Iain Buchan

Adherence to HAART: A Systematic Review of Developed and Developing Nation Patient-Reported Barriers and Facilitators

Background Adherence to highly active antiretroviral therapy (HAART) medication is the greatest patient-enabled predictor of treatment success and mortality for those who have access to drugs. We systematically reviewed the literature to determine patient-reported barriers and facilitators to adhering to antiretroviral therapy. Methods and Findings We examined both developed and developing nations. We searched the following databases: AMED (inception to June 2005), Campbell Collaboration (inception to June 2005), CinAhl (inception to June 2005), Cochrane Library (inception to June 2005), Embase (inception to June 2005), ERIC (inception to June 2005), MedLine (inception to June 2005), and NHS EED (inception to June 2005). We retrieved studies conducted in both developed and developing nation settings that examined barriers and facilitators addressing adherence. Both qualitative and quantitative studies were included. We independently, in duplicate, extracted data reported in qualitative studies addressing adherence. We then examined all quantitative studies addressing barriers and facilitators noted from the qualitative studies. In order to place the findings of the qualitative studies in a generalizable context, we meta-analyzed the surveys to determine a best estimate of the overall prevalence of issues. We included 37 qualitative studies and 47 studies using a quantitative methodology (surveys). Seventy-two studies (35 qualitative) were conducted in developed nations, while the remaining 12 (two qualitative) were conducted in developing nations. Important barriers reported in both economic settings included fear of disclosure, concomitant substance abuse, forgetfulness, suspicions of treatment, regimens that are too complicated, number of pills required, decreased quality of life, work and family responsibilities, falling asleep, and access to medication. Important facilitators reported by patients in developed nation settings included having a sense of self-worth, seeing positive effects of antiretrovirals, accepting their seropositivity, understanding the need for strict adherence, making use of reminder tools, and having a simple regimen. Among 37 separate meta-analyses examining the generalizability of these findings, we found large heterogeneity. Conclusions We found that important barriers to adherence are consistent across multiple settings and countries. Research is urgently needed to determine patient-important factors for adherence in developing world settings. Clinicians should use this information to engage in open discussion with patients to promote adherence and identify barriers and facilitators within their own populations.

Smoking and age-related macular degeneration: A review of association

PurposeAge-related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss in the Western world. As there is no effective treatment for all types of AMD, identifying modifiable risk factors is of great importance. This review evaluates the epidemiological evidence associating smoking with AMD.MethodsSystematic review of published epidemiological studies evaluated against established criteria for evidence of a causal relationship.ResultsIn total, 17 studies (cross-sectional studies, prospective cohort studies, and case–control studies) were included in the review. A total of 13 studies found a statistically significant association between smoking and AMD with increased risk of AMD of two- to three-fold in current-smokers compared with never-smokers. Five studies found no association between smoking and AMD. There was also evidence of dose-response, a temporal relationship and reversibility of effect.ConclusionThe literature review confirmed a strong association between current smoking and AMD, which fulfilled established causality criteria. Cigarette smoking is likely to have toxic effects on the retina. In spite of the strength of this evidence, there appears to be a lack of awareness about the risks of developing eye disease from smoking among both healthcare professionals and the general public.

Body Fat Distribution and Risk of Coronary Heart Disease in Men and Women in the European Prospective Investigation Into Cancer and Nutrition in Norfolk Cohort A Population-Based Prospective Study

Background— Body fat distribution has been cross-sectionally associated with atherosclerotic disease risk factors, but the prospective relation with coronary heart disease remains uncertain. Methods and Results— We examined the prospective relation between fat distribution indices and coronary heart disease among 24 508 men and women 45 to 79 years of age using proportional hazards regression. During a mean 9.1 years of follow-up, 1708 men and 892 women developed coronary heart disease. The risk for developing subsequent coronary heart disease increased continuously across the range of waist-hip ratio. Hazard ratios (95% CI) of the top versus bottom fifth of waist-hip ratio were 1.55 (1.28 to 1.73) in men and 1.91 (1.44 to 2.54) in women after adjustment for body mass index and other coronary heart disease risk factors. Hazard ratios increased with waist circumference, but risk estimates for waist circumference without hip circumference adjustment were lower by 10% to 18%. After adjustment for waist circumference, body mass index, and coronary heart disease risk factors, hazard ratios for 1-SD increase in hip circumference were 0.80 (95% CI, 0.74 to 0.87) in men and 0.80 (95% CI, 0.69 to 0.93) in women. Hazard ratios for body mass index were greatly attenuated when we adjusted for waist-hip ratio or waist circumference and other covariates. Conclusions— Indices of abdominal obesity were more consistently and strongly predictive of coronary heart disease than body mass index. These simple and inexpensive measurements could be used to assess obesity-related coronary heart disease risk in relatively healthy men and women.

