Dental disease in companion rabbits under UK primary veterinary care: Frequency and risk factors.

BACKGROUND: Some prior evidence has suggested that lop-eared rabbits and those with brachycephalic skull conformations have a higher dental disease risk. This retrospective cohort study reports the frequency and conformational risk factors for primary-care veterinary diagnosis with dental disease in companion rabbits in the UK. METHODS: Anonymised VetCompass clinical records were manually reviewed to confirm dental disease cases. Risk factor analysis used multivariable binary logistic regression modelling. RESULTS: From 161,979 rabbits under primary veterinary care in 2019, the 1-year period prevalence of overall dental disease was 15.36% (95% confidence interval [CI]: 14.78-15.96). The prevalence of dental disease affecting incisors was 3.14% (95% CI: 2.87-3.44), and for cheek teeth it was 13.72% (95% CI: 13.17-14.29). Neither lop-eared conformation nor brachycephalic skull conformation was significantly associated with increased odds of dental disease. Dental disease odds increased as age increased and decreased as bodyweight increased. LIMITATIONS: This study retrospectively accessed clinical records, so breed names may sometimes be imprecise. CONCLUSION: The high overall prevalence of dental disease represents a major welfare concern for all companion rabbits, regardless of conformation. This information can be used to encourage regular routine dental assessment of rabbits of all conformations to promote earlier diagnosis, paying particular attention to older rabbits and those with low bodyweight.

Antihypertensive medication class and diastolic orthostatic hypertension in older Caribbean adult patients.

In the Caribbean there is limited data on orthostatic hypertension (OHT) in elderly hypertensive patients with atherosclerotic disease who are at risk for cardiovascular events. The authors examined the association of antihypertensive classes of drugs with diastolic OHT in patients 60 year and older with hypertension and hyperlipidemia attending public primary care facilities. These relationships were evaluated in a cross-sectional study of hypertensive hyperlipidemic older patients (n = 400) to determine orthostatic changes in blood pressure based on seated to standing measurements. OHT was defined as an increase in systolic blood pressure of ≥20 mm Hg and/or increase in diastolic blood pressure of ≥10 mm Hg upon orthostasis at 3 min. Patients were categorized based on their orthostatic blood pressure response: orthostatic normotensive (n = 200) and blood pressure dysregulated (n = 200) of which 168 were diastolic OHT. Multivariable logistic regression models were used to examine associations of antihypertensive classes and diastolic OHT. Renin-angiotensin-aldosterone-system (RAAS) blockers were the most commonly prescribed (79.3%), followed by diuretics (DIUs) (61.6%), dihydropyridine calcium channel blockers (dCCBs) (53.8%), and beta-blockers (BBs) (19.3%). Most normotensive (76.0%) and diastolic OHT (75.0%) patients were prescribed two or more antihypertensive medications. Pharmaceutical prescription of triple combination RAAS blockers + dCCBs + DIUs (OR, 0.55; 95% CI, 0.31-0.99) or RAAS blockers + dCCBs + BBs (OR, 0.23; 95% CI, 0.06-0.92) showed a protective effect of diastolic OHT in analyses adjusted for age, sex, sitting diastolic blood pressure, and comorbidities. Our study suggests prescription of triple combination antihypertensive drugs of RAAS blockers + dCCBs + DIUs or RAAS blockers + dCCBs + BBs may reduce the likelihood of diastolic OHT.

Vitamin D Deficiency at Diagnosis Increases All-Cause and Prostate Cancer-specific Mortality in Jamaican Men.

