Eczematous skin reaction to atopy patch testing with cockroach in patients with atopic dermatitis

BACKGROUND: Aeroallergens from house dust mite (HDM) may be an important trigger in a subgroup of patients with atopic dermatitis (AD). HDM and cockroach (CR) contain cross-reactive allergens, such as tropomyosin. OBJECTIVE: To investigate the diagnostic value of patch testing with an aeroallergen and the role of CR allergen and HDM allergen in persons with AD. METHODS: We performed skin prick tests (SPT) with a panel of common aeroallergens and total serum immunoglobulin (Ig)E and specific IgE tests for CR and HDM on 23 patients with AD and 9 nonatopic control participants. Atopy patch tests (APT) were performed with CR and HDM extracts on clinically uninvolved skin on the back, and evaluated after 48 and 72 hours. RESULTS: A positive APT reaction to CR was found in 10/23 (43%) patients with AD. No positive reactions were observed in the nonatopic control participants. Positive APT reactions for CR showed no significant correlation with SPT or specific IgE levels for this allergen. Twelve of the 23 (52%) patients with AD were also sensitized to HDM. There was no significant correlation between positive results for SPT, APT, and specific IgE to CR and HDM. CONCLUSION: We demonstrate that CR allergens can induce positive patch test reactions in patients with AD. The absence of a significant correlation to SPT and specific IgE antibodies suggests that T-cell- and IgE-sensitization may be mediated by different allergens. There was no significant relationship between CR and HDM sensitivity, thus indicating no major cross-reactivity.

Incidence and risk factors of homicide-suicide in Swiss households: National Cohort study

BACKGROUND Homicide-suicides are rare but catastrophic events. This study examined the epidemiology of homicide-suicide in Switzerland. METHODS The study identified homicide-suicide events 1991-2008 in persons from the same household in the Swiss National Cohort, which links census and mortality records. The analysis examined the association of the risk of dying in a homicide-suicide event with socio-demographic variables, measured at the individual-level, household composition variables and area-level variables. Proportional hazards regression models were calculated for male perpetrators and female victims. Results are presented as age-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI). RESULTS The study identified 158 deaths from homicide-suicide events, including 85 murder victims (62 women, 4 men, 19 children and adolescents) and 68 male and 5 female perpetrators. The incidence was 3 events per million households and year. Firearms were the most prominent method for both homicides and suicides. The risk of perpetrating homicide-suicide was higher in divorced than in married men (HR 3.64; 95%CI 1.56-8.49), in foreigners without permanent residency compared to Swiss citizens (HR 3.95; 1.52-10.2), higher in men without religious affiliations than in Catholics (HR 2.23; 1.14-4.36) and higher in crowded households (HR 4.85; 1.72-13.6 comparing ≥2 with <1 persons/room). There was no association with education, occupation or nationality, the number of children, the language region or degree of urbanicity. Associations were similar for female victims. CONCLUSIONS This national longitudinal study shows that living conditions associated with psychological stress and lower levels of social support are associated with homicide-suicide events in Switzerland.

Religion and suicide in patients with mental illness or cancer

In Switzerland, the highest rates of suicide are observed in persons without religious affiliation and the lowest in Catholics, with Protestants in an intermediate position. We examined whether this association was modified by concomitant psychiatric diagnoses or malignancies, based on 6,909 suicides (ICD-10 codes X60-X84) recorded in 3.69 million adult residents 2001-2008. Suicides were related to mental illness or cancer if codes F or C, respectively, were mentioned on the death certificate. The protective effect of religion was substantially stronger if a diagnosis of cancer was mentioned on the death certificate and weaker if a mental illness was mentioned.

The Incidence of AIDS-Defining Illnesses at a Current CD4 Count >=200 Cells/ L in the Post-Combination Antiretroviral Therapy Era

Background. Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. Methods. Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL. Results. A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0–21.1 per 1000 PYFU) with current CD4 200–349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6–4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500–749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10–1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79–1.07), compared to a current CD4 of 750–999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25–1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01–1.25), comparing persons with a current CD4 of 500–749 cells/µL to 750–999 cells/µL. Discussion. The incidence of ADIs was higher in individuals with a current CD4 count of 500–749 cells/µL compared to those with a CD4 count of 750–999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.

Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene.

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8 x 10(-5)), establishing a novel phenotype for this genetic variant.

The temporal impulse response function in infantile nystagmus.

Despite rapid to-and-fro motion of the retinal image that results from their incessant involuntary eye movements, persons with infantile nystagmus (IN) rarely report the perception of motion smear. We performed two experiments to determine if the reduction of perceived motion smear in persons with IN is associated with an increase in the speed of the temporal impulse response. In Experiment 1, increment thresholds were determined for pairs of successively presented flashes of a long horizontal line, presented on a 65-cd/m2 background field. The stimulus-onset asynchrony (SOA) between the first and second flash varied from 5.9 to 234 ms. In experiment 2, temporal contrast sensitivity functions were determined for a 3-cpd horizontal square-wave grating that underwent counterphase flicker at temporal frequencies between 1 and 40 Hz. Data were obtained for 2 subjects with predominantly pendular IN and 8 normal observers in Experiment 1 and for 3 subjects with IN and 4 normal observers in Experiment 2. Temporal impulse response functions (TIRFs) were estimated as the impulse response of a linear second-order system that provided the best fit to the increment threshold data in Experiment 1 and to the temporal contrast sensitivity functions in Experiment 2. Estimated TIRFs of the subjects with pendular IN have natural temporal frequencies that are significantly faster than those of normal observers (ca. 13 vs. 9 Hz), indicating an accelerated temporal response to visual stimuli. This increase in response speed is too small to account by itself for the virtual absence of perceived motion smear in subjects with IN, and additional neural mechanisms are considered.

Does cigarette smoking modify the association between change in body mass index during young adulthood and risk of coronary mortality during middle-age in men? Twenty-five year follow-up results from the Chicago Western Electric Study

Many persons in the U.S. gain weight during young adulthood, and the prevalence of obesity has been increasing among young adults. Although obesity and physical inactivity are generally recognized as risk factors for coronary heart disease (CHD), the magnitude of their effect on risk may have been seriously underestimated due to failure to adequately handle the problem of cigarette smoking. Since cigarette smoking causes weight loss, physically inactive cigarette smokers may remain relatively lean because they smoke cigarettes. We hypothesize cigarette smoking modifies the association between weight gain during young adulthood and risk of coronary heart disease during middle age, and that the true effect of weight gain during young adulthood on risk of CHD can be assessed only in persons who have not smoked cigarettes. Specifically, we hypothesize that weight gain during young adulthood is positively associated with risk of CHD during middle-age in nonsmokers but that the association is much smaller or absent entirely among cigarette smokers. The purpose of this study was to test this hypothesis. The population for analysis was comprised of 1,934 middle-aged, employed men whose average age at the baseline examination was 48.7 years. Information collected at the baseline examinations in 1958 and 1959 included recalled weight at age 20, present weight, height, smoking status, and other CHD risk factors. To decrease the effect of intraindividual variation, the mean values of the 1958 and 1959 baseline examinations were used in analyses. Change in body mass index ($\Delta$BMI) during young adulthood was the primary exposure variable and was measured as BMI at baseline (kg/m$\sp2)$ minus BMI at age 20 (kg/m$\sp2).$ Proportional hazards regression analysis was used to generate relative risks of CHD mortality by category of $\Delta$BMI and cigarette smoking status after adjustment for age, family history of CVD, major organ system disease, BMI at age 20, and number of cigarettes smoked per day. Adjustment was not performed for systolic blood pressure or total serum cholesterol as these were regarded as intervening variables. Vital status was known for all men on the 25th anniversary of their baseline examinations. 705 deaths (including 319 CHD deaths) occurred over 40,136 person-years of experience. $\Delta$BMI was positively associated with risk of CHD mortality in never-smokers, but not in ever-smokers (p for interaction = 0.067). For never-smokers with $\Delta$BMI of stable, low gain, moderate gain, and high gain, adjusted relative risks were 1.00, 1.62, 1.61, and 2.78, respectively (p for trend = 0.010). For ever-smokers, with $\Delta$BMI of stable, low gain, moderate gain, and high gain, adjusted relative risks were 1.00, 0.74, 1.07, and 1.06, respectively (p for trend = 0.422). These results support the research hypothesis that cigarette smoking modifies the association between weight gain and CHD mortality. Current estimates of the magnitude of effect of obesity and physical inactivity on risk of coronary mortality may have been seriously underestimated due to inadequate handling of cigarette smoking. ^