Prevalence of overweight and obese children between 1989 and 1998: population based series of cross sectional studies

Abstract Objective: To determine trends in weight, height, and body mass index in children between 1989 and 1998. Design: Retrospective series of cross sectional studies of routinely collected data. Setting: Primary care in the Wirral Health Authority. Participants: 35 662 infants aged 1-3 months (representing 88% of live births) and 28 768 children aged 2.9-4.0 years. 21 582 infants and children (25.1%) were excluded because of missing or inaccurate data. Main outcome measures: Weight, height, sex, and age routinely recorded by health visitors. Height, weight, and body mass index standardised for age and sex. SD score >1.04 for body mass index (>85th centile) was defined as overweight and >1.64 (>95th centile) as obese. Body mass index was not calculated in infants as it is difficult to interpret. Results: From 1989 to 1998 there was a highly significant increasing trend in the proportion of overweight children (14.7% to 23.6%; P<0.001) and obese children (5.4% to 9.2%; P<0.001). There was also a highly significant increasing trend in the mean SD score for weight (0.05 to 0.29; P<0.001) and body mass index (−0.15 to 0.31; P<0.001) but not height. Infants showed a small but significantly increasing trend in mean SD score for weight (−0.17 to −0.05; P=0.005). Conclusions: From 1989 to 1998 there was a highly significant increase in weight and body mass index in children under 4 years of age. Routinely collected data are valuable in identifying anthropometric trends in populations.

Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies

Background: Coeliac disease (CD) is a disorder that may depend on genetic, immunological, and environmental factors. Recent observational studies suggest that breast feeding may prevent the development of CD. Aim: To evaluate articles that compared effects of breast feeding on risk of CD. Methods: Systematic review and meta-analysis of observational studies published between 1966 and June 2004 that examined the association between breast feeding and the development of CD. Results: Six case-control studies met the inclusion criteria. With the exception of one small study, all the included studies found an association between increasing duration of breast feeding and decreased risk of developing CD. Meta-analysis showed that the risk of CD was significantly reduced in infants who were breast feeding at the time of gluten introduction (pooled odds ratio 0.48, 95% CI 0.40 to 0.59) compared with infants who were not breast feeding during this period. Conclusions: Breast feeding may offer protection against the development of CD. Breast feeding during the introduction of dietary gluten, and increasing duration of breast feeding were associated with reduced risk of developing CD. It is, however, not clear from the primary studies whether breast feeding delays the onset of symptoms or provides a permanent protection against the disease. Long term prospective cohort studies are required to investigate further the relation between breast feeding and CD.

BEYOND ATOPY: MULTIPLE PATTERNS OF SENSITIZATION IN RELATION TO ASTHMA IN A BIRTH COHORT STUDY

RATIONALE The pattern of IgE response (over time or to specific allergens) may reflect different atopic vulnerabilities which are related to the presence of asthma in a fundamentally different way from current definition of atopy. OBJECTIVES To redefine the atopic phenotype by identifying latent structure within a complex dataset, taking into account the timing and type of sensitization to specific allergens, and relating these novel phenotypes to asthma. METHODS In a population-based birth cohort in which multiple skin and IgE tests have been taken throughout childhood, we used a machine learning approach to cluster children into multiple atopic classes in an unsupervised way. We then investigated the relation between these classes and asthma (symptoms, hospitalizations, lung function and airway reactivity). MEASUREMENTS AND MAIN RESULTS A five-class model indicated a complex latent structure, in which children with atopic vulnerability were clustered into four distinct classes (Multiple Early [112/1053, 10.6%]; Multiple Late [171/1053, 16.2%]; Dust Mite [47/1053, 4.5%]; and Non-dust Mite [100/1053, 9.5%]), with a fifth class describing children with No Latent Vulnerability (623/1053, 59.2%). The association with asthma was considerably stronger for Multiple Early compared with other classes and conventionally defined atopy (odds ratio [95% CI]: 29.3 [11.1-77.2] versus 12.4 [4.8-32.2] versus 11.6 [4.8-27.9] for Multiple Early class versus Ever Atopic versus Atopic age 8). Lung function and airway reactivity were significantly poorer among children in Multiple Early class. Cox regression demonstrated a highly significant increase in risk of hospital admissions for wheeze/asthma after age 3 yr only among children in the Multiple Early class (HR 9.2 [3.5-24.0], P < 0.001). CONCLUSIONS IgE antibody responses do not reflect a single phenotype of atopy, but several different atopic vulnerabilities which differ in their relation with asthma presence and severity.

Twelve month outcome of depression in general practice: does detection or disclosure make a difference?

Abstract Objectives : To assess the extent to which the outcome of depression among primary care attenders may be affected by medical diagnosis or by feedback of questionnaire results in unrecognised cases. Design : Prospective 12 month study including a randomised controlled trial of the effects of disclosure, with data on depression status and clinical management collected by questionnaire and interview. Setting : Two group practices in north Liverpool. Subjects : 1099/1444 (76%) consecutive adult attenders completed the Beck depression inventory, of whom 179 with scores of at least 14 were followed up. Interventions : Disclosure of a random 45% (52/116) of depression scores to general practitioners for subjects whose depression was undetected. Main outcome measures : Depression status estimated by depression score at start of study and at six and 12 months, with subsample validation against ICD−10 criteria. Results : Questionnaire response rates were 76% (136/179) at six months and 68% (122/179) at 12 months and were higher for women than men. The median depression score was 19 (interquartile range 15 to 22) initially, decreasing to 16 (11 to 23) at 12 months. The median depression score decreased significantly (two sided test, P=0.019) in subjects whose depression was unrecognised at the index consultation but increased in those whose depression had been detected by their general practitioners. Disclosure of cases of unrecognised depression to general practitioners had no effect on outcome. Intention to treat was associated with a worse prognosis, although only a minority of subjects received adequate treatment. Conclusions : Disclosure of undetected depression did not improve prognosis. A diagnosis of depression in general practice should be considered simply as a marker of its severity.

