Patients' views and experiences on the supported self-management/patient-initiated follow up pathway for breast cancer.

PURPOSE: To explore patients' expectations and experience of Supportive Self-Management (SSM)/ Patient Initiated Follow Up (PIFU) following breast cancer treatments over a 12-month period. METHODS: In total, 32/110 (29%) patient participants in the PRAGMATIC (Patients' experiences of a suppoRted self-manAGeMent pAThway In breast Cancer) study were interviewed at baseline, 3, 6, 9 and 12 months. Interviews in this sub-study used a mix-methods approach to explore understanding of the pathway, confidence in self-management, triggers to seek help and/or re-engage with the clinical breast team and impact of the COVID-19 pandemic. Responses to pre-assigned categories were summarised as counts/ percentages and collated in tabular or graphic format. Free responses were recorded verbatim and reviewed using framework analysis. RESULTS: Participants regarded the SSM/PIFU pathway as a way to save time and money for them and the National Health Service (NHS) (14/32; 44%) and as a means of assuming responsibility for their own follow-up (18/32; 56%). Most maintained (very/somewhat) confidence in managing their BC follow-up care (baseline 31/32, 97%; 12 months 29/31, 93%). During the year, 19% (5/26) stopped endocrine therapy altogether because of side effects. Qualitative analysis revealed general satisfaction with SSM/PIFU and described the breast care nurses as reassuring and empathic. However, there was a lingering anxiety about identifying signs and symptoms correctly, particularly for those with screen-detected cancers. There was also uncertainty about who to contact for psychological support. The COVID-19 pandemic discouraged some participants from contacting the helpline as they did not want to overburden the NHS. CONCLUSIONS: The results show that during the first year on the SSM/PIFU pathway, most patients felt confident managing their own care. Clinical teams should benefit from understanding patients' expectations and experiences and potentially modify the service for men with BC and/or those with screen-detected breast cancers.

Variants in EXOSC9 Disrupt the RNA Exosome and Result in Cerebellar Atrophy with Spinal Motor Neuronopathy.

The exosome is a conserved multi-protein complex that is essential for correct RNA processing. Recessive variants in exosome components EXOSC3, EXOSC8, and RBM7 cause various constellations of pontocerebellar hypoplasia (PCH), spinal muscular atrophy (SMA), and central nervous system demyelination. Here, we report on four unrelated affected individuals with recessive variants in EXOSC9 and the effect of the variants on the function of the RNA exosome in vitro in affected individuals' fibroblasts and skeletal muscle and in vivo in zebrafish. The clinical presentation was severe, early-onset, progressive SMA-like motor neuronopathy, cerebellar atrophy, and in one affected individual, congenital fractures of the long bones. Three affected individuals of different ethnicity carried the homozygous c.41T>C (p.Leu14Pro) variant, whereas one affected individual was compound heterozygous for c.41T>C (p.Leu14Pro) and c.481C>T (p.Arg161∗). We detected reduced EXOSC9 in fibroblasts and skeletal muscle and observed a reduction of the whole multi-subunit exosome complex on blue-native polyacrylamide gel electrophoresis. RNA sequencing of fibroblasts and skeletal muscle detected significant >2-fold changes in genes involved in neuronal development and cerebellar and motor neuron degeneration, demonstrating the widespread effect of the variants. Morpholino oligonucleotide knockdown and CRISPR/Cas9-mediated mutagenesis of exosc9 in zebrafish recapitulated aspects of the human phenotype, as they have in other zebrafish models of exosomal disease. Specifically, portions of the cerebellum and hindbrain were absent, and motor neurons failed to develop and migrate properly. In summary, we show that variants in EXOSC9 result in a neurological syndrome combining cerebellar atrophy and spinal motoneuronopathy, thus expanding the list of human exosomopathies.

Effect of an innovative model of complexity care on family caregiver experience: Qualitative study in family practice.

