Oncogenic MTOR signaling axis compensates BTK inhibition in a Chronic Lymphocytic Leukemia patient with Richter Transformation: A Case Report and Review of the Literature.

INTRODUCTION: Targeting the B cell receptor (BCR) pathway via ibrutinib, a specific inhibitor of Bruton's tyrosine kinase, has shown marked clinical efficacy in treatment of patients with chronic lymphocytic leukemia (CLL), thus becoming a preferred first line option independent of risk factors. However, acquired resistance to ibrutinib poses a major clinical problem and requires the development of novel treatment combinations to increase efficacy and counteract resistance development and clinical relapse rates. CASE PRESENTATION: In this study, we performed exome and transcriptome analyses of an ibrutinib resistant CLL patient in order to investigate genes and expression patterns associated with ibrutinib resistance. Here we provide evidence that ibrutinib resistance can be attributed to aberrant mammalian target of rapamycin (MTOR) signaling. CONCLUSION: Thus, our study proposes that combined use of MTOR inhibitors with ibrutinib could be a possible option to overcome therapy resistance in ibrutinib treated patients.

Post-randomization Differences in Condomless Vaginal Sex Among Women Randomized to Intramuscular Depot Medroxyprogesterone Acetate Injections, a Copper Intrauterine Device or a Levonorgestrel Implant in the ECHO Trial.

The Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial found no substantial difference in HIV acquisition risk between women randomised to injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. We evaluated post-randomization sexual behavior using an objective marker of condomless vaginal sex in a subset of participants. We conducted a sub-study among 458 ECHO participants at three sites (Cape Town, Johannesburg, Kisumu) to evaluate the frequency of condomless vaginal sex, measured by prostate specific antigen (PSA) detection in vaginal swabs, collected at the month 6 and final visit and the concordance of self-reported condomless vaginal sex with PSA detection, by randomized arm. We compared PSA detection frequency and concordance of PSA and self-reported condomless vaginal sex, by randomized group using Cochran-Mantel-Haenszel tests and adjusted generalized logistic growth curve models. PSA was detected less frequently in the DMPA-IM (16%), compared to the Cu-IUD (21%) and LNG implant (24%) groups, although results were not statistically significant in the unadjusted model when accounting for pre-specified multiple-testing criteria. There were significant differences in PSA detection between the DMPA-IM and LNG-implant groups (odds ratio 0.61 (95% CI 0.40, 0.94) in the adjusted model. There was moderate discordance between self-reported condomless vaginal sex and detection of PSA that was similar across randomized groups. These data suggest that women randomized to Cu-IUD and LNG implant may have had condomless sex more frequently than women randomized to DMPA-IM. The discordance between detectable PSA and self-reported sexual behaviour has important implications for design of future HIV prevention studies.

Evaluating a Targeted Cancer Therapy Approach Mediated by RNA trans-Splicing In Vitro and in a Xenograft Model for Epidermolysis Bullosa-Associated Skin Cancer.

Conventional anti-cancer therapies based on chemo- and/or radiotherapy represent highly effective means to kill cancer cells but lack tumor specificity and, therefore, result in a wide range of iatrogenic effects. A promising approach to overcome this obstacle is spliceosome-mediated RNA trans-splicing (SMaRT), which can be leveraged to target tumor cells while leaving normal cells unharmed. Notably, a previously established RNA trans-splicing molecule (RTM44) showed efficacy and specificity in exchanging the coding sequence of a cancer target gene (Ct-SLCO1B3) with the suicide gene HSV1-thymidine kinase in a colorectal cancer model, thereby rendering tumor cells sensitive to the prodrug ganciclovir (GCV). In the present work, we expand the application of this approach, using the same RTM44 in aggressive skin cancer arising in the rare genetic skin disease recessive dystrophic epidermolysis bullosa (RDEB). Stable expression of RTM44, but not a splicing-deficient control (NC), in RDEB-SCC cells resulted in expression of the expected fusion product at the mRNA and protein level. Importantly, systemic GCV treatment of mice bearing RTM44-expressing cancer cells resulted in a significant reduction in tumor volume and weight compared with controls. Thus, our results demonstrate the applicability of RTM44-mediated targeting of the cancer gene Ct-SLCO1B3 in a different malignancy.