Incident cancer burden attributable to excess body mass index in 30 European countries

Excess adiposity is associated with increased risks of developing adult malignancies. To inform public health policy and guide further research, the incident cancer burden attributable to excess body mass index (BMI ≥ 25 kg/m2) across 30 European countries were estimated. Population attributable risks (PARs) were calculated using European‐ and gender‐specific risk estimates from a published meta‐analysis and gender‐specific mean BMI estimates from a World Health Organization Global Infobase. Country‐specific numbers of new cancers were derived from Globocan2002. A ten‐year lag‐period between risk exposure and cancer incidence was assumed and 95% confidence intervals (CI) were estimated in Monte Carlo simulations. In 2002, there were 2,171,351 new all cancer diagnoses in the 30 countries of Europe. Estimated PARs were 2.5% (95% CI 1.5–3.6%) in men and 4.1% (2.3–5.9%) in women. These collectively corresponded to 70,288 (95% CI 40,069–100,668) new cases. Sensitivity analyses revealed estimates were most influenced by the assumed shape of the BMI distribution in the population and cancer‐specific risk estimates. In a scenario analysis of a plausible contemporary (2008) population, the estimated PARs increased to 3.2% (2.1–4.3%) and 8.6% (5.6–11.5%), respectively, in men and women. Endometrial, post‐menopausal breast and colorectal cancers accounted for 65% of these cancers. This analysis quantifies the burden of incident cancers attributable to excess BMI in Europe. The estimates reported here provide a baseline for future modelling, and underline the need for research into interventions to control weight in the context of endometrial, breast and colorectal cancer.

Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis

OBJECTIVE Glycemic variability is emerging as a measure of glycemic control, which may be a reliable predictor of complications. This systematic review and meta-analysis evaluates the association between HbA1c variability and micro- and macrovascular complications and mortality in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS Medline and Embase were searched (2004–2015) for studies describing associations between HbA1c variability and adverse outcomes in patients with type 1 and type 2 diabetes. Data extraction was performed independently by two reviewers. Random-effects meta-analysis was performed with stratification according to the measure of HbA1c variability, method of analysis, and diabetes type. RESULTS Seven studies evaluated HbA1c variability among patients with type 1 diabetes and showed an association of HbA1c variability with renal disease (risk ratio 1.56 [95% CI 1.08–2.25], two studies), cardiovascular events (1.98 [1.39–2.82]), and retinopathy (2.11 [1.54–2.89]). Thirteen studies evaluated HbA1c variability among patients with type 2 diabetes. Higher HbA1c variability was associated with higher risk of renal disease (1.34 [1.15–1.57], two studies), macrovascular events (1.21 [1.06–1.38]), ulceration/gangrene (1.50 [1.06–2.12]), cardiovascular disease (1.27 [1.15–1.40]), and mortality (1.34 [1.18–1.53]). Most studies were retrospective with lack of adjustment for potential confounders, and inconsistency existed in the definition of HbA1c variability. CONCLUSIONS HbA1c variability was positively associated with micro- and macrovascular complications and mortality independently of the HbA1c level and might play a future role in clinical risk assessment.

Cardiorespiratory fitness and body mass index of 9-11-year-old English children: A serial cross-sectional study from 1998 to 2004

Objective:To examine the changes over time in cardiorespiratory fitness and body mass index (BMI) of children.Design:Serial cross-sectional, population-based study.Setting:Primary schools in Liverpool, UK.Participants:A total of 15 621 children (50% boys), representing 74% of eligible 9–11-year olds in the annual school cohorts between 1998/9 and 2003/4, who took part in a 20m multi-stage shuttle run test (20mMST).Main outcome measures:Weight, height, BMI (kg/m2) and obesity using the International Obesity Taskforce definition.Results:Median (95% confidence interval) 20mMST score (number of runs) fell in boys from 48.9 (47.9–49.9) in 1998/9 to 38.1 (36.8–39.4) in 2003/4, and in girls from 35.8 (35.0–36.6) to 28.1 (27.2–29.1) over the same period. Fitness scores fell across all strata of BMI (P<0.001). Moreover, BMI increased over the same 6-year period even among children in fittest third of 20mMST.Conclusion:In a series of uniform cross-sectional assessments of school-aged children, BMI increased whereas cardiorespiratory fitness levels decreased within a 6-year period. Even among lean children, fitness scores decreased. Public health measures to reduce obesity, such as increasing physical activity, may help raise fitness levels among all children – not just the overweight or obese.