BACKGROUND: 25 hydroxyvitamin D [25(OH)D] and serum calcium have been associated with incident prostate cancer (PCa). However, there is limited data on whether these metabolites predict survival in men of African descent, a population disproportionately affected by PCa. We studied the relationship of 25(OH)D at PCa diagnosis with all-cause and cancer-specific mortality among Jamaican men and examined whether serum calcium modified any associations. METHODS: Serum 25(OH)D from 152 Jamaican men with incident PCa within the Prostate Cancer Risk Evaluation (PROSCARE) study were re-evaluated approximately 11 years after enrollment. 25(OH)D analyses were stratified using the using Holick criteria. PCa-specific and all-cause mortality were examined in Kaplan-Meier survival curves and Cox regression models adjusted for age, body mass index (BMI), smoking and Gleason score. Restricted cubic splines evaluated nonlinear associations. Serum calcium was assessed as an effect modifier of the association between 25(OH)D and mortality. RESULTS: Of cases with available 25(OH)D, 64 men with PCa survived, 38 deaths were PCa specific and 36 died of other causes. At baseline, 9.9% of cases were vitamin D deficient and 61.2% were vitamin D sufficient. Compared to 25(OH)D sufficient men, those with 25(OH)D <20.0 ng/mL concentrations were associated with higher PCa-specific mortality (adjusted HR, 4.95; 95% CI, 1.68, 14.63, P = .004) and all-cause mortality (adjusted HR, 2.40; 95%CI, 1.33, 4. 32, P = .003). Serum calcium was not associated with survival and did not modify any associations with 25(OH)D. CONCLUSIONS: 25(OH)D deficiency at PCa diagnosis predicted decreased survival for overall and PCa-specific cancer in Caribbean men of African ancestry.

Increased risk of severe cutaneous adverse reactions when cladribine is used together with other medications with a propensity for skin reactions.

Cladribine is a purine analog used in first-line treatment of hairy cell leukemia and in relapsed/refractory chronic lymphocytic anemia. Although cladribine is typically associated with mild, self-limited skin reactions, there is increasing evidence that cladribine may increase the risk of severe cutaneous adverse reactions (SCAR) when combined with drugs classically associated with SCAR (e.g. allopurinol) beyond what would be expected for either drug alone, possibly due to cladribine-induced lymphopenia. We analyzed all SCAR cases reported for cladribine in Janssen's Global Safety Database and found that 26/35 (74.3%) reported concomitant drugs known to be associated with SCAR, most commonly sulfamethoxazole/trimethoprim (SMX/TMP) and allopurinol. In addition, a review of the WHO VigiBase showed that several drugs, including penicillins, SMX/TMP, and allopurinol had a statistically significant contribution to cladribine-associated SCAR. These results lend further support that cladribine may increase the propensity of these drugs to cause SCARs.

Health-related quality of life in long-term Caribbean prostate cancer survivors: comparisons with prostate cancer-free men.

PURPOSE: Prostate cancer (PCa) and its treatment can impact health-related quality of life (HRQoL). There are few studies of HRQoL in long-term PCa survivors of African ancestry from low- and middle-income countries. We examined the effect of PCa treatment on HRQoL of Jamaican PCa survivors compared with cancer-free controls and explored the effect of demographic and clinical factors on these outcomes. METHODS: PCa survivors (n = 64) treated with and without ADT along with PCa-free controls (n = 88) from a case-control study of 10 years post enrolment. HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30). Effects of demographic and clinical variables on HRQoL on PCa and type of therapy were evaluated in multivariable linear regression models. RESULTS: HRQoL of PCa survivors (overall and by treatment group) indicated a high quality of life, comparable to PCa-free men. However, ADT-treated survivors had lower physical functioning that was of small clinical relevance compared with those not on ADT. Symptom burden scores of PCa survivors and controls were similar excluding fatigue and dyspnoea which were highest in men on ADT and controls. In multivariable models, PCa was not an important determinant of overall HRQoL, functioning or symptom burdens. Underlying medical conditions and marital status were the main contributors to HRQoL in PCa survivors. CONCLUSION: PCa cancer status was not an independent determinant of long-term HRQoL in Jamaican men. Interventions addressing social factors and comorbid illnesses could improve HRQOL in long-term PCa survivors.

Addressing Inequity Through Public Health, Community Development, Arts, and Culture: Confluence of Fields and the Opportunity to Reframe, Retool, and Repair.