Algorithmic jingle jungle: A comparison of implementations of principal axis factoring and promax rotation in R and SPSS.

A statistical procedure is assumed to produce comparable results across programs. Using the case of an exploratory factor analysis procedure-principal axis factoring (PAF) and promax rotation-we show that this assumption is not always justified. Procedures with equal names are sometimes implemented differently across programs: a jingle fallacy. Focusing on two popular statistical analysis programs, we indeed discovered a jingle jungle for the above procedure: Both PAF and promax rotation are implemented differently in the psych R package and in SPSS. Based on analyses with 247 real and 216,000 simulated data sets implementing 108 different data structures, we show that these differences in implementations can result in fairly different factor solutions for a variety of different data structures. Differences in the solutions for real data sets ranged from negligible to very large, with 42% displaying at least one different indicator-to-factor correspondence. A simulation study revealed systematic differences in accuracies between different implementations, and large variation between data structures, with small numbers of indicators per factor, high factor intercorrelations, and weak factors resulting in the lowest accuracies. Moreover, although there was no single combination of settings that was superior for all data structures, we identified implementations of PAF and promax that maximize performance on average. We recommend researchers to use these implementations as best way through the jungle, discuss model averaging as a potential alternative, and highlight the importance of adhering to best practices of scale construction.

What's Sex Got to Do With It? Understanding Potential Confounding and Exposure Misclassification in Mechanistic Sexually Transmitted Infection Research.

We conducted a prospective study of 13 heterosexual couples to understand the impact of recent condomless vaginal sex on vaginal immune marker measurement and potential exposure misclassification due to the presence of semen. All immune markers were detectable in semen and concentrations of vaginal immune markers varied by sex recency.

B-cell-specific IRF4 deletion accelerates chronic lymphocytic leukemia development by enhanced tumor immune evasion.

Chronic lymphocytic leukemia (CLL) is a heterogenous disease that is highly dependent on a cross talk of CLL cells with the microenvironment, in particular with T cells. T cells derived from CLL patients or murine CLL models are skewed to an antigen-experienced T-cell subset, indicating a certain degree of antitumor recognition, but they are also exhausted, preventing an effective antitumor immune response. Here we describe a novel mechanism of CLL tumor immune evasion that is independent of T-cell exhaustion, using B-cell-specific deletion of the transcription factor IRF4 (interferon regulatory factor 4) in Tcl-1 transgenic mice developing a murine CLL highly similar to the human disease. We show enhanced CLL disease progression in IRF4-deficient Tcl-1 tg mice, associated with a severe downregulation of genes involved in T-cell activation, including genes involved in antigen processing/presentation and T-cell costimulation, which massively reduced T-cell subset skewing and exhaustion. We found a strong analogy in the human disease, with inferior prognosis of CLL patients with low IRF4 expression in independent CLL patient cohorts, failed T-cell skewing to antigen-experienced subsets, decreased costimulation capacity, and downregulation of genes involved in T-cell activation. These results have therapeutic relevance because our findings on molecular mechanisms of immune privilege may be responsible for the failure of immune-therapeutic strategies in CLL and may lead to improved targeting in the future.

Contraceptive knowledge among women at risk of unintended pregnancy in Kingston, Jamaica.

