Statin utilisation in a real-world setting: a retrospective analysis in relation to arterial and cardiovascular autonomic function

Randomized trials suggest that statin treatment may lower blood pressure and influence cardiovascular autonomic function (CVAF), but the impact of duration of usage, discontinuation, and adherence to this therapy is unknown. We examined these issues with regard to blood pressure (BP)-related variables in a large, population-based study. Participants were 4942 adults (58% male; aged 50–84 years): 2179 on statin treatment and 2763 untreated. Days of utilization, adherence (proportion of days covered ≥0.8), and discontinuation (non-use for ≥30 days immediately prior to BP measurement) of three statins (atorvastatin, pravastatin, and simvastatin) over a period of up to 2 years was monitored retrospectively from electronic databases. Systolic BP (SBP), diastolic BP (DBP), augmentation index, excess pressure, reservoir pressure, and CVAF (pulse rate and BP variability) parameters were calculated from aortic pressure waveforms derived from suprasystolic brachial measurement. Days of statin treatment had inverse relationships with pulse rate variability parameters in cardiac arrhythmic participants (20–25% lower than in statin non-users) and with most arterial function parameters in everyone. For example, compared to untreated participants, those treated for ≥659 days had 3.0 mmHg lower aortic SBP (P < 0.01). Discontinuation was associated with higher brachial DBP and aortic DBP (for both, β = 2.0 mmHg, P = 0.008). Compared to non-adherent statin users, adherent users had lower levels of brachial SBP, brachial DBP, aortic DBP, aortic SBP, and peak reservoir pressure (β = −1.4 to −2.6 mmHg). In conclusion, in a real-world setting, statin-therapy duration, non-discontinuation and adherence associate inversely with BP variables and, in cardiac arrhythmias, CVAF parameters

Effect of Monthly, High-Dose, Long-Term Vitamin D on Lung Function: A Randomized Controlled Trial.

Although observational studies suggest positive vitamin D-lung function associations, randomized trials are inconsistent. We examined effects of vitamin D supplementation on lung function. We recruited 442 adults (50-84 years, 58% male) into a randomized, double-blinded, placebo-controlled trial. Participants received, for 1.1 years (median; range = 0.9-1.5 years), either (1) vitamin D₃ 200,000 IU, followed by monthly 100,000 IU doses (n = 226); or (2) placebo monthly (n = 216). At baseline and follow-up, spirometry yielded forced expiratory volume in 1 s (FEV1; primary outcome). Mean (standard deviation) 25-hydroxyvitamin D increased from 61 (24) nmol/L at baseline to 119 (45) nmol/L at follow-up in the vitamin D group, but was unchanged in the placebo group. There were no significant lung function improvements (vitamin D versus placebo) in the total sample, vitamin D-deficient participants or asthma/chronic obstructive pulmonary disease (COPD) participants. However, among ever-smokers (n = 217), the mean (95% confidence interval) FEV1 increase in the vitamin D versus placebo was 57 (4, 109) mL (p = 0.03). FEV1 increases were larger among vitamin D-deficient ever-smokers (n = 54): 122 (8, 236) mL (p = 0.04). FEV1 improvements were largest among ever-smokers with asthma/COPD (n = 60): 160 (53, 268) mL (p = 0.004). Thus, vitamin D supplementation did not improve lung function among everyone, but benefited ever-smokers, especially those with vitamin D deficiency or asthma/COPD

Sizing the association between lifestyle behaviours and fatness in a large, heterogeneous sample of youth of multiple ethnicities from 4 countries

Background:&nbsp;The magnitude of the relationship between lifestyle risk factors for obesity and adiposity is not clear.&nbsp;The aim of this study was to clarify this in order to determine the level of importance of lifestyle factors in obesity&nbsp;aetiology.Methods: A cross-sectional analysis was carried out on data on youth who were not trying to change weight&nbsp;(n = 5714), aged 12 to 22 years and from 8 ethnic groups living in New Zealand, Australia, Fiji and Tonga.&nbsp;Demographic and lifestyle data were measured by questionnaires. Fatness was measured by body mass index (BMI),&nbsp;BMI z-score and bioimpedance analysis, which was used to estimate percent body fat and total fat mass (TFM).&nbsp;Associations between lifestyle and body composition variables were examined using linear regression and forest plots.Results: TV watching was positively related to fatness in a dose-dependent manner. Strong, dose-dependent&nbsp;associations were observed between fatness and soft drink consumption (positive relationship), breakfast consumption&nbsp;(inverse relationship) and after-school physical activity (inverse relationship). Breakfast consumption-fatness associations&nbsp;varied in size across ethnic groups. Lifestyle risk factors for obesity were associated with percentage differences in body&nbsp;composition variables that were greatest for TFM and smallest for BMI.Conclusions: Lifestyle factors were most strongly related to TFM, which suggests that studies that use BMI alone to&nbsp;quantify fatness underestimate the full effect of lifestyle on adiposity. This study clarifies the size of lifestyle-fatness&nbsp;relationships observed in previous studies.</div

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

Probenecid Blocks Human P2X7 Receptor-Induced Dye Uptake via a Pannexin-1 Independent Mechanism

P2X7 is a ligand-gated ion channel which is activated by ATP and displays secondary permeability characteristics. The mechanism of development of the secondary permeability pathway is currently unclear, although a role for the hemichannel protein pannexin-1 has been suggested. In this study we investigated the role of pannexin-1 in P2X7-induced dye uptake and ATP-induced IL-1β secretion from human monocytes. We found no pharmacological evidence for involvement of pannexin-1 in P2X7-mediated dye uptake in transfected HEK-293 cells with no inhibition seen for carbenoxolone and the pannexin-1 mimetic inhibitory peptide, 10Panx1. However, we found that probenecid inhibited P2X7-induced cationic and anionic dye uptake in stably transfected human P2X7 HEK-293 cells. An IC50 value of 203 μM was calculated for blockade of ATP-induced responses at human P2X7. Probenecid also reduced dye uptake and IL-1β secretion from human CD14+ monocytes whereas carbenoxolone and 10Panx1 showed no inhibitory effect. Patch clamp and calcium indicator experiments revealed that probenecid directly blocks the human P2X7 receptor

Priority Health Needs and Challenges in New Zealand Pacific Communities-A Qualitative Analysis of Healthcare Delivery during the COVID-19 Pandemic.