As the public health field deepens its focus on social and environmental determinants of health and, as that field expands its attention to finding allied interests in the community development field, a critical opportunity to better understand the power of arts and culture in pursuit of shared goals has emerged. This is an extraordinary time in which the confluence of public health, community development, and the arts can lead to transformational ways of working, resulting in changes in industry standards in all three fields and most importantly, more healthy, just, and equitable communities. Drawing from 30 years of work to better understand the roles of arts and cultural activity in historically marginalized communities, this article presents reasons for and ways in which these fields can and should be allied. Specifically, it calls attention to gaps in community development and planning that have resulted in the fields' lack of attention to historic and present harm in the form of often racialized dehumanization. It also draws attention to the role of the arts in the critical collective work of reframing community concerns and conditions, retooling or finding new more effective ways of working toward repair-the redress of historic and current harm experienced in low-income and historically marginalized communities. The essay lifts up the possibility of transformational work and also presents important barriers that must be overcome by stakeholders from all three fields.

Tackling Diversity in Prostate Cancer Clinical Trials: A Report From the Diversity Working Group of the IRONMAN Registry.

Prostate cancer disproportionately affects racial and ethnic minority populations. Reasons for disparate outcomes among minority patients are multifaceted and complex, involving factors at the patient, provider, and system levels. Although advancements in our understanding of disease biology have led to novel therapeutics for men with advanced prostate cancer, including the introduction of biomarker-driven therapeutics, pivotal translational studies and clinical trials are underrepresented by minority populations. Despite attempts to bridge the disparities gap, there remains an unmet need to expand minority engagement and participation in clinical trials to better define the impact of therapy on efficacy outcomes, quality of life, and role of biomarkers in diverse patient populations. The IRONMAN registry (ClinicalTrials.gov identifier: NCT03151629), a global, prospective, population-based study, was borne from this unmet medical need to address persistent gaps in our knowledge of advanced prostate cancer. Through integrated collection of clinical outcomes, patient-reported outcomes, epidemiologic data, and biospecimens, IRONMAN has the goal of expanding our understanding of how and why prostate cancer outcomes differ by race and ethnicity. To this end, the Diversity Working Group of the IRONMAN registry has developed informed strategies for site selection, recruitment, engagement and retention, and trial design and eligibility criteria to ensure broad inclusion and needs awareness of minority participants. In concert with systematic strategies to tackle the complex levels of disparate care, our ultimate goal is to expand minority engagement in clinical research and bridge the disparities gap in prostate cancer care.

Impact of diet on CVD and diabetes mortality in Latin America and the Caribbean: a comparative risk assessment analysis.

OBJECTIVE: To quantify diet-related burdens of cardiometabolic diseases (CMD) by country, age and sex in Latin America and the Caribbean (LAC). DESIGN: Intakes of eleven key dietary factors were obtained from the Global Dietary Database Consortium. Aetiologic effects of dietary factors on CMD outcomes were obtained from meta-analyses. We combined these inputs with cause-specific mortality data to compute country-, age- and sex-specific absolute and proportional CMD mortality of eleven dietary factors in 1990 and 2010. SETTING: Thirty-two countries in LAC. PARTICIPANTS: Adults aged 25 years and older. RESULTS: In 2010, an estimated 513 371 (95 % uncertainty interval (UI) 423 286-547 841; 53·8 %) cardiometabolic deaths were related to suboptimal diet. Largest diet-related CMD burdens were related to low intake of nuts/seeds (109 831 deaths (95 % UI 71 920-121 079); 11·5 %), low fruit intake (106 285 deaths (95 % UI 94 904-112 320); 11·1 %) and high processed meat consumption (89 381 deaths (95 % UI 82 984-97 196); 9·4 %). Among countries, highest CMD burdens (deaths per million adults) attributable to diet were in Trinidad and Tobago (1779) and Guyana (1700) and the lowest were in Peru (492) and The Bahamas (504). Between 1990 and 2010, greatest decline (35 %) in diet-attributable CMD mortality was related to greater consumption of fruit, while greatest increase (7·2 %) was related to increased intakes of sugar-sweetened beverages. CONCLUSIONS: Suboptimal intakes of commonly consumed foods were associated with substantial CMD mortality in LAC with significant heterogeneity across countries. Improved access to healthful foods, such as nuts and fruits, and limits in availability of unhealthful factors, such as processed foods, would reduce diet-related burdens of CMD in LAC.

The Association of General and Central Obesity with Dietary Patterns and Socioeconomic Status in Adult Women in Botswana.