Depression in early adulthood: prevalence and psychosocial correlates among young Swiss men

QUESTION UNDER STUDY Depression in young adults is common, but data from Switzerland are scarce. Our study gives a point prevalence estimate of depression in young Swiss men, and describes the association between depression and education, material and social resources, and job/school satisfaction. METHODS We used data from the cross-sectional Swiss Federal Surveys of Adolescents (ch-x) from 2010 to 2011 comprising 9,066 males aged between 18 and 25 years. Depression was assessed by means of self-reports using the Patient Health Questionnaire (PHQ-9). Persons were categorised into three groups: depression, subthreshold depression, and no depression. We assessed the relationship between depression and education, material and social resources, and satisfaction with job/school. Differences according to depression status were tested with chi-square tests for categorical variables and one-way analyses of variance for continuous variables. RESULTS Point prevalence of depression (3.60%) and subthreshold depression (3.62%) was high. Poor mental health was associated with lower education in young adults (p <0.001), and with their parents' education (p = 0.024). Social resources in persons with depression and subthreshold depression were substantially reduced (i.e., social support and satisfaction with social relations; both p <0.001). Young men with depression and subthreshold depression also reported a current lack of satisfaction with job/school (p <0.001). CONCLUSIONS Prevalence of (subthreshold) depression is high in young Swiss men. Depression at this age might result in a bad long-term prognosis owing to its association with low satisfaction with job/school and low self-efficacy. Interventions should especially consider the lower social resources of young men with depression.

Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus Patients in Rural Tanzania: A Preventable Cause of Early Mortality

Background.  Cryptococcal meningitis is a leading cause of death in people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome. The World Health Organizations recommends pre-antiretroviral treatment (ART) cryptococcal antigen (CRAG) screening in persons with CD4 below 100 cells/µL. We assessed the prevalence and outcome of cryptococcal antigenemia in rural southern Tanzania. Methods.  We conducted a retrospective study including all ART-naive adults with CD4 <150 cells/µL prospectively enrolled in the Kilombero and Ulanga Antiretroviral Cohort between 2008 and 2012. Cryptococcal antigen was assessed in cryopreserved pre-ART plasma. Cox regression estimated the composite outcome of death or loss to follow-up (LFU) by CRAG status and fluconazole use. Results.  Of 750 ART-naive adults, 28 (3.7%) were CRAG-positive, corresponding to a prevalence of 4.4% (23 of 520) in CD4 <100 and 2.2% (5 of 230) in CD4 100-150 cells/µL. Within 1 year, 75% (21 of 28) of CRAG-positive and 42% (302 of 722) of CRAG-negative patients were dead or LFU (P<.001), with no differences across CD4 strata. Cryptococcal antigen positivity was an independent predictor of death or LFU after adjusting for relevant confounders (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.29-4.83; P = .006). Cryptococcal meningitis occurred in 39% (11 of 28) of CRAG-positive patients, with similar retention-in-care regardless of meningitis diagnosis (P = .8). Cryptococcal antigen titer >1:160 was associated with meningitis development (odds ratio, 4.83; 95% CI, 1.24-8.41; P = .008). Fluconazole receipt decreased death or LFU in CRAG-positive patients (HR, 0.18; 95% CI, .04-.78; P = .022). Conclusions.  Cryptococcal antigenemia predicted mortality or LFU among ART-naive HIV-infected persons with CD4 <150 cells/µL, and fluconazole increased survival or retention-in-care, suggesting that targeted pre-ART CRAG screening may decrease early mortality or LFU. A CRAG screening threshold of CD4 <100 cells/µL missed 18% of CRAG-positive patients, suggesting guidelines should consider a higher threshold.

