Beta-blocker use and breast cancer outcomes: a meta-analysis.

PURPOSE: Beta blockers (BBs) are commonly used cardiovascular medications, and their association with breast cancer outcomes has been examined in several previous observational studies and meta-analyses. In this study, an updated meta-analysis was undertaken to ascertain the association between BBs and both breast cancer death (BCD) and breast cancer recurrence (BCR). METHODS: Articles were sourced from various databases up until the 14th of August 2023. Effect estimates were pooled using the random effects model, and the Higgins I2 statistic was computed to ascertain heterogeneity. Subgroup analyses were conducted by the potential for immortal time bias (ITB), the exposure period (prediagnosis vs postdiagnosis), and type of BB (selective vs non-selective). Publication bias was assessed using funnel plots and Egger's regression tests. RESULTS: Twenty-four studies were included. Pooled results showed that there was no statistically significant association between BB use and both BCD (19 studies, hazard ratio = 0.90, 95% CI 0.78-1.04) and BCR (16 studies, HR = 0.87, 95% CI 0.71-1.08). After removing studies with ITB, the associations were attenuated towards the null. There was no effect modification for either outcome when stratifying by the exposure period or type of BB. There was clear evidence of publication bias for both outcomes. CONCLUSION: In this meta-analysis, we found no evidence of an association between BB use and both BCD and BCR. Removing studies with ITB attenuated the associations towards the null, but there was no effect modification by the exposure period or type of BB.

Associations between transport modes and site-specific cancers: a systematic review and meta-analysis.

BACKGROUND: Physical inactivity is a global public health problem. A practical solution would be to build physical activity into the daily routine by using active modes of transport. Choice of transport mode can influence cancer risk through their effects on levels of physical activity, sedentary time, and environmental pollution. This review synthesizes existing evidence on the associations of specific transport modes with risks of site-specific cancers. METHODS: Relevant literature was searched in PubMed, Embase, and Scopus from 1914 to 17th February 2023. For cancer sites with effect measures available for a specific transport mode from two or more studies, random effects meta-analyses were performed to pool relative risks (RR) comparing the highest vs. lowest activity group as well as per 10 Metabolic Equivalent of Task (MET) hour increment in transport-related physical activity per week (∼150 min of walking or 90 min of cycling). RESULTS: 27 eligible studies (11 cohort, 15 case-control, and 1 case-cohort) were identified, which reported the associations of transport modes with 10 site-specific cancers. In the meta-analysis, 10 MET hour increment in transport-related physical activity per week was associated with a reduction in risk for endometrial cancer (RR: 0.91, 95% CI: 0.83-0.997), colorectal cancer (RR: 0.95, 95% CI: 0.91-0.99) and breast cancer (RR: 0.99, 95% CI: 0.89-0.996). The highest level of walking only or walking and cycling combined modes, compared to the lowest level, were significantly associated with a 12% and 30% reduced risk of breast and endometrial cancers respectively. Cycling, compared to motorized modes, was associated with a lower risk of overall cancer incidence and mortality. CONCLUSION: Active transport appears to reduce cancer risk, but evidence for cancer sites other than colorectum, breast, and endometrium is currently limited.

Ethnic variation in access to publicly funded care for unintentional injuries in older adults in Aotearoa New Zealand: a retrospective study.

BACKGROUND: Maori (the Indigenous people of Aotearoa New Zealand (NZ)) are more likely to experience injury than non-Maori, but less likely to have effective access to publicly funded injury care services. It is unknown if this pattern extends into older age. This retrospective study analysed Accident Compensation Corporation (ACC; national no-fault injury compensation scheme) claims data to investigate ethnic variation in unintentional injury claims and related costs for older adults (≥50 years). METHODS: Injury claims data for older adults residing in two regions of NZ between January 2014 and December 2018 were reviewed. Age-standardised claims rates (per person year) standardised rate ratios were calculated and compared between Maori and non-Maori. ACC claim costs (medical treatment; earning-related compensation) were estimated, with total and average costs per claim compared between the two groups. RESULTS: There were 149 275 ACC claims (18 369 Maori; 130 906 non-Maori) among 64 238 individuals (9284 Maori; 54 954 non-Maori). The age-standardised rate of ACC claims for unintentional injury was 46% higher among non-Maori (95% CI 44% to 48%) than Maori. The ACC spend for non-Maori was NZ$155 277 962 compared with NZ$30 446 673 for Maori. Maori had a significantly higher average cost per claim (NZ$1658 vs NZ$1186, p<0.001). CONCLUSIONS: Results of this study highlight differences in the manner in which different groups of older adults access injury compensation in NZ, indicating the need to invest in injury prevention initiatives that target older Maori, as well as initiatives supporting improved ACC access for older Maori.

