Looking back on 'Causal Thinking in the Health Sciences'

It has now been over a quarter of a century since the publication of Mervyn Susser's Causal Thinking in the Health Sciences (1973, Oxford University Press), the first book-length treatment of causal reasoning and inference in our field. Major contributions of this work were its holistic focus on the origins of health outcomes in the context of ecologic systems and its invigoration of the literature on causal criteria in epidemiology. Although a recent resurgence of interest in social context has revivified many points made by Susser, a formal basis for causal analysis consistent with this ecologic perspective has failed to emerge in public health research. Susser's discussion of causal criteria, on the other hand, helped spur a vigorous dialogue that has persisted unabated to the present day. Although the basic outline of the criteria has evolved little, their applications, interrelations, and relative contributions to causal judgments have been the subject of continued and sometimes contentious debate

Patterns of incident genital human papillomavirus infection in women: A literature review and meta-analysis

Human papillomavirus (HPV) infection acquisition is a necessary step in the development of cervical cancer. No study has systematically quantified the rate of newly acquired HPV infections from the published literature and determined its relationship with age. We performed a systematic review and meta-analysis to describe incident HPV infections in women. Medline® and Thomson Reuters Web of Science via PubMed® databases were searched. A total of 46 of 5136 studies met inclusion criteria and contributed results. We conducted a meta-regression analysis of 13 studies, which reported incidence rate estimates on over 13 high-risk HPV types, to provide pooled stratum-specific incidence rates and rate ratios for key population and study characteristics among 8488 women. Studies with mean age < 30 years had relatively higher HPV incidence rates compared to studies with mean age ≥30 years: relative risk = 3.12; 95% CI: 1.41–6.93. HPV-16 was most frequently detected, followed by HPV-18: relative risk = 0.47; 95% CI: 0.33–0.67, and by HPV-58: relative risk = 0.45; 95% CI: 0.27–0.74. Younger age is a key predictor of genital HPV incidence in women. These data on the relative distribution of incident HPV infections will provide a baseline comparison for monitoring of changes in HPV incidence following the implementation of population-level HPV vaccination

Clinical Correlates and Prognostic Significance of the Ventilatory Response to Exercise in Chronic Heart Failure

AbstractObjectives. This study sought to investigate the clinical characteristics of patients with chronic heart failure and an increased ventilatory response to exercise and to examine the prognostic usefulness of this response.Background. The ventilatory response to exercise is increased in many patients with chronic heart failure and may be characterized by the regression slope relating minute ventilation to carbon dioxide output (V̇e–V̇co2slope) during exercise.Methods. One hundred seventy-three consecutive patients (155 men; mean [±SD] age 59.8 ± 11.5 years; radionuclide left ventricular ejection fraction [LVEF] 28.4 ± 14.6%) underwent cardiopulmonary exercise testing (peak oxygen consumption 18.5 ± 7.3 ml/kg per min; V̇e–V̇co2slope 34.8 ± 10.6) over a 2-year period. Using 1.96 standard deviations above the mean V̇e–V̇co2slope of 68 healthy age-matched subjects (mean slope 26.3 ± 4.1), we defined a high ventilatory response to exercise as a slope >34.Results. Eighty-three patients (48%) had an increased V̇e–V̇co2slope (mean 43.1 ± 8.9). There was a difference in age (62.2 vs. 57.3 years, p = 0.005), New York Heart Association functional class (2.9 vs. 2.1, p < 0.001), LVEF (24.7 vs. 31.9%, p = 0.0016), peak oxygen consumption (14.9 vs. 21.7 ml/kg per min, p < 0.0001) and radiographic cardiothoracic ratio (0.58 vs. 0.55, p = 0.002) between these patients and those with a normal slope. In the univariate Cox proportional hazards model, the V̇e–V̇co2slope was an important prognostic factor (p < 0.0001). In the multivariate Cox analyses using several variables (age, peak oxygen consumption, V̇e–V̇co2slope and LVEF), the V̇e–V̇co2slope gave additional prognostic information (p = 0.018) beyond peak oxygen consumption (p = 0.022). Kaplan-Meier survival curves at 18 months demonstrated a survival rate of 95% in patients with a normal V̇e–V̇co2slope compared with 69% in those with a high slope (p < 0.0001).Conclusions. A high V̇e–V̇co2slope selects patients with more severe heart failure and is an independent prognostic marker. The V̇e–V̇co2slope may be used as a supplementary index in the assessment of patients with chronic heart failure.(J Am Coll Cardiol 1997;29:1585–90