OBJECTIVE: To investigate the experiences of family caregivers who participated in an innovative model of interprofessional team-based care specifically designed for elderly patients with complex care needs. DESIGN: Qualitative study. SETTING: Large academic family practice in Toronto, Ont. PARTICIPANTS: Family caregivers of elderly patients who had attended the IMPACT (Interprofessional Model of Practice for Aging and Complex Treatments) clinic (N = 13). METHODS: Individual semistructured interviews, which were conducted face-to-face, audiorecorded, transcribed verbatim, and analyzed using the constant comparative method. MAIN FINDINGS: Family caregivers who attended the IMPACT clinic believed it enhanced caregiver experience and capacity. Caregivers experienced increased validation and engagement with the treatment team. Feelings of isolation were reduced, resulting in increased confidence and greater feelings of empowerment in their caregiver role. CONCLUSION: While the needs and value of caregivers are increasingly acknowledged, health care teams continue to struggle with how to relate to and engage with family caregivers-how best to support them and work with them in the context of their family members' care. Interprofessional teams who adopt the IMPACT model-providing synchronous, real-time interventions that include the caregiver-can facilitate increased caregiver capacity, confidence, and empowerment.

Addressing smoking among people living with HIV: a cross-sectional survey of Australian HIV health practitioners' practices and attitudes.

People living with HIV (PLHIV) have high rates of tobacco smoking, and smoking is a leading cause of premature mortality and morbidity. It is important to understand HIV healthcare providers' practices and attitudes towards addressing smoking with their patients. An online survey that measured: (i) use of the 5A framework for addressing smoking (Ask, Assess, Advise, Assist, Arrange) and (ii) attitudes and barriers to addressing smoking cessation was distributed by relevant professional bodies. Eligible participants were Australian health practitioners providing healthcare to PLHIV. Of the 179 respondents, most reported practising at least one of the 5As: Ask (94%); Assess (78%); Advise (82%); Assist (89%); and Arrange (73%). Practising the full 5A framework (completing at least one activity from each A) was less common (62%) and associated with having undertaken smoking cessation training (OR 2.1, CI 1.1-3.9), being a medical practitioner (OR 6.0, CI 3.1-11.6), having greater perceived knowledge and resources (OR 1.7, CI 1.3-2.4) and more positive attitudes (OR 1.5, CI 1.1-2.0). Common barriers to delivering cessation assistance related to knowledge and availability of resources. Development and greater dissemination of effective smoking cessation training and resources may be required to ensure healthcare practitioners have the capacity to complete all aspects of the 5A framework for smoking cessation and support their patients with HIV who smoke.

Pseudomonas aeruginosa minor pilins prime type IVa pilus assembly and promote surface display of the PilY1 adhesin.

Type IV pili (T4P) contain hundreds of major subunits, but minor subunits are also required for assembly and function. Here we show that Pseudomonas aeruginosa minor pilins prime pilus assembly and traffic the pilus-associated adhesin and anti-retraction protein, PilY1, to the cell surface. PilV, PilW, and PilX require PilY1 for inclusion in surface pili and vice versa, suggestive of complex formation. PilE requires PilVWXY1 for inclusion, suggesting that it binds a novel interface created by two or more components. FimU is incorporated independently of the others and is proposed to couple the putative minor pilin-PilY1 complex to the major subunit. The production of small amounts of T4P by a mutant lacking the minor pilin operon was traced to expression of minor pseudopilins from the P. aeruginosa type II secretion (T2S) system, showing that under retraction-deficient conditions, T2S minor subunits can prime T4P assembly. Deletion of all minor subunits abrogated pilus assembly. In a strain lacking the minor pseudopilins, PilVWXY1 and either FimU or PilE comprised the minimal set of components required for pilus assembly. Supporting functional conservation of T2S and T4P minor components, our 1.4 Å crystal structure of FimU revealed striking architectural similarity to its T2S ortholog GspH, despite minimal sequence identity. We propose that PilVWXY1 form a priming complex for assembly and that PilE and FimU together stably couple the complex to the major subunit. Trafficking of the anti-retraction factor PilY1 to the cell surface allows for production of pili of sufficient length to support adherence and motility.