Long-Term Follow-up of Subjects With Iliac Occlusive Disease Treated With the Viabahn VBX Balloon-Expandable Endoprosthesis.

INTRODUCTION: This physician-initiated study provides 5-year (i.e., long-term) treatment durability data from 3 top recruitment sites that participated in the prospective, multicenter, nonrandomized, single-arm VBX FLEX clinical study (ClinicalTrials.gov identifier: NCT02080871). It evaluates the long-term treatment durability of the GORE VIABAHN VBX Balloon Expandable Endoprosthesis (VBX Stent-Graft) in the treatment of subjects with de novo or restenotic aortoiliac lesions. MATERIALS AND METHODS: A total of 59 subjects with 94 treated lesions were enrolled at the 3 participating sites from the original 140 intent-to-treat subjects in the VBX FLEX study. The primary durability endpoint was long-term primary patency. Secondary long-term outcomes included freedom from target lesion revascularization (TLR), freedom from target vessel revascularization (TVR), as well as resting ankle-brachial index (ABI), Rutherford category, EuroQol 5 Dimensions, and Walking Impairment status. RESULTS: Fifty-nine subjects participated and twenty-eight (47.5%) were available through the end of the study at 5-year follow-up (the median follow-up time was 6.6 years due to complications resulting from COVID-19 precautions). At 3 and 5 years, the Kaplan-Meier estimates for freedom from all-cause mortality were 94.5% and 81.7%, respectively. The Kaplan-Meier estimates for primary patency at 3 and 5 years were 94.0% and 89.5% (by lesion) and 91.7% and 84.4% (by subject). Primary assisted patency at 3 and 5 years were 93.3% and 93.3%. Kaplan-Meier estimate for freedom from TLR at 5 years was 89.1%. The majority of subjects were asymptomatic (Rutherford category 0) at 3 years (29/59; 72%), and at 5-year follow-up (18/28; 64%). The 5-year mean resting ankle-brachial index was 0.95±0.18, an improvement of 0.15±0.26 from the baseline (p<0.001). Quality of life measures also showed sustained improvement through long-term follow-up. CONCLUSION: The 5-year long-term follow-up data underscore the robustness and durability of the Viabahn Balloon-Expandable Endoprosthesis for treating aortoiliac occlusive disease. CLINICAL IMPACT: Durable improvement after endovascular treatment of iliac occlusive disease is clinically important because many of these patients are claudicants with significant life expectancy. This study is the first to evaluate the long-term outcomes in patients with iliac occlusive disease treated with the Viabahn VBX balloon-expandable endopirostheses. The study reports excellent long-term patency outcomes with prolonged clinical benefit. These durable results are likely to be an important consideration for clinicians undertaking iliac artery revascularization procedures.

Self-compassion, Stress, and Eating Behaviour: Exploring the Effects of Self-compassion on Dietary Choice and Food Craving After Laboratory-Induced Stress.

BACKGROUND: Stress has been linked to high-fat and high-sugar food consumption. Self-compassion is associated with better emotional and physiological responses to stress. The current study explored whether trait self-compassion or induced state self-compassion could improve dietary choice and food craving after a stress induction. METHOD: Fifty-three university students completed an online survey assessing self-compassion, eating restraint, and general perceived stress before attending a laboratory visit. In the laboratory, participants were randomised to a neutral writing control or a self-compassion letter writing condition before a stress induction. Measures of heart rate, heart rate variability, state self-compassion, dietary choice, and state food cravings were taken. RESULTS: The brief self-compassion intervention did not sufficiently increase state self-compassion in the intervention group compared to the neutral writing condition. There was no effect of the written self-compassion intervention on heart rate, heart rate variability, dietary choice, or food craving. However, higher trait self-compassion was associated with healthier dietary choices (F(1, 49) = 5.35, p = .025, R2 = .098). CONCLUSION: Results suggest that higher trait self-compassion improved dietary choice after stress in a controlled environment in a university population. Further research is warranted to explore whether brief self-compassion interventions can improve state self-compassion and thereby influence dietary choices and food cravings after a stress induction.