Reply to: comparative effectiveness medicines research cannot assess efficacy

We appreciate the insightful comments from Drs. Dal-Ré and Carcas in their letter to the editor regarding our paper “Publication of comparative effectiveness research (CER) has not increased in high-impact medical journals, 2004–2013

Publication of comparative effectiveness research has not increased in high-impact medical journals, 2004-2013

Objective To explore the impact of increasing interest and investment in patient-centered research, this study sought to describe patterns of comparative effectiveness research (CER) and patient-reported outcomes (PROs) in pharmacologic intervention studies published in widely read medical journals from 2004-2013. Design and Setting We identified 2335 articles published in five widely read medical journals from 2004-2013 with ≥1 intervention meeting the US Food and Drug Administration's definitions for a drug, biologic, or vaccine. Six trained reviewers extracted characteristics from a 20% random sample of articles (468 studies). We calculated the proportion of studies with CER and PROs. Trends were summarized using locally-weighted means and 95% confidence intervals. Results Of the 468 sampled studies, 30% used CER designs and 33% assessed PROs. The proportion of studies using CER designs did not meaningfully increase over the study period. However, we observed an increase in the use of PROs. Conclusions Among pharmacological intervention studies published in widely read medical journals from 2004-2013, we identified no increase in CER. Randomized, placebo-controlled trials continue to be the dominant study design for assessing pharmacologic interventions. Increasing trends in PRO use may indicate greater acceptance of these outcomes as evidence for clinical benefit

Reasons for hormonal contraceptive use in a cohort of African-American women living in the Detroit area

Objectives: To characterize reasons for hormonal contraceptive (HC) use in 1,455 African-American women, aged 23–35 years. Study design: The community-based cohort members were recruited from the Detroit, Michigan area in 2010–2012. HC history was collected via telephone interview. Results: Seven percent reported HC use exclusively for non-contraceptive purposes, and 49% reported non-contraceptive reasons in addition to contraception. Non-contraceptive reasons were reported for all HC types, but were most common for combined oral contraceptives. Primary reasons were for irregular cycles, heavy bleeding, and pain. Conclusions: In this large cohort of Black women, HC use to treat menstrual problems was common. Implications: HCs were commonly used for both pregnancy prevention and management of menstrual symptoms, but some women used HCs exclusively for menstrual symptom relief. The importance for women of non-contraceptive reasons for HC use may not be adequately recognized, and published data on Black women's reasons for HC use remain limited

The effect of the COVID-19 pandemic on mental health in individuals with pre-existing mental illness