Structural and functional studies of the Pseudomonas aeruginosa minor pilin, PilE.

Many bacterial pathogens, including Pseudomonas aeruginosa, use type IVa pili (T4aP) for attachment and twitching motility. T4aP are composed primarily of major pilin subunits, which are repeatedly assembled and disassembled to mediate function. A group of pilin-like proteins, the minor pilins FimU and PilVWXE, prime pilus assembly and are incorporated into the pilus. We showed previously that minor pilin PilE depends on the putative priming subcomplex PilVWX and the non-pilin protein PilY1 for incorporation into pili, and that with FimU, PilE may couple the priming subcomplex to the major pilin PilA, allowing for efficient pilus assembly. Here we provide further support for this model, showing interaction of PilE with other minor pilins and the major pilin. A 1.25 Å crystal structure of PilEΔ1-28 shows a typical type IV pilin fold, demonstrating how it may be incorporated into the pilus. Despite limited sequence identity, PilE is structurally similar to Neisseria meningitidis minor pilins PilXNm and PilVNm, recently suggested via characterization of mCherry fusions to modulate pilus assembly from within the periplasm. A P. aeruginosa PilE-mCherry fusion failed to complement twitching motility or piliation of a pilE mutant. However, in a retraction-deficient strain where surface piliation depends solely on PilE, the fusion construct restored some surface piliation. PilE-mCherry was present in sheared surface fractions, suggesting that it was incorporated into pili. Together, these data provide evidence that PilE, the sole P. aeruginosa equivalent of PilXNm and PilVNm, likely connects a priming subcomplex to the major pilin, promoting efficient assembly of T4aP.

The genome of the model beetle and pest Tribolium castaneum.

Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.

The Impact of Measurement Model Misspecification on Coefficient Omega Estimates of Composite Reliability.

Coefficient omega indices are model-based composite reliability estimates that have become increasingly popular. A coefficient omega index estimates how reliably an observed composite score measures a target construct as represented by a factor in a factor-analysis model; as such, the accuracy of omega estimates is likely to depend on correct model specification. The current paper presents a simulation study to investigate the performance of omega-unidimensional (based on the parameters of a one-factor model) and omega-hierarchical (based on a bifactor model) under correct and incorrect model misspecification for high and low reliability composites and different scale lengths. Our results show that coefficient omega estimates are unbiased when calculated from the parameter estimates of a properly specified model. However, omega-unidimensional produced positively biased estimates when the population model was characterized by unmodeled error correlations or multidimensionality, whereas omega-hierarchical was only slightly biased when the population model was either a one-factor model with correlated errors or a higher-order model. These biases were higher when population reliability was lower and increased with scale length. Researchers should carefully evaluate the feasibility of a one-factor model before estimating and reporting omega-unidimensional.

Targeted Prostate Health Checks, a novel system to identify men with prostate cancer-A pilot study.

Objectives: The objective of this study is to report the pilot phase of the Targeted Prostate Health Check programme that aims to identify men in the Surrey and Sussex region who have prostate cancer and who failed to be detected during the Covid era. Subjects and methods: Men aged 50 to 70, or 45 to 70 if Black or with a family history of prostate cancer, were identified from participating general practitioner (GP) records. Short message service (SMS) texts invited men to visit www.talkprostate.co.uk for information on prostate cancer and give consent to prostate-specific antigen (PSA) checks coordinated by a third-party virtual healthcare provider. Elevated age-related PSA levels, or levels below age-related thresholds but at 3 ng/mL or more, triggered referral to a rapid access urology clinic. GPs were informed of the results. Results: From 1842 text messages inviting 1549 people, 544 men consented to a PSA check. From 500 phlebotomy appointments, 485 (30% of invited men) took the PSA test of whom 68 (14%) were referred with an elevated PSA. After clinical review with multiparametric magnetic resonance imaging (mp-MRI), 22 patients underwent transperineal biopsies, and prostate cancer was detected in 18 men of whom 17 (95%) had clinically significant cancer. Conclusion: Our Targeted Prostate Cancer Health Check system identifies men at risk without burdening primary care. Awareness on prostate cancer risk was raised in 1549 invited men, half of whom were further educated via the registration website. One third of invited men were checked in whom clinically significant prostate cancer was found in 3.5%.

