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Biomedical subjects

Mark R Nelson

Publications and source records attributed to Mark R Nelson.

At least 19 recordsLinked to original sources
PubMed2026

Polygenic Risk Identifies Older Adults Who May Benefit From Aspirin for the Primary Prevention of Ischemic Stroke.

BACKGROUND: Low-dose aspirin is no longer recommended for routine primary prevention in older adults due to bleeding risks outweighing vascular benefits. We hypothesized that an integrative polygenic score (iPGS) could identify a subgroup of older individuals who derive net benefit from aspirin for the primary prevention of ischemic stroke. METHODS: We performed post hoc analysis of the ASPREE randomized, placebo-controlled trial (Aspirin in Reducing Events in the Elderly) of daily 100-mg aspirin, in 12 031 genotyped participants of European ancestry aged >70 years without prior cardiovascular disease. The iPGS was derived from >1.2 million variants and evaluated both continuously and by quintiles. Cox models assessed associations between polygenic risk, ischemic stroke, and major bleeding events, and tested the interaction between the iPGS and treatment allocation, with adjustment for baseline lifestyle and clinical covariates. RESULTS: The mean age of participants was 75.1 years, and 54.9% were women. Over a median of 4.6 years, 187 ischemic strokes and 373 major bleeds occurred, including 101 intracranial bleeds (46 hemorrhagic strokes). Each 1-SD increase in the iPGS was associated with higher incident ischemic stroke risk (hazard ratio, 1.39 [95% CI, 1.20-1.62]). An interaction between the continuous iPGS and aspirin allocation was observed for ischemic stroke (P=0.04) but not major bleeding. In the highest iPGS quintile, aspirin reduced ischemic stroke by 51% (hazard ratio, 0.49 [95% CI, 0.28-0.85]) without significantly increasing major bleeding (hazard ratio, 1.15 [95% CI, 0.71-1.88]). No benefit was observed in the overall cohort or in lower-risk quintiles. CONCLUSIONS: Among older adults, high polygenic risk identifies individuals who may experience substantial stroke reduction with aspirin, with no excess bleeding. These findings raise the possibility that genomic risk stratification may enable targeted aspirin use for the primary prevention of ischemic stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.

Humans↗
PubMed2006

Self-reported adherence with medication and cardiovascular disease outcomes in the Second Australian National Blood Pressure Study (ANBP2).

OBJECTIVE: To investigate whether responses to a previously validated four-item medication adherence questionnaire were associated with adverse cardiovascular events. DESIGN: Survey conducted among a cohort of participants in the Second Australian National Blood Pressure Study. SETTING: Australian general practice. PARTICIPANTS: 4039 older people with hypertension. MAIN OUTCOME MEASURES: All major cardiovascular events or death; first specific cardiovascular event. RESULTS: Subjects who adhered to their medication regimen (compared with non-adherent subjects) were significantly less likely to experience a first cardiovascular event or a first non-fatal cardiovascular event (hazard ratio [HR] for both, 0.81; 95% CI, 0.67-0.98; P = 0.03); a fatal other cardiovascular event (HR, 0.68; 95% CI, 0.48-0.99; P = 0.04); or a first occurrence of heart failure (HR, 0.58; 95% CI, 0.37-0.90; P = 0.02). Those who answered yes to "Did you ever forget to take your medication?" were significantly more likely to experience a cardiovascular event or death (HR, 1.28; 95% CI, 1.04-1.57; P = 0.02); a first cardiovascular event or death (HR, 1.31; 95% CI, 1.07-1.60; P = 0.01); a first cardiovascular event (HR, 1.34; 95% CI, 1.09-1.65; P = 0.01); or a first non-fatal cardiovascular event (HR, 1.35; 95% CI, 1.09-1.66; P = 0.01). Those who answered yes to "Sometimes, if you felt worse when you took your medicine, did you stop taking it?" were significantly more likely to experience a first occurrence of heart failure (HR, 2.06; 95% CI, 1.16-3.64; P = 0.01). CONCLUSIONS: Subjects who adhered to their medication regimen were less likely to experience major cardiovascular events or death. The question relating to forgetting to take medication identified non-adherent subjects likely to experience a cardiovascular event or death. Clinicians could use this question to identify patients with hypertension who are likely to benefit from medication adherence strategies.

