Cancer prevention in primary care. Current trends and some prospects for the future--II.

Cancer control encompasses the whole spectrum from prevention and early diagnosis to treatment and palliation. The key to the future of cancer control will be to establish multidisciplinary approaches to each type of cancer across this spectrum. For primary prevention this requires some understanding of the causes of each cancer. Although understanding of the aetiology of cancer has greatly improved, prospects for the primary prevention of many common cancers remain remote. Other approaches currently under evaluation include chemoprevention and the use of biomarkers (discussed last week). The identification of predisposing genes for some of the common cancers may have a considerable impact on the ability to recognise those at risk. Overall, however, mortality trends indicate that reduction of smoking remains the main priority for cancer prevention in the United Kingdom. For primary care teams, brief interventions to reduce smoking are likely to achieve the greatest benefit. This should be seen as part of broader policies aimed at achieving change in the whole population. The government must acknowledge its major responsibility to cancer prevention by banning all forms of advertising and promotion of tobacco.     

Cancer prevention in primary care. Current trends and some prospects for the future--1.

Cancer control encompasses the whole spectrum from prevention and early diagnosis to treatment and palliation. The key to the future of cancer control will be to establish multidisciplinary approaches to each type of cancer across this spectrum. For primary prevention this requires some understanding of the causes of each cancer. Although understanding of the aetiology of cancer has greatly improved, prospects for the primary prevention of many common cancers remain remote. Other approaches currently under evaluation include chemoprevention and the use of biomarkers. The identification of predisposing genes for some of the common cancers may have a considerable impact on the ability to recognise those at risk. Overall, however, mortality trends indicate that reduction of smoking remains the main priority for cancer prevention in the United Kingdom. For primary care teams, brief interventions to reduce smoking are likely to achieve the greatest benefit. This should be seen as part of broader policies aimed at achieving change in the whole population. The government must acknowledge its major responsibility to cancer prevention by banning all forms of advertising and promotion of tobacco.     

Smoking and cancer: smoking cessation.

Smoking is the single most important cause of cancer. The risk of developing cancer is reduced by stopping smoking and decreases substantially after five years. Reduction in smoking must be central to any programme aimed seriously at the prevention of cancer. An individual approach, based in primary care, has the potential to bring about modest but important reductions in risk. Many randomised trials have shown the effectiveness of various smoking cessation interventions in primary care. Given resource limitations in primary care, individual effort should be focused on those at highest risk who are motivated to stop smoking. A population strategy has considerable advantages over the high risk approach as the potential for reducing morbidity and mortality in the whole population is much greater. The government must acknowledge its major responsibility; the outstanding example of its failure to do this is its persistent refusal to ban outright all forms of advertising and promotion of tobacco. There is clear evidence that a ban would contribute to a reduction in smoking prevalence and especially in the uptake of smoking by children.     

Diet and cancer.

Accumulating data indicate that modifications in diet may reduce the risk of cancer by as much as one third and possibly by as much as two thirds. On the basis of the existing evidence, however, it is not possible to be certain which cancers are causally related to diet and what proportion of them are due to specific components of the diet. Diet is currently thought to be a major factor in the aetiology of cancers of the large bowel and stomach, and it may also be important in the aetiology of several other cancers. With the exception of strong and consistent evidence of the protective effect of fruit and vegetables, practical dietary interventions that reduce the risk of cancer are difficult to formulate as, in general, the evidence is theoretical or contradictory and too weak to justify specific intervention. Authoritative guidelines on dietary management in primary care are conspicuously absent because of lack of research. The success of an individual based strategy will depend on adequate education, training, and support being made available to the relevant members of primary care teams.     

Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development,internal validation,and net benefit analysis

BackgroundUnexpected weight loss (UWL) is a presenting feature of cancer in primary care. Existing research proposes simple combinations of clinical features (risk factors, symptoms, signs, and blood test data) that, when present, warrant cancer investigation. More complex combinations may modify cancer risk to sufficiently rule-out the need for investigation. We aimed to identify which clinical features can be used together to stratify patients with UWL based on their risk of cancer.Methods and findingsWe used data from 63,973 adults (age: mean 59 years, standard deviation 21 years; 42% male) to predict cancer in patients with UWL recorded in a large representative United Kingdom primary care electronic health record between January 1, 2000 and December 31, 2012. We derived 3 clinical prediction models using logistic regression and backwards stepwise covariate selection: Sm, symptoms-only model; STm, symptoms and tests model; Tm, tests-only model. Fifty imputations replaced missing data. Estimates of discrimination and calibration were derived using 10-fold internal cross-validation. Simple clinical risk scores are presented for models with the greatest clinical utility in decision curve analysis. The STm and Tm showed improved discrimination (area under the curve ≥ 0.91), calibration, and greater clinical utility than the Sm. The Tm was simplest including age-group, sex, albumin, alkaline phosphatase, liver enzymes, C-reactive protein, haemoglobin, platelets, and total white cell count. A Tm score of 5 balanced ruling-in (sensitivity 84.0%, positive likelihood ratio 5.36) and ruling-out (specificity 84.3%, negative likelihood ratio 0.19) further cancer investigation. A Tm score of 1 prioritised ruling-out (sensitivity 97.5%). At this threshold, 35 people presenting with UWL in primary care would be referred for investigation for each person with cancer referred, and 1,730 people would be spared referral for each person with cancer not referred. Study limitations include using a retrospective routinely collected dataset, a reliance on coding to identify UWL, and missing data for some predictors.ConclusionsOur findings suggest that combinations of simple blood test abnormalities could be used to identify patients with UWL who warrant referral for investigation, while people with combinations of normal results could be exempted from referral.

Dr. Brian D Nicholson and colleagues investigate whether combinations of routine blood tests could be used to stratify patients in UK with unexpected weight loss based on their risk of cancer.     

Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: A cohort study

BackgroundThe diagnostic assessment of abdominal symptoms in primary care presents a challenge. Evidence is needed about the positive predictive values (PPVs) of abdominal symptoms for different cancers and inflammatory bowel disease (IBD).Methods and findingsUsing data from The Health Improvement Network (THIN) in the United Kingdom (2000–2017), we estimated the PPVs for diagnosis of (i) cancer (overall and for different cancer sites); (ii) IBD; and (iii) either cancer or IBD in the year post-consultation with each of 6 abdominal symptoms: dysphagia (n = 86,193 patients), abdominal bloating/distension (n = 100,856), change in bowel habit (n = 106,715), rectal bleeding (n = 235,094), dyspepsia (n = 517,326), and abdominal pain (n = 890,490). The median age ranged from 54 (abdominal pain) to 63 years (dysphagia and change in bowel habit); the ratio of women/men ranged from 50%:50% (rectal bleeding) to 73%:27% (abdominal bloating/distension). Across all studied symptoms, the risk of diagnosis of cancer and the risk of diagnosis of IBD were of similar magnitude, particularly in women, and younger men. Estimated PPVs were greatest for change in bowel habit in men (4.64% cancer and 2.82% IBD) and for rectal bleeding in women (2.39% cancer and 2.57% IBD) and lowest for dyspepsia (for cancer: 1.41% men and 1.03% women; for IBD: 0.89% men and 1.00% women). Considering PPVs for specific cancers, change in bowel habit and rectal bleeding had the highest PPVs for colon and rectal cancer; dysphagia for esophageal cancer; and abdominal bloating/distension (in women) for ovarian cancer. The highest PPVs of abdominal pain (either sex) and abdominal bloating/distension (men only) were for non-abdominal cancer sites. For the composite outcome of diagnosis of either cancer or IBD, PPVs of rectal bleeding exceeded the National Institute of Health and Care Excellence (NICE)-recommended specialist referral threshold of 3% in all age–sex strata, as did PPVs of abdominal pain, change in bowel habit, and dyspepsia, in those aged 60 years and over. Study limitations include reliance on accuracy and completeness of coding of symptoms and disease outcomes.ConclusionsBased on evidence from more than 1.9 million patients presenting in primary care, the findings provide estimated PPVs that could be used to guide specialist referral decisions, considering the PPVs of common abdominal symptoms for cancer alongside that for IBD and their composite outcome (cancer or IBD), taking into account the variable PPVs of different abdominal symptoms for different cancers sites. Jointly assessing the risk of cancer or IBD can better support decision-making and prompt diagnosis of both conditions, optimising specialist referrals or investigations, particularly in women.