Time trends in avoidable cancer mortality in Switzerland and neighbouring European countries 1996-2010.

QUESTION UNDER STUDY What are the trends in avoidable cancer mortality in Switzerland and neighbouring countries? METHODS Mortality data and population estimates 1996-2010 were obtained from the Swiss Federal Statistical Office for Switzerland and the World Health Organization Mortality Database (http://www.who.int/healthinfo/mortality_data/en/) for Austria, Germany, France and Italy. Age standardised mortality rates (ASMRs, European standard) per 100 000 person-years were calculated for the population <75 years old by sex for the following groups of cancer deaths: (1) avoidable through primary prevention; (2) avoidable through early detection and treatment; (3) avoidable through improved treatment and medical care; and (4) remaining cancer deaths. To assess time trends in ASMRs, estimated annual percentage changes (EAPCs) with 95% confidence intervals (95% CIs) were calculated. RESULTS In Switzerland and neighbouring countries cancer mortality in persons <75 years old continuously decreased 1996-2010. Avoidable cancer mortality decreased in all groups of avoidable cancer deaths in both sexes, with one exception. ASMRs for causes avoidable through primary prevention increased in females in all countries (in Switzerland from 16.2 to 20.3 per 100 000 person years, EAPC 2.0 [95% CI 1.4 to 2.6]). Compared with its neighbouring countries, Switzerland showed the lowest rates for all groups of avoidable cancer mortality in males 2008-2010. CONCLUSION Overall avoidable cancer mortality decreased, indicating achievements in cancer care and related health policies. However, increasing trends in avoidable cancer mortality through primary prevention for females suggest there is a need in Switzerland and its European neighbouring countries to improve primary prevention.

Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons.

BACKGROUND The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. GUIDELINE HIGHLIGHTS The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. CONCLUSIONS The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview.

Qualitative study: Understanding Mexican American women's experience in intimate partner violence

The purpose of this qualitative study was to gain an understanding of the experiences of Mexican American women living with intimate partner abuse relevant to the process of disclosure of abuse. Limited research exists on the experiences of women who are of Mexican descent living with intimate partner abuse and their disclosure of abuse. Factors that influence disclosure for other populations are well articulated in the literature however, these factors have not been adequately verified in persons of Mexican descent. Data are reported from in-depth interviews with 26 clients at a shelter and an outreach agency in a south Texas-Mexico border community. Semi-structured interview guide was used to elicit information over an 11 month period. A grounded theory ethnography approach was used to analyze data. Verification strategies and constant comparison techniques (e.g. investigator responsiveness, methodological coherence, sampling adequacy, an active analytic stance, and saturation) enhanced rigor of analysis. Nineteen Mexican immigrant women and seven Mexican American women participated in the study. Several themes were discerned related to women's experiences in abuse: painful living, questioning endurance, and confronting reality. In almost every participant's account there was a description of repeated victimization by her intimate partner or partners, and again, by others within and outside her network. The participants discussed several cultural factors (e.g. embarrassment, concerns for family, avoidance of causing pain to family, protection of partner, avoidance of being judged) that hindered their decisions whether or not to disclose. Participants noted that healthcare workers rarely asked probing questions regarding abuse. The timing and process of disclosure took many turns for women in this study. Some of the factors hindering women from disclosing were found to be influenced by cultural practices. The consequences of disclosure for many of the women led them to re-victimization. Implications for practice to avoid missed opportunities with women living in abuse are to: ask questions routinely to encourage disclosure of abuse and offer community resource information for women living in abuse or both.^