Comparison of percentile tables and algorithm-based calculators for classification of blood pressures in children and adolescents with obesity: A secondary analysis of a clinical trial.

AIM: Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in a cohort of children affected by obesity using tables versus digital calculations in two sets of guidelines. METHODS: This study was a secondary analysis of data collected from a randomised clinical trial of a multidisciplinary life-style assessment and intervention program. Baseline data from 237 children with a body mass index >99th percentile or >91st percentile with weight-related comorbidities and available BP measurements were analysed. We assessed agreement between tables and algorithms in classification of elevated BP/pre-hypertension and hypertension based on the American Academy of Paediatrics (AAP) clinical practice guidelines (CPG) and the older Fourth Report using Cohen's weighted kappa. The prevalence of hypertensive diagnoses was also compared between the two guidelines. RESULTS: Agreement between BP tables and algorithmic calculation of percentiles was discordant, though improved in the AAP CPG compared to the Fourth Report (Cohen's kappa = 0.70 vs. 0.57, respectively). None (0%) were missed diagnoses, and 59 (24.9%) were false positives for the Fourth Report, and 0 (0%) were missed diagnoses, and 49 (20.9%) were false positives for the AAP CPG. Under the recent guidelines, there was an increase in prevalence of 6.0% (95% confidence interval (CI) 2.5-9.4%; P = 0.0001) for BP ≥90th percentile, and of 3.0% (95% CI 0.4-5.6%; p = 0.016) for hypertension (BP ≥ 95th percentile) in the cohort (18.0% and 6.8%, respectively, increased from 12.0% and 3.8%). CONCLUSIONS: Digital calculators over tables in clinical practice are recommended where possible to improve the accuracy of paediatric BP classification. Substantial rates of elevated BP/Hypertension were found in this cohort of children and adolescents with overweight and obesity.

A prospective observational study on the effect of emboli exposure on cerebral autoregulation in cardiac surgery requiring cardiopulmonary bypass.

OBJECTIVE: Cerebrovascular autoregulation impairment has been associated with stroke risk in cardiac surgery. We hypothesized that greater arterial emboli exposure in open-chamber surgery might promote dysautoreguation. METHODS: Forty patients underwent closed or open-chamber surgery. Transcranial Doppler detected emboli and measured bilateral middle cerebral artery flow velocities. Cerebral autoregulation was assessed by averaging the mean velocity index ("Mx," a continuous moving correlation between cerebral blood flow velocity and mean arterial pressure) over 30 min before and after aortic cross-clamp removal. RESULTS: Median (interquartile range) emboli counts were 775 (415, 1211) and 2664 (793, 3734) in the closed-chamber and open-chamber groups. Most appeared after the removal of the aortic cross-clamp (open-chamber 1631 (606, 2296)), (closed-chamber 229 (142, 384)), with emphasis on the right hemisphere (open-chamber: 826 (371, 1622)), (closed-chamber 181 (66, 276)). Linear mixed model analyses of mean velocity index change showed no significant overall effect of group (0.08, 95% CI: -0.04, 0.21; p = 0.19) or side (0.01, 95% CI: -0.03, 0.05; p = 0.74). There was an interaction between group and side (p = 0.001), manifesting as a greater increase in mean velocity index in the right hemisphere in the open than the closed group (mean difference: 0.15, 95% CI: 0.02, 0.27; p = 0.03). CONCLUSIONS: Overall, change in mean velocity index before and after cross-clamp removal did not differ between groups. However, most emboli entered the right cerebral hemisphere where this change was significantly greater in the open-chamber group, suggesting a possible association between embolic exposure and dysautoregulation.