Low contraceptive knowledge may limit contraception initiation or continuation and, consequently, could represent an important, modifiable cause of unintended pregnancy. The objective of this analysis was to identify correlates of knowledge among women at risk of unintended pregnancy. We analyzed data from a study of 222 young women attending a public clinic in Kingston in November 2018 to March 2019. We measured contraceptive knowledge with seven questions on method reversibility, ability to use covertly, contraindications, and side effects. We used multivariable linear regression to evaluate the correlates of summary knowledge scores and report beta coefficients, which represent differences in mean summary knowledge scores. The mean knowledge score was low (2.7; range = 0-7). Only 30.2% of the participants correctly identified intrauterine devices as more effective than oral contraception, male condoms, and withdrawal. Women who reported that their provider discussed contraception scored higher (adjusted ß = 0.37, p = 0.05) than those not reporting this. Women who perceived implants as very/mostly safe scored higher (adjusted ß = 0.45, p = 0.01) than those perceiving the device as mostly/very unsafe. Finally, compared to contraception non-users, women using less-effective contraception had a lower score (adjusted ß = -0.40, p = 0.04) while those using effective contraception did not differ in scores (ß = -0.30, p = 0.18). Overall, we found poor contraceptive knowledge among young women in Kingston. Providers appeared to hold an important role in women's understanding of contraception.

A POLE Splice Site Deletion Detected in a Patient with Biclonal CLL and Prostate Cancer: A Case Report.

Chronic lymphocytic leukemia (CLL) is considered a clonal B cell malignancy. Sporadically, CLL cases with multiple productive heavy and light-chain rearrangements were detected, thus leading to a bi- or oligoclonal CLL disease with leukemic cells originating either from different B cells or otherwise descending from secondary immunoglobulin rearrangement events. This suggests a potential role of clonal hematopoiesis or germline predisposition in these cases. During the screening of 75 CLL cases for kappa and lambda light-chain rearrangements, we could detect a single case with CLL cells expressing two distinct kappa and lambda light chains paired with two separate immunoglobulin heavy-chain variable regions. Furthermore, this patient also developed a prostate carcinoma. Targeted genome sequencing of highly purified light-chain specific CLL clones from this patient and from the prostate carcinoma revealed the presence of a rare germline polymorphism in the POLE gene. Hence, our data suggest that the detected SNP may predispose for cancer, particularly for CLL.

Evidence for Non-Cancer-Specific T Cell Exhaustion in the Tcl1 Mouse Model for Chronic Lymphocytic Leukemia.

The reinvigoration of anti-cancer immunity by immune checkpoint therapies has greatly improved cancer treatment. In chronic lymphocytic leukemia (CLL), patients as well as in the Tcl1 mouse model for CLL, PD1-expressing, exhausted T cells significantly expand alongside CLL development; nevertheless, PD1 inhibition has no clinical benefit. Hence, exhausted T cells are either not activatable by simple PD1 blocking in CLL and/or only an insufficient number of exhausted T cells are CLL-specific. In this study, we examined the latter hypothesis by exploiting the Tcl1 transgenic CLL mouse model in combination with TCR transgene expression specific for a non-cancer antigen. Following CLL tumor development, increased PD1 levels were detected on non-CLL specific T cells that seem dependent on the presence of (tumor-) antigen-specific T cells. Transcriptome analysis confirmed a similar exhaustion phenotype of non-CLL specific and endogenous PD1pos T cells. Our results indicate that in the CLL mouse model, a substantial fraction of non-CLL specific T cells becomes exhausted during disease progression in a bystander effect. These findings have important implications for the general efficacy assessment of immune checkpoint therapies in CLL.

Selective Activation of CNS and Reference PPARGC1A Promoters Is Associated with Distinct Gene Programs Relevant for Neurodegenerative Diseases.