Dietary patterns and their association with general and central obesity among adult women were studied using a cross-sectional survey with multistage cluster sampling in urban and rural areas nationwide in Botswana. The participants in the study were adult women (N = 1019), 18-75 years old. The dietary patterns were identified using principal component analysis, and their associations with the body mass index and the weight-for-height ratio were examined. Factor analysis with varimax rotation was used to identify six dietary patterns (fast foods, refined carbohydrates, vegetables and fruits, fish and nuts, Botswana traditional foods, and organ and red meat dietary pattern). Overall, 24.5% of the women were overweight (BMI 25.0-29.99 kg/m2) and 24.5% were obese (BMI > 30 kg/m2). A waist-to-height ratio greater than 0.5 was observed for 42.2% of the women. With adjustment for age and education, individuals in the highest tertile of the Botswana traditional food pattern had a significantly higher risk of general obesity (RR = 1.40, 95% CI: 1.07-1.84) and central obesity (RR = 1.20, 95% CI: 0.97-1.48). With respect to the fish and nut pattern, a significant association was observed with central obesity only (RR = 1.43, 95% CI: 1.18-1.72). The Botswana traditional food pattern, characterised by a high carbohydrate intake, was found to be associated with a high risk of obesity in this study. However, more research is required to assess other factors contributing to obesity in women so that appropriate intervention programs can be put in place to help control this epidemic.

Interactive effect of TLR SNPs and exposure to sexually transmitted infections on prostate cancer risk in Jamaican men.

BACKGROUND: Prostate cancer (PC) risk increases with African ancestry and a history of sexually transmitted infections (STIs). Also, single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes influence PC risk. This pilot study explores interactions between STIs and TLR-related SNPs in relation to PC risk among Jamaican men. METHODS: This case-control study evaluates two TLR related SNPs in 356 Jamaican men (194 controls and 162 cases) with or without history of STIs using stepwise penalized logistic regression in multivariable analyses. RESULTS: Age (odds ratio [OR] = 1.08; 95% confidence interval [CI]: 1.04-1>.12; p < .001) and IRF3_rs2304206 GG genotype (OR = 0.47; 95% CI: 0.29-0<.78; p = .003) modulated PC risk in people with history of STIs. In the population with no history of STIs, resulting interactions between risk factors did not survive correction for multiple hypothesis testing. CONCLUSION: Overall, an interaction between the IFR3_rs2304206 variant and a history of exposure to STIs leads to greater decrease of PC risk than the presence of polymorphic genotype alone. These findings are suggestive and require further validation. Identification of gene variants along with detection of lifestyle behaviors may contribute to identification of men at a greater risk of PC development in the population.

Central adiposity at diagnosis may reduce prostate cancer-specific mortality in African-Caribbean men with prostate cancer: 10-year follow-up of participants in a case-control study.

PURPOSE: General and central adiposity are associated with the risk of developing prostate cancer (PCa), but the role of these exposures on PCa survival among men of African ancestry are less studied. This study aimed to investigate the association of anthropometry at diagnosis with all-cause and PCa-specific mortality and evaluate whether androgen deprivation therapy (ADT) modulated this risk. METHODS: Associations between body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) at diagnosis and mortality were examined in 242 men with newly diagnosed PCa enrolled between 2005 and 2007 and re-evaluated 10.9 years later. Multi-variable Cox proportional hazard models were used to examine associations of body size variables (using standard WHO cut-points and as continuous variables) with mortality, adjusted for sociodemographic characteristics, Gleason score, smoking, diabetes, primary treatment, and ADT therapy. RESULTS: A total of 139 deaths (all-cause mortality 6.98/100 person-years) occurred (PCa-specific deaths, 56; other causes, 66; causes unknown, 17). In multi-variable analysis BMI, WC and WHR categories at diagnosis were not associated with all-cause mortality even after adjusting for ADT. While WHR (but not BMI or WC) when included as a continuous variable predicted lower PCa-specific mortality (multi-variable adjusted WHR per 0.1 difference: HR, 0.50; 95%CI 0.28, 0.93), the effect disappeared with ADT covariance and excluding deaths within the first 2 years. CONCLUSION: Our study suggests that central adiposity as measured by WHR may improve long-term survival among men of African ancestry. Metabolic studies to understand the mechanism for this association are needed.