Outcomes of intuitive eating interventions: a systematic review and meta-analysis.

Intuitive eating (IE) is an approach to health promotion that fosters a positive relationship with food and the body. The objective of this review was to aggregate and analyse the literature on IE interventions, thereby offering an early investigation of methodological approaches to intervention. This review was conducted in accordance with the preferred reporting items for systematic review and meta-analysis protocols (PRISMA) guidelines. Searching was conducted in four electronic databases. Studies were eligible for inclusion if they delivered an IE intervention and used the Intuitive Eating Scale (IES). Nine studies were included in this review. Six were eligible for meta-analysis, though only outcomes on the IES were examined; all other measures were examined individually. All interventions led to improvements on measures of IE, with a large pooled effect size (1.50 [1.15, 1.85]) and positive changes on a variety of other outcomes relating to health. This pattern preliminarily suggests that IE interventions change psychological processes as intended and can be useful in promoting health behaviour. The present review offers a synthesis of existing approaches to IE interventions and an evaluation of which specific variants appear to be more effective. This paper provides a basis upon which future interventions can be developed to improve approaches to psychoeducation.Clinical ImplicationsInterventions contributed to improvements in measures of IE lasting up to 6 months.Interventions contributed to positive changes on outcomes such as quality of life, body image, and body appreciation.Self-management through IE-based interventions may be feasible and effective.

Bullying, discrimination, and sexual harassment among intensive care unit nurses in Australia and New Zealand: An online survey.

BACKGROUND: Bullying, discrimination, and sexual harassment are significant problems within healthcare organisations but are often under-reported. Consequences of these behaviours within a healthcare setting are wide ranging, affecting workplace environments, personal well-being, and patient care and leading to increased staff turnover and quality of patient care and outcomes. Whilst there has been some work undertaken in the general nursing workforce, there is a dearth of evidence regarding the extent and impact of these behaviours on the nursing workforce in intensive care units (ICUs) in Australia and New Zealand. OBJECTIVE: We aimed to determine self-reported occurrences of bullying, discrimination, and sexual harassment amongst ICU nurses in Australia and New Zealand. METHODS: A prospective, cross-sectional, online survey of ICU nurses in Australia and New Zealand was undertaken in May-June 2021, distributed through formal colleges, societies, and social media. Questions included demographics and three separate sections addressing bullying, sexual harassment, and discrimination. RESULTS: In 679 survey responses, the overall reported occurrences of bullying, discrimination, and sexual harassment in the last 12 months were 57.1%, 32.6%, and 1.9%, respectively. Perpetrators of bullying were predominantly nurses (59.6%, with 57.9% being ICU nurses); perpetrators of discrimination were nurses (51.7%, with 49.3% being ICU nurses); and perpetrators of sexual harassment were patients (34.6%). Respondents most commonly (66%) did not report these behaviours as they did not feel confident that the issue would be resolved or addressed. CONCLUSIONS: Determining the true extent of bullying, discrimination, and sexual harassment behaviours within the ICU nursing community in Australia and New Zealand is difficult; however, it is clear a problem exists. These behaviours require recognition, reporting, and an effective resolution, rather than normalisation within healthcare professions and workplace settings in order to support and retain ICU nursing staff.

Post-diagnostic beta blocker use and breast cancer-specific mortality: a population-based cohort study.

PURPOSE: Beta blockers (BB) have been associated with improved, worsened, or unchanged breast cancer outcomes in previous studies. This study examines the association between the post-diagnostic use of BBs and death from breast cancer in a large, representative sample of New Zealand (NZ) women with breast cancer. METHODS: Women diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to national pharmaceutical data, hospital discharges, and death records. The median follow-up time was 4.51 years. Cox proportional hazard models were used to estimate the hazard of breast cancer-specific death (BCD) associated with any post-diagnostic BB use. RESULTS: Of the 14,976 women included in analyses, 21% used a BB after diagnosis. BB use (vs non-use) was associated with a small and nonstatistically significant increased risk of BCD (adjusted hazard ratio: 1.11; 95% CI 0.95-1.29). A statistically significant increased risk confined to short-term use (0-3 months) was seen (HR = 1.40; 1.14-1.73), and this risk steadily decreased with increasing duration of use and became a statistically significant protective effect at 3 + years of use (HR = 0.55; 0.34-0.88). CONCLUSION: Our findings suggest that any increased risk associated with BB use may be driven by risk in the initial few months of use. Long-term BB use may be associated with a reduction in BCD.

