Effects of blood pressure lowering on cardiovascular risk according to baseline body-mass index: a meta-analysis of randomised trials.

BACKGROUND: The cardiovascular benefits of blood pressure lowering in obese people compared with people of normal weight might depend on choice of drug. We compared the effects of blood pressure-lowering regimens on cardiovascular risk in groups of patients categorised by baseline body-mass index (BMI). METHODS: We used individual patient data from trials included in the Blood Pressure Lowering Treatment Trialists' Collaboration to compare the effects of different classes of blood pressure-lowering regimens for the primary outcome of total major cardiovascular events (stroke, coronary heart disease, heart failure, and cardiovascular death). We used meta-analyses and meta-regressions to assess interactions between treatment and BMI when fitted as either a categorical variable (<25 kg/m(2), 25 to <30 kg/m(2), and ≥30 kg/m(2)) or a continuous variable. FINDINGS: Analyses were based on 135,715 individuals from 22 trials who had 14,353 major cardiovascular events. None of the six primary comparisons showed evidence that protection varied by drug class across the three BMI groups (all p for trend >0·20). When analysed as a continuous variable, angiotensin-converting-enzyme inhibitors gave slightly greater protection for each 5 kg/m(2) higher BMI than did calcium antagonists (hazard ratio 0·93, 95% CI 0·89-0·98; p=0·004) or diuretics (0·93, 0·89-0·98; p=0·002). The meta-regressions showed no relation between BMI category and the risk reduction for a given fall in systolic blood pressure. By contrast with a previous report, we noted no relation between BMI and the efficacy of calcium antagonists compared with diuretics. INTERPRETATION: We found little evidence that selection of a particular class of blood pressure-lowering drug will lead to substantially different outcomes for individuals who are obese compared with those who are lean. FUNDING: None.

Blood pressure lowering and major cardiovascular events in people with and without chronic kidney disease: meta-analysis of randomised controlled trials.

OBJECTIVE: To define the cardiovascular effects of lowering blood pressure in people with chronic kidney disease. DESIGN: Collaborative prospective meta-analysis of randomised trials. DATA SOURCES AND ELIGIBILITY: Participating randomised trials of drugs to lower blood pressure compared with placebo or each other or that compare different blood pressure targets, with at least 1000 patient years of follow-up per arm. MAIN OUTCOME MEASURES: Major cardiovascular events (stroke, myocardial infarction, heart failure, or cardiovascular death) in composite and individually and all cause death. PARTICIPANTS: 26 trials (152,290 participants), including 30,295 individuals with reduced estimated glomerular filtration rate (eGFR), which was defined as eGFR <60 mL/min/1.73 m(2). DATA EXTRACTION: Individual participant data were available for 23 trials, with summary data from another three. Meta-analysis according to baseline kidney function was performed. Pooled hazard ratios per 5 mm Hg lower blood pressure were estimated with a random effects model. RESULTS: Compared with placebo, blood pressure lowering regimens reduced the risk of major cardiovascular events by about a sixth per 5 mm Hg reduction in systolic blood pressure in individuals with (hazard ratio 0.83, 95% confidence interval 0.76 to 0.90) and without reduced eGFR (0.83, 0.79 to 0.88), with no evidence for any difference in effect (P=1.00 for homogeneity). The results were similar irrespective of whether blood pressure was reduced by regimens based on angiotensin converting enzyme inhibitors, calcium antagonists, or diuretics/ß blockers. There was no evidence that the effects of different drug classes on major cardiovascular events varied between patients with different eGFR (all P>0.60 for homogeneity). CONCLUSIONS: Blood pressure lowering is an effective strategy for preventing cardiovascular events among people with moderately reduced eGFR. There is little evidence from these overviews to support the preferential choice of particular drug classes for the prevention of cardiovascular events in chronic kidney disease.

The design and rationale of the Australian Cooperative National Registry of Acute Coronary care, Guideline Adherence and Clinical Events (CONCORDANCE).