Annie Herbert and co-workers study possible relevance of common abdominal symptoms for specialist referral in UK primary care.     

A sociobehavioural perspective on genetic testing and counselling for heritable breast,ovarian and colon cancer.

Testing for susceptibility to heritable breast, ovarian and colon cancer has unique psychosocial costs. Negative test results may not be sufficient to relieve anxiety, and positive results can cause sufficient distress to compromise patient compliance with surveillance and risk reduction measures. More needs to be learned about how sociocultural factors affect the understanding of risk, how decisions to undergo testing are made and how information about increased risk affects family dynamics. As the demand for testing and counselling grows, health care providers will be faced with new challenges and dilemmas. A better understanding of genetics by the public is needed to mitigate deterministic attitudes that can lead to the neglect of health promotion. Also of concern are the socioeconomic implications of being identified as having a high risk for heritable cancer and the dangers inherent in using genetics to explain sociological phenomena. Health care providers must take the lead in ensuring that developments in genetics are used to the benefit of all.     

Health promotion priorities for general practice: constructing and using "indicative prevalences".

OBJECTIVE--To construct indicative prevalences for a range of diseases and risk markers and use them in planning health promotion interventions in primary health care. DESIGN--Indicative prevalences comprised point prevalence, incidence, and mortality measures. Use of data from Office of Population Censuses and Surveys, Northern Regional Health Authority, and Newcastle health and lifestyle survey 1991, and research papers to determine prevalence adjusted for age and sex in a hypothetical practice with a list of 10,000 patients. SETTING--Newcastle upon Tyne, England. RESULTS--Indicative prevalences were highest for common risk markers such as failure to achieve exercise targets (6871), moderate to extreme obesity (2785), and smoking (2689); moderate for overt disease such as angina (175) and stroke (20/year); and low for events such as suicide (1/year) and deaths from malignant melanoma (2/10 years). CONCLUSIONS--Given limited time and resources, brief interventions to reduce smoking and the systematic case finding and management of patients with hypertension, angina, and previous myocardial infarction are likely to be the highest priorities for health promotion in primary care.     

The geography of genetics: an analysis of referral patterns to a cancer genetics service

This study uses a geographical information system (GIS) and statistical analysis to look for patterns in referrals to a British cancer genetics service. In this case, familial cancers are taken to be those that can develop when an individual inherits DNA mutations that cause an increased risk of cancer. Between 1998 and 2006 the Cancer Genetics Service for Wales received nearly 11,000 referrals for patients resident in Wales and it is the service database recording those referrals which is the subject of this secondary analysis. Using postcodes to match referred patients to areas, deprivation scores were assigned. Referral rates per 10,000 head of population across the 8-year study period by unitary authority are presented, as is information on referrals from primary and secondary care sources by year. Each patient referred has their family history of cancer recorded and is assigned to a risk category; high, medium or average. There are correlations between number of GPs (General Practitioners) in a practice, number of patients referred from a practice, and deprivation as measured by the overall Welsh Index of Multiple Deprivation 2005, such that the two former factors increase as deprivation decreases. Over time there were changes in referral sources, with referrals from primary care overtaking those from secondary care in percentage and absolute terms. There were also changes in the types of cancer referred, risk categories seen and to which centre referrals were made. Referral patterns reveal an inverse relationship between deprivation and health service availability and use.     

Reducing alcohol intake.