BACKGROUND: The Pacific community in New Zealand experienced an increased risk of COVID-19 transmission due to delayed contact tracing, along with a disproportionate prevalence of health challenges. The community is representative of a diverse population who proudly identify with the vibrant Pacific Island nations of Samoa, Tonga, Cook Islands, Niue, Fiji, etc. Pacific communities in New Zealand face a higher burden of health challenges compared to other groups. These challenges include obesity, high blood pressure, diabetes, mental health disorders, respiratory issues, smoking, excessive alcohol consumption, disabilities, and chronic conditions. Concerns were raised regarding the oversight of Pacific community views in the initial pandemic response planning. Pacific healthcare professionals expressed concerns about inadequate state support and the need for active involvement in decision making. METHODS: This article reports thematic analyses of text data gained from open-ended questions from a purposive anonymous online survey completed by Pacific healthcare professionals in New Zealand. RESULTS: The participants shared their experiences and opinions, which generated four major themes highlighting priority health needs and challenges. These themes included the necessity for a culturally appropriate healthcare plan, adequate resourcing, addressing discrimination, and emphasising a united and collaborative effort for consistency. The research's limitation is the narrow scope of open-ended questions in the questionnaire survey. However, conducting semi-structured face-to-face interviews can provide more in-depth data and offer further insights beyond the four broad themes identified in the analysis. CONCLUSIONS: The findings can inform the development of future research to provide more in-depth data and offer further insights beyond the four broad themes identified in the analysis. This will help develop future tailored healthcare delivery plans that address specific Pacific community needs.fals

Effect of Monthly High-Dose Vitamin D Supplementation on Risk of Cancer: the Vitamin D Assessment Study (a Randomized Controlled Trial)

Importance: Previous randomized controlled trials have provided inconsistent results on the effect of vitamin D supplementation on cancer incidence. Objective: To determine if monthly high-dose vitamin D supplementation, without calcium, reduces cancer incidence and cancer mortality in the general population. Design: Randomized, double-blind, placebo-controlled trial, participants recruited from April 2011 to November 2012, follow-up until December 2015. Setting: Recruited mostly from family practices in Auckland, New Zealand. Participants: Community-resident adults, aged 50-84 years. Out of 47,905 adults invited from family practices, and 163 from community groups, 5,110 participants were randomized to vitamin D3 (n=2,558) or placebo (n=2,552). Two participants withdrew consent, and all others (n=5,108) were included in the primary analysis. Intervention: Oral vitamin D3, initial bolus dose of 200,000 IU, followed one month later by monthly doses of 100,000 IU, or placebo, for median of 3.3 years (range: 2.5–4.2 years). Main Outcomes and Measures: The post-hoc primary outcome was all primary neoplasms (invasive and in-situ), aside from non-melanoma skin cancers, diagnosed from randomization to stopping the study medication (31 July 2015). Secondary outcomes were all neoplasms: from randomization to 31 December 2015; from >12 months after randomization to both stopping the study medication and also to 31 December 2015; and fatal neoplasms from randomization to 31 December 2015.Major funding was provided by the Health Research Council of New Zealand (grant 10/400), and by the Accident Compensation Corporation of New Zealand

Relations of Demographic and Clinical Factors With Cardiovascular Autonomic Function in a Population-Based Study: An Assessment By Quantile Regression

BACKGROUND: The relationships of many factors with cardiovascular autonomic function (CVAF) outcome parameters may not be uniform across the entire distribution of the outcome. We examined how demographic and clinical factors varied with different subgroups of CVAF parameters. METHODS: Quantile regression was applied to a cross-sectional analysis of 4,167 adults (56% male; age range, 50–84 years) from 4 ethnic groups (3,419 New Zealand European, 303 Pacific, 227 Maori, and 218 South Asian) and without diagnosed cardiac arrhythmia. Pulse rate variability (root mean square of successive differences (RMSSD) and SD of pulse intervals) and baroreflex sensitivity were response variables. Independent variables were age, sex, ethnicity, brachial and aortic blood pressure (BP) variables, body mass index (BMI), and diabetes. RESULTS: Ordinary linear regression showed that age, sex, Pacific and Maori ethnicity, BP variables, BMI, and diabetes were associated with CVAF parameters. But quantile regression revealed that, across CVAF percentiles, the slopes for these relationships: (i) varied by more than 10-fold in several cases and sometimes changed direction and (ii) noticeably differed in magnitude often (by >3–fold in several cases) compared to ordinary linear regression coefficients. For instance, age was inversely associated with RMSSD at the 10th percentile of this parameter (β = −0.12 ms/year, 95% confidence interval = −0.18 to −0.09 ms/year) but had a positive relationship at the 90th percentile (β = 3.17 ms/year, 95% confidence interval = 2.50 to 4.04 ms/year). CONCLUSIONS: The relationships of demographic and clinical factors with CVAF parameters are, in many cases, not uniform. Quantile regression provides an improved assessment of these associations