The benefits and acceptability of virtual reality interventions for women with metastatic breast cancer in their homes; a pilot randomised trial.

BACKGROUND: Women with metastatic breast cancer (MBC) report debilitating physical and psychological symptoms, including fatigue, anxiety, and pain, that greatly impact their quality of life. Immersive virtual reality (VR) has been proposed as an adjunctive pain therapy for patients with cancer, and evidence suggests it may also decrease symptoms of anxiety and depression. The purpose of this pilot study was to assess whether VR should be pursued as a feasible and acceptable adjunctive therapy to alleviate physical and psychological symptoms in women with MBC. METHODS: We conducted a pilot study testing the acceptability and efficacy of VR interventions with MBC patients to improve quality of life and to produce enduring decreases in fatigue, pain, depression, anxiety, and stress. Participants completed two different week-long VR experiences, reporting the prevalence of symptoms immediately before and after each study week, and 48 h later. Linear mixed models including fixed effects (VR intervention, counterbalancing order, and study week) and random effects (participant) were used to assess the effect of immersive VR on all outcome measures. RESULTS: Thirty-eight women with MBC completed the VR interventions and were included in analyses. Significant improvements post-intervention and/or 48 h later were demonstrated for quality of life, fatigue, pain, depression, anxiety, and stress. Across the entire study period, these differences met the criteria of a clinically important difference for quality of life, fatigue, depression, and stress. Participants reported feelings of relaxation and enjoyment and were highly likely to use the interventions gain. CONCLUSIONS: Our results demonstrate that VR experiences offer enduring benefits to the physical and psychological well-being of women with MBC. VR interventions are a feasible and acceptable intervention that can be conducted in a patient's own home. Such interventions are worthy of future investigation as a novel approach to improving quality of life in a patient population that have often been overlooked. TRIAL REGISTRATION: Prospectively registered on 25th October 2019 with Australian New Zealand Clinical Trials Registry (ref: ACTRN12619001480178 ).

The role of protective psychological factors, self-care behaviors, and HbA1c in young adults with type 1 diabetes.

OBJECTIVE: To investigate whether protective psychological factors in young adults with type 1 diabetes are associated with more optimal self-care behaviors and HbA1c, and to explore possible mediators between protective psychological factors and HbA1c. RESEARCH DESIGN AND METHODS: This cross-sectional study examined the associations between protective psychological factors (optimism, positive efficacy expectancies, and self-compassion), maladaptive psychological factors (depression, anxiety, and stress), self-care behaviors, and HbA1c in 113 young adults (17-25 years) with type 1 diabetes in Auckland, New Zealand. Pearson's correlations, multiple linear regressions, and multiple mediation analyses were used to examine associations and mediators. RESULTS: Higher positive efficacy expectancies (beliefs about coping with difficulties) were associated with more optimal HbA1c (ß = -0.26, 95% CI: -1.99 to -0.45) and more optimal self-care behaviors (ß = 0.33, 95% CI: 0.28 to 0.92) in the adjusted models. Higher levels of self-compassion were associated with more optimal self-care behaviors (ß = 0.27, 95% CI: 0.09 to 0.43). Depression was associated with less optimal self-care behaviors (ß = -0.35, 95% CI: -1.33 to -0.43) and stress was associated with less optimal HbA1c (ß = 0.26, 95% CI: 0.27 to 1.21). Mediation results suggested that self-care behaviors mediated the relationship between all three of the protective psychological factors and more optimal HbA1c, and that lower stress also mediated the relationship between higher self-compassion and more optimal HbA1c. CONCLUSIONS: This study adds to the emerging literature that protective psychological factors may play an adaptive role in improving health outcomes in young adults with type 1 diabetes. Interventions targeting protective psychological factors present a promising approach to optimizing wellbeing and self-care in youth with type 1 diabetes.