The transcriptional regulator peroxisome proliferator activated receptor gamma coactivator 1A (PGC-1α), encoded by PPARGC1A, has been linked to neurodegenerative diseases. Recently discovered CNS-specific PPARGC1A transcripts are initiated far upstream of the reference promoter, spliced to exon 2 of the reference gene, and are more abundant than reference gene transcripts in post-mortem human brain samples. The proteins translated from the CNS and reference transcripts differ only at their N-terminal regions. To dissect functional differences between CNS-specific isoforms and reference proteins, we used clustered regularly interspaced short palindromic repeats transcriptional activation (CRISPRa) for selective endogenous activation of the CNS or the reference promoters in SH-SY5Y cells. Expression and/or exon usage of the targets was ascertained by RNA sequencing. Compared to controls, more differentially expressed genes were observed after activation of the CNS than the reference gene promoter, while the magnitude of alternative exon usage was comparable between activation of the two promoters. Promoter-selective associations were observed with canonical signaling pathways, mitochondrial and nervous system functions and neurological diseases. The distinct N-terminal as well as the shared downstream regions of PGC-1α isoforms affect the exon usage of numerous genes. Furthermore, associations of risk genes of amyotrophic lateral sclerosis and Parkinson's disease were noted with differentially expressed genes resulting from the activation of the CNS and reference gene promoter, respectively. Thus, CNS-specific isoforms markedly amplify the biological functions of PPARGC1A and CNS-specific isoforms and reference proteins have common, complementary and selective functions relevant for neurodegenerative diseases.

Modeling choice paradoxes under risk: From prospect theories to sampling-based accounts.

Important developments in the study of decision making have been based on the establishment and testing of choice paradoxes (e.g., Allais') that reject different theories (e.g., Expected Utility Theory). One of the most popular and celebrated models in the literature, Cumulative Prospect Theory (CPT), has managed to retain its status despite a growing body of empirical evidence stemming from a collection of choice paradoxes that reject it. Two alternative models, Transfer of Attention Exchange (TAX) and an extension of Decision Field Theory (DFTe), have been proposed as possible alternatives to CPT. To date, no study has directly compared these three models within the context of a large set of lottery problems that tests different choice paradoxes. The present study accomplishes this by using a large and diverse set of lottery problems, involving both potential gains and losses. Our results support the presence and robustness of a set of 'strong' choice paradoxes that reject CPT irrespective of its parametric form. Model comparison results show that DFTe provides the best account for the present set of lottery problems, as it is able to accommodate the choice data at large in a parsimonious fashion. The success of DFTe shows that many behavioral phenomena, including paradoxes that CPT cannot account for, can be successfully captured by a simple noisy-sampling process. Overall, our results suggest that researchers should move away from CPT, and focus their efforts on alternative models such as DFTe.

Educational and health outcomes of children treated for asthma: Scotland-wide record linkage study of 683 716 children.

BACKGROUND: The global prevalence of childhood asthma is increasing. The condition impacts physical and psychosocial morbidity; therefore, wide-ranging effects on health and education outcomes are plausible. METHODS: Linkage of eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions and unemployment, provided data on 683 716 children attending Scottish schools between 2009 and 2013. We compared schoolchildren on medication for asthma with peers, adjusting for sociodemographic, maternity and comorbidity confounders, and explored effect modifiers and mediators. RESULTS: The 45 900 (6.0%) children treated for asthma had an increased risk of hospitalisation, particularly within the first year of treatment (incidence rate ratio 1.98, 95% CI 1.93-2.04), and increased mortality (HR 1.77, 95% CI 1.30-2.40). They were more likely to have special educational need for mental (OR 1.76, 95% CI 1.49-2.08) and physical (OR 2.76, 95% CI 2.57-2.95) health reasons, and performed worse in school exams (OR 1.11, 95% CI 1.06-1.16). Higher absenteeism (incidence rate ratio 1.25, 95% CI 1.24-1.26) partially explained their poorer attainment. CONCLUSIONS: Children with treated asthma have poorer education and health outcomes than their peers. Educational interventions that mitigate the adverse effects of absenteeism should be considered.

Minimalist barcodes for sponges: a case study classifying African freshwater Spongillida.

