The Prevalence and Symptom Profile of Asthma–COPD Overlap: The HUNT Study

The concept of asthma and COPD as separate conditions has been questioned, and the term asthma–COPD overlap syndrome has been introduced. We assessed the prevalence, symptoms, and lifestyle factors of asthma–COPD overlap (ACO) in a large Norwegian population-based study.

From 2006 to 2008, a total of 50,777 residents of Nord-Trøndelag participated in the Nord-Trøndelag Health Study, Norway. They completed questionnaires regarding respiratory symptoms, disease status, and medication use. We estimated the prevalence and 95% confidence intervals of ACO. Additionally, spirometry was used to estimate the prevalence of ACO in a subgroup.

The prevalence of self-reported ACO was 1.9%, and in age groups <40, 40–60 and ≥60 years it was 0.7%, 1.4%, and 3.2%, respectively. Among those reporting COPD, the proportion of ACO was 0.56. In the spirometry subgroup when ACO was defined as doctor diagnosed asthma ever and FEV₁/FVC < 0.70, the prevalence of ACO was 2.0%. All respiratory symptoms, separately or in combination, as well as medication use were reported most frequently in those with ACO compared to the other groups. Strikingly, we observed a two-fold higher proportion of allergic rhinitis in ACO compared to COPD only.

In this Norwegian population, the prevalence of self-reported ACO was 1.9%, and the corresponding proportion of ACO among those with COPD was 0.56. Participants with ACO generally had the highest proportions of respiratory symptoms compared to asthma or COPD.     

Lessons Learned about Implementing Research Evidence into Clinical Practice

The mission of the Veterans Health Administration's (VHA) quality enhancement research initiative (QUERI) is to enhance the quality of VHA health care by implementing clinical research findings into routine care. This paper presents lessons that QUERI investigators have learned through their initial attempts to pursue the QUERI mission. The lessons in this paper represent those that were common across multiple QUERI projects and were mutually agreed on as having substantial impact on the success of implementation. While the lessons are consistent with commonly recognized ingredients of successful implementation efforts, the examples highlight the fact that, even with a thorough knowledge of the literature and thoughtful planning, unexpected circumstances arise during implementation efforts that require flexibility and adaptability. The findings stress the importance of utilizing formative evaluation techniques to identify barriers to successful implementation and strategies to address these barriers.     

Increased fracture rates in Turner's syndrome: a nationwide questionnaire survey

BACKGROUND AND OBJECTIVES: Reduced bone mineral content (BMC) and bone mineral density (BMD) have previously been reported in Turner's syndrome, although appropriate GH treatment and early induction of puberty seem to permit normal bone mass accumulation. Furthermore, an increased risk of fractures and osteoporosis have been reported in a registry study. The aim of the present study was to further characterize the risk of fractures in TS and to explore risk factors, in a historical follow-up survey based on a self-administered questionnaire. STUDY GROUPS: The questionnaire was issued to all females with TS (n = 632) in Denmark and to 1888 randomly selected controls (C) matched for age and geographical region. A total of 322 patients (51%) and 1169 controls (62%) returned the questionnaire. RESULTS: TS women were younger than C (30 years, range: 1-73 years vs. 34 years, range 2-82 years, P < 0.0005), smoked less often (17%vs. 27%, P < 0.0005), and had less frequent spontaneous menstruation (18%vs. 86%, P < 0.0005). In contrast, they used hormonal replacement therapy (HRT) more often (71%vs. 7%, P < 0.0005). The median age at start of HRT was 16 years (range 8-59 years) in TS vs. 42 years (range 12-53 years) in C (P < 0.0005). Above the age of 15 years, 83% of TS and 8% of C used HRT. GH had been used by 37% of TS but only 0.2% of C. Both type 1 and 2 diabetes were increased sevenfold among TS. Altogether, 77 individuals with TS had 109 fractures. The fracture risk was increased in TS [hazard ratio (HR, status) 1.35, confidence interval (CI) 1.04-1.75, P = 0.025]. Time to first fracture was reduced in TS (53 +/- 2 vs. 63 +/- 1; log-rank P = 0.03). Spontaneous menstruation was protective in females above 13 years of age (HR: 0.70, CI 0.54-0.93, P = 0.012). A history of parental fractures increased the risk (HR 1.92, CI 1.62-2.27, P < 0.001). Fractures of the forearm was more frequent among TS (P = 0.02). CONCLUSION: The present nationwide survey, based on questionnaires, confirms an increased risk of early fractures in TS, especially in those without ovarian function and with a positive family history of fracture and osteoporosis. It thereby emphasizes the need for being vigilant with respect to BMD measurements in these patients.     