Aged↗
PubMed2005

Transmission of hepatitis C virus among HIV-positive homosexual men and response to a 24-week course of pegylated interferon and ribavirin.

OBJECTIVE: To evaluate treatment outcome of acute hepatitis C virus (HCV) in HIV-positive individuals. DESIGN: Open-label, prospective study conducted in London, January 1997-December 2003. METHODS: Patients in whom acute HCV infection had been diagnosed had sequential HCV RNA levels measured at 0, 4, 12, 24, 32, and 48 weeks. If HCV RNA positive at 12 weeks, patients were offered pegylated interferon alpha-2b 1.5 microg/kg/wk and ribavirin 800-1200 mg/d for 24 weeks. Patients with increasing HCV RNA titers were offered treatment earlier. RESULTS: Fifty male homosexuals with a mean age 37 years were identified: 44 from abnormal liver function test results, 4 from sexual contact with an HCV-positive partner, and 2 at HIV seroconversion. Overall, 12 individuals became HCV RNA negative spontaneously. This was significantly associated with high baseline median CD4(+) count (P = 0.029), CD4(+) count >500 cells/mm(3) (P = 0.017), and lower HCV RNA titers (P = 0.017). Only 27 patients accepted treatment, 16 (59%) of whom reached sustained virologic response. This was associated with higher peak mean alanine aminotransferase (P < 0.001) and higher baseline CD4% (P = 0.041). CONCLUSIONS: Sustained virologic response rates in HIV-positive patients treated for acute HCV infection are lower than in HIV-negative subjects. Because a high percentage of individuals seroconvert spontaneously, treatment should be delayed until after 12 weeks.

Acute Disease↗
PubMed2005

Epidemiological modelling of routine use of low dose aspirin for the primary prevention of coronary heart disease and stroke in those aged > or =70.

OBJECTIVE: To investigate the routine use of low dose aspirin in people aged > or = 70 without overt cardiovascular disease. DESIGN: Epidemiological modelling in a hypothetical population. SETTING: Reference populations of men and women in the year 2000 from the state of Victoria, Australia. SUBJECTS: 10,000 men and 10,000 women aged 70-74 with no cardiovascular disease. MAIN OUTCOME MEASURES: First ever myocardial infarction or unstable angina, ischaemic or haemorrhagic stroke, and major gastrointestinal haemorrhage. Health adjusted years of life lived. RESULTS: The proportional benefit gained from the use of low dose aspirin by the prevention of myocardial infarctions (-389 in men, -321 in women) and ischaemic stroke (-19 in men and -35 in women) is offset by excess gastrointestinal (499 in men, 572 in women) and intracranial (76 in men, 54 in women) bleeding. The results in health adjusted years of life lived (which take into account length and quality of life) are equivocal for aspirin causing net harm or net benefit. CONCLUSION: Epidemiological modelling suggests that any benefits of low dose aspirin on risk of cardiovascular disease in people aged > or = 70 are offset by adverse events. These findings are tempered by wide confidence intervals, indicating that the overall outcome could be beneficial or adverse.

Aged↗
PubMed2005

Predictors of failure to initiate randomized treatment in a large trial of antihypertensive drug therapy in the aged.