African sponges, particularly freshwater sponges, are understudied relative to demosponges in most other geographical regions. Freshwater sponges (Spongillida) likely share a common ancestor; however, their evolutionary history, particularly during their radiation into endemic and allegedly cosmopolitan groups, is unclear. Freshwater sponges of at least 58 species of 17 genera and four families are described from Central and Eastern Africa, but the diversity is underestimated due to limited distinguishable morphological features. The discovery of additional cryptic species is very likely with the use of molecular techniques such as DNA barcoding. The Royal Museum of Central Africa (MRAC, Tervuren, Belgium) hosts one of the largest collections of (Central) African freshwater sponge type material. Type specimens in theory constitute ideal targets for molecular taxonomy; however, the success is frequently hampered by DNA degradation and deamination, which are a consequence of suboptimal preservation techniques. Therefore, we genotyped African demosponge holotype material of the MRAC with specific short primers suitable for degenerated tissue and compare the results with the current, morphology-based classification. Our results demonstrate the utility of minimalistic barcodes for identification of sponges, potentially enabling efficient identification of individuals in taxonomic or metabarcoding studies, and highlight inconsistencies in the current freshwater sponge classification.

Educational and health outcomes of children and adolescents receiving antiepileptic medication: Scotland-wide record linkage study of 766 244 schoolchildren.

BACKGROUND: Childhood epilepsy can adversely affect education and employment in addition to health. Previous studies are small or highly selective producing conflicting results. This retrospective cohort study aims to compare educational and health outcomes of children receiving antiepileptic medication versus peers. METHODS: Record linkage of Scotland-wide databases covering dispensed prescriptions, acute and psychiatric hospitalisations, maternity records, deaths, annual pupil census, school absences/exclusions, special educational needs, school examinations, and (un)employment provided data on 766,244 children attending Scottish schools between 2009 and 2013. Outcomes were adjusted for sociodemographic and maternity confounders and comorbid conditions. RESULTS: Compared with peers, children on antiepileptic medication were more likely to experience school absence (Incidence Rate Ratio [IRR] 1.43, 95% CI: 1.38, 1.48), special educational needs (Odds ratio [OR] 9.60, 95% CI: 9.02, 10.23), achieve the lowest level of attainment (OR 3.43, 95% CI: 2.74, 4.29) be unemployed (OR 1.82, 95% CI: 1.60, 2.07), be admitted to hospital (Hazard Ratio [HR] 3.56, 95% CI: 3.42, 3.70), and die (HR 22.02, 95% CI: 17.00, 28.53). Absenteeism partly explained poorer attainment and higher unemployment. Girls and younger children on antiepileptic medication had higher risk of poor outcomes. CONCLUSIONS: Children on antiepileptic medication fare worse than peers across educational and health outcomes. In order to reduce school absenteeism and mitigate its effects, children with epilepsy should receive integrated care from a multidisciplinary team that spans education and healthcare.

Mortality, ethnicity, and country of birth on a national scale, 2001-2013: A retrospective cohort (Scottish Health and Ethnicity Linkage Study).