Effects of long-term estrogen replacement therapy versus combined hormone replacement therapy on nitric oxide-dependent vasomotor function

Postmenopausal hormone replacement therapy (HRT) with estrogen may increase production of the predominant endothelium-derived vasodilator nitric oxide (NO) and consequently improve vascular reactivity. In contrast, concurrent progestin therapy may oppose this beneficial effect. We studied the effect of long-term estrogen HRT and combined HRT on vasomotor function and on plasma nitrate, which reflects the amount of NO in the circulation. As lipid peroxidation affects NO production and impairs endothelial function, we also measured the amount of the in vivo lipid peroxidation marker urinary 8-iso-prostaglandin F(2 alpha). The study group comprised 15 women receiving estradiol valerate HRT (mean age, 56 yr; treatment duration, 10.5 yr) and 15 women receiving combined HRT with estradiol valerate and levonorgestrel (mean age, 58 yr; treatment duration, 11.3 yr). The peak flow velocity (PFV) and pulsatility index of the common carotid and internal carotid artery and the abdominal aorta were measured by ultrasonography after long-term HRT (baseline), after a 4-wk pause and again 3 wk after reintroducing HRT. A statistically significant interaction between the groups and time points was observed in the PFV of the internal carotid artery (P = 0.011). In women taking estradiol valerate, the PFV values decreased significantly after withdrawal of HRT (P = 0.007) and increased again to the baseline level after reintroduction of therapy (P < 0.001). In women receiving combined HRT, the PFV remained stable over all study periods. At baseline, the PFV of women taking estradiol valerate correlated with the plasma nitrate concentration in the common carotid artery (r = 0.646; P = 0.009) and in the abdominal aorta (r = 0.579; P = 0.024). For pulsatility index and urinary 8-iso-prostaglandin F(2 alpha) excretion, there were no significant differences between the groups. Our results suggest that the favorable effects of long-term estrogen treatment on blood flow are at least partly mediated through NO. The addition of levonorgestrel to the treatment regimen appears to abolish this effect.     

Medical marijuana laws and adolescent marijuana use in the United States: a systematic review and meta‐analysis

Aims

To conduct a systematic review and meta‐analysis of studies in order to estimate the effect of US medical marijuana laws (MMLs) on past‐month marijuana use prevalence among adolescents.

Methods

A total of 2999 papers from 17 literature sources were screened systematically. Eleven studies, developed from four ongoing large national surveys, were meta‐analyzed. Estimates of MML effects on any past‐month marijuana use prevalence from included studies were obtained from comparisons of pre–post MML changes in MML states to changes in non‐MML states over comparable time‐periods. These estimates were standardized and entered into a meta‐analysis model with fixed‐effects for each study. Heterogeneity among the study estimates by national data survey was tested with an omnibus F‐test. Estimates of effects on additional marijuana outcomes, of MML provisions (e.g. dispensaries) and among demographic subgroups were abstracted and summarized. Key methodological and modeling characteristics were also described. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed.

Results

None of the 11 studies found significant estimates of pre–post MML changes compared with contemporaneous changes in non‐MML states for marijuana use prevalence among adolescents. The meta‐analysis yielded a non‐significant pooled estimate (standardized mean difference) of ?0.003 (95% confidence interval = ?0.012, +0.007). Four studies compared MML with non‐MML states on pre‐MML differences and all found higher rates of past‐month marijuana use in MML states pre‐MML passage. Additional tests of specific MML provisions, of MML effects on additional marijuana outcomes and among subgroups generally yielded non‐significant results, although limited heterogeneity may warrant further study.

Conclusions

Synthesis of the current evidence does not support the hypothesis that US medical marijuana laws (MMLs) until 2014 have led to increases in adolescent marijuana use prevalence. Limited heterogeneity exists among estimates of effects of MMLs on other patterns of marijuana use, of effects within particular population subgroups and of effects of specific MML provisions.

     

Prevalence of C282Y and E168X HFE mutations in an Italian population of Northern European ancestry

BACKGROUND AND OBJECTIVES: In Italy, the prevalence of C282Y is lower than in Northern European countries. We hypothesized a higher prevalence of C282Y in Northern than in Southern Italian populations. We previously identified a nonsense mutation (E168X) in hemochromatosis probands originating from a region in the north-west of Italy. We aimed to define the prevalence of C282Y and E168X in that region and the origin of the E168X mutation by haplotype analysis. DESIGN AND METHODS: Six-hundred and six blood donors were investigated for C282Y, H63D, S65C and E168X mutations by polymerase chain reaction (PCR)-restriction assays. Three hundred were also tested for rare HFE and TFR2 mutations by reverse-hybridization test strips. D6S265, D6S105 and D6S1281 microsatellites were analyzed to define E168X 6p-associated haplotypes. RESULTS: One C282Y homozygote, thirteen C282Y/ H63D compound heterozygotes, four E168X heterozygotes and three E168X/H63D compound heterozygotes were found. The allele frequencies of C282Y, H63D, S65C, and E168X were 4.7%, 14.9%, 0.74% and 0.58%, respectively. INTERPRETATION AND CONCLUSIONS: The prevalence of C282Y in the region investigated was much higher than that previously reported in Italy. This finding is probably due to the heavy Celtic component of this north-western population and suggests that in populations of Northern Italian descent screening studies for hemochromatosis could be cost-effective. The prevalence of E168X in this region, although low, suggests that the mutation probably originated here many years ago and its frequency increased as a result of a local founder effect. Given its severity, we suggest that the E168X mutation should be searched for in all hemochromatosis patients of Northern ancestry with an incomplete HFE genotype.     