Adherence, Sexual Behavior and Sexually Transmitted Infections in a New Zealand Prospective PrEP Cohort: 12 Months Follow-up and Ethnic Disparities.

Inequities in pre-exposure prophylaxis (PrEP) experiences will impede HIV epidemic elimination among gay and bisexual men (GBM). Ethnicity is a strong marker of inequity in the United States, but evidence from other countries is lacking. We investigated experiences on-PrEP to 12 months follow-up in a prospective cohort of 150 GBM in Auckland, New Zealand with an equity quota of 50% non-Europeans. Retention at 12 months was 85.9%, lower among Maori/Pacific (75.6%) than non-Maori/Pacific participants (90.1%). Missed pills increased over time and were higher among Maori/Pacific. PrEP breaks increased, by 12 months 35.7% of Maori/Pacific and 15.7% of non-Maori/Pacific participants had done so. Condomless receptive anal intercourse partners were stable over time. STIs were common but chlamydia declined; 12-month incidence was 8.7% for syphilis, 36.0% gonorrhoea, 46.0% chlamydia, 44.7% rectal STI, 64.0% any STI. Structural interventions and delivery innovations are needed to ensure ethnic minority GBM gain equal benefit from PrEP.Clinical trial number ACTRN12616001387415.

Feasibility and acceptability of a paearahi (Indigenous Whanau Ora navigator) intervention for unintentional injury prevention for older Maori: non-randomised, non-comparator trial study protocol.

BACKGROUND: Maori (the Indigenous population of Aotearoa New Zealand) experience increased burden of unintentional injury and reduced access to publicly funded injury prevention and rehabilitation services, compared with non-Maori. Maori-led models of care have been shown to improve outcomes for Maori. Paearahi navigate across sectors (including health, education, housing and employment) to advocate for the best possible outcomes for individuals and families. This study aims to (1) test the acceptability and feasibility and (2) undertake exploratory efficacy analysis of a paearahi injury intervention for Maori older adults. METHODS: A prospective non-randomised, non-comparator study with preintervention and postintervention measurements of predefined outcomes. Eligible participants who consented to participate (Maori, 55+ years, community-dwelling and enrolled in one of three study general practices) will undergo a multivisit paearahi intervention. The intervention includes home-hazard assessment, basic health screening, teaching of strength and balance exercises, education relating to injury prevention and access to injury-related, referral and connection to other health and social services) and participants can choose to have whanau (family) involved in the intervention. OUTCOMES: The primary outcome of interest is participant, whanau and paearahi acceptability of the intervention. Secondary outcomes include intervention feasibility, cost-effectiveness and exploratory efficacy (including preintervention and postintervention unintentional injury-related hospitalisation, primary care access and public injury-related claims). DISCUSSION: The findings of this intervention research will be used to inform injury care models for older Maori and process for Maori-led health intervention development more generally. TRIAL REGISTRATION NUMBER: ACTRN12621001691831p.

Chr15q25 genetic variant (rs16969968) independently confers risk of lung cancer, COPD and smoking intensity in a prospective study of high-risk smokers.

IMPORTANCE: While cholinergic receptor nicotinic alpha 5 (CHRNA5) variants have been linked to lung cancer, chronic obstructive pulmonary disease (COPD) and smoking addiction in case-controls studies, their corelationship is not well understood and requires retesting in a cohort study. OBJECTIVE: To re-examine the association between the CHRNA5 variant (rs16969968 AA genotype) and the development of lung cancer, relative to its association with COPD and smoking. METHODS: In 9270 Non-Hispanic white subjects from the National Lung Screening Trial, a substudy of high-risk smokers were followed for an average of 6.4 years. We compared CHRNA5 genotype according to baseline smoking exposure, lung function and COPD status. We also compared the lung cancer incidence rate, and used multiple logistic regression and mediation analysis to examine the role of the AA genotype of the CHRNA5 variant in smoking exposure, COPD and lung cancer. RESULTS: As previously reported, we found the AA high-risk genotype was associated with lower lung function (p=0.005), greater smoking intensity (p<0.001), the presence of COPD (OR 1.28 (95% CI 1.10 to 1.49) p=0.0015) and the development of lung cancer (HR 1.41, (95% CI 1.03 to 1.93) p=0.03). In a mediation analyses, the AA genotype was independently associated with smoking intensity (OR 1.42 (95% CI 1.25 to 1.60, p<0.0001), COPD (OR 1.25, (95% CI 1.66 to 2.53), p=0.0015) and developing lung cancer (OR 1.37, (95% CI 1.03 to 1.82) p=0.03). CONCLUSION: In this large-prospective study, we found the CHRNA5 rs 16 969 968 AA genotype to be independently associated with smoking exposure, COPD and lung cancer (triple whammy effect).