BACKGROUND: Migrant and ethnic minority groups are often assumed to have poor health relative to the majority population. Few countries have the capacity to study a key indicator, mortality, by ethnicity and country of birth. We hypothesized at least 10% differences in mortality by ethnic group in Scotland that would not be wholly attenuated by adjustment for socio-economic factors or country of birth. METHODS AND FINDINGS: We linked the Scottish 2001 Census to mortality data (2001-2013) in 4.62 million people (91% of estimated population), calculating age-adjusted mortality rate ratios (RRs; multiplied by 100 as percentages) with 95% confidence intervals (CIs) for 13 ethnic groups, with the White Scottish group as reference (ethnic group classification follows the Scottish 2001 Census). The Scottish Index of Multiple Deprivation, education status, and household tenure were socio-economic status (SES) confounding variables and born in the UK or Republic of Ireland (UK/RoI) an interacting and confounding variable. Smoking and diabetes data were from a primary care sub-sample (about 53,000 people). Males and females in most minority groups had lower age-adjusted mortality RRs than the White Scottish group. The 95% CIs provided good evidence that the RR was more than 10% lower in the following ethnic groups: Other White British (72.3 [95% CI 64.2, 81.3] in males and 75.2 [68.0, 83.2] in females); Other White (80.8 [72.8, 89.8] in males and 76.2 [68.6, 84.7] in females); Indian (62.6 [51.6, 76.0] in males and 60.7 [50.4, 73.1] in females); Pakistani (66.1 [57.4, 76.2] in males and 73.8 [63.7, 85.5] in females); Bangladeshi males (50.7 [32.5, 79.1]); Caribbean females (57.5 [38.5, 85.9]); and Chinese (52.2 [43.7, 62.5] in males and 65.8 [55.3, 78.2] in females). The differences were diminished but not eliminated after adjusting for UK/RoI birth and SES variables. A mortality advantage was evident in all 12 minority groups for those born abroad, but in only 6/12 male groups and 5/12 female groups of those born in the UK/RoI. In the primary care sub-sample, after adjustment for age, UK/RoI born, SES, smoking, and diabetes, the RR was not lower in Indian males (114.7 [95% CI 78.3, 167.9]) and Pakistani females (103.9 [73.9, 145.9]) than in White Scottish males and females, respectively. The main limitations were the inability to include deaths abroad and the small number of deaths in some ethnic minority groups, especially for people born in the UK/RoI. CONCLUSIONS: There was relatively low mortality for many ethnic minority groups compared to the White Scottish majority. The mortality advantage was less clear in UK/RoI-born minority group offspring than in immigrants. These differences need explaining, and health-related behaviours seem important. Similar analyses are required internationally to fulfil agreed goals for monitoring, understanding, and improving health in ethnically diverse societies and to apply to health policy, especially on health inequalities and inequities.

COL7A1 Editing via CRISPR/Cas9 in Recessive Dystrophic Epidermolysis Bullosa.

Designer nucleases allow specific and precise genomic modifications and represent versatile molecular tools for the correction of disease-associated mutations. In this study, we have exploited an ex vivo CRISPR/Cas9-mediated homology-directed repair approach for the correction of a frequent inherited mutation in exon 80 of COL7A1, which impairs type VII collagen expression, causing the severe blistering skin disease recessive dystrophic epidermolysis bullosa. Upon CRISPR/Cas9 treatment of patient-derived keratinocytes, using either the wild-type Cas9 or D10A nickase, corrected single-cell clones expressed and secreted similar levels of type VII collagen as control keratinocytes. Transplantation of skin equivalents grown from corrected keratinocytes onto immunodeficient mice showed phenotypic reversion with normal localization of type VII collagen at the basement membrane zone, compared with uncorrected keratinocytes, as well as fully stratified and differentiated skin layers without indication of blister development. Next-generation sequencing revealed on-target efficiency of up to 30%, whereas nuclease-mediated off-target site modifications at predicted genomic loci were not detected. These data demonstrate the potential of the CRISPR/Cas9 technology as a possible ex vivo treatment option for genetic skin diseases in the future.

Sexual Relationship Power and Semen Exposure Among Female Patients at a Sexually Transmitted Infection Clinic in Kingston, Jamaica.

Women's power in sexual relationships is thought to be an important predictor of condom use. However, research on correlates of condom use often relies on participant reporting of behavior, which has questionable validity. We evaluated the association between scores from the modified Sexual Relationship Power Scale (SRPS-M) and biological detection of semen exposure in a prospective study of adult women attending a sexually transmitted infection clinic in Kingston, Jamaica with cervicitis or abnormal vaginal discharge in 2010-2011. At enrollment, women were counseled to avoid sex while on treatment and were asked to return in 6 days for a follow-up visit. At both study visits, women were administered a questionnaire and had vaginal swabs collected to test for prostate-specific antigen (PSA), a biological marker of recent semen exposure. We found no significant association at enrollment or follow-up between SRPS-M scores and semen exposure, as measured with either self-reported data or PSA positivity. Semen biomarkers could be used to develop and validate new scales on relationship power and self-efficacy related to condom use.

Fold stability during endolysosomal acidification is a key factor for allergenicity and immunogenicity of the major birch pollen allergen.