A practical model for identification of children at risk of excess energy intake in the developing world.

OBJECTIVE: We describe diet quality by demographic factors and weight status among Barbadian children and examine associations with excess energy intake (EI). A screening tool for the identification of children at risk of excess EI was developed. DESIGN: In a cross-sectional survey, the Diet Quality Index-International (DQI-I) was used to assess dietary intakes from repeat 24h recalls among 362 children aged 9-10 years. Participants were selected by probability proportional to size. A model to identify excess energy intake from easily measured components of the DQI-I was developed. SETTING: Barbados.ParticipantsPrimary-school children in Barbados. RESULTS: Over one-third of children were overweight/obese, and mean EI for boys (8644 (se 174·5) kJ/d (2066 (se 41·7) kcal/d)) and girls (8912 (se 169·9) kJ/d (2130 (se 40·6) kcal/d)) exceeded the RDA. Children consuming a variety of food groups, more vegetables and fruits, and lower percentage energy contribution from empty-calorie foods showed reduced likelihood of excess EI. Intake of more than 2400 mg Na/d and higher macronutrient and fatty acid ratios were positively related to the consumption of excess energy. A model using five DQI-I components (overall food group variety, variety for protein source, vegetables, fruits and empty calorie intake) had high sensitivity for identification of children at risk of excess EI. CONCLUSIONS: Children's diet quality, despite low intakes of fruit and vegetables, was within acceptable ranges as assessed by the DQI-I and RDA; however, portion size was large and EI high. A practical model for identification of children at risk of excess EI has been developed.

Correction to: Burden of caregivers of adult patients with schizophrenia in a predominantly African ancestry population.

In the original publication, the co-author name Kelly-Marie Chen was misspelled and Shenae Miller was missed in the author group. The correct author group has been provided in this correction.

The genetic basis of disease.

Genetics plays a role, to a greater or lesser extent, in all diseases. Variations in our DNA and differences in how that DNA functions (alone or in combinations), alongside the environment (which encompasses lifestyle), contribute to disease processes. This review explores the genetic basis of human disease, including single gene disorders, chromosomal imbalances, epigenetics, cancer and complex disorders, and considers how our understanding and technological advances can be applied to provision of appropriate diagnosis, management and therapy for patients.

Effects of cholesterol, C-reactive protein, and interleukin-6 on prostate cancer risk in a population of African ancestry.

PURPOSE: To investigate the association between serum cholesterol and prostate cancer and whether any effect may be mediated through inflammatory markers. METHODS: Data from a case-control study of 40-80 years old Jamaican male patients (229 cases; 252 controls) were used. Cases had incident histologically-confirmed prostate cancer and controls were men with normal digital rectal examination and prostate-specific antigen (PSA) < 4 µg/L or free: total PSA > 0.15 obtained from the same clinic. Total and HDL cholesterol, interleukin-6 (IL-6), and C-reactive protein (CRP) were measured from a non-fasting sample. Multivariable logistic regression models were used to evaluate the associations between these factors and prostate cancer, adjusting for age, body mass index, waist circumference, family history of prostate cancer, diabetes, hypertension, use of cholesterol-lowering drugs, and smoking. RESULTS: Total cholesterol [Mean (cases, 4.71 ± 1.07; controls, 4.64 ± 1.07 mmol/L)], CRP [median (cases, 2.11; controls, 2.09 µg/ml)], and IL-6: [median (cases, 3.34; controls, 3.24 pg/ml)] did not differ by PCA status. Higher total cholesterol was associated with an increased risk of low-grade disease after adjusting for potential confounders [multivariable-adjusted OR (95% CI): tertile 2: 3.32(1.66, 6.45), tertile 3: 2.14(1.07, 4.32)]. Total cholesterol was unrelated to overall prostate cancer or high-grade disease. There was no significant association between HDL cholesterol or any of the inflammatory markers with prostate cancer. CONCLUSIONS: Increasing total cholesterol but not inflammatory markers were associated with low-grade prostate cancer in Caribbean men.

Inflammation polymorphisms and prostate cancer risk in Jamaican men: Role of obesity/body size.

