Community based service providers' perspectives on frequent and/or avoidable admission of older people with chronic disease in rural NSW: a qualitative study

Background: Frequent and potentially avoidable hospital admission amongst older patients with ambulatory care sensitive (ACS) chronic conditions is a major topic for research internationally, driven by the imperative to understand and therefore reduce hospital admissions. Research to date has mostly focused on analysis of routine data using ACS as a proxy for 'potentially avoidable'. There has been less research on the antecedents of frequent and/or avoidable admission from the perspectives of patients or those offering community based care and support for these patients. This study aimed to explore community based service providers' perspectives on the factors contributing to admission among older patients with chronic disease and a history of frequent and potentially avoidable admission. Methods. 15 semi-structured interviews with community based providers of health care and other services, and an emergency department physician were conducted. Summary documents were produced and thematic analysis undertaken. Results: A range of complex barriers which limit or inhibit access to services were reported. We classified these as external and internal barriers. Important external barriers included: complexity of provision of services, patients' limited awareness of different services and their inexperience in accessing services, patients needing a higher level or longer length of service than they currently have access to, or an actual lack of available services, patient poverty, rurality, and transport. Important internal barriers included: fear (of change for example), a 'stoic' attitude to life, and for some, the difficulty of accepting their changed health status. Conclusions: The factors underlying frequent and/or potentially avoidable admission are numerous and complex. Identifying strategies to improve services or interventions for this group requires understanding patient, carer and service providers' perspectives. Improving accessibility of services is also complex, and includes consideration of patients' social, emotional and psychological ability and willingness to use services as well as those services being available and easily accessed

Multifocal multi-organ ischaemia and infarction in a preterm baby due to maternal intravenous cocaine use: a case report

<p>Abstract</p> <p>Introduction</p> <p>Although the adverse effects of cocaine use in pregnancy are well recognised, we believe this case highlights the importance of considering the route of administration, and suggests the possibility of multifocal damage relating to intravenous use.</p> <p>Case presentation</p> <p>A Caucasian female baby of 29-weeks' gestation was spontaneously delivered and subsequently developed multi-organ failure considered unrelated to simple prematurity. Intensive care was re-orientated following the development of massive intraventricular haemorrhage.</p> <p>Conclusion</p> <p>This case illustrates the need for regular cranial ultrasound in babies of pregnancies at risk due to intravenous cocaine use and also the necessity of counselling women who misuse cocaine in the antenatal period. As such, this article will be of most interest to paediatric and obstetric staff.</p

Development of a National Pain Management Competency Profile to Guide Entry-Level Physiotherapy Education in Canada

Background National strategies from North America call for substantive improvements in entry-level pain management education to help reduce the burden of chronic pain. Past work has generated a valuable set of interprofessional pain management competencies to guide the education of future health professionals. However, there has been very limited work that has explored the development of such competencies for individual professions in different regions. Developing profession-specific competencies tailored to the local context is a necessary first step to integrate them within local regulatory systems. Our group is working toward this goal within the context of entry-level physiotherapy (PT) programs across Canada. Aims This study aimed to create a consensus-based competency profile for pain management, specific to the Canadian PT context. Methods A modified Delphi design was used to achieve consensus across Canadian university-based and clinical pain educators. Results Representatives from 14 entry-level PT programs (93% of Canadian programs) and six clinical educators were recruited. After two rounds, a total of 15 competencies reached the predetermined endorsement threshold (75%). Most participants (85%) reported being “very satisfied” with the process. Conclusions This process achieved consensus on a novel pain management competency profile specific to the Canadian PT context. The resulting profile delineates the necessary abilities required by physiotherapists to manage pain upon entry to practice. Participants were very satisfied with the process. This study also contributes to the emerging literature on integrated research in pain management by profiling research methodology that can be used to inform related work in other health professions and regions

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi

INTRODUCTION: Pneumococcal infections cause a high death toll in Sub Saharan Africa (SSA) but the recently rolled out pneumococcal conjugate vaccines (PCV) will reduce the disease burden. To better understand the population impact of these vaccines, comprehensive analysis of large collections of pneumococcal isolates sampled prior to vaccination is required. Here we present a population genomic study of the invasive pneumococcal isolates sampled before the implementation of PCV13 in Malawi. MATERIALS AND METHODS: We retrospectively sampled and whole genome sequenced 585 invasive isolates from 2004 to 2010. We determine the pneumococcal population genetic structure and assessed serotype prevalence, antibiotic resistance rates, and the occurrence of serotype switching. RESULTS: Population structure analysis revealed 22 genetically distinct sequence clusters (SCs), which consisted of closely related isolates. Serotype 1 (ST217), a vaccine-associated serotype in clade SC2, showed highest prevalence (19.3%), and was associated with the highest MDR rate (81.9%) followed by serotype 12F, a non-vaccine serotype in clade SC10 with an MDR rate of 57.9%. Prevalence of serotypes was stable prior to vaccination although there was an increase in the PMEN19 clone, serotype 5 ST289, in clade SC1 in 2010 suggesting a potential undetected local outbreak. Coalescent analysis revealed recent emergence of the SCs and there was evidence of natural capsule switching in the absence of vaccine induced selection pressure. Furthermore, majority of the highly prevalent capsule-switched isolates were associated with acquisition of vaccine-targeted capsules. CONCLUSIONS: This study provides descriptions of capsule-switched serotypes and serotypes with potential to cause serotype replacement post-vaccination such as 12F. Continued surveillance is critical to monitor these serotypes and antibiotic resistance in order to design better infection prevention and control measures such as inclusion of emerging replacement serotypes in future conjugate vaccines