Alcohol is second in importance only to smoking as a proved cause of cancer. The risk associated with excessive alcohol consumption can be reduced by adopting national and local population based policies. The population approach is aimed at reducing the level of consumption across the whole population, which contains many modest drinkers. Underlying this approach is the fact that a larger proportion of the total morbidity and mortality attributed to alcohol in a population occurs in modest drinkers, even though individually they are at lower risk. This approach should be complemented by risk reduction initiatives in primary care, focused on high risk individuals. Several studies have shown the efficacy of brief interventions by general practitioners in patients with excessive alcohol consumption. Brief interventions, taking 5 to 10 minutes, use simple assessments to identify those at risk and provide information and advice. Evidence exists that general practitioners underuse opportunities to identify and advise patients about excessive drinking.     

Prevention of psychosocial problems in children with chronic illness.

Children with chronic illness and disability are at considerably increased risk of psychosocial problems, such as neurosis, attention deficit and poor adjustment to school. Health care professionals, especially primary care physicians, can do a great deal to prevent such problems in these children and their families. The approach outlined here is based on an understanding of the transactional model of development, in which the child interacts with--and to some extent creates--the social environment, and on a "noncategorical" concept in which common elements in chronic illness are recognized and emphasized. The physician''s role is to inform the family of the child''s condition as soon as possible, to offer hope, encouragement and guidance, to watch the child''s development, to maintain a shared view of the child and family, and, if possible, to ensure continuity of care.     

Risk-Specific Optimal Cancer Screening Schedules: An Application to Breast Cancer Early Detection

The optimal schedules for breast cancer screening in terms of examination frequency and ages at examination are of practical interest. A decision-theoretic approach is explored to search for optimal cancer screening programs which should achieve maximum survival benefit while balancing the associated cost to the health care system. We propose a class of utility functions that account for costs associated with screening examinations and value of survival benefit under a non-stable disease model. We consider two different optimization criteria: optimize the number of screening examinations with equal screening intervals between exams but without a prefixed total cost; and optimize the ages at which screening should be given for a fixed total cost. We show that an optimal solution exists under each of the two frameworks. The proposed methods may consider women at different levels of risk for breast cancer so that the optimal screening strategies will be tailored according to a woman’s risk of developing the disease. Results of a numerical study are presented and the proposed models are illustrated with various data inputs. We also use the data inputs from the Health Insurance Plan of New York (HIP) and Canadian National Breast Screening Study (CNBSS) to illustrate the proposed models and to compare the utility values between the optimal schedules and the actual schedules in the HIP and CNBSS trials. Here, the utility is defined as the difference in cure rates between cases found at screening examinations and cases found between screening examinations while accounting for the cost of examinations, under a given screening schedule.     

Estrogens and women's health: interrelation of coronary heart disease, breast cancer and osteoporosis

The determinants of blood levels of estrogen, estrogen metabolites, and relation to receptors and post-transitional effects are the likely primary cause of breast cancer. Very high risk women for breast cancer can now be identified by measuring bone mineral density and hormone levels. These high risk women have rates of breast cancer similar to risk of myocardial infarction. They are candidates for SERM therapies to reduce risk of breast cancer. The completion of the Women's Health Initiative and other such trials will likely provide a definite association of risk and benefit of both estrogen alone and estrogen-progesterone therapy, coronary heart disease, osteoporotic fracture, and breast cancer. The potential intervention of hormone replacement therapy, obesity, or weight gain and increased atherogenic lipoproteinemia may be of concern and confound the results of clinical trials. Estrogens, clearly, are important in the risk of bone loss and osteoporotic fracture. Obesity is the primary determinant of postmenopausal estrogen levels and reduced risk of fracture. Weight reduction may increase rates of bone loss and fracture. Clinical trials that evaluate weight loss should monitor effects on bone. The beneficial addition of increased physical activity, higher dose of calcium or vitamin D, or use of bone reabsorption drugs in coordination with weight loss should be evaluated. Any therapy that raises blood estrogen or metabolite activity and decreases bone loss may increase risk of breast cancer. Future clinical trials must evaluate multiple endpoints such as CHD, osteoporosis, and breast cancer within the study. The use of surrogate markers such as bone mineral density, coronary calcium, carotid intimal medial thickness and plaque, endothelial function, breast density, hormone levels and metabolites could enhance the evaluation of risk factors, genetic-environmental intervention, and new therapies.     

From intervention to impact: modelling the potential mortality impact achievable by different longlasting, insecticide-treated net delivery strategies

ABSTRACT: BACKGROUND: The current target of universal access to long-lasting, insecticide-treated nets (LLIN) is 80% coverage to reduce malaria deaths by 75% by 2015. So far, campaigns have been the main channel for large-scale delivery of LLINs, however the World Health Organization has recommended that equal priority should be given to delivery via routine antenatal care (ANC) and immunization systems (EPI) to target pregnant women and children from birth. These various channels of LLIN delivery are targeted to children of different ages. Since risk of mortality varies with child age and LLIN effectiveness declines with net age, it was hypothesized that the age at which a child receives a new LLIN, and therefore the delivery channel, is important in optimizing the health impact of a net. METHODS: A simple dynamic mathematical model was developed of delivery and impact of LLINs among children under five years of age and their household members, incorporating data on age-specific malaria death rates, net use by household structure, and net efficacy over time. RESULTS: The presented analysis finds that supplementing a universal mass campaign with extra ANC delivery would achieve a 1.4 times higher mortality reduction than campaign delivery alone, reflecting that children born in the years between campaigns would otherwise have access to old nets or no nets at an age of high risk. The relative advantage of supplementary ANC delivery is still present though smaller if malaria transmission levels are lower or if there is a strong mass effect achieved by mass campaigns. CONCLUSION: These results indicate that LLIN delivery policies must take into account the age of greatest malaria risk. Emphasis should be placed on supporting routine delivery of LLINs to young children as well as campaigns. Lucy C Okell and Lucy Smith Paintain contributed equally.     

A conceptual framework for the revision of the ICD-10 classification of mental and behavioural disorders

The World Health Organization (WHO) is revising the ICD-10 classification of mental and behavioural disorders, under the leadership of the Department of Mental Health and Substance Abuse and within the framework of the overall revision framework as directed by the World Health Assembly. This article describes WHO’s perspective and priorities for mental and behavioural disorders classification in ICD-11, based on the recommendations of the International Advisory Group for the Revision of ICD-10 Mental and Behavioural Disorders. The WHO considers that the classification should be developed in consultation with stakeholders, which include WHO member countries, multidisciplinary health professionals, and users of mental health services and their families. Attention to the cultural framework must be a key element in defining future classification concepts. Uses of the ICD that must be considered include clinical applications, research, teaching and training, health statistics, and public health. The Advisory Group has determined that the current revision represents a particular opportunity to improve the classification’s clinical utility, particularly in global primary care settings where there is the greatest opportunity to identify people who need mental health treatment. Based on WHO’s mission and constitution, the usefulness of the classification in helping WHO member countries, particularly low- and middle-income countries, to reduce the disease burden associated with mental disorders is among the highest priorities for the revision. This article describes the foundation provided by the recommendations of the Advisory Group for the current phase of work.     

Present state and possibilities for improvement of cancer prevention and early detection in the Osijek-Baranya county

Cancer morbidity and mortality are on a steady increase in Croatia. Technologic possibilities for appropriate management are available for four cancer sites, i.e. cancer of the breast, cervix uteri, colorectum and prostate, and include cancer prevention and early detection in individuals yet free from manifest signs of the disease. The magnitude of the problem, the experience acquired to date, health care personnel available, and additional resources required to launch a systematic program of early detection of the disease are presented. The program should be initially launched in a county with greatest experience in early detection of cancer, where health care service is ready to immediately start its implementation. The role of family physician, gynecologic service at primary health care level, and polyclinic-consultation hospital service in program implementation is described. The following three possible options for early detection of cancer are analyzed and proposed: minimal program (early detection every 3 years), medium program (the same individuals examined every 2 years), and optimal program proposed by the American Cancer Society and other national and international organizations.     

Costs and Cost-Effectiveness of Hypertension Screening and Treatment in Adults with Hypertension in Rural Nigeria in the Context of a Health Insurance Program

BackgroundHigh blood pressure is a leading risk factor for death and disability in sub-Saharan Africa (SSA). We evaluated the costs and cost-effectiveness of hypertension care provided within the Kwara State Health Insurance (KSHI) program in rural Nigeria.MethodsA Markov model was developed to assess the costs and cost-effectiveness of population-level hypertension screening and subsequent antihypertensive treatment for the population at-risk of cardiovascular disease (CVD) within the KSHI program. The primary outcome was the incremental cost per disability-adjusted life year (DALY) averted in the KSHI scenario compared to no access to hypertension care. We used setting-specific and empirically-collected data to inform the model. We defined two strategies to assess eligibility for antihypertensive treatment based on 1) presence of hypertension grade 1 and 10-year CVD risk of >20%, or grade 2 hypertension irrespective of 10-year CVD risk (hypertension and risk based strategy) and 2) presence of hypertension in combination with a CVD risk of >20% (risk based strategy). We generated 95% confidence intervals around the primary outcome through probabilistic sensitivity analysis. We conducted one-way sensitivity analyses across key model parameters and assessed the sensitivity of our results to the performance of the reference scenario.ResultsScreening and treatment for hypertension was potentially cost-effective but the results were sensitive to changes in underlying assumptions with a wide range of uncertainty. The incremental cost-effectiveness ratio for the first and second strategy respectively ranged from US$ 1,406 to US$ 7,815 and US$ 732 to US$ 2,959 per DALY averted, depending on the assumptions on risk reduction after treatment and compared to no access to antihypertensive treatment.ConclusionsHypertension care within a subsidized private health insurance program may be cost-effective in rural Nigeria and public-private partnerships such as the KSHI program may provide opportunities to finance CVD prevention care in SSA.     

Modification of interleukin-15 serum levels in workers exposed to chemotherapeutic agents

Cytostatic anticancer drugs are known as carcinogenic, mutagenic, and teratogenic risk factors for health care workers occupationally exposed. It has been demonstrated that the administration of interleukin-15 in rat models of colon carcinoma protects against chemotherapy-induced gastrointestinal toxicities. We found that occupational exposure to chemotherapeutic antiblastic agents in vivo modified circulating levels of interleukin-15 in 17 health care workers exposed to antineoplastic drugs in relation to their jobs and in as many healthy age- and sex-matched subjects. Health care workers displayed significantly higher circulating interleukin-15 levels compared to their age-matched controls. If this increase representing an anticancer response remains to be established, these findings strengthen the idea of a therapeutic use of interleukin-15 in the field of cancer.     

Pulmonary aspergillosis and endophthalmitis: complications of Cushing's syndrome.

Ischemic heart disease continues to be the leading cause of death among middle-aged people in industrialized countries. However, in North America the rates of death and disability from coronary artery disease (CAD) have declined, mostly because of a reduction of the main modifiable risk factors (high serum cholesterol levels, smoking and hypertension). Intervention trials have consistently shown that the lowering of the severity of risk factors decreases the incidence of CAD. These studies have introduced the goals of preventive cardiology to clinicians but have not provided the necessary knowledge and skills to achieve them. Unfortunately, with the exception of hypertension, the risk factors for CAD are infrequently assessed and managed in ambulatory patients. Incorporation of detection and intervention strategies derived from recent epidemiologic, behavioural and biomedical research into the existing primary health care system may be the most efficient and effective approach to further reducing the impact of CAD. The family physician''s office is the ideal location to implement behavioural change strategies. However, primary care intervention to decrease the risk of ischemic heart disease among people at high risk has yet to be studied. In addition, whether the same clinicians who render primary care can assume the responsibility for surveillance and preventive care has to be demonstrated.