BACKGROUND: The identification of factors that contribute to noncompliance with trial drug initiation where virtually complete compliance might be expected, may help identify patients whose management is least likely to comply with clinical guidelines and study protocols. METHODS: Examination of cross-sectional and longitudinal data arising from the Second Australian National Blood Pressure Study. Prevalence rate ratios (RR) and 95% confidence intervals (CI) estimated from log-binomial models were used to assess associations between subject characteristics and whether the randomized drug was prescribed at trial randomization. The study population consisted of 6083 hypertensive Australians aged 65 to 84 years. RESULTS: After adjusting for each variable in a multivariate model the following were significant predictors of failure to prescribe RR (95% CI): not previously prescribed antihypertensive drugs 2.89 (2.52-3.32); lower systolic blood pressure (BP) 1.51 (1.59-1.43) or diastolic BP 1.18 (1.22-1.13); younger age 80 to 84 v 65 to 79 years 0.75 (0.59-0.95); total cholesterol >or=6.6 v <or=5.0 mmol/L 1.27 (1.06-1.53); and not ever having had a raised cholesterol 1.20 (1.04-1.40). There was no difference in cardiovascular disease end points and death in those who were and were not initiated on drug therapy at randomization. CONCLUSIONS: Failure to initiate antihypertensive therapy for patients at the randomization visit was associated with lower BP measurements, previous drug therapy, younger age, and a historic or current raised cholesterol, but not with overt cardiovascular disease or other risk factors. There was no difference in cardiovascular disease end points and death in those who were and were not initiated on drug therapy at randomization.

Age Factors↗
PubMed2005

Clinical characteristics of IRIS syndrome in patients with HIV and tuberculosis.

BACKGROUND: Some patients with HIV/tuberculosis (TB) coinfection who are on anti-TB treatment and highly active antiretroviral therapy (HAART) will develop an exacerbation of symptoms, signs or radiological manifestations of TB that are not due to relapse or recurrence of their TB. The aetiology of these immune reconstitution inflammatory syndrome (IRIS) reactions is unknown but it is presumed that they occur, at least in part, as a consequence of HAART-related reconstitution of immunity. METHODS: Patients who were diagnosed with their first episode of definitive or presumed TB between January 2001 and July 2003 were identified from the Chelsea and Westminster TB/HIV database. The patients were classified into those who developed IRIS and those who did not using a set definition of the syndrome. Demographic, clinical and laboratory data relating to both HIV and TB were compared between the two groups. RESULTS: A total of 55 cases of TB were identified, of which 45 cases were confirmed on culture or gene probe and 10 were presumed cases. Fourteen cases (25.5%) developed IRIS with a median (range) duration of 2.53 (0.53-14.97) months. The median baseline CD4 [interquartile range (IQR)] for the IRIS group was significantly lower at 80 (33-117) cells/mm3 (P = 0.05) than the non-IRIS group at 139 (77-284) cells/mm3. A significantly greater proportion of patients in the IRIS group [11/14 (78.60%), P = 0.011] had baseline CD4 < 100cells/mm3 compared with the non-IRIS group [16/41 (39.0%)]. There was no significant difference between the two groups when comparing the log10 baseline viral load (VL). Eight (57.0%) patients in the IRIS group had disseminated TB at baseline compared with seven (17.0%) in the non-IRIS group (P = 0.006). In those who had a detectable VL at baseline, the median fold change (IQR) in CD4 from baseline to 3 months was significantly higher in the IRIS group patients, 1.5 (0.6-5.6), compared with 0.7 (-0.2 to 1.0) for those in the non-IRIS group (P = 0.046). CONCLUSIONS: Patients who develop IRIS are more likely to present with disseminated TB, have a CD4 count < 100 cells/mm3 and have a prompt rise in CD4 count in the initial 3 months of HAART.

Adult↗
PubMed2005

Secondary prevention of CHD.

BACKGROUND: Coronary heart disease (CHD) is still the single largest health problem for Australia. It is considered essentially preventable. Risk of future events is highest in those who already have manifest disease (secondary prevention) and hence are likely to benefit from aggressive therapy. OBJECTIVE: This article explores issues of management of risk factors postacute myocardial infarction using a case vignette of a woman who consults her general practitioner after discharge from hospital. DISCUSSION: The consultation allows the GP to reassess the patient's CHD risk factor management including lifestyle factors, and reinforce the need for lifelong use of proven secondary prevention drug therapies and participation in a rehabilitation program. Reflective learning from this case should assist the treating GP and her or his colleagues to help other patients avoid a similar fate.