BACKGROUND: There is evidence that the COVID-19 pandemic has negatively affected mental health, but most studies have been conducted in the general population. AIMS: To identify factors associated with mental health during the COVID-19 pandemic in individuals with pre-existing mental illness. METHOD: Participants (N = 2869, 78% women, ages 18–94 years) from a UK cohort (the National Centre for Mental Health) with a history of mental illness completed a cross-sectional online survey in June to August 2020. Mental health assessments were the GAD-7 (anxiety), PHQ-9 (depression) and WHO-5 (well-being) questionnaires, and a self-report question on whether their mental health had changed during the pandemic. Regressions examined associations between mental health outcomes and hypothesised risk factors. Secondary analyses examined associations between specific mental health diagnoses and mental health. RESULTS: A total of 60% of participants reported that mental health had worsened during the pandemic. Younger age, difficulty accessing mental health services, low income, income affected by COVID-19, worry about COVID-19, reduced sleep and increased alcohol/drug use were associated with increased depression and anxiety symptoms and reduced well-being. Feeling socially supported by friends/family/services was associated with better mental health and well-being. Participants with a history of anxiety, depression, post-traumatic stress disorder or eating disorder were more likely to report that mental health had worsened during the pandemic than individuals without a history of these diagnoses. CONCLUSIONS: We identified factors associated with worse mental health during the COVID-19 pandemic in individuals with pre-existing mental illness, in addition to specific groups potentially at elevated risk of poor mental health during the pandemic

Fusion of secretory vesicles isolated from rat liver

Secretory vesicles isolated from rat liver were found to fuse after exposure to Ca2+. Vescle fusion is characterized by the occurrence of twinned vesicles with a continuous cleavage plane between two vesicles in freeze-fracture electron microscopy. The number of fused vesicles increases with increasing Ca2+-concentrations and is half maximal around 10–6 m. Other divalent cations (Ba2+, Sr2+, and Mg2+) were ineffective. Mg2+ inhibits Ca2+-induced fusion. Therefore, the fusion of secretory vesiclesin vitro is Ca2+ specific and exhibits properties similar to the exocytotic process of various secretory cells. Various substances affecting secretionin vivo (microtubular inhibitors, local anethetics, ionophores) were tested for their effect on membrane fusion in our system. The fusion of isolated secretory vesicles from liver was found to differ from that of pure phospholipid membranes in its temperature dependence, in its much lower requirement for Ca2+, and in its Ca2+-specificity. Chemical and enzymatic modifications of the vesicle membrane indicate that glycoproteins may account for these differences

PREDICTING THE SUMMER TEMPERATURE OF SMALL STREAMS IN SOUTHWESTERN WISCONSIN 1

One of the biggest challenges in managing cold water streams in the Midwest is understanding how stream temperature is controlled by the complex interactions among meteorologic processes, channel geometry, and ground water inflow. Inflow of cold ground water, shade provided by riparian vegetation, and channel width are the most important factors controlling summer stream temperatures. A simple screening model was used to quantitatively evaluate the importance of these factors and guide management decisions. The model uses an analytical solution to the heat transport equation to predict steady-state temperature throughout a stream reach. The model matches field data from four streams in southwestern Wisconsin quite well (typically within 1°C) and helps explain the observed warming and cooling trends along each stream reach. The distribution of ground water inflow throughout a stream reach has an important influence on stream temperature, and springs are especially effective at providing thermal refuge for fish. Although simple, this model provides insight into the importance of ground water and the impact different management strategies, such as planting trees to increase shade, may have on summer stream temperature.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74032/1/j.1752-1688.2005.tb03714.x.pd

Recovered memories, satanic abuse, Dissociative Identity Disorder and false memories in the UK: a survey of Clinical Psychologists and Hypnotherapists

An online survey was conducted to examine psychological therapists’ experiences of, and beliefs about, cases of recovered memory, satanic / ritualistic abuse, Multiple Personality Disorder / Dissociative Identity Disorder, and false memory. Chartered Clinical Psychologists (n=183) and Hypnotherapists (n=119) responded. In terms of their experiences, Chartered Clinical Psychologists reported seeing more cases of satanic / ritualistic abuse compared to Hypnotherapists who, in turn, reported encountering more cases of childhood sexual abuse recovered for the first time in therapy, and more cases of suspected false memory. Chartered Clinical Psychologists were more likely to rate the essential accuracy of reports of satanic / ritualistic abuse as higher than Hypnotherapists. Belief in the accuracy of satanic / ritualistic abuse and Multiple Personality Disorder / Dissociative Identity Disorder reports correlated negatively with the belief that false memories were possible