The IMPACT clinic: innovative model of interprofessional primary care for elderly patients with complex health care needs.

PROBLEM ADDRESSED: The growing number of elderly patients with multiple chronic conditions presents an urgent challenge in primary care. Current practice models are not well suited to addressing the complex health care needs of this patient population. OBJECTIVE OF PROGRAM: The primary objective of the IMPACT (Interprofessional Model of Practice for Aging and Complex Treatments) clinic was to design and evaluate a new interprofessional model of care for community-dwelling seniors with complex health care needs. A secondary objective was to explore the potential of this new model as an interprofessional training opportunity. PROGRAM DESCRIPTION: The IMPACT clinic is an innovative new model of interprofessional primary care for elderly patients with complex health care needs. The comprehensive team comprises family physicians, a community nurse, a pharmacist, a physiotherapist, an occupational therapist, a dietitian, and a community social worker. The model is designed to accommodate trainees from each discipline. Patient appointments are 1.5 to 2 hours in length, during which time a diverse range of medical, functional, and psychosocial issues are investigated by the full interprofessional team. CONCLUSION: The IMPACT model is congruent with ongoing policy initiatives in primary care reform and enhanced community-based care for seniors. The clinic has been pilot-tested in 1 family practice unit and modeled at 3 other sites with positive feedback from patients and families, clinicians, and trainees. Evaluation data indicate that interprofessional primary care models hold great promise for the growing challenge of managing complex chronic disease.

Female victims of acquaintance rape in college: Incidence and effects of encounters with perpetrators.

Objectives: Acquaintance rape is the most common type of rape perpetrated against college women, but little information exists on later encounters with the perpetrator, lifestyle changes, and symptoms of posttraumatic stress disorder (PTSD). Participants: The sample consisted of 463 college-attending females, 16% of which indicated they were raped since attending college. Methods: The current study examines the incidence and effects of acquaintance rape perpetrated against female college students at a large, public university in the southeastern United States. Results: Eighty-four percent of the women who indicated they had experienced a rape since attending college knew their perpetrator, and 65.5% encountered their perpetrator after the attack. Participants who encountered their perpetrator after the attack reported more lifestyle changes and higher PTSD symptom severity on the PTSD Checklist for DSM-5 (PCL-5). Conclusions: The current research suggests that the effects of acquaintance rape in college is a complicated area needing further research. There is evidence to support negative effects on victims based on interactions with perpetrators.

Assessing the quality of reporting on quality improvement initiatives in plastic surgery: A systematic review.

BACKGROUND: There has been a recent increase in the number and complexity of quality improvement studies in plastic surgery. To assist with the development of thorough quality improvement reporting practices, with the goal of improving the transferability of these initiatives, we conducted a systematic review of studies describing the implementation of quality improvement initiatives in plastic surgery. We used the SQUIRE 2.0 (Standards for Quality Improvement Reporting Excellence) guideline to appraise the quality of reporting of these initiatives. METHODS: English-language articles published in Embase, MEDLINE, CINAHL, and the Cochrane databases were searched. Quantitative studies evaluating the implementation of quality improvement initiatives in plastic surgery were included. The primary endpoint of interest in this review was the distribution of studies per SQUIRE 2.0 criteria scores in proportions. Abstract screening, full-text screening, and data extraction were completed independently and in duplicate by the review team. RESULTS: We screened 7046 studies, of which 103 full texts were assessed, and 50 met inclusion criteria. In our assessment, only 7 studies (14%) met all 18 SQUIRE 2.0 criteria. SQUIRE 2.0 criteria that were met most frequently were abstract, problem description, rationale, and specific aims. The lowest SQUIRE 2.0 scores appeared in funding, conclusion, and interpretation criteria. CONCLUSIONS: Improvements in QI reporting in plastic surgery, especially in the realm of funding, costs, strategic trade-offs, project sustainability, and potential for spread to other contexts, will further advance the transferability of QI initiatives, which could lead to significant strides in improving patient care.