BACKGROUND: Cardiovascular observational registries characterise patients and describe the manner and use of therapeutic strategies. They facilitate analyses on the quality of care among participating institutions and document variations in clinical practice which can be benchmarked against best practice recommendations. The Cooperative National Registry of Acute Coronary care, Guideline Adherence and Clinical Events (CONCORDANCE) is an Australian observational registry that describes management and outcomes in patients with acute coronary syndromes (ACS) and feeds back both performance and outcome measures to participating hospitals. METHODS: The CONCORDANCE registry has been designed within a comparative effectiveness research (CER) framework to collect and report data from hospitals located in geographically diverse regions of Australia. Information including patient demographics, presenting characteristics, past medical history, in-hospital management and outcomes at six months and two years are entered into a web-based database using an electronic clinical record form (eCRF). Individual hospital information is returned to the sites in a real time confidential report detailing information on key performance indicator (KPI) process measures and outcomes benchmarked against the aggregated study cohort. Governance rules ensure data security and protect patient and clinician confidentiality. Consistent with a CER framework, additional characteristics of the registry include: (a) the capacity to evaluate associations between the inter and intra hospital systems and the provision of evidence based care and outcomes, (b) ongoing data collection from representative hospitals which allow spatial and temporal analysis of change in practice and the application of treatment modalities in the real world setting and (c) the provision of a data spine for quality improvement strategies and practical clinical trials. CONCLUSION: The CONCORDANCE registry is a clinician-driven initiative describing clinical care for ACS patients admitted to Australian hospitals. The registry generates high quality data which is fed back to clinicians, and key stakeholders in ACS care. Using a CER approach, the registry describes the translation of randomised trial evidence into practice, and provides insights into strategies that could improve care and ultimately patient outcomes.

Intensive glucose control and macrovascular outcomes in type 2 diabetes.

AIMS/HYPOTHESIS: Improved glucose control in type 2 diabetes is known to reduce the risk of microvascular events. There is, however, continuing uncertainty about its impact on macrovascular disease. The aim of these analyses was to generate more precise estimates of the effects of more-intensive, compared with less-intensive, glucose control on the risk of major cardiovascular events amongst patients with type 2 diabetes. METHODS: A prospectively planned group-level meta-analysis in which characteristics of trials to be included, outcomes of interest, analyses and subgroup definitions were all pre-specified. RESULTS: A total of 27,049 participants and 2,370 major vascular events contributed to the meta-analyses. Allocation to more-intensive, compared with less-intensive, glucose control reduced the risk of major cardiovascular events by 9% (HR 0.91, 95% CI 0.84-0.99), primarily because of a 15% reduced risk of myocardial infarction (HR 0.85, 95% CI 0.76-0.94). Mortality was not decreased, with non-significant HRs of 1.04 for all-cause mortality (95% CI 0.90-1.20) and 1.10 for cardiovascular death (95% CI 0.84-1.42). Intensively treated participants had significantly more major hypoglycaemic events (HR 2.48, 95% CI 1.91-3.21). Exploratory subgroup analyses suggested the possibility of a differential effect for major cardiovascular events in participants with and without macrovascular disease (HR 1.00, 95% CI 0.89-1.13, vs HR 0.84, 95% CI 0.74-0.94, respectively; interaction p = 0.04). CONCLUSIONS/INTERPRETATION: Targeting more-intensive glucose lowering modestly reduced major macrovascular events and increased major hypoglycaemia over 4.4 years in persons with type 2 diabetes. The analyses suggest that glucose-lowering regimens should be tailored to the individual.

Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials.

OBJECTIVE: To quantify the relative risk reductions achieved with different regimens to lower blood pressure in younger and older adults. DESIGN: Meta-analyses and meta-regression analyses used to compare the effects on the primary outcome between two age groups (<65 v > or =65 years). Evidence for an interaction between age and the effects of treatment sought by fitting age as a continuous variable and estimating overall effects across trials. PRIMARY OUTCOME: total major cardiovascular events. RESULTS: 31 trials, with 190 606 participants, were included. The meta-analyses showed no clear difference between age groups in the effects of lowering blood pressure or any difference between the effects of the drug classes on major cardiovascular events (all P> or =0.24). Neither was there any significant interaction between age and treatment when age was fitted as a continuous variable (all P>0.09). The meta-regressions also showed no difference in effects between the two age groups for the outcome of major cardiovascular events (<65 v > or =65; P=0.38). CONCLUSIONS: Reduction of blood pressure produces benefits in younger (<65 years) and older (> or =65 years) adults, with no strong evidence that protection against major vascular events afforded by different drug classes varies substantially with age.

Prospective observational study of acute coronary syndromes in China: practice patterns and outcomes.

