The increasing number of people living with HIV aged 50 years and older has been recognised around the world yet non-pharmacologic HIV behavioural and cognitive interventions specifically targeted to older adults are limited. Evidence is needed to guide the response to this affected group.
We conducted a systematic review of the available published literature in MEDLINE, Embase and the Education Resources Information Center. A search strategy was defined with high sensitivity but low specificity to identify behavioural interventions with outcomes in the areas of treatment adherence, HIV testing uptake, increased HIV knowledge and uptake of prevention measures. Data from relevant articles were extracted into excel.
Twelve articles were identified all of which originated from the Americas. Eight of the interventions were conducted among older adults living with HIV and four for HIV-negative older adults. Five studies included control groups. Of the included studies, four focused on general knowledge of HIV, three emphasised mental health and coping, two focused on reduced sexual risk behaviour, two on physical status and one on referral for care. Only four of the studies were randomised controlled trials and seven – including all of the studies among HIV-negative older adults – did not include controls at all. A few of the studies conducted statistical testing on small samples of 16 or 11 older adults making inference based on the results difficult. The most relevant study demonstrated that using telephone-based interventions can reduce risky sexual behaviour among older adults with control reporting 3.24 times (95% CI 1.79-5.85) as many occasions of unprotected sex at follow-up as participants. Overall however, few of the articles are sufficiently rigorous to suggest broad replication or to be considered representative and applicable in other settings.
More evidence is needed on what interventions work among older adults to support prevention, adherence and testing. More methodological rigourised needed in the studies targeting older adults. Specifically, including control groups in all studies is needed as well as sufficient sample size to allow for statistical testing. Addition of specific bio-marker or validated behavioural or cognitive outcomes would also strengthen the studies.
Older adults; HIV; Interventions; Systematic review; Effectiveness
As low- and middle-income countries face continued shortages of human resources for health and the double burden of infectious and chronic diseases, there is renewed international interest in the potential for community health workers to assume a growing role in strengthening health systems. A growing list of tasks, some of them complex, is being shifted to community health workers’ job descriptions. Health Surveillance Assistants (HSAs) - as the community health worker cadre in Malawi is known - play a vital role in providing essential health services and connecting the community with the formal health care sector. The objective of this study was to understand the performed versus documented roles of the HSAs, to examine how tasks were prioritized, and to understand HSAs’ perspectives on their roles and responsibilities.
A situational analysis of the HSA cadre and its contribution to the delivery of health services in Zomba district, Malawi was conducted. Focus groups and interviews were conducted with 70 HSAs. Observations of three HSAs performing duties and work diaries from five HSAs were collected. Lastly, six policy-maker and seven HSA supervisor interviews and a document review were used to further understand the cadre’s role and to triangulate collected data.
HSAs performed a variety of tasks in addition to those outlined in the job description resulting in issues of overloading, specialization and competing demands existing in the context of task-shifting and prioritization. Not all HSAs were resistant to the expansion of their role despite role confusion and HSAs feeling they lacked adequate training, remuneration and supervision. HSAs also said that increasing workload was making completing their primary duties challenging. Considerations for policy-makers include the division of roles of HSAs in prevention versus curative care; community versus centre-based activities; and the potential specialization of HSAs.
This study provides insights into HSAs’ perceptions of their work, their expanding role and their willingness to change the scope of their practice. There are clear decision points for policy-makers regarding future direction in policy and planning in order to maximize the cadre’s effectiveness in addressing the country’s health priorities.
Community health workers; Lay health workers; Task-shifting; Health promotion; Task- prioritization
Provide an up-to-date national picture of the medical, midwifery and nursing workforce distribution in Australia with a focus on overseas immigration and on production sustainability challenges.
Using 2006 and 2011 Australian census data, analysis was conducted on medical practitioners (doctors) and on midwifery and nursing professionals.