The remarkably high prevalence of epilepsy and seizure history in fetal alcohol spectrum disorders.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is the umbrella term that describes the range of adverse developmental outcomes that may occur in the offspring of mothers who drink alcohol during pregnancy. FASD is associated with several comorbidities including epilepsy. The objective of the study was to evaluate the prevalence of epilepsy or a history of seizures in subjects with FASD and the contribution of relevant risk factors. METHODS: A retrospective chart review was conducted on all active charts (N = 1063) at two FASD clinics. After exclusion of subjects without a confirmed diagnosis, a total of 425 subjects between the ages of 2-49 were included in the analysis. The relationships between FASD diagnosis and other risk factors for co-occurrence of epilepsy or a seizure disorder (e.g., extent of exposure to alcohol and other drugs, type of birth, and trauma) were examined using chi-square and multivariate multinomial logistic regression. RESULTS: Twenty-five (5.9%) individuals in the study population had a confirmed diagnosis of epilepsy, and 50 (11.8%) had at least one documented seizure episode, yielding an overall prevalence of 17.7% in this population. Importantly, a history of epilepsy or seizures was not different across the three diagnostic subgroups. In those subjects with available maternal drinking histories, first trimester exposure or drinking throughout all three trimesters were the predominant forms of fetal exposure. None of the other risk factors were associated with a greater prevalence of epilepsy or seizures. CONCLUSIONS: There is a remarkably high prevalence of epilepsy/seizures in the FASD population.

Most nursing home social service directors lack training in working with lesbian, gay, and bisexual residents.

The purpose of this descriptive study is to report findings from a nationally representative mail-in survey of nursing home social service directors (n = 1,071) who were asked if they had received at least one hour of training in six different areas of cultural competency in the past five years. Of the six areas, the lowest percentage of directors reported having training in homophobia. Three-fourths of the sample had not received even one hour of homophobia training over the past five years. Directors who were more recently educated were more likely to report having received homophobia training, as were directors with a college degree, and those who worked in nursing homes located in the West and South regions of the United States. Directors with the most experience were less likely to report having received training. Findings call for immediate development and dissemination of heterosexism and homophobia training of social service staff, policy changes within the nursing home, and policy advocacy priorities for social workers.

Lumbosacral ventral spinal nerve root atrophy identified on MRI in a case of spinal muscular atrophy type II.

Spinal muscular atrophies are rare genetic disorders most often caused by homozygous deletion mutations in SMN1 that lead to progressive neurodegeneration of anterior horn cells. Ventral spinal root atrophy is a consistent pathological finding in post-mortem examinations of patients who suffered from various subtypes of spinal muscular atrophy; however, corresponding radiographic findings have not been previously reported. We present a patient with hypotonia and weakness who was found to have ventral spinal root atrophy in the lumbosacral region on MRI and was subsequently diagnosed with spinal muscular atrophy. More systematic analyses of imaging studies in spinal muscular atrophy will help determine whether such findings have the potential to serve as reliable diagnostic markers for clinical evaluations or as outcome measure for clinical trials.

Isolation of a gammaherpesvirus similar to asinine herpesvirus-2 (AHV-2) from a mule and a survey of mules and donkeys for AHV-2 infection by real-time PCR.

Equids are commonly infected by herpesviruses, but isolation of herpesviruses from mules has apparently not been previously reported. Furthermore, the genomic relationships among the various equid herpesviruses are poorly characterized. We describe the isolation and preliminary characterization of a mule gammaherpesvirus tentatively identified as asinine herpesvirus-2 (AHV-2; also designated equid herpesvirus-7 (EHV-7)) from the nasal secretions (NS) of a healthy mule in northern California. The virus was initially identified by transmission electron microscopic examination of lysates of cell culture inoculated with NS collected from the mule. A 913 nucleotide sequence of the DNA polymerase gene was amplified using degenerate primers, and comparison of this sequence with those of various other herpesviruses showed that the mule herpesvirus was most closely related to EHV-2 (AHV-2 sequences were not available for comparison). The sequence of a shorter portion (166 nucleotides) of the mule herpesvirus DNA polymerase gene was identical to that of the published sequence of an asinine gammaherpesvirus, previously designated as AHV-4-3 (AY054992). AHV-2 was detected by real-time polymerase chain reaction assay in the NS of approximately 8% of a cohort of 114 healthy mules and 13 donkeys.

Successful treatment of head shaking by use of infrared diode laser deflation and coagulation of corpora nigra cysts and behavioral modification in a horse.

CASE DESCRIPTION: A 15-year-old Saddlebred gelding used for competitive pleasure driving had a 1-year history of head shaking while pulling a cart. CLINICAL FINDINGS: The horse had cystic corpora nigra in both eyes and concomitant classic and operant conditioned responses to wearing a bridle with bilateral eye covers (blinkers). TREATMENT AND OUTCOME: Deflation and coagulation of the cysts with an infrared diode laser and behavior modification consisting of desensitization and counter-conditioning were used to successfully restore performance. CLINICAL RELEVANCE: Behavioral changes in horses can result from a combination of physical and psychologic causes. A combination of appropriate medical treatment of physical abnormalities and a behavioral modification plan is necessary to successfully treat behavioral problems in these patients.

Australian mental health care practitioners' practices and attitudes for encouraging smoking cessation and tobacco harm reduction in smokers with severe mental illness.

Reducing the burden of physical illness among people living with severe mental illnesses (SMI) is a key priority. Smoking is strongly associated with SMIs resulting in excessive smoking related morbidity and mortality in smokers with SMI. Smoking cessation advice and assistance from mental health practitioners would assist with reducing smoking and smoking-related harms in this group. This study examined the attitudes and practices of Australian mental health practitioners towards smoking cessation and tobacco harm reduction for smokers with SMI, including adherence to the 5As (ask, assess, advise, assist and arrange follow up) of smoking cessation. We surveyed 267 Australian mental health practitioners using a cross-sectional, online survey. Most practitioners (77.5%) asked their clients about smoking and provided health education (66.7%) but fewer provided direct assistance (31.1-39.7%). Most believed that tobacco harm reduction strategies are effective for reducing smoking related risks (88.4%) and that abstinence from all nicotine should not be the only goal discussed with smokers with SMI (77.9%). Many respondents were unsure about the safety (56.9%) and efficacy (39.3%) of e-cigarettes. Practitioners trained in smoking cessation were more likely (OR: 2.9, CI: 1.5-5.9) to help their clients to stop smoking. Community mental health practitioners (OR: 0.3, CI: 0.1-0.9) and practitioners who were current smokers (OR: 0.3, CI: 0.1-0.9) were less likely to adhere to the 5As of smoking cessation intervention. The results of this study emphasize the importance and need for providing smoking cessation training to mental health practitioners especially community mental health practitioners.

Congenital Syphilis Masquerading as Leukemia.

As of late, the incidence of congenital syphilis in the United States is increasing. Each new case represents a failure of preventing, diagnosing, and treating syphilis in pregnant women. Pediatricians should confirm that all women have received adequate screening for and management of syphilis during pregnancy. Congenital syphilis is easily treatable but may be a diagnostic challenge with high morbidity and mortality.