and to have anemia, a capreomycin-containing DRTB regimen and zidovudine-based ART. Treatment success was observed among 437 (65.6%) and did not differ between the genders. However, mortality was higher among men than women (25.7% vs. 18.5%, p = 0.030) and men had a shorter mean (standard error) survival time (16.8 (0.42) vs. 19.0 (0.46) months), Log Rank test (p = 0.046). Predictors of mortality, after adjusting for gender, were cigarette smoking (aHR = 4.87, 95% CI 1.28–18.58, p = 0.020), an increase in alanine aminotransferase levels (aHR = 1.05, 95% CI 1.02–1.07, p < 0.001), and history of ART default (aHR = 3.86, 95% CI 1.31–11.37, p = 0.014) while a higher baseline CD4 count was associated with lower mortality (aHR = 0.94, 95% CI 0.89–0.99, p = 0.013 for every 10 cells/mm3 increment). Conclusion Mortality was higher among men than women with DRTB/HIV co-infection which could be explained by several sociodemographic and clinical differences.Funding for this research was obtained from the East African Public Health Laboratory Networking (EAPHLN) Project, Uganda under the Ministry of Health, which was supported by the World Bank. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Apoptosis of Fashigh CD4+ synovial T cells by borrelia-reactive Fas-ligand(high) gamma delta T cells in Lyme arthritis

The function of the minor subset of T lymphocytes bearing the gamma delta T cell antigen receptor is uncertain. Although some gamma delta T cells react to microbial products, responsiveness has only rarely been demonstrated toward a bacterial antigen from a naturally occurring human infection. Synovial fluid lymphocytes from patients with Lyme arthritis contain a large proportion of gamma delta cells that proliferate in response to the causative spirochete, Borrelia burgdorferi. Furthermore, synovial gamma delta T cell clones express elevated and sustained levels of the ligand for Fas (APO-1, CD95) compared to alpha beta T cells, and induce apoptosis of Fashigh CD4+ synovial lymphocytes. The findings suggest that gamma delta T cells contribute to defense in human infections, as well as manifest an immunoregulatory function at inflammatory sites by a Fas-dependent process