Geriatrics training in general internal medicine fellowship programs: current practice, barriers, and strategies for improvement

To ensure its growth and prosperity, general internal medicine will need to embrace care of the elderly, research on aging, and geriatrics education as components of its core mission. Experts agree that general internal medicine fellows could benefit from increased opportunities in research on aging and geriatrics education; however, important barriers will hamper efforts to integrate geriatrics training into general internal medicine fellowship programs. This article reviews the barriers to integration and proposes solutions for overcoming those barriers. As a result of interviews and meetings with a broad representation of general internists, geriatricians, funding agencies, and policymakers, we propose 2 interventions: 1) the development of institutional program grants to foster collaboration between general internal medicine and geriatrics faculty in the training of general internal medicine fellows and 2) the creation of a 3-year fellowship program combining general internal medicine and geriatrics. This article discusses the importance of evaluating these and other programs intended to increase the geriatrics experience of general internal medicine fellows, and it describes the potential implications of these changes for a broad array of stakeholder institutions.     

Circulating markers of oxidative stress and liver fibrosis in Sudanese subjects at risk of schistosomiasis and hepatitis

Epidemiological studies in the developing world are frequently biased by the simultaneous presence of several infectious pathogens. In the present study, we examined the usefulness of circulating markers of oxidative stress and liver fibrosis to investigate the distinct forms of chronic liver inflammations associated with schistosomiasis and viral hepatitis, respectively. The study was performed in a Sudanese population exposed to Schistosoma. Circulating hyaluronic acid (HA) was used as a marker of liver fibrosis; the severity of schistosomiasis was determined by ultrasonic examination; viral hepatitis infection was ascertained by circulating anti-hepatitis antibodies. Serum markers were examined also in Sudanese subjects not exposed to Schistosoma infection and in French control subjects. We found a drastic decrease of lycopene levels in the subjects exposed to schistosomiasis in comparison with non-exposed Sudanese and French control subjects. Retinol, alpha-tocopherol and five carotenoids were unchanged. Lycopene depletion was unlikely to be due to variations of nutritional origin, since the lycopene/beta-carotene ratio was five-fold lower in the population at risk of schistosomiasis than in the other groups. We found that high HA serum levels were associated with severe periportal fibrosis but not with viral infection. Conversely, levels of the oxidized lipid malondialdehyde (MDA) were associated with viral infection but not with the severity of schistosomiasis, even though the two infections had additive effects. We concluded that serum markers are valuable tools for investigating the complex effects of co-existing factors of chronic liver inflammation.     

Longitudinal analysis of alcohol consumption and health of middle-aged women in Australia

Aims To assess the prospective association between alcohol consumption and self‐rated health: in particular whether there is a relationship between stable alcohol intake and health; whether health is affected by changes in alcohol consumption; whether having a chronic condition alters the relationships between stable and changing alcohol intake and health; and whether the health of longer‐term abstainers is different from more recent and intermittent abstainers. Design Longitudinal analysis of a prospective, population‐based study. Setting Australia. Participants A total of 13 585 randomly selected 45–50‐year‐old women surveyed in 1996, of whom 9396 (69%) were resurveyed in 1998, 2001 and 2004. Measurements Estimates for the General Health subscale of the SF‐36 for different levels of alcohol intake adjusted for having a chronic condition, depression, smoking and other factors. Findings Longitudinal models of consistent alcohol intake showed mean scores for general health of moderate drinkers were significantly better than that of non‐drinkers [mean difference = 4.3, standard error (SE) = 0.61], occasional drinkers (mean difference = 3.1, SE = 0.52) and heavy drinkers (mean difference = 2.1, SE = 1.00). Among moderate drinkers, a decrease or variation in alcohol consumption was associated with a significant decline of three to four points in general health. Similar results were obtained when women with an existing chronic condition were excluded from these models. The health of recent abstainers and intermittent drinkers was the same as longer‐term abstainers. Conclusions Consistent moderate drinkers had the best health even after adjustment for having a chronic condition, depression and life‐style factors. Poorer health was associated with decreased alcohol intake among occasional and moderate drinkers.