Of the 70,231 medical practitioners in Australia in 2011, 32,919 (47.3%) were Australian-born, with the next largest groups bring born in South Asia and Southeast Asia. In 2006, 51.9% of medical practitioners were born in Australia. Of the 239,924 midwifery and nursing professionals in Australia, 127,911 (66.8%) were born in Australia, with the next largest groups being born in the United Kingdom and Ireland and in Southeast Asia. In 2006, 69.8% of midwifery and nursing professionals were born in Australia. Western Australia has the highest percentage of foreign-born health workers. There is a higher percentage of Australia-born health workers in rural areas than in urban areas (82% of midwifery and nursing professional in rural areas are Australian-born versus 59% in urban areas). Of the 15,168 additional medical practitioners in Australia between the 2006 and 2011 censuses, 10,452 (68.9%) were foreign-born, including large increases from such countries as India, Nepal, Philippines, and Zimbabwe. We estimate that Australia has saved US$1.7 billion in medical education costs through the arrival of foreign-born medical practitioners over the past five years.
The Australian health system is increasingly reliant on foreign-born health workers. This raises questions of medical education sustainability in Australia and on Australia’s recruitment from countries facing critical shortages of health workers.
Australia; Doctors; Health workforce; Migration; Nurses
A battery of clinical assessments was used in the Lililwan* Project, Australia’s first population-based Fetal Alcohol Spectrum Disorders (FASD) prevalence study, conducted in the remote Fitzroy Valley, Western Australia. One objective was to develop and assess test-retest reliability of an acceptable questionnaire for collecting health information in remote Aboriginal communities feasible for use in the Lililwan Project.
A questionnaire was developed by paediatricians to assist in diagnosis of FASD. Content was based on a literature review of FASD diagnostic criteria, existing questionnaires and risk factors for FASD and birth defects. Aboriginal community members, including qualified Aboriginal language interpreters, adapted the questionnaire to ensure language and cultural components were appropriate for use in the Fitzroy Valley. Locally developed pictorial aids were used for gathering accurate information on alcohol use. Aboriginal ‘community navigators’ assisted researchers to translate the questions into Kimberley Kriol or local Aboriginal languages depending on participant preference.
A subset of 14 questions was assessed for test-retest reliability in 30 parents/carers of children in the Lililwan Project cohort, who were interviewed by one rater using the entire questionnaire, then by a second rater who repeated 14 critical questions at least 6 hours later.
The full questionnaire contained 112 items and took 50 minutes to administer. For a subset of 14 items from the full questionnaire percent exact agreement between raters ranged from 59-100%, and was below 70% for only 1 question. Test-retest reliability was excellent (Kappa 0.81-1.00) for 5 items, substantial (Kappa 0.61-0.80) for 5 items, and moderate, fair or slight (Kappa ≤0.60) for the remaining 4 items tested. Test-retest reliability for questions relating to alcohol use in pregnancy was excellent. When questions had moderate, fair or slight agreement, information was obtained from alternate sources e.g. medical records. Qualitative feedback from parents/carers confirmed acceptability of the questionnaire.
This questionnaire had acceptable test-retest reliability and could be used to collect demographic, socio-cultural and biomedical information relevant to the diagnosis of FASD in Aboriginal communities throughout Australia and elsewhere. Community input is crucial when developing and administering questionnaires for use in cross-cultural contexts.
*Lililwan is a Kimberley Kriol word meaning ‘all the little ones’. Kimberley Kriol is the main language spoken by Aboriginal people in the Fitzroy Valley.
Fetal alcohol syndrome (FAS); Fetal alcohol spectrum disorders (FASD); Aboriginal and Torres Strait Islander; Indigenous; Questionnaire development; Diagnosis; Reliability testing; Reproducibility of results; Test-retest; Percent exact agreement
In sub-Saharan Africa, early mortality is high following initiation of antiretroviral therapy (ART). We investigated 6-month outcomes and factors associated with mortality in HIV-infected adults being assessed for ART initiation and presenting with weight loss, chronic fever or diarrhea, and with negative TB sputum microscopy.
A prospective cohort study was conducted in Malawi, investigating mortality in relation to ART uptake, microbiological findings and treatment of opportunistic infection (OIs), 6 months after meeting ART eligibility criteria.
Of 469 consecutive adults eligible for ART, 74(16%) died within 6 months of enrolment, at a median of 41 days (IQR 20–81). 370(79%) started ART at a median time of 18 days (IQR 7–40) after enrolment. Six-month case-fatality rates were higher in patients with OIs; 25/121(21%) in confirmed/clinical TB and 10/50(20%) with blood stream infection (BSI) compared to 41/308(13%) in patients with no infection identified. Median TB treatment start was 27 days (IQR 17–65) after enrolment and mortality [8 deaths (44%)] was significantly higher among 18 culture-positive patients with delayed TB diagnosis compared to patients diagnosed clinically and treated promptly with subsequent culture confirmation [6/34 (18%);p = 0.04]. Adjusted multivariable analysis, excluding deaths in the first 21 days, showed weight loss >10%, low CD4 count, severe anemia, laboratory-only TB diagnosis, and not initiating ART to be independently associated with increased risk of death.