OBJECTIVE: To describe the investigation and management of patients admitted to hospitals in China with suspected acute coronary syndromes (ACS) and to identify potential areas for improvement in practice. DESIGN: A multicentre prospective survey of sociodemographic characteristics, medical history, clinical features, in-hospital investigations, treatment practices and major events among patients with suspected ACS. SETTING: Large urban public hospitals. PATIENTS: Consecutive patients admitted to in-patient facilities with a diagnosis of suspected acute myocardial infarction (MI) or unstable angina pectoris. MAIN OUTCOME MEASURES: Myocardial infarction/re-infarction, heart failure, death. RESULTS: Between September 2004 and May 2005, data were collected prospectively from 2973 patients admitted to 51 hospitals in 18 provinces of China. An initial diagnosis of ST elevation MI, non-ST elevation MI and unstable angina was made in 43%, 11% and 46% of patients, respectively. Diagnosis was inconsistent with objective measures in up to 20% of cases. At both tertiary and non-tertiary centres, there was little evidence that clinical risk stratification was used to determine the intensity of investigation and management. The mortality rate during hospitalisation was 5% overall and similar in tertiary and non-tertiary centres, but reported in-hospital re-infarction rates (8%) and heart failure rates (16%) were substantially higher at non-tertiary centres. CONCLUSION: This study has identified a number of areas in the management of ACS patients, including diagnosis and risk stratification, which deviate from current guidelines. These findings will help inform the introduction of widely used quality improvement initiatives such as clinical pathways.

Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system.

OBJECTIVES: To evaluate the blood pressure-dependent and independent effects of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on major cardiovascular events. METHODS: Using data from 26 large-scale trials comparing an ACEI or an ARB with placebo or another drug class, meta-regression analyses were conducted in which treatment-specific relative risks for major cause-specific outcomes [stroke, major coronary heart disease (CHD) events and heart failure] were regressed against follow-up blood pressure differences. RESULTS: From a total of 146 838 individuals with high blood pressure or an elevated risk of cardiovascular disease, 22 666 major cardiovascular events were documented during follow-up. The analyses showed comparable blood pressure-dependent reductions in risk with ACEI and ARB (P >or= 0.3 for all three outcomes). The analyses also showed that ACEI produced a blood pressure-independent reduction in the relative risk of CHD of approximately 9% (95% confidence interval 3-14%). No similar effect was detected for ARB, and there was some evidence of a difference between ACEI and ARB in this regard (P = 0.002). For both stroke and heart failure there was no evidence of any blood pressure-independent effects of either ACEI or ARB. CONCLUSION: There are similar blood pressure-dependent effects of ACEI and ARB for the risks of stroke, CHD and heart failure. For ACEI, but not ARB, there is evidence of blood pressure-independent effects on the risk of major coronary disease events.

Optical assessment of skin blood content and oxygenation.

The alteration of blood flow in the skin and subcutaneous tissue due to mechanical loading is of great importance in the prevention of decubitus ulcers. A technique is described for assessing changes in blood content optically. The results indicate that such changes occur after loading even though the deformation is maintained constant.

National study of adverse reactions after vaccination with bacille Calmette-Guérin.

Few large prospective studies of adverse reactions after bacille Calmette-Guérin (BCG) vaccination are available. In a prospective national study of such adverse reactions among 918 subjects (aged 1 day to 54 years) over a 14-month period, 45 vaccinees (5%) reported 53 adverse reactions (23 injection-site abscesses, 14 severe local reactions, 10 cases of lymphadenitis, and 6 other reactions). Only 1% of vaccinees required medical attention. Reactions, particularly lymphadenitis, were significantly less common in infants <6 months old (but not in subjects aged > or =6 months) vaccinated by trained (vs. untrained) providers (relative risk [RR], 0.24; 95% confidence interval [CI], 0.09-0.68). Injection-site abscesses (RR, 2.96; 95% CI, 1.11-7.90) and severe local reactions (RR, 4.93; 95% CI, 1.11-21.90) were significantly more common in older vaccinees. Local reactions were more frequently reported by adult females than by adult males (RR, 7.18; 95% CI, 1.59-32.45). Adverse reactions were not significantly associated with any currently available vaccine batch, previous receipt of BCG vaccine, or concomitant administration of other vaccines.

Home oxygen status and rehospitalisation and primary care requirements of infants with chronic lung disease.

OBJECTIVES: To determine whether the rehospitalisation and primary care requirements of infants with chronic lung disease (CLD) during the first two years after birth were influenced by a requirement for supplementary oxygen after discharge from the neonatal intensive care unit. METHODS: Review of records from both the hospital and general practitioner. PATIENTS: 235 infants, median gestational age 27 (range 22-31) weeks, 88 of whom were receiving supplementary oxygen when discharged home. RESULTS: Overall, the infants required a median of 2 (range 0-20) admissions per patient, 8 (0-41) outpatient attendances, 13 (0-76) contacts with the general practitioner, and 17 (0-169) consultations with other primary healthcare professionals. The home oxygen patients required significantly more and longer admissions (p < 0.01) and more outpatient attendances (p < 0.05). The total cost of care per infant of the home oxygen group was greater (p < 0.001); this reