Mechanistic studies of mycobacterial glycolipid biosynthesis by the mannosyltransferase PimE.

Tuberculosis (TB), exceeded in mortality only by COVID-19 among global infectious diseases, is caused by Mycobacterium tuberculosis (Mtb). The pathogenicity of Mtb is largely attributed to its complex cell envelope, which includes a class of glycolipids called phosphatidyl-myo-inositol mannosides (PIMs), found uniquely in mycobacteria and its related corynebacterineae. These glycolipids maintain the integrity of the mycobacterial cell envelope, regulate its permeability, and mediate host-pathogen interactions. PIMs consist of a phosphatidyl-myo-inositol core decorated with one to six mannose residues and up to four acyl chains. The mannosyltransferase PimE catalyzes the transfer of the fifth PIM mannose residue from a polyprenyl phosphate-mannose (PPM) donor. This step in the biosynthesis of higher-order PIMs contributes to the proper assembly and function of the mycobacterial cell envelope; however, the structural basis for substrate recognition and the catalytic mechanism of PimE remain poorly understood. Here, we present the cryo-electron microscopy (cryo-EM) structures of PimE from Mycobacterium abscessus captured in its apo form and in a product-bound complex with the reaction product Ac1PIM5 and the by-product polyprenyl phosphate (PP), determined at 3.0 Å and 3.5 Å, respectively. The structures reveal the active site within a distinctive binding cavity that accommodates both donor and acceptor substrates/products. Within the cavity, we identified residues involved in substrate coordination and catalysis, which we confirmed through in vitro enzymatic assays and further validated by in vivo complementation experiments. Molecular dynamics simulations were applied to identify the access pathways and the dynamics involved in substrate binding. Integrating structural, biochemical, genetic, and computational experiments, our study provides comprehensive insights into how PimE functions, opening potential avenues for development of novel anti-TB therapeutics.

Special considerations in managing pain and psychosocial distress in patients with opioid use disorder and cancer: the role of the supportive care and psycho-oncology interdisciplinary team.

People with a substance use disorder (SUD) have shortened lifespans due to complications from their substance use and challenges engaging with traditional health care settings and institutions. This impact on life expectancy is especially prominent in patients with co-occurring SUDs and cancer, and often has a much worse prognosis from the cancer than a similar patient without a SUD. Palliative care teams are experts in serious illness communication and symptom management and have become increasingly embedded in the routine care of patients with cancer. We argue that the skill set of palliative care teams is uniquely suited for addressing the needs of this oft marginalized group. We provide a comprehensive review of tools for addressing these needs, including medications that can both treat pain and opioid use disorder (OUD), and highlight psychosocial approaches to treating patients with OUD and cancer in a way that is respectful and effective. Using a trauma informed framework, we focus on the application of harm reduction principles from addiction medicine and the principles of clear communication, accompaniment, and emotional presence from palliative care to maximize support. We also focus on ways to reduce stigma in the delivery of care, by providing language that reduces barriers and increases patient engagement. Finally, we describe a clinic embedded within our institution's cancer center which aims to serve patients with cancer and SUDs, built on the framework of harm reduction, accompaniment and trauma informed care (TIC). Overall, we aim to provide context for addressing the common challenges that arise with patients with cancer and OUD, including the direct impact of psychosocial stress on substance use and cancer treatment, delays in disease directed treatment that can potentially impact further treatment options and outcomes, challenging pain management due to greater opioid debt, and potential loss of primary coping mechanism through substance use in the face of potential terminal diagnosis.

Psychosocial Distress Screening Among Interprofessional Palliative Care Teams: A Narrative Review.

With increased need for palliative care and limited staffing resources, non-social workers are increasingly responsible for screening for urgent psychosocial distress. The National Consensus Project guidelines call for all palliative care team members to be competent in screening across domains. Yet, in contrast to an abundance of evidence-informed tools for palliative social work assessments, standardization for interprofessional psychosocial screening is lacking. This lack of standardized practice may lead to harmful disparities in care delivery. The purpose of this narrative review is to examine current literature on evidence-informed practices for psychosocial screening within palliative care. Google Scholar, a university Summon library search engine, and prominent palliative care journals were searched using the same phrases to locate articles for inclusion. Each article was reviewed and synthesized across common themes. Although an abundance of validated screening tools exists for outpatient oncology-specific settings, there is minimal guidance on psychosocial screening tools intended for specialty palliative care. The most oft-cited tools have been met with concern for validity across diverse palliative care populations and settings. Additional research is needed to operationalize and measure brief psychosocial screening tools that can be validated for use by interprofessional palliative care teams, a stepping-stone for increased equity in palliative care practice.

Amyloidosis and Considerations for the Hand Surgeon.

Amyloidosis can lead to cardiac, renal, and other multiorgan failure. New treatments have become available that can prolong survival but rely on early diagnosis. Manifestations of amyloidosis in hand surgery include carpal tunnel syndrome, trigger finger, peripheral neuropathy, and spontaneous distal biceps rupture. Often, these can predate systemic amyloidosis, offering hand surgeons an opportunity to diagnose patients with amyloidosis before systemic disease, refer them for treatment, and potentially alter disease course and prolong survival. In this review, we describe the pathophysiology and two most common subtypes of amyloidosis seen by hand surgeons. We provide guidance on biopsy practices and referral for patients with amyloidosis. Lastly, we provide a brief overview of the treatments for amyloidosis and their effect on disease course.

Reducing Sialylation Enhances Electrotaxis of Corneal Epithelial Cells.

Corneal wound healing is a complex biological process that integrates a host of different signals to coordinate cell behavior. Upon wounding, there is the generation of an endogenous wound electric field that serves as a powerful cue to guide cell migration. Concurrently, the corneal epithelium reduces sialylated glycoforms, suggesting that sialylation plays an important role during electrotaxis. Here, we show that pretreating human telomerase-immortalized corneal epithelial (hTCEpi) cells with a sialyltransferase inhibitor, P-3FAX-Neu5Ac (3F-Neu5Ac), improves electrotaxis by enhancing directionality, but not speed. This was recapitulated using Kifunensine, which inhibits cleavage of mannoses and therefore precludes sialylation on N-glycans. We also identified that 3F-Neu5Ac enhanced the responsiveness of the hTCEpi cell population to the electric field and that pretreated hTCEpi cells showed increased directionality even at low voltages. Furthermore, when we increased sialylation using N-azidoacetylmannosamine-tetraacylated (Ac4ManNAz), hTCEpi cells showed a decrease in both speed and directionality. Importantly, pretreating enucleated eyes with 3F-Neu5Ac significantly improved re-epithelialization in an ex vivo model of a corneal injury. Finally, we show that in hTCEpi cells, sialylation is increased by growth factor deprivation and reduced by PDGF-BB. Taken together, our results suggest that during corneal wound healing, reduced sialylated glycoforms enhance electrotaxis and re-epithelialization, potentially opening new avenues to promote corneal wound healing.

Trauma-Informed Care for Inpatient Palliative Care Social Work: Applying Existing Models at the Bedside.

Coexisting serious illness and posttraumatic stress place hospitalized individuals at risk for complex pain, anxiety, and retraumatization. Hospital palliative care social workers increasingly recognize the value of trauma-informed care (TIC) for reducing harm in the inpatient setting. Despite this recognition, there is limited operationalization of TIC principles for inpatient interventions. This paper integrates each TIC principle with inpatient psychosocial interventions to advance trauma-informed competencies among inpatient palliative care social workers and to provide a foundation for future TIC implementation research.

Missed opportunities for diagnosis of hepatitis B and C in individuals diagnosed with decompensated cirrhosis or hepatocellular carcinoma.

BACKGROUND AND AIM: This study aimed to assess utilization of health-care services in people with decompensated cirrhosis (DC) or hepatocellular carcinoma (HCC) and a "late diagnosis" of hepatitis B or hepatitis C. METHODS: Hepatitis B and C cases during 1997-2016 in Victoria, Australia, were linked with hospitalizations, deaths, liver cancer diagnoses, and medical services. A late diagnosis was defined as hepatitis B or hepatitis C notification occurring after, at the same time, or within 2 years preceding an HCC/DC diagnosis. Services provided during the 10-year period before HCC/DC diagnosis were assessed, including general practitioner (GP) or specialist visits, emergency department presentations, hospital admissions, and blood tests. RESULTS: Of the 25 766 notified cases of hepatitis B, 751 (2.9%) were diagnosed with HCC/DC, and hepatitis B was diagnosed late in 385 (51.3%). Of 44 317 cases of hepatitis C, 2576 (5.8%) were diagnosed with HCC/DC, and hepatitis C was diagnosed late in 857 (33.3%). Although late diagnosis dropped over time, missed opportunities for timely diagnosis were observed. Most people diagnosed late had visited a GP (97.4% for hepatitis B, 98.9% for hepatitis C) or had a blood test (90.9% for hepatitis B, 88.6% for hepatitis C) during the 10 years before HCC/DC diagnosis. The median number of GP visits was 24 and 32, and blood tests 7 and 8, for hepatitis B and C, respectively. CONCLUSIONS: Late diagnosis of viral hepatitis remains a concern, with the majority having frequent health-care service provision in the preceding period, indicating missed opportunities for diagnosis.

Considerations for Hand Surgery in Patients With Scleroderma.

Systemic sclerosis (scleroderma, SSc) is an autoimmune disease that causes significant dysfunction to multiple organ systems, including the musculoskeletal system. It poses significant challenges to the hand surgeon, including calcinosis, ischemic changes, Raynaud phenomenon, tendinopathies, synovitis, and joint contractures. Patients with SSc also suffer from multiorgan dysfunction, which makes them high-risk surgical patients. The hand surgeon must understand the pathophysiology, treatment strategies, and special operative considerations required in this population to avoid complications and help maintain or improve hand function.

Splice-switching of the insulin receptor pre-mRNA alleviates tumorigenic hallmarks in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is an aggressive pediatric tumor with a poor prognosis for metastasis and recurrent disease. Large-scale sequencing endeavors demonstrate that Rhabdomyosarcomas have a dearth of precisely targetable driver mutations. However, IGF-2 signaling is known to be grossly altered in RMS. The insulin receptor (IR) exists in two alternatively spliced isoforms, IR-A and IR-B. The IGF-2 signaling molecule binds both its innate IGF-1 receptor as well as the insulin receptor variant A (IR-A) with high affinity. Mitogenic and proliferative signaling via the canonical IGF-2 pathway is, therefore, augmented by IR-A. This study shows that RMS patients express increased IR-A levels compared to control tissues that predominantly express the IR-B isoform. We also found that Hif-1α is significantly increased in RMS tumors, portraying their hypoxic phenotype. Concordantly, the alternative splicing of IR adapts to produce more IR-A in response to hypoxic stress. Upon examining the pre-mRNA structure of the gene, we identified a potential hypoxia-responsive element, which is also the binding site for the RNA-binding protein CUG-BP1 (CELF1). We designed Splice Switching Oligonucleotides (SSO) against this binding site to decrease IR-A levels in RMS cell lines and, consequently, rescue the IR-B expression levels. SSO treatment resulted in a significant reduction in cell proliferation, migration, and angiogenesis. Our data shows promising insight into how impeding the IGF-2 pathway by reducing IR-A expression mitigates tumor growth. It is evident that Rhabdomyosarcomas use IR alternative splicing as yet another survival strategy that can be exploited as a therapeutic intervention in conjunction with already established anti-IGF-1 receptor therapies.

Unplanned Emergency Visits and Admissions After Orthopaedic Ambulatory Surgery in the First 2 Years of Operation of a University Ambulatory Surgery Center.

BACKGROUND: Ambulatory surgeries have increased in recent decades to help improve efficiency and cost; however, there is a potential need for unplanned postoperative admission, clinic visits, or evaluation in the emergency department (ED). PURPOSE/HYPOTHESIS: The purpose was to determine the frequency, reasons, and factors influencing hospitalizations, return to clinic, and/or ED encounters within 24 hours of ambulatory surgery. The time frame for data collection was the first 2 years of operation of a university sports medicine ambulatory surgery center (ASC). We hypothesized that the percentage of encounters would be low and primarily because of pain or postoperative complication. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A retrospective review was performed of all patients undergoing ambulatory surgery at an ASC during the first 2 years of its operation (November 2016 to October 2018). Data including age, sex, Current Procedural Terminology code, procedure performed, American Society of Anesthesiologists classification, body mass index, medical history, and tobacco use were collected. Patients seeking care in the ED, inpatient, or outpatient setting within the first 24 hours after surgery were identified and the reasons for these encounters were categorized into 1 of 3 groups: (1) medical complication, (2) postoperative pain, or (3) other postoperative complication. Logistic regression models were used to assess risk factors for these encounters. RESULTS: A total of 4650 sports medicine procedures were performed at the university ASC during the study period. A total of 35 patients (0.75%) sought additional care within 24 hours of surgery. Medical complications were the primary reason for seeking care (n = 16; 45.7%). Patients who sought treatment within 24 hours of surgery tended to be older, had more medical comorbidities, and were more likely to have undergone upper extremity (particularly shoulder) procedures. In the multivariable analysis, patients with higher ASA scores were more likely to seek additional care (P < .005) and there was a trend toward increased risk of seeking additional care with upper extremity surgery (P = .077). CONCLUSION: Orthopaedic procedures performed in an ASC result in a relatively low percentage of patients seeking additional care within the first 24 hours after surgery, consistent with other reports in the literature. Upper extremity procedures, particularly those of the shoulder, may carry an increased risk of requiring medical treatment within 24 hours of surgery. Even in the first 2 years of operation of a university-based ASC, low rates of postoperative complications and unplanned admissions can be maintained.

COVID-19 Lessons: The Alignment of Palliative Medicine and Trauma-Informed Care.

As the COVID-19 pandemic wears on, its psychological, emotional, and existential toll continues to grow and indeed may now rival the physical suffering caused by the illness. Patients, caregivers, and health-care workers are particularly at risk for trauma responses and would be well served by trauma-informed care practices to minimize both immediate and long-term psychological distress. Given the significant overlap between the core tenets of trauma-informed care and accepted guidelines for the provision of quality palliative care (PC), PC teams are particularly well poised to both incorporate such practices into routine care and to argue for their integration across health systems. We outline this intersection to highlight the uniquely powerful role PC teams can play to reduce the long-term psychological impact of the COVID-19 pandemic.

Rapid Implementation of Inpatient Telepalliative Medicine Consultations During COVID-19 Pandemic.

As coronavirus disease 2019 cases increase throughout the country and health care systems grapple with the need to decrease provider exposure and minimize personal protective equipment use while maintaining high-quality patient care, our specialty is called on to consider new methods of delivering inpatient palliative care (PC). Telepalliative medicine has been used to great effect in outpatient and home-based PC but has had fewer applications in the inpatient setting. As we plan for decreased provider availability because of quarantine and redeployment and seek to reach increasingly isolated hospitalized patients in the face of coronavirus disease 2019, the need for telepalliative medicine in the inpatient setting is now clear. We describe our rapid and ongoing implementation of telepalliative medicine consultation for our inpatient PC teams and discuss lessons learned and recommendations for programs considering similar care models.

Transgenic Analyses of Homer2 Function Within Nucleus Accumbens Subregions in the Regulation of Methamphetamine Reward and Reinforcement in Mice.

Problems associated with the abuse of amphetamine-type stimulants, including methamphetamine (MA), pose serious health and socioeconomic issues world-wide. While it is well-established that MA's psychopharmacological effects involve interactions with monoamine neurotransmission, accumulating evidence from animal models implicates dysregulated glutamate in MA addiction vulnerability and use disorder. Recently, we discovered an association between genetic vulnerability to MA-taking and increased expression of the glutamate receptor scaffolding protein Homer2 within both the shell and core subregions of the nucleus accumbens (NAC) and demonstrated a necessary role for Homer2 within the shell subregion in MA reward and reinforcement in mice. This report extends our earlier work by interrogating the functional relevance of Homer2 within the NAC core for the conditioned rewarding and reinforcing properties of MA. C57BL/6J mice with a virus-mediated knockdown of Homer2b expression within the NAC core were first tested for the development and expression of a MA-induced conditioned place-preference/CPP (four pairings of 2 mg/kg MA) and then were trained to self-administer oral MA under operant-conditioning procedures (5-80 mg/L). Homer2b knockdown in the NAC core augmented a MA-CPP and shifted the dose-response function for MA-reinforced responding, above control levels. To determine whether Homer2b within NAC subregions played an active role in regulating MA reward and reinforcement, we characterized the MA phenotype of constitutive Homer2 knockout (KO) mice and then assayed the effects of virus-mediated overexpression of Homer2b within the NAC shell and core of wild-type and KO mice. In line with the results of NAC core knockdown, Homer2 deletion potentiated MA-induced CPP, MA-reinforced responding and intake, as well as both cue- and MA-primed reinstatement of MA-seeking following extinction. However, there was no effect of Homer2b overexpression within the NAC core or the shell on the KO phenotype. These data provide new evidence indicating a globally suppressive role for Homer2 in MA-seeking and MA-taking but argue against specific NAC subregions as the neural loci through which Homer2 actively regulates MA addiction-related behaviors.

Understanding barriers, enablers, and long-term adherence to a health behavior intervention in people with multiple sclerosis.

Background: The optimal management strategy for multiple sclerosis (MS), and many other chronic diseases, likely involves health behavior modification. Multimodal behavioral interventions may be most effective, but little is known about long-term adherence in people with MS.Methods: This qualitative study assessed barriers and enablers to long-term adherence by people with MS who self-selected for a 5-day health behavior intervention 3-5 years prior. Thirteen women and five men participated in semi-structured phone interviews, which were transcribed and thematically analyzed.Results: The experience was described as useful for information gathering, decision making, and practical strategies regarding health behaviors. The majority still followed supplementation and dietary recommendations most of the time, although consuming non-recommended food while eating out was common. Support at home, ability and enjoyment in food preparation, and ability to resist unhealthy foods were both barriers and enablers. Adherence to "time-consuming" exercise and meditation recommendations were less common and episodic. Many reported competing interests on time from work and family; and barriers including injuries and symptoms, weather, financial or geographical barriers, and lack of person-centred support and motivation. Increased fitness and mobility, weight loss, and a sense of accomplishment and control were advantages and motivators. Practical and attitudinal strategies employed included planning, tailoring activities to ability and preference, and self-monitoring.Conclusion: While most people attempted to engage with all components of the intervention initially, only some still engaged with all components, and none to the recommended levels. These data can inform future quantitative studies and health behavior interventions.Implications for rehabilitationA multimodal group lifestyle intervention may be useful to assist people with multiple sclerosis in information gathering, decision making, attitudinal changes, and practical strategies regarding health behaviors; as well as providing a sense of hope for the future and control over wellbeing.While participants are unlikely to engage with all components of a multimodal intervention to the recommended level, they are likely to make improvements to one or more health behaviors.Experiential learning, including going through recipes and ingredient lists, and practicing meditation and physical exercises, is helpful to instigate behavior change.The initiation and maintenance of behavior change was assisted by support from family, friends, and health practitioners; and practical strategies employed by participants, including planning, self-monitoring, and tailoring activities to ability and preference.

Longitudinal Associations of Modifiable Lifestyle Factors With Positive Depression-Screen Over 2.5-Years in an International Cohort of People Living With Multiple Sclerosis.

Background: Depression is common and has a significant impact on quality of life for many people with multiple sclerosis (MS). A preventive management approach via modification of lifestyle risk factors holds potential benefits. We examined the relationship between modifiable lifestyle factors and depression risk and the change in depression over 2.5 years. Methods: Sample recruited using online platforms. 2,224 (88.9%) at baseline and 1,309 (93.4%) at 2.5 years follow up completed the necessary survey data. Depression risk was measured by the Patient Health Questionnaire-2 (PHQ-2) at baseline and Patient Health Questionniare-9 (PHQ-9) at 2.5-years follow-up. Multivariable regression models assessed the relationships between lifestyle factors and depression risk, adjusted for sex, age, fatigue, disability, antidepressant medication use, and baseline depression score, as appropriate. Results: The prevalence of depression risk at 2.5-years follow-up in this cohort was 14.5% using the PHQ-2 and 21.7% using the PHQ-9. Moderate alcohol intake, being a non-smoker, diet quality, no meat or dairy intake, vitamin D supplementation, omega 3 supplement use, regular exercise, and meditation at baseline were associated with lower frequencies of positive depression-screen 2.5 years later. Moderate alcohol intake was associated with greater likelihood of becoming depression-free and a lower likelihood of becoming depressed at 2.5-years follow-up. Meditating at least once a week was associated with a decreased frequency of losing depression risk, against our expectation. After adjusting for potential confounders, smoking, diet, physical activity, and vitamin D and omega-3 supplementation were not associated with a change in risk for depression. Conclusion: In a large prospective cohort study of people with MS and depression, in line with the emerging treatment paradigm of early intervention, these results suggest a role for some lifestyle factors in depression risk. Further studies should endeavor to explore the impact of positive lifestyle change and improving depression in people living with MS.

Longitudinal Associations of the Healthy Lifestyle Index Score With Quality of Life in People With Multiple Sclerosis: A Prospective Cohort Study.

Objective: To explore the association between combined lifestyle risk factors with quality of life in people with multiple sclerosis (MS) over 2.5 years. Methods: People with MS were recruited to participate in a comprehensive online survey regarding their demographic and clinical characteristics, health-related quality of life (HRQOL), and lifestyle behaviors including physical activity, alcohol consumption, cigarette smoking, body mass index, and dietary habits measured at baseline and 2.5-year follow-up. A combined healthy lifestyle index score (HLIS) was constructed by assigning scores of 0-4 to each of the lifestyle risk factors, for which higher values indicate healthier lifestyle behavior. Multivariable linear regression modeling was used to assess whether the HLIS at baseline was associated with the physical and mental HRQOL over the study period in this sample of people with MS. Results: Of 2,466 participants with confirmed MS, 1,401 (57%) completed the follow-up. Multivariable linear regression analyses demonstrated that every 5-point increase (of a possible total of 20) in the baseline HLIS was associated with 1.7 (95% CI: 0.2-3.2) and 2.5 (95% CI: 1.0-4.0) higher scores in the change in physical and mental HRQOL components from baseline to follow-up respectively. Conclusion: Findings suggest the importance of healthy lifestyle behavior in quality of life in MS. A healthy lifestyle program focusing on these behaviors has the potential to positively influence health-related quality of life for people with MS.

Health outcomes and adherence to a healthy lifestyle after a multimodal intervention in people with multiple sclerosis: Three year follow-up.

BACKGROUND: Modifiable risk factors such as smoking and sedentary lifestyle adversely affect multiple sclerosis (MS) progression. Few multimodal behavioural interventions have been conducted for people with MS, and follow-up beyond 1 year is rare for lifestyle interventions. This study assessed adoption and adherence to healthy lifestyle behaviours and health outcomes 3 years after a lifestyle modification intervention, using generalized estimating equation models to account for within-participant correlation over time. METHODS: 95 people with MS completed baseline surveys before participating in 5-day MS lifestyle risk-factor modification workshops. 76 and 78 participants completed the 1-year and 3-year follow-up surveys respectively. Mean age at 3-year follow-up was 47 years, 72% were female, most (62.8%) had MS for 5 years or less, and 73% had relapsing remitting MS (RRMS). RESULTS: Compared to baseline, participants reported clinically meaningful increases in physical (mean difference (MD): 8.0, 95% Confidence Interval (CI): 5.2-10.8) and mental health (MD: 9.2, CI: 5.8-12.6) quality of life (QOL) at 1-year, and physical (MD: 8.7, CI: 5.3-12.2) and mental health (MD: 8.0, CI: 4.2-11.8) QOL at 3-year follow-up. There was a small decrease in disability from baseline to 1-year follow-up (MD: 0.9, CI: 0.9,1.0) and to 3-year follow-up (MD: 1.0, CI: 0.9,1.0), which was not clinically meaningful. Of those with RRMS, compared to baseline, fewer had a relapse during the year before 1-year follow-up (OR: 0.1, CI 0.0-0.2) and 3-year follow-up (OR: 0.15, CI 0.06-0.33). Participants' healthy diet score, the proportion meditating ≥1 hours a week, supplementing with ≥ 5000IU vitamin D daily, and supplementing with omega-3 flaxseed oil increased at 1-year follow-up and was sustained, although slightly lower at 3-year follow-up. However, there was no evidence for a change in physical activity and not enough smokers to make meaningful comparisons. Medication use increased at 1-year follow-up and at 3-year follow-up. CONCLUSION: The results provide evidence that lifestyle risk factor modification is feasible and sustainable over time, in a small self-selected and motivated sample of people with MS. Furthermore, participation in a lifestyle intervention is not associated with a decrease in MS medication use.

Outcomes of treatment in men with prostate cancer at the cancer centre Bahamas.

PURPOSE: This is a first report from The Bahamas of management and long-term outcomes in men with non-metastatic prostate cancer treated with radiotherapy, with or without androgen deprivation therapy, from 2004 to 2016. METHODS: Patients were characterized by baseline factors, stratified by risk groups using tumor stage (clinical T-stage), prostate-specific antigen (PSA) test result and Gleason grade, and sorted by treatment combinations (by radiation volume and use of androgen deprivation). RESULTS: Overall, 205/216 men were Afro-Caribbean. Median age was 66. There were 18 low-, 77 intermediate-, and 121 high-risk patients, treated with prostate-only versus pelvis plus prostate radiotherapy, many receiving 2 years of androgen suppression. Time to commence radiation was about 6 months from initial diagnosis. In those not relapsing, global PSA nadir was reached in 4 years and was under 1.0, reduced from a mean at baseline of 31. At 10 years, disease-free experience (32 relapses) was 68% and overall survival was 87%, although only 2/12 deaths were related to prostate cancer. This experience compares favorably with recently published outcomes from other countries using very similar treatments. CONCLUSIONS: This study establishes benchmark statistics from diagnosis to long-term follow-up. Outcomes in Bahamian men are consistent with expectations from risk-stratified guidelines followed in developed countries.

Pain in People with Multiple Sclerosis: Associations with Modifiable Lifestyle Factors, Fatigue, Depression, Anxiety, and Mental Health Quality of Life.

BACKGROUND: People with multiple sclerosis (MS) often experience pain, which can interfere with mobility, employment, and quality of life (QOL). METHODS: This cross-sectional study explored associations between pain, demographic, disease, and modifiable lifestyle factors in an international sample of people with MS recruited online. RESULTS: Substantial pain, of moderate/severe intensity and interfering at least moderately with work/household or enjoyment of life in the past 4 weeks, was reported by 682/2,362 (28.9%). Substantial pain was associated with fatigue (odds ratio (OR): 6.7, 95% confidence interval (CI): 4.9,9.3), depression (OR:4.0, 95% CI:3.2,5.1), anxiety (OR:2.4, 95% CI:1.9,2.9), and lower mental health QOL (Mean Difference: -14.7, 95% CI:-16.6,-12.8). Regression analyses showed that smoking (OR: 2.0, 95% CI:1.35,2.87) and obesity (OR:2.1, 95% CI: 1.5,2.8), moderate alcohol use (OR: 0.7, 95% CI:0.5,0.9), moderate (OR 0.7, 95% CI: 0.55,0.98) or high (OR 0.6, 95% CI: 0.4,0.8) physical activity level, and healthy diet (OR 0.8, 95% CI: 0.75,0.95, per 10 points) were associated with substantial pain. CONCLUSION: Our results show clear associations with modifiable lifestyle factors and substantial pain in MS. These factors are already considered in the prevention and management of pain in other populations but have not previously been considered in MS. Conversely, pain and associated common MS comorbidities, such as depression, anxiety, and fatigue, may hamper efforts to start or maintain healthy behaviors. Strategies to overcome these barriers need to be considered. Further research should clarify the direction of these associations.