Mortality remains high among chronically ill patients eligible for ART. Prompt initiation of ART is vital: more than half of deaths were among patients who never started ART. Diagnostic and treatment delay for TB was strongly associated with risk of death. More than half of deaths occurred without identification of a specific infection. ART programmes need access to rapid point-of-care-diagnostic tools for OIs. The role of early empiric OI treatment in this population requires further evaluation in clinical trials.
Injury is a leading cause of morbidity and mortality worldwide, and even more so in low and middle-income countries (LMICs). Iran is a LMIC and lacks information regarding injury for program and policy purposes. This study aimed to describe the incidence and patterns of injury in one province in South Eastern Iran.
A hospital-based, retrospective case review using a routinely collected registry in all Emergency Departments in Sistan and Baluchistan province, Iran for 12 months in 2007–2008.
In total 18,155 injuries were recorded during the study period. The majority of injuries in South Eastern Iran were due to road traffic crashes. Individuals living in urban areas sustained more injuries compared to individuals from rural areas. Males typically experienced more injuries than females. Males were most likely to be injured in a street/alley or village whereas females were most likely to be injured in or around the home. In urban areas, road traffic related injuries were observed to affect older age groups more than younger age groups. Poisoning was most common in the youngest age group, 0 to 4 years.
This study provides data on incidence and patterns of injury in South Eastern Iran. Knowledge of injury burden, such as this paper, is likely to help policy makers and planners with health service planning and injury prevention.
Iran; Injury; Road traffic crash; Urban/rural; Sex
There has been increasing focus on the role of health systems in low and middle-income countries. Despite this, very little evidence exists on how best to build health systems program and research capacity in educational programs. The current experiences in building capacity in health systems in five of the most prominent global health programs at Australian universities are outlined. The strengths and weaknesses of various approaches and techniques are provided along with examples of global practice in order to provide a foundation for future discussion and thus improvements in global health systems education.
Current antiretroviral treatment (ART) models in Africa are labour intensive and require a high number of skilled staff. In the context of constraints in human resources for health, task shifting is considered a feasible alternative for ART service delivery. In 2006, Dignitas International in partnership with the Malawi Ministry of Health trained a cadre of expert patients at the HIV Clinic at a tertiary referral hospital in Zomba, Malawi. Expert patients were trained to assist with clinic tasks including measurement of vital signs, anthropometry and counseling.
A descriptive observational study using mixed methods was conducted two years after the start of program implementation. Semi-structured interviews were conducted with 20 patients, seven expert patients and six formal health care providers to explore perceptions towards the expert patients’ contributions in the clinic. Structured exit interviews with 81 patients, assessed whether essential ART information was conveyed during counseling sessions. Vital signs and anthropometry measurements performed by expert patients were repeated by a nurse to assess accuracy of measurements. Direct observations quantified the time spent with each patient.
There were minor differences in measurement of patients’ weight, height and temperature between the expert patients and the nurse. The majority of patients exiting a counseling session reported, without prompting, at least three side effects of ART, correct actions to be taken on observing a side-effect, and correct consequences of non-adherence to ART. Expert patients carried out 368 hours of nurse tasks each month, saving two and a half full-time nurse equivalents per month. Formal health care workers and patients accept and value expert patients’ involvement in ART provision and care. Expert patients felt valued by patients for being a ‘role model’, or a ‘model of hope’, promoting positive living and adherence to ART.
Expert patients add value to the ART services at a tertiary referral HIV clinic in Malawi. Expert patients carry out shifted tasks acceptably, saving formal health staff time, and also act as ‘living testimonies’ of the benefits of ART and can be a means of achieving greater involvement of People Living with HIV in HIV treatment programs.
