Primary care-based screening and management of depression amongst heavy drinking patients: Interim secondary outcomes of a three-country quasi-experimental study in Latin America.

INTRODUCTION: Implementation of evidence-based care for heavy drinking and depression remains low in global health systems. We tested the impact of providing community support, training, and clinical packages of varied intensity on depression screening and management for heavy drinking patients in Latin American primary healthcare. MATERIALS AND METHODS: Quasi-experimental study involving 58 primary healthcare units in Colombia, Mexico and Peru randomized to receive: (1) usual care (control); (2) training using a brief clinical package; (3) community support plus training using a brief clinical package; (4) community support plus training using a standard clinical package. Outcomes were proportion of: (1) heavy drinking patients screened for depression; (2) screen-positive patients receiving appropriate support; (3) all consulting patients screened for depression, irrespective of drinking status. RESULTS: 550/615 identified heavy drinkers were screened for depression (89.4%). 147/230 patients screening positive for depression received appropriate support (64%). Amongst identified heavy drinkers, adjusting for country, sex, age and provider profession, provision of community support and training had no impact on depression activity rates. Intensity of clinical package also did not affect delivery rates, with comparable performance for brief and standard versions. However, amongst all consulting patients, training providers resulted in significantly higher rates of alcohol measurement and in turn higher depression screening rates; 2.7 times higher compared to those not trained. CONCLUSIONS: Training using a brief clinical package increased depression screening rates in Latin American primary healthcare. It is not possible to determine the effectiveness of community support on depression activity rates due to the impact of COVID-19.

Use of alcohol, tobacco, cannabis, and other substances during the first wave of the SARS-CoV-2 pandemic in Europe: a survey on 36,000 European substance users.

BACKGROUND: SARS-CoV-2 reached Europe in early 2020 and disrupted the private and public life of its citizens, with potential implications for substance use. The objective of this study was to describe possible changes in substance use in the first months of the SARS-CoV-2 pandemic in Europe. METHODS: Data were obtained from a cross-sectional online survey of 36,538 adult substance users from 21 European countries conducted between April 24 and July 22 of 2020. Self-perceived changes in substance use were measured by asking respondents whether their use had decreased (slightly or substantially), increased (slightly or substantially), or not changed during the past month. The survey covered alcohol (frequency, quantity, and heavy episodic drinking occasions), tobacco, cannabis, and other illicit drug use. Sample weighted data were descriptively analysed and compared across substances. RESULTS: Across all countries, use of all substances remained unchanged for around half of the respondents, while the remainder reported either a decrease or increase in their substance use. For alcohol use, overall, a larger proportion of respondents indicated a decrease than those reporting an increase. In contrast, more respondents reported increases in their tobacco and cannabis use during the previous month compared to those reporting decreased use. No distinct direction of change was reported for other substance use. CONCLUSIONS: Our findings suggest changes in use of alcohol, tobacco and cannabis during the initial months of the pandemic in several European countries. This study offers initial insights into changes in substance use. Other data sources, such as sales statistics, should be used to corroborate these preliminary findings.

Impact of the introduction and withdrawal of financial incentives on the delivery of alcohol screening and brief advice in English primary health care: an interrupted time-series analysis.

