Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

Background Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95–0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19–20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55–12.43). Conclusions LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP.

Risk factors for anal cancer in persons infected with HIV: a nested case-control study in the Swiss HIV Cohort Study

Although persons infected with human immunodeficiency virus (HIV), particularly men who have sex with men, are at excess risk for anal cancer, it has been difficult to disentangle the influences of anal exposure to human papillomavirus (HPV) infection, immunodeficiency, and combined antiretroviral therapy. A case-control study that included 59 anal cancer cases and 295 individually matched controls was nested in the Swiss HIV Cohort Study (1988-2011). In a subset of 41 cases and 114 controls, HPV antibodies were tested. A majority of anal cancer cases (73%) were men who have sex with men. Current smoking was significantly associated with anal cancer (odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.25, 5.34), as were antibodies against L1 (OR = 4.52, 95% CI: 2.00, 10.20) and E6 (OR = ∞, 95% CI: 4.64, ∞) of HPV16, as well as low CD4+ cell counts, whether measured at nadir (OR per 100-cell/μL decrease = 1.53, 95% CI: 1.18, 2.00) or at cancer diagnosis (OR per 100-cell/μL decrease = 1.24, 95% CI: 1.08, 1.42). However, the influence of CD4+ cell counts appeared to be strongest 6-7 years prior to anal cancer diagnosis (OR for <200 vs. ≥500 cells/μL = 14.0, 95% CI: 3.85, 50.9). Smoking cessation and avoidance of even moderate levels of immunosuppression appear to be important in reducing long-term anal cancer risks.

Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Terrorists Among Us: Effects of a Suspect's Group Membership, Terrorist Past, and Knowledge on Lay Persons' Interrogation Severity Recommendations

Support among US citizens for severe interrogation has been recognized as drawing upon utilitarian as well as on retributive motivation (Carlsmith & Sood, 2009). Two studies were conducted to expand on these findings in a Swiss sample. In Study 1, participants rated the severity of different interrogation techniques, which were scaled to provide an alternative measure of interrogation severity. In Study 2, retributive motivation was manipulated by varying the terrorist past of a male suspect, and utilitarian motivation was manipulated by varying the probability that the suspect could provide valuable information. Additionally, we manipulated the suspect’s group membership. The results of the vignette study suggest that the number and severity of recommended interrogation techniques is mainly influenced by whether the suspect might provide valuable information. Whether the suspect had a terrorist past was an additional influence that, however, was primarily attributable to the suspect’s group membership: If the suspect belonged to the ingroup, participants’ harsher interrogation recommendations were affected by that person’s past, whereas recommendations were not significantly influenced by a terrorist past if the suspect was an outgroup member.

Evaluation of a novel photography-based home assessment protocol for identification of environmental risk factors for falls in elderly persons

PRINCIPLES To evaluate the validity and feasibility of a novel photography-based home assessment (PhoHA) protocol, as a possible substitute for on-site home assessment (OsHA). METHODS A total of 20 patients aged ≥65 years who were hospitalised in a rehabilitation centre for musculoskeletal disorders affecting mobility participated in this prospective validation study. For PhoHA, occupational therapists rated photographs and measurements of patients' homes provided by patients' confidants. For OsHA, occupational therapists conducted a conventional home visit. RESULTS Information obtained by PhoHA was 79.1% complete (1,120 environmental factors identified by PhoHA vs 1416 by OsHA). Of the 1,120 factors, 749 had dichotomous (potential hazards) and 371 continuous scores (measurements with tape measure). Validity of PhoHA to potential hazards was good (sensitivity 78.9%, specificity 84.9%), except for two subdomains (pathways, slippery surfaces). Pearson's correlation coefficient for the validity of measurements was 0.87 (95% confidence interval [CI 0.80-0.92, p <0.001). Agreement between methods was 0.52 (95%CI 0.34-0.67, p <0.001, Cohen's kappa coefficient) for dichotomous and 0.86 (95%CI 0.79-0.91, p <0.001, intraclass correlation coefficient) for continuous scores. Costs of PhoHA were 53.0% lower than those of OsHA (p <0.001). CONCLUSIONS PhoHA has good concurrent validity for environmental assessment if instructions for confidants are improved. PhoHA is potentially a cost-effective method for environmental assessment.

Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent

There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n=372) and European (n=958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care.

Personality dimensions in persons symptomatically at risk of psychosis: pronounced but lacking a characteristic profile

AIM Personality dimensions are frequently abnormal in psychosis. We examined if these abnormalities form a personality profile that is characteristic for patients symptomatically at risk of psychosis. METHODS Four higher order personality dimensions were assessed in 104 at-risk patients, 67 clinical and 97 healthy controls with the 'Dimensional Assessment of Personality Pathology', and analysed by two-step cluster procedure to detect personality profiles. Logistic regression was used to test for predictors of profile assignment. RESULTS Low and high scorers were distinguished by two profiles. Patients were more likely high scorers. The presence of clinically relevant depression, though equally frequent in clinical groups, best predicted high scorers among patients. CONCLUSIONS Though at-risk patients were significantly more often high scorers, this seemed to be a general reflection of the level of psychopathology rather than a group characteristic. Thus, personality dimensions might be of little value for facilitating early detection but might be important to consider in early intervention approaches.

Apolipoprotein E genotypes and cognitive functions in healthy elderly persons

Objectives- We investigated whether apoE genotypes correlate with cognitive functions in clinically healthy persons. Methods - In 1993 and 1995, we measured information processing speed, delayed free recall and semantic aspects of long-term memory in 227 men and 105 women aged 65 and over, a randomly selected subsample of the prospective Basel Study. Cardiovascular risk factors and education were assessed. Results -E2 were more prevalent in old-old (>75 years, 23.5% vs 15%) compared to E4 than in young-old (<75 years, 19.3% vs 23.5%). Taking into account age and education, subjects with ɛ3/ɛ4 or ɛ4/ɛ4 alleles (E4) performed lowest in all 3 tests compared to those homozygous for ɛ3 (E3) or carriers of one or two ɛ2 alleles (E2) (reaction time P=0.009, free recall P=0.05, WAIS-R vocabulary P<0.05). In old-old there was a significant difference between E2 and E4 for reaction time (P=0.02) and free recall (P<0.02) but not for vocabulary (P=0.086). In all 3 groups there were no significant changes after 2 years. The subgroup with the genotype ɛ2/ɛ4 performed consistently best in the cognitive tests. Cholesterol was significantly increased in the E4 and E3 group compared to the E2 group. Conclusion - ApoE genotype correlates with cognitive performance. The increased prevalence of E2 in the old-old and the significantly lower plasma cholesterol levels suggest differential morbidity and mortality as important factors influencing the prevalence of cognitive disorders in late life.