Task Shifting; Expert patients; Antiretroviral treatment; Malawi
Healthcare professionals’ participation in short-term medical missions to low and middle income countries (LMIC) to provide healthcare has become common over the past 50 years yet little is known about the quantity and quality of these missions. The aim of this study was to review medical mission publications over 25 years to better understand missions and their potential impact on health systems in LMICs.
A literature review was conducted by searching Medline for articles published from 1985–2009 about medical missions to LMICs, revealing 2512 publications. Exclusion criteria such as receiving country and mission length were applied, leaving 230 relevant articles. A data extraction sheet was used to collect information, including sending/receiving countries and funding source.
The majority of articles were descriptive and lacked contextual or theoretical analysis. Most missions were short-term (1 day – 1 month). The most common sending countries were the U.S. and Canada. The top destination country was Honduras, while regionally Africa received the highest number of missions. Health care professionals typically responded to presenting health needs, ranging from primary care to surgical relief. Cleft lip/palate surgeries were the next most common type of care provided.
Based on the articles reviewed, there is significant scope for improvement in mission planning, monitoring and evaluation as well as global and/or national policies regarding foreign medical missions. To promote optimum performance by mission staff, training in such areas as cross-cultural communication and contextual realities of mission sites should be provided. With the large number of missions conducted worldwide, efforts to ensure efficacy, harmonisation with existing government programming and transparency are needed.
medical missions; low- and middle-income countries; volunteer; human resources
There are minimal data available on critical care case-mix, care processes and outcomes in lower and middle income countries (LMICs). The objectives of this paper were to gather data in the Solomon Islands in order to gain a better understanding of common presentations of critical illness, available hospital resources, and what resources would be helpful in improving the care of these patients in the future.
This study used a mixed methods approach, including a cross sectional survey of respondents' opinions regarding critical care needs, ethnographic information and qualitative data.
The four most common conditions leading to critical illness in the Solomon Islands are malaria, diseases of the respiratory system including pneumonia and influenza, diabetes mellitus and tuberculosis. Complications of surgery and trauma less frequently result in critical illness. Respondents emphasised the need for basic critical care resources in LMICs, including equipment such as oximeters and oxygen concentrators; greater access to medications and blood products; laboratory services; staff education; and the need for at least one national critical care facility.
A large degree of critical illness in LMICs is likely due to inadequate resources for primary prevention and healthcare; however, for patients who fall through the net of prevention, there may be simple therapies and context-appropriate resources to mitigate the high burden of morbidity and mortality. Emphasis should be on the development and acquisition of simple and inexpensive tools rather than complicated equipment, to prevent critical care from unduly diverting resources away from other important parts of the health system.
Critical care; Critical illness; Solomon Islands; Lower and middle income countries
Nearly 3 million people in resource-poor countries receive antiretrovirals for the treatment of HIV/AIDS, yet millions more require treatment. Key barriers to treatment scale up are shortages of trained health care workers, and challenges integrating HIV/AIDS care with primary care.
PALM PLUS (Practical Approach to Lung Health and HIV/AIDS in Malawi) is an intervention designed to simplify and integrate existing Malawian national guidelines into a single, simple, user-friendly guideline for mid-level health care workers. Training utilizes a peer-to-peer educational outreach approach. Research is being undertaken to evaluate this intervention to generate evidence that will guide future decision-making for consideration of roll out in Malawi. The research consists of a cluster randomized trial in 30 public health centres in Zomba District that measures the effect of the intervention on staff satisfaction and retention, quality of patient care, and costs through quantitative, qualitative and health economics methods.
Results and outcomes
In the first phase of qualitative inquiry respondents from intervention sites demonstrated in-depth knowledge of PALM PLUS compared to those from control sites. Participants in intervention sites felt that the PALM PLUS tool empowered them to provide better health services to patients. Interim staff retention data shows that there were, on average, 3 to 4 staff departing from the control and intervention sites per month. Additional qualitative, quantitative and economic analyses are planned.
Dignitas International and the Knowledge Translation Unit at the University of Cape Town Lung Institute have led the adaptation and development of the PALM PLUS intervention, using experience gained through the implementation of the South African precursor, PALSA PLUS. The Malawian partners, REACH Trust and the Research Unit at the Ministry of Health, have led the qualitative and economic evaluations. Dignitas and Ministry of Health have facilitated interaction with implementers and policy-makers.
Challenges and successes
This initiative is an example of South-South knowledge translation between South Africa and Malawi, mediated by a Canadian academic-NGO hybrid. Our success in developing and rolling out PALM PLUS in Malawi suggests that it is possible to adapt and implement this intervention for use in other resource-limited settings.
There are approximately 3 million people aged 50 and older in sub-Saharan Africa who are HIV-positive. Despite this, little is known about the characteristics of older adults who are on treatment and their treatment outcomes.
A retrospective cohort analysis was performed using routinely collected data with Malawi Ministry of Health monitoring tools from facilities providing antiretroviral therapy services in Zomba district. Patients aged 25 years and older initiated on treatment from July 2005 to June 2010 were included. Differences in survival, by age group, were determined using Kaplan–Meier survival plots and Cox proportional hazards regression models.
There were 10,888 patients aged 25 and older. Patients aged 50 and older (N = 1419) were more likely to be male (P<0.0001) and located in rural areas (P = 0.003) than those aged 25–49. Crude survival estimates among those aged 50–59 were not statistically different from those aged 25–49 (P = 0.925). However, survival among those aged 60 and older (N = 345) was worse (P = 0.019) than among those 25–59. In the proportional hazards model, after controlling for sex and stage at initiation, survival in those aged 50–59 did not differ significantly from those aged 25–49 (hazard ratio 1.00 (95% CI: 0.79 to 1.27; P = 0.998) but the hazard ratio was 1.46 (95% CI: 1.03 to 2.06; P = 0.032) for those aged 60 and older compared to those aged 25–49.
Treatment outcomes of those aged 50–59 are similar to those aged 25–49. A better understanding of how older adults present for and respond to treatment is critical to improving HIV services.
There is little published research investigating sex work in Namibia, particularly in rural areas. Therefore, the aim of this paper was to determine the views of women engaged in sex work in the Oshakati area of Namibia concerning the main factors influencing their use, or non-use, of male condoms during transactional sexual exchanges.
Qualitative interviews were used to better understand the perceptions, experiences and economic considerations of female sex workers in Namibia who were involved in a Behavior Change Communication Program encouraging safer sex practices among high-risk populations in 2006 and 2007.
While the Behavior Change Communication Program has made significant strides in educating and empowering young women to negotiate more consistent condom use with sexual partners, the gendered economic inequalities and power imbalances within rural and semi-urban Namibian society that favor men hinder further advancement towards positive behavioral change for HIV prevention and also hinder the development of the loving relationships sought by some sex workers.
This study found that sex workers and transactional sex encounters are heterogeneous entities dependent upon the characteristics of the man (known, stranger, wealthy, attractive to the woman) and the woman (in financial need, desiring love). These features all influence condom use. The 3 E's 'education, empowerment and economic independence' are critical factors needed to encourage and facilitate consistent condom use to prevent HIV transmission. Without financial independence and occupational alternatives building on their health education and empowerment, women who engage in sex work-and transactional sex more generally-will remain largely marginalized from Namibian society, and will continue engaging in risky sexual practices that facilitate HIV acquisition and transmission throughout the community.
Epilepsy affects an estimated 50 million people and accounts for approximately 1% of days lost to ill health globally, making it one of the most common, serious neurological disorders. While there are abundant global data on epilepsy incidence, prevalence and treatment, there is a paucity of Australian incidence data. There is also a general lack of information on the psychosocial impact and socioeconomic consequences of a new diagnosis of epilepsy on an individual, their family, household, and community which are often specific to the health and social system of each country.
The Sydney Epilepsy Incidence Study to Measure Illness Consequences (SEISMIC) is an Australian population-based epilepsy incidence and outcome study that will recruit every newly diagnosed case of epilepsy in the Sydney South West Area Health Service to an epilepsy register. Multiple and overlapping sources of notification will be used to identify all new cases of epilepsy over a 24 month period in the Eastern Zone of the Sydney South West Area Health Service (SSWAHS) and follow up will occur over 12 months. SEISMIC will use the International League Against Epilepsy (ILAE) definitions and classifications for epidemiologic studies of epilepsy. The study will examine outcomes including mood, quality of life, employment, education performance, driving status, marital and social problems, medication use, health care usage, costs and stigma.