AIM: To evaluate the impact of the introduction and withdrawal of financial incentives on alcohol screening and brief advice delivery in English primary care. DESIGN: Interrupted time-series using data from The Health Improvement Network (THIN) database. Data were split into three periods: (1) before the introduction of financial incentives (1 January 2006-31 March 2008); (2) during the implementation of financial incentives (1 April 2008-31 March 2015); and (3) after the withdrawal of financial incentives (1 April 2015-31 December 2016). Segmented regression models were fitted, with slope and step change coefficients at both intervention points. SETTING: England. PARTICIPANTS: Newly registered patients (16+) in 500 primary care practices for 2006-16 (n = 4 278 723). MEASUREMENTS: The outcome measures were percentage of patients each month who: (1) were screened for alcohol use; (2) screened positive for higher-risk drinking; and (3) were reported as having received brief advice on alcohol consumption. FINDINGS: There was no significant change in the percentage of newly registered patients who were screened for alcohol use when financial incentives were introduced. However, the percentage fell (P < 0.001) immediately when incentives were withdrawn, and fell by a further 2.96 [95% confidence interval (CI) = 2.21-3.70] patients per 1000 each month thereafter. After the introduction of incentives, there was an immediate increase of 9.05 (95% CI = 3.87-14.23) per 1000 patients screening positive for higher-risk drinking, but no significant further change over time. Withdrawal of financial incentives was associated with an immediate fall in screen-positive rates of 29.96 (95% CI = 19.56-40.35) per 1000 patients, followed by a rise each month thereafter of 2.14 (95% CI = 1.51-2.77) per 1000. Screen-positive patients recorded as receiving alcohol brief advice increased by 20.15 (95% CI = 12.30-28.00) per 1000 following the introduction of financial incentives, and continued to increase by 0.39 (95% CI = 0.26-0.53) per 1000 monthly until withdrawal. At this point, delivery of brief advice fell by 18.33 (95% CI = 11.97-24.69) per 1000 patients and continued to fall by a further 0.70 (95% CI = 0.28-1.12) per 1000 per month. CONCLUSIONS: Removing a financial incentive for alcohol prevention in English primary care was associated with an immediate and sustained reduction in the rate of screening for alcohol use and brief advice provision. This contrasts with no, or limited, increase in screening and brief advice delivery rates following the introduction of the scheme.

Impact of financial incentives on alcohol intervention delivery in primary care: a mixed-methods study.

BACKGROUND: Local and national financial incentives were introduced in England between 2008 and 2015 to encourage screening and brief alcohol intervention delivery in primary care. We used routine Read Code data and interviews with General Practitioners (GPs) to assess their impact. METHODS: A sequential explanatory mixed-methods study was conducted in 16 general practices representing 106,700 patients and 99 GPs across two areas in Northern England. Data were extracted on screening and brief alcohol intervention delivery for 2010-11 and rates were calculated by practice incentive status. Semi-structured interviews with 14 GPs explored which factors influence intervention delivery and recording in routine consultations. RESULTS: Screening and brief alcohol intervention rates were higher in financially incentivised compared to non-incentivised practices. However absolute rates were low across all practices. Rates of short screening test administration ranged from 0.05% (95% CI: 0.03-0.08) in non-incentivised practices to 3.92% (95% CI: 3.70-4.14) in nationally incentivised practices. For the full AUDIT, rates were also highest in nationally incentivised practices (3.68%, 95% CI: 3.47-3.90) and lowest in non-incentivised practices (0.17%, 95% CI: 0.13-0.22). Delivery of alcohol interventions was highest in practices signed up to the national incentive scheme (9.23%, 95% CI: 8.91-9.57) and lowest in non-incentivised practices (4.73%, 95% CI: 4.50-4.96). GP Interviews highlighted a range of influences on alcohol intervention delivery and subsequent recording including: the hierarchy of different financial incentive schemes; mixed belief in the efficacy of alcohol interventions; the difficulty of codifying complex conditions; and GPs' beliefs about patient-centred practice. CONCLUSIONS: Financial incentives have had some success in encouraging screening and brief alcohol interventions in England, but levels of recorded activity remain low. To improve performance, future policies must prioritise alcohol prevention work within the quality and outcomes framework, and address the values, attitudes and beliefs that shape how GPs' provide care.

Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men.