Evidence for a causal association between milk intake and cardiometabolic disease outcomes using a two-sample Mendelian Randomization analysis in up to 1,904,220 individuals.

BACKGROUND: High milk intake has been associated with cardio-metabolic risk. We conducted a Mendelian Randomization (MR) study to obtain evidence for the causal relationship between milk consumption and cardio-metabolic traits using the lactase persistence (LCT-13910 C > T, rs4988235) variant as an instrumental variable. METHODS: We tested the association of LCT genotype with milk consumption (for validation) and with cardio-metabolic traits (for a possible causal association) in a meta-analysis of the data from three large-scale population-based studies (1958 British Birth Cohort, Health and Retirement study, and UK Biobank) with up to 417,236 participants and using summary statistics from consortia meta-analyses on intermediate traits (N = 123,665-697,307) and extended to cover disease endpoints (N = 86,995-149,821). RESULTS: In the UK Biobank, carriers of 'T' allele of LCT variant were more likely to consume milk (P = 7.02 × 10-14). In meta-analysis including UK Biobank, the 1958BC, the HRS, and consortia-based studies, under an additive model, 'T' allele was associated with higher body mass index (BMI) (Pmeta-analysis = 4.68 × 10-12) and lower total cholesterol (TC) (P = 2.40 × 10-36), low-density lipoprotein cholesterol (LDL-C) (P = 2.08 × 10-26) and high-density lipoprotein cholesterol (HDL-C) (P = 9.40 × 10-13). In consortia meta-analyses, 'T' allele was associated with a lower risk of coronary artery disease (OR:0.86, 95% CI:0.75-0.99) but not with type 2 diabetes (OR:1.06, 95% CI:0.97-1.16). Furthermore, the two-sample MR analysis showed a causal association between genetically instrumented milk intake and higher BMI (P = 3.60 × 10-5) and body fat (total body fat, leg fat, arm fat and trunk fat; P < 1.37 × 10-6) and lower LDL-C (P = 3.60 × 10-6), TC (P = 1.90 × 10-6) and HDL-C (P = 3.00 × 10-5). CONCLUSIONS: Our large-scale MR study provides genetic evidence for the association of milk consumption with higher BMI but lower serum cholesterol levels. These data suggest no need to limit milk intakes with respect to cardiovascular disease risk, with the suggested benefits requiring confirmation in further studies.

Success Rates of Debridement, Antibiotics, and Implant Retention in 230 Infected Total Knee Arthroplasties: Implications for Classification of Periprosthetic Joint Infection.

BACKGROUND: Prosthetic joint infection (PJI) is the most common cause of failure following total knee arthroplasty (TKA). This study aimed to determine the success of debridement, antibiotics, and implant retention (DAIR) in a large cohort of TKA PJIs and assess the utility of current classification systems in predicting DAIR outcomes in early postoperative, late hematogenous, and chronic PJIs. METHODS: In a multicenter review over 15 years, 230 patients underwent DAIR for first episode PJI following primary TKA. Patient demographics, disease and surgical factors, treatment regime, and outcomes were identified. Univariate and multivariate survival analyses were performed to identify factors associated with successful DAIR. Continuous variables with predictive value were further analyzed using receiver operating characteristic curves. The ability to predict DAIR outcomes of multiple classification systems was also assessed. RESULTS: Patients were followed for an average of 6.9 years. The overall success rate of DAIR was 53.9%. On receiver operating characteristic analysis, 3 months (area under the curve = 0.63) and 1-year age (area under the curve = 0.66) of implant cut-offs was similarly predictive of outcomes. On multivariate survival analysis, DAIR was successful in 64% of "early" PJIs (implant <1 year) vs 38% of "late hematogenous" PJIs (implant >1 year; odds ratio [OR] 1.78, P = .01). For late PJIs (implant >1 year), Staphylococcus aureus (OR 4.70, P < .001) and gram-negative infections (OR 2.56, P = .031) were risk factors for DAIR failure. CONCLUSION: DAIR has a high failure rate in all PJIs occurring more than a year post primary TKA, particularly when caused by S aureus or gram-negative bacteria. The age of implant is an important predictor of DAIR outcomes.