Houston Rescue and Restore Coalition human trafficking needs assessment

Background. Human trafficking, or "modern day slavery", is a complex public health issue that we must understand more fully before it can be effectively tackled. There have been very few empirical studies on human trafficking and estimates of global and national human trafficking victims vary widely. Free the Slaves, a non-profit organization, estimates that there are at least 27 million people in the world at any given time that can be classified as victims of human trafficking. Houston, Texas has been identified as a place where human trafficking may be more likely to exist due to its close proximity to Mexico and due to economic and population factors. Houston Rescue and Restore Coalition (HRRC) is a local organization that exists to raise awareness of human trafficking in Houston, Texas. To better serve victims of human trafficking, HRRC commissioned a community assessment of the services available to victims of human trafficking in the greater Houston metropolitan area.^ Purpose. The current study assessed the capacity of organizations and agencies within the greater Houston metropolitan area to deal with human trafficking issues; in particular, knowledge regarding human trafficking issues among these organizations and agencies was evaluated.^ Methods. A cross-sectional study design was used to conduct surveys with key informants/stakeholders from organizations and agencies within the greater Houston metropolitan area. The survey instrument included 41 items in three parts, and consisted of multiple choice questions, open-ended essay questions, and closed-ended 5 point Likert questions.^ Results. The findings from this study indicate that efforts must be made to increase comprehensive awareness of the issue of human trafficking, including the federal and state laws that have been enacted to combat this problem. The data also indicate that there are limited services provided to human trafficking victims within the greater Houston metropolitan area.^ Conclusion. The results of the survey will provide Houston Rescue and Restore Coalition with information that will assist them in targeting their efforts to combat human trafficking in Houston, Texas.^

Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2

CC chemokine receptor 2 (CCR2) is a prominent receptor for the monocyte chemoattractant protein (MCP) group of CC chemokines. Mice generated by gene targeting to lack CCR2 exhibit normal leukocyte rolling but have a pronounced defect in MCP-1-induced leukocyte firm adhesion to microvascular endothelium and reduced leukocyte extravasation. Constitutive macrophage trafficking into the peritoneal cavity was not significantly different between CCR2-deficient and wild-type mice. However, after intraperitoneal thioglycollate injection, the number of peritoneal macrophages in CCR2-deficient mice did not rise above basal levels, whereas in wild-type mice the number of macrophages at 36 h was ≈3.5 times the basal level. The CCR2-deficient mice showed enhanced early accumulation and delayed clearance of neutrophils and eosinophils. However, by 5 days neutrophils and eosinophils in both CCR2-deficient and wild-type mice had returned to near basal levels, indicating that resolution of this inflammatory response can occur in the absence of macrophage influx and CCR2-mediated activation of the resident peritoneal macrophages. After intravenous injection with yeast β-glucan, wild-type mice formed numerous large, well-defined granulomas throughout the liver parenchyma, whereas CCR2-deficient mice had much fewer and smaller granulomas. These results demonstrate that CCR2 is a major regulator of induced macrophage trafficking in vivo.

Increased levels of plasma lysosomal enzymes in patients with Lowe syndrome

Lowe syndrome is an X-linked disorder that has a complex phenotype that includes progressive renal failure and blindness. The disease is caused by mutations in an inositol polyphosphate 5-phosphatase designated OCRL. It has been shown that the OCRL protein is found on the surface of lysosomes and that a renal tubular cell line deficient in OCRL accumulated substrate phosphatidylinositol 4,5-bisphosphate. Because this lipid is required for vesicle trafficking from lysosomes, we postulate that there is a defect in lysosomal enzyme trafficking in patients with Lowe syndrome that leads to increased extracellular lysosomal enzymes and might lead to tissue damage and contribute to the pathogenesis of the disease. We have measured seven lysosomal enzymes in the plasma of 15 patients with Lowe syndrome and 15 age-matched male controls. We find a 1.6- to 2.0-fold increase in all of the enzymes measured. When the data was analyzed by quintiles of activity for all of the enzymes, we found that 95% of values in the lowest quintile come from normal subjects whereas in the highest quintile 85% of the values are from patients with Lowe syndrome. The increased enzyme levels are not attributable to renal insufficiency because there was no difference in enzyme activity in the four patients with the highest creatinine levels compared with the six patients with the lowest creatinine values.