Yawn Contagion and Empathy in Homo sapiens

The ability to share others' emotions, or empathy, is crucial for complex social interactions. Clinical, psychological, and neurobiological clues suggest a link between yawn contagion and empathy in humans (Homo sapiens). However, no behavioral evidence has been provided so far. We tested the effect of different variables (e.g., country of origin, sex, yawn characteristics) on yawn contagion by running mixed models applied to observational data collected over 1 year on adult (>16 years old) human subjects. Only social bonding predicted the occurrence, frequency, and latency of yawn contagion. As with other measures of empathy, the rate of contagion was greatest in response to kin, then friends, then acquaintances, and lastly strangers. Related individuals (r≥0.25) showed the greatest contagion, in terms of both occurrence of yawning and frequency of yawns. Strangers and acquaintances showed a longer delay in the yawn response (latency) compared to friends and kin. This outcome suggests that the neuronal activation magnitude related to yawn contagion can differ as a function of subject familiarity. In conclusion, our results demonstrate that yawn contagion is primarily driven by the emotional closeness between individuals and not by other variables, such as gender and nationality

Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03-6.30, P = 3.1 × 10-9). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics

High and Low Molecular Weight Hyaluronic Acid Differentially Regulate Human Fibrocyte Differentiation

Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×10(6) Da). During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8-8×10(5) Da).In this report, we show that HMWHA potentiates the differentiation of human monocytes into fibrocytes, while LMWHA inhibits fibrocyte differentiation. Digestion of HMWHA with hyaluronidase produces small hyaluronic acid fragments, and these fragments inhibit fibrocyte differentiation. Monocytes internalize HMWHA and LMWHA equally well, suggesting that the opposing effects on fibrocyte differentiation are not due to differential internalization of HMWHA or LMWHA. Adding HMWHA to PBMC does not appear to affect the levels of the hyaluronic acid receptor CD44, whereas adding LMWHA decreases CD44 levels. The addition of anti-CD44 antibodies potentiates fibrocyte differentiation, suggesting that CD44 mediates at least some of the effect of hyaluronic acid on fibrocyte differentiation. The fibrocyte differentiation-inhibiting factor serum amyloid P (SAP) inhibits HMWHA-induced fibrocyte differentiation and potentiates LMWHA-induced inhibition. Conversely, LMWHA inhibits the ability of HMWHA, interleukin-4 (IL-4), or interleukin-13 (IL-13) to promote fibrocyte differentiation.We hypothesize that hyaluronic acid signals at least in part through CD44 to regulate fibrocyte differentiation, with a dominance hierarchy of SAP>LMWHA≥HMWHA>IL-4 or IL-13

Sex differences evident in elevated anxiety symptoms in multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis

IntroductionImmune-mediated inflammatory diseases (IMID), such as multiple sclerosis (MS), inflammatory bowel disease (IBD) or rheumatoid arthritis (RA) have high rates of elevated anxiety symptoms. This can may worsen functioning and increase IMID disease burden. The rate of and factors associated with elevated anxiety symptoms may differ between males and females, which, in turn can affect diagnosis and disease management. We evaluated whether the frequency and factors associated with comorbid elevated anxiety symptoms in those with an IMID differed by sex.MethodsParticipants with an IMID (MS, IBD or RA) completed two anxiety measures (HADS, GAD-7). We used logistic regression to investigate whether sex differences exist in the presence of comorbid elevated anxiety symptoms or in the endorsement of individual anxiety items in those with an IMID.ResultsOf 656 participants, females with an IMID were more likely to have elevated anxiety symptoms compared to males (adjusted odds ratio [aOR] 2.05; 95%CI: 1.2, 3.6). Younger age, higher depressive symptoms and income were also associated with elevated anxiety symptoms in IMID. Lower income in males with an IMID, but not females, was associated with elevated anxiety symptoms (aOR: 4.8; 95%CI: 1.5, 15.6). No other factors demonstrated a sex difference. Males had nearly twice the odds of endorsing restlessness on the GAD-7 (OR = 1.8, 95%CI: 1.07, 3.15) compared to females.DiscussionWe found evidence for sex differences in the factors associated with experiencing elevated anxiety symptoms in those with an IMID. These findings could be helpful to sensitize clinicians to monitor for comorbid anxiety symptoms in males with an IMID