African ancestry and obesity are associated with higher risk of prostate cancer (PC). In a pilot study, we explored interactions between obesity (as measured by waist to hip ratio (WHR)) and inflammatory SNPs in relation to PC risk among Jamaican men. This study evaluated 87 chemokine and cytokine associated SNPs in obese and normal weight cases (N=109) and controls (N=102) using a stepwise penalized logistic regression approach in multivariable analyses. Upon stratification by WHR (normal weight (WHR<0.90) or obese (WHR≥0.90)), inheritance of CCR6 rs2023305 AG+GG (OR=1.75, p=0.007), CCR9 rs7613548 AG+GG (OR=1.71, p=0.012) and IL10ra rs2229113 AG+GG (OR=1.45, p=0.01) genotypes was associated with increase in overall or low grade (Gleason score<7) PC risk among normal weight men. These odds were elevated among obese men who possessed the CCR5 rs1799987 AG+GG (OR=1.95, p=0.003) and RNASEL rs12135247 CT+TT genotypes (OR=1.59, p=0.05). CCR7 rs3136685 AG+GG (p=0.032) was associated with a 1.52-1.70 fold increase in the risk of high grade cancer (Gleason score≥7) among obese men. CCR7 variant emerged as an important factor associated with high grade PC risk among obese men in our analyses. Overall, genetic loci found significant in normal weight men were not significant in obese men and vice-versa, partially explaining the role of obesity on PC risk among black men. Also, older age was an important risk factor both in normal weight and obese men but only with regard to low grade PC. Associations of inflammatory SNPs with obesity are suggestive and require further validation in larger cohorts to help develop an understanding of PC risk among obese and non-obese men of African descent.

A limited survey-based uncontrolled follow-up study of children born after ooplasmic transplantation in a single centre.

Experimental ooplasmic transplantation from donor to recipient oocyte took place between 1996 and 2001 at Saint Barnabas Medical Center, USA. Indication for 33 patients was repeated implantation failure. Thirteen couples had 17 babies. One patient delivered twins from mixed ooplasmic and donor egg embryos. A limited survey-based follow-up study on the children is reported: 12 out of 13 parents completed a questionnaire on pregnancy, birth, health, academic performance and disclosure. Parents of a quadruplet did not participate. Prenatal development and delivery were uneventful. School grades ranged from good to excellent. Children were of good health. Body mass index (BMI) was normal in 12 out of 13 children. One child had chronic migraine headaches, two mild asthma, three minor vision and three minor skin problems. One boy from a boy/girl twin was diagnosed with borderline pervasive developmental disorder - not otherwise specified at age 18 months, but with no later symptoms. One couple disclosed the use of egg donor to their child. One reported intention to disclose; six were undecided and four reported they would not disclose. This limited follow-up strategy presents a high risk of bias. Parents may not assent to standardized clinical analysis owing to lack of disclosure to their children.

Burden of caregivers of adult patients with schizophrenia in a predominantly African ancestry population.

PURPOSE: There is relative inattention to caregiving burden in black populations in developing economies. This study seeks to assess the level of perceived burden and social determinants of burden of care in caregivers of adult patients with schizophrenia. METHODS: In this cross-sectional study, 115 dyads of patients with schizophrenia caregivers attending public mental health clinics were consecutively recruited. Burden of care was evaluated using the 22-item Zarit Burden Scale (maximum score, 88). Multiple linear regression model explored factors associated with caregiver burden. RESULTS: Caregivers were predominantly females (75.7 %) and were on average 50.8 ± 15.0 years. Most patients with schizophrenia were males (65.2 %) and were on average 43.6 ± 17.2 years old. Caregivers showed on average, mild-to-moderate burden (score, 30.0 ± 14.7; median, 28.0). There was tendency for caregivers of patients who were parents or spouses to have higher levels of burden. In multivariable analyses, higher burden of caregiving was associated with patient's inability to perform self-care (B ± SE, 5.12 ± 1.40; p = 0.0001), closer kinship and higher numbers of psychotic episodes in previous year. The length of caregiving relationship was inversely related. CONCLUSIONS: Poorer functioning and demographic factors were important determinants of caregiver burden. Community mental health services should include self-care interventions in rehabilitation programs in Jamaica.