BACKGROUND: The search for intrinsic factors, which account for a protein's capability to act as an allergen, is ongoing. Fold stability has been identified as a molecular feature that affects processing and presentation, thereby influencing an antigen's immunologic properties. OBJECTIVE: We assessed how changes in fold stability modulate the immunogenicity and sensitization capacity of the major birch pollen allergen Bet v 1. METHODS: By exploiting an exhaustive virtual mutation screening, we generated mutants of the prototype allergen Bet v 1 with enhanced thermal and chemical stability and rigidity. Structural changes were analyzed by means of x-ray crystallography, nuclear magnetic resonance, and molecular dynamics simulations. Stability was monitored by using differential scanning calorimetry, circular dichroism, and Fourier transform infrared spectroscopy. Endolysosomal degradation was simulated in vitro by using the microsomal fraction of JAWS II cells, followed by liquid chromatography coupled to mass spectrometry. Immunologic properties were characterized in vitro by using a human T-cell line specific for the immunodominant epitope of Bet v 1 and in vivo in an adjuvant-free BALB/c mouse model. RESULTS: Fold stabilization of Bet v 1 was pH dependent and resulted in resistance to endosomal degradation at a pH of 5 or greater, affecting presentation of the immunodominant T-cell epitope in vitro. These properties translated in vivo into a strong allergy-promoting TH2-type immune response. Efficient TH2 cell activation required both an increased stability at the pH of the early endosome and efficient degradation at lower pH in the late endosomal/lysosomal compartment. CONCLUSIONS: Our data indicate that differential pH-dependent fold stability along endosomal maturation is an essential protein-inherent determinant of allergenicity.

Ethnic variations in asthma hospital admission, readmission and death: a retrospective, national cohort study of 4.62 million people in Scotland.

BACKGROUND: Our previous meta-analysis found that South Asians and Blacks in the UK were at a substantially increased risk of hospital admission from asthma. These estimates were, however, derived from pooling data from a limited number of now dated studies, confined to only three very broad ethnic groups (i.e. Whites, South Asians and Blacks) and failed to take account of possible sex-related differences in outcomes within these ethnic groups. We undertook the first study investigating ethnic variations in asthma outcomes across an entire population. METHODS: This retrospective 9-year cohort study linked Scotland's hospitalisation/death records on asthma to the 2001 census (providing ethnic group). We calculated age, country of birth and Scottish Index of Multiple Deprivation adjusted incident rate ratios (IRRs) for hospitalisation or death by sex for the period May 2001-2010. We calculated hazard ratios (HRs) for asthma readmission and subsequent asthma death. RESULTS: We were able to link data on 4.62 million people (91.8% of the Scottish population), yielding over 38 million patient-years of data, 1,845 asthma deaths, 113,795 first asthma admissions, and 107,710 readmissions (40,075 of which were for asthma). There were substantial ethnic variations in the rate of hospitalisation/death in both males and females. When compared to the reference Scottish White population, the highest age-adjusted rates were in Pakistani males (IRR = 1.59; 95% CI, 1.30-1.94) and females (IRR = 1.50; 95% CI, 1.06-2.11) and Indian males (IRR = 1.34; 95% CI, 1.16-1.54), and the lowest were seen in Chinese males (IRR = 0.62; 95% CI, 0.41-0.94) and females (IRR = 0.49; 95% CI, 0.39-0.61). CONCLUSION: There are very substantial ethnic variations in hospital admission/deaths from asthma in Scotland, with Pakistanis having the worst and Chinese having the best outcomes. Cultural factors, including self-management and health seeking behaviours, and variations in the quality of primary care provision are the most likely explanations for these differences and these now need to be formally investigated.

Differences in misreporting of sexual behavior over time: implications for HIV trials.

We used data from a prospective study of 300 women attending a sexually transmitted infection clinic in Kingston, Jamaica, to compare participant self-report of recent semen exposure to actual semen exposure measured by prostate-specific antigen in vaginal swabs. Underreporting of semen exposure was significantly more frequent at follow-up than baseline, suggesting that the accuracy of reports of sexual behavior may vary over time.