Adrenergic beta-Antagonists↗
PubMed2005

New drugs.

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Anti-HIV Agents↗
PubMed2004

Tetanus vaccination with IL-2 during highly active antiretroviral therapy induces sustained and pronounced specific CD4 T-cell responses.

HIV-1 infection results in profound dysfunction of the CD4 T-cell population. Although highly active antiretroviral therapy allows the reconstitution of CD4 T-cell numbers, functional abnormalities remain, including inadequate responses to vaccination. IL-2 increases CD4 T-cell numbers and function. We report the effects of IL-2 given with tetanus vaccination in two patients in a larger immunotherapy study. In one case IL-2 induced sustained responses, which may have been caused by the timing of IL-2 with vaccination.

Anti-HIV Agents↗
PubMed2004

Atazanavir enhances saquinavir hard-gel concentrations in a ritonavir-boosted once-daily regimen.

OBJECTIVE: To determine the pharmacokinetics of saquinavir hard-gel capsules/ritonavir/atazanavir co-administered once daily at 1600/100/300 mg in HIV-infected individuals. METHODS: Eighteen patients receiving saquinavir/ritonavir switched to 1600/100 mg once daily a minimum of 3 days before the study. On study day 1, levels of saquinavir and ritonavir were determined over 24 h. Atazanavir (300 mg once daily) was then added to the regimen. On day 11, a pharmacokinetic analysis was performed. Atazanavir was discontinued on day 32. Drug concentrations were measured by high-pressure liquid chromatography-tandem mass spectrometry. Geometric mean ratios (GMR) and 95% confidence intervals (CI) were used to compare saquinavir and ritonavir pharmacokinetic parameters, with and without atazanavir. A safety analysis was performed at screening, days 1, 11, 32 and follow-up. RESULTS: After the addition of atazanavir, statistically significant increases in saquinavir trough plasma concentration (Ctrough GMR, 95% CI 2.12, 1.72-3.50), maximum plasma concentration (Cmax 1.42, 1.24-1.94), area under the plasma concentration-time curve from 0-24 h (AUC0-24 1.60, 1.35-2.43) and ritonavir Cmax (1.58, 1.32-2.08), AUC0-24 (1.41, 1.22-1.74) were observed. The pharmacokinetics of atazanavir compared with those obtained in patients receiving atazanavir/ritonavir without saquinavir. Four patients developed scleral icterus and two jaundice. Total and unconjugated bilirubin increased approximately fivefold during atazanavir therapy. CONCLUSION: The addition of atazanavir to saquinavir/ritonavir increased saquinavir Ctrough, Cmax and AUC0-24 by 112, 42 and 60%. Ritonavir Cmax and AUCo-24 increased by 34 and 41%. The regimen was well tolerated, with no significant change in laboratory parameters, except for the occurrence of hyperbilirubinemia.

Adult↗
PubMed2004

Self-rated health in a population of expatriate workers and partners in Riyadh, Saudi Arabia.

BACKGROUND: Anthropological theory suggests that expatriate workers progress through a sequence of adaptive stages during their adjustment to a new environment. The psychological and physiological effects of this adaptation process may be reflected in changes in self-rated general health. AIMS: To explore the relationship between self-rated general health, duration of expatriate assignment and two health-related behaviours: physical exercise and cigarette smoking. METHOD: A self-administered questionnaire recorded the demographics, self-rated general health, exercise and smoking behaviours of the adult non-Saudi residents of an expatriate compound in Riyadh, Saudi Arabia. RESULTS: The mean self-rated general health of the study group was better than comparable UK and New Zealand population norms. Self-rated general health was not associated with duration of assignment, but was associated with physical exercise, including a dose-response effect. Middle Eastern expatriates had lower self-rated health scores and a higher prevalence of cigarette smoking than other expatriates. CONCLUSIONS: While the sampling frame limits generalization, physical exercise may promote expatriates' general health. Middle Eastern expatriates may be a target group for smoking health education.

Adult↗