BACKGROUND: Estimates of intraindividual variation in hormone levels provide the basis for interpreting hormone measurements clinically and for developing eligibility criteria for trials of hormone replacement therapy. However, reliable systematic estimates of such variation are lacking. OBJECTIVE: To estimate intraindividual variation of serum total, free and bioavailable testosterone (T), dihydrotestosterone (DHT), SHBG, LH, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), oestrone, oestradiol and cortisol, and the contributions of biological and assay variation to the total. DESIGN: Paired blood samples were obtained 1-3 days apart at entry and again 3 months and 6 months later (maximum six samples per subject). Each sample consisted of a pool of equal aliquots of two blood draws 20 min apart. STUDY PARTICIPANTS: Men aged 30-79 years were randomly selected from the respondents to the Boston Area Community Health Survey, a study of the health of the general population of Boston, MA, USA. Analysis was based on 132 men, including 121 who completed all six visits, 8 who completed the first two visits and 3 who completed the first four visits. MEASUREMENTS: Day-to-day and 3-month (long-term) intraindividual standard deviations, after transforming measurements to logarithms to eliminate the contribution of hormone level to intraindividual variation. RESULTS: Biological variation generally accounted for more of total intraindividual variation than did assay variation. Day-to-day biological variation accounted for more of the total than did long-term biological variation. Short-term variability was greater in hormones with pulsatile secretion (e.g. LH) than those that exhibit less ultradian variation. Depending on the hormone, the intraindividual standard deviations imply that a clinician can expect to see a difference exceeding 18-28% about half the time when two measurements are made on a subject. The difference will exceed 27-54% about a quarter of the time. CONCLUSIONS: Given the level of intraindividual variability in hormone levels found in this study, one sample is generally not sufficient to characterize an individual's hormone levels but collecting more than three is probably not warranted. This is true for clinical measurements and for hormone measurements used to determine eligibility for a clinical trial of hormone replacement therapy.

Lack of seasonal variation in serum sex hormone levels in middle-aged to older men in the Boston area.

CONTEXT: Previous studies of seasonal variation of testosterone and other hormones in men have produced mixed results regarding the number and timing of peaks and nadirs and whether hormones vary seasonally at all. Wide variation in study designs, sample sizes, analytical methods, and characteristics of the study populations may account for the heterogeneity of results. OBJECTIVE: The objective of the study was to determine whether serum total, free, and bioavailable testosterone, dihydrotestosterone, SHBG, LH, dehydroepiandrosterone, dehydroepiandrosterone sulfate, estrone, estradiol, and cortisol vary seasonally in men. DESIGN: Two blood samples were drawn 1-3 d apart at study entry and again 3 and 6 months later (maximum six samples per subject). Hormone levels 1-3 d apart were averaged to reduce short-term intrasubject variation. SETTING: The study population consisted of a community-dwelling population (Boston, MA). STUDY PARTICIPANTS: One hundred thirty-four men 30-79 yr old were randomly selected from the respondents to the Boston Area Community Health Survey. One hundred twenty-one men who completed all six visits were included in the analysis. MAIN OUTCOME MEASURES: In a repeated-measures analysis, 3-month change in hormone levels, measured twice per subject, and in a sinusoidal nonlinear regression with random subject effects, average hormone level in samples 1-3 d apart were measured. RESULTS: Aside from cortisol, no evidence of seasonal variation in hormone levels was found. The amplitude of seasonal variation was much smaller than total intraindividual variation for all hormones considered. CONCLUSIONS: Seasonal variation is likely an unimportant source of variation clinically and in epidemiological studies of hormone levels.

The natural progression and remission of erectile dysfunction: results from the Massachusetts Male Aging Study.

PURPOSE: Erectile dysfunction affects more than 150 million men and is strongly associated with cardiovascular disease. A 1992 National Institutes of Health consensus development panel identified erectile dysfunction progression and spontaneous remission as priorities for investigation, but there are few data describing the natural course of the disorder following its initial presentation. This analysis estimates the frequency of erectile dysfunction progression and remission among aging men, and assesses the relation of progression/remission to demographics, socioeconomic factors, comorbidities and modifiable lifestyle characteristics. MATERIALS AND METHODS: Data from the Massachusetts Male Aging Study, a longitudinal study of men (401) 40 to 70 years old, were analyzed to assess erectile dysfunction severity following initial presentation of symptoms. Logistic regression was used to estimate the odds of erectile dysfunction progression/remission as a function of covariates. RESULTS: A total of 141 subjects (35%) exhibited erectile dysfunction remission (95% CI: 30%, 40%). Of 323 subjects with minimal or moderate baseline erectile dysfunction 107 (33%) exhibited erectile dysfunction progression (95% CI: 28%, 38%). The 78 subjects with complete erectile dysfunction were considered ineligible for progression and 45 (58%) of these exhibited complete erectile dysfunction at followup. Age and body mass index were associated with progression and remission, while smoking and self-assessed health status were associated with progression only. CONCLUSIONS: Natural remission and progression occur in a substantial number of men with erectile dysfunction. The association of body mass index with remission and progression, and the association of smoking and health status with progression, offer potential avenues for facilitating remission and delaying progression using nonpharmacological intervention. The benefits of such interventions for overall men's health may be far-reaching.