This study is designed to examine how clinical, psychological factors, socioeconomic circumstances, and healthcare delivery influence the experience of epilepsy for individuals and families allowing better targeting of specific services and informing policy makers and practitioners. In addition, the study will provide the basis for a longitudinal population-based cohort study and potentially inform qualitative sub-studies and randomised controlled trials of intervention strategies. The study has been registered on the Australia New Zealand Clinical Trial Registration database with ANZCTRN12609000059268.
In low-income countries, only about a third of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) patients eligible for anti-retroviral treatment currently receive it. Providing decentralized treatment close to where patients live is crucial to a faster scale up, however, a key obstacle is limited health system capacity due to a shortage of trained health-care workers and challenges of integrating HIV/AIDS care with other primary care services (e.g. tuberculosis, malaria, respiratory conditions). This study will test an adapted primary care health care worker training and guideline intervention, Practical Approach to Lung Health and HIV/AIDS Malawi (PALM PLUS), on staff retention and satisfaction, and quality of patient care.
A cluster-randomized trial design is being used to compare usual care with a standardized clinical guideline and training intervention, PALM PLUS. The intervention targets middle-cadre health care workers (nurses, clinical officers, medical assistants) in 30 rural primary care health centres in a single district in Malawi. PALM PLUS is an integrated, symptom-based and user-friendly guideline consistent with Malawian national treatment protocols. Training is standardized and based on an educational outreach approach. Trainers will be front-line peer healthcare workers trained to provide outreach training and support to their fellow front-line healthcare workers during focused (1-2 hours), intermittent, interactive sessions on-site in health centers. Primary outcomes are health care worker retention and satisfaction. Secondary outcomes are clinical outcomes measured at the health centre level for HIV/AIDS, tuberculosis, prevention-of-mother-to-child-transmission of HIV and other primary care conditions. Effect sizes and 95% confidence intervals for outcomes will be presented. Assessment of outcomes will occur at 1 year post- implementation.
The PALM PLUS trial aims to address a key problem: strengthening middle-cadre health care workers to support the broader scale up of HIV/AIDS services and their integration into primary care. The trial will test whether the PALM PLUS intervention improves staff satisfaction and retention, as well as the quality of patient care, when compared to usual practice.
Current controlled Trials: ISRCTN47805230
Some motor vehicle crashes, particularly single-vehicle crashes, may result from intentional self-harm. We conducted a prospective cohort study to assess the risk that intentional self-harm poses for motor vehicle crashes among young drivers.
We prospectively linked survey data from newly licensed drivers aged 17–24 years to data on licensing attempts and police-reported motor vehicle crashes during the follow-up period. We investigated the role of recent engagement in self-harm on the risk of a crash. We took into account potential confounders, including number of hours of driving per week, psychological symptoms and substance abuse.
We included 18 871 drivers who participated in the DRIVE Study for whom data on self-harm and motor vehicle crashes were available. The mean follow-up was 2 years. Overall, 1495 drivers had 1 or more crashes during the follow-up period. A total of 871 drivers (4.6%) reported that they had engaged in self-harm in the year before the survey. These drivers were at significantly increased risk of a motor vehicle crash compared with drivers who reported no self-harm (relative risk [RR] 1.42, 95% confidence interval [CI] 1.15–1.76). The risk remained significant, even after adjustment for age, sex, average hours of driving per week, previous crash, psychological distress, duration of sleep, risky driving behaviour, substance use, remoteness of residence and socio-economic status (RR 1.37, 95% CI 1.09–1.72). Most of the drivers who reported self-harm and had a subsequent crash were involved in a multiple-vehicle crash (84.1% [74/88]).
Engagement in self-harm behaviour was an independent risk factor for subsequent motor vehicle crash among young drivers, with most crashes involving multiple vehicles.
Although smoking is an established causal factor for upper aero digestive tract cancer (UADTC), most of the evidence originates from the West. Thus, we analysed data from 455,409 subjects in the Asia Pacific Cohort Studies Collaboration. Over a median of around six years follow-up, 371 deaths from UADTC were observed. The hazard ratio (95% confidence interval) for current smokers, compared with those who had never smoked, was 2.36 (1.76 – 3.16), adjusted for age and alcohol drinking. Tobacco control policies are urgently required in Asia to prevent millions of deaths from UADTC that smoking will otherwise cause.
Cancer of the pharynx; cancer of the larynx; cancer of the esophagus; smoking; alcohol