Infection and periprosthetic fracture are the leading causes of failure after aseptic revision total knee arthroplasty.

AIM: The purpose of this study was to clarify the medium to long term survival of aseptic revision total knee arthroplasty (RTKAs) and identify the common modes of failure following RTKAs. MATERIALS AND METHODS: A multi-center, retrospective study included all aseptic RTKAs performed at three tertiary referral hospitals between 2003 and 2016. Patients were excluded if the revision was for prosthetic joint infection (PJI) or they had previously undergone revision surgery. Minor revisions not involving the tibial or femoral components were also excluded. Demographics, surgical data and post-operative outcomes were recorded and analyzed. Survival analysis was performed and the reasons for revision failure identified. RESULTS: Of 235 aseptic RTKAs identified, 14.8% underwent re-revision at mean follow-up of 8.3 years. Survivorship of RTKA was 93% at 2 years and 83% at 8 years. Average age at revision was 72.9 years (range 53-91.5). The most common reasons for failure following RTKA were periprosthetic joint infection (PJI) (40%), periprosthetic fracture (25.7%) and aseptic loosening (14.3%). Of those whose RTKA failed, the average survival was 3.33 years (8 days-11.4 years). No demographic or surgical factors were found to influence RTKA survival on univariate or multivariate analysis. CONCLUSION: PJI and periprosthetic fracture are the leading causes of re-revision surgery following aseptic revision TKA. Efforts to improve outcomes of aseptic revision TKA should focus on these areas, particularly prevention of PJI.

Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.

Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.

The antidotes atropine and pralidoxime distinctively recover cardiorespiratory components impaired by acute poisoning with chlorpyrifos in rats.

In a previous work we showed that the organophosphate pesticide (OP) chlorpyrifos (CPF) reduces the protective chemoreflex and baroreflex responses in rats. However, whether the antidotes atropine (ATR) and pralidoxime (2-PAM) are capable of restoring these reflex functions remains unexplored. Rats were poisoned with CPF (30 mg.kg-1, i.p.) and one hour after the intoxication, ATR (10 mg.kg-1, i.p.) and 2-PAM (40 mg.kg-1, i.p.) were administrated separately or in combination. Cardiorespiratory parameters were recorded in awake rats 24 h after CPF. Systolic blood pressure (SBP) and heart rate (HR) variability and spontaneous baroreflex sensitivity (sBRS) were derived from undisturbed recordings (30 min), while chemoreflex was assessed through potassium cyanide (KCN) i.v. injections (10, 20, 40, 80 µg/rat). CPF poisoning increased SBP variability and low frequency/high frequency (LF/HF) ratio of the HR variability spectrum, indicating autonomic imbalance with increased cardiac sympathetic tone. sBRS was not changed. Treatment with 2-PAM restored SBP variability, whilst both antidotes increased LF/HF ratio. CPF poisoning reduced the hypertensive, bradycardic and tachypneic chemoreflex responses. Chemoreflex-induced hypertensive response was restored by 2-PAM treatment, while ATR recovered the bradycardic response. Both antidotes restored the chemoreflex tachypneic response. Our data show distinct effects of ATR and 2-PAM on cardiorespiratory parameters affected by OP poisoning. While 2-PAM rescued the chemoreflex hypertensive response, ATR reversed chemoreflex bradycardic dysfunction. Although 2-PAM clinical use is questioned in some countries, our data indicate that summation of effects of both antidotes appears beneficial on the cardiorespiratory system and peripheral chemoreflex function.