A population-level decline in serum testosterone levels in American men.

CONTEXT: Age-specific estimates of mean testosterone (T) concentrations appear to vary by year of observation and by birth cohort, and estimates of longitudinal declines in T typically outstrip cross-sectional decreases. These observations motivate a hypothesis of a population-level decrease in T over calendar time, independent of chronological aging. OBJECTIVE: The goal of this study was to establish the magnitude of population-level changes in serum T concentrations and the degree to which they are explained by secular changes in relative weight and other factors. DESIGN: We describe a prospective cohort study of health and endocrine functioning in randomly selected men of age 45-79 yr. We provide three data collection waves: baseline (T1: 1987-1999) and two follow-ups (T2: 1995-1997, T3: 2002-2004). SETTING: This was an observational study of randomly selected men residing in greater Boston, Massachusetts. PARTICIPANTS: Data obtained from 1374, 906, and 489 men at T1, T2, and T3, respectively, totaling 2769 observations taken on 1532 men. MAIN OUTCOME MEASURES: The main outcome measures were serum total T and calculated bioavailable T. RESULTS: We observe a substantial age-independent decline in T that does not appear to be attributable to observed changes in explanatory factors, including health and lifestyle characteristics such as smoking and obesity. The estimated population-level declines are greater in magnitude than the cross-sectional declines in T typically associated with age. CONCLUSIONS: These results indicate that recent years have seen a substantial, and as yet unrecognized, age-independent population-level decrease in T in American men, potentially attributable to birth cohort differences or to health or environmental effects not captured in observed data.

Normal, bound and nonbound testosterone levels in normally ageing men: results from the Massachusetts Male Ageing Study.

OBJECTIVE: There is little consensus on what androgen levels are 'normal' for healthy, ageing men. Using data from the Massachusetts Male Ageing Study (MMAS), we estimated age-specific, normal androgen levels for men aged 40-79 years while accounting for health status and behavioural factors known to influence hormone levels. DESIGN: Prospective, observational study. PATIENTS: Community-based random sample of men aged 40-79 years: n = 1677 men studied at T1 (1987-1989), n = 1031 at T2 (1995-1997) and n = 631 at T3 (2002-2004), for a total of 3339 observations. The average number of years between the T1 and T2 interviews was 8.8 (range 7.1-10.4 years) and 6.4 (range 5.6-7.9 years) between T2 and T3. MEASUREMENTS: Serum total testosterone (T) and sex hormone-binding globulin (SHBG) were measured on nonfasting blood samples collected within 4 h of subject's awakening. Free and bio-available T were calculated from T and SHBG using the Sodergard equation. Trained interviewers administered an in-home questionnaire of health, medication and lifestyle. Participants were considered apparently healthy if all of the following were met: (i) absence of self-reported chronic disease (diabetes, heart disease, high blood pressure, cancer, ulcer); (ii) not on prescription medication believed to affect hormone levels; (iii) body mass index (BMI) not exceeding 29 kg/m2; (iv) alcohol consumption less than or equal to six drinks/day; and (v) nonsmoking. RESULTS: Chronic disease and high BMI significantly decreased whereas smoking tended to increase total, free and bio-available T concentrations. Apparently healthy men had significantly higher median hormone concentrations at most time points than did not apparently healthy men. Due to the opposite effects of smoking and the other components of the definition, apparently healthy men were compared to nonsmoking, apparently unhealthy men. The former group had significantly higher androgen levels (Wilcoxon rank-sum P-values ranged from 0.01 to 0.0001) for all hormones at all interviews. Ninety-five percent of apparently healthy men in their 40s, 50s, 60s and 70s would be expected to have total T in the range (2.5-97.5th percentile): 8.7-31.7, 7.5-30.4, 6.8-29.8 and 5.4-28.4 nm (251-914, 216-876, 196-859, 156-818 ng/dl), respectively. CONCLUSIONS: Age, health and lifestyle factors impact androgen levels and should be accounted for in calculations of normal reference ranges. We propose the following age-specific thresholds, below which a man is considered to have an abnormally low total T: 8.7, 7.5, 6.8 and 5.4 nm (251, 216, 196 and 156 ng/dl) for men in their 40s, 50s, 60s and 70s, respectively. These cutoffs correspond to the 2.5th percentile in our data; thus, approximately 2.5% of men aged 40-79 years would have abnormally low T levels based on hormone levels alone.

Overexpression of estrogen receptor-alpha in the endometrial carcinoma cell line Ishikawa: inhibition of growth and angiogenic factors.

BACKGROUND: A high level of estrogen receptor-alpha (ER-alpha) is believed to be favorable in the prognosis and treatment of endometrial, ovarian, and breast cancer. High levels of ER-alpha have been shown to inhibit the growth and invasive, metastatic potential of breast cancer cell lines. To bring about these inhibitory effects, ER-alpha probably acts through other cellular factors involved in the regulation of cell growth. OBJECTIVE: To investigate the role of high levels ER-alpha in growth inhibition of endometrial cancer cells. METHODS: A human ER-alpha cDNA was stably overexpressed in an endometrial cancer cell line, namely, Ishikawa. ER-alpha-overexpressing, parent, and control Ishikawa cells were grown in vitro and their growth rates were compared by cell count. ER-alpha-overexpressing and parent Ishikawa cells were also grown in vitro as tumors in a chicken chorioallantoic membrane (CAM) model, and tumor growth and angiogenesis was measured. Finally, levels of angiogenesis-modulating factors, nitric oxide synthase (NOS), and vascular endothelial growth factor (VEGF) were examined in relation to ER overexpression. RESULTS: The growth of Ishikawa cells was found inhibited in culture as well as in the CAM model. Angiogenesis of CAM tumors was also found inhibited in ER-overexpressing cells. Angiogenic factor VEGF was inhibited whereas the activity of NOS was found elevated following ER overexpression. CONCLUSION: Our work on the Ishikawa cell line indicates that high levels of ER-alpha in endometrial cancer may inhibit cancer growth by modulating angiogenic factors, thereby limiting the blood supply to the growing tumor. Our results support the earlier data from other groups that have shown a positive correlation between high ER content and better prognosis of endometrial cancers.

Influence of patient characteristics on doctors' questioning and lifestyle advice for coronary heart disease: a UK/US video experiment.

BACKGROUND: Risk factors for coronary heart disease (CHD) vary with patient characteristics but we do not know how this influences doctors' questioning and advice giving. AIMS: To find out whether four patient characteristics - age (55 versus 75 years), sex, class, and race - influence primary care doctors' questioning style and advice giving in the United Kingdom (UK) and United States (US). DESIGN OF STUDY: A factorial experiment using video simulation of a patient consulting with CHD symptoms, designed to systematically alter their age, sex, class, and race. SETTING: Surrey, south east London and the West Midlands in the UK, and Massachusetts in the US. METHOD: A stratified random sample of 128 general practitioners (GPs) in the UK and 128 primary care doctors in the US were shown video vignettes in their practices of patient consultations, and interviewed about patient management strategies. RESULTS: Sex and age influence doctors' questioning of patients presenting with CHD. Men are asked more questions overall, particularly about smoking and drinking. Middle-aged patients are asked more about their lifestyle. Advice about smoking is given to more men than women, and to more mid-life than older patients. Women doctors question patients about their lifestyle more often, and give more advice to patients about their diet. CONCLUSION: Doctors' questioning strategies are influenced by patients' sex and age, suggesting that doctors may miss smoking- and alcohol-related factors among women and older patients with CHD. Doctors give more advice about smoking to men, despite sex equality in smoking prevalence. Therefore, doctors' information seeking and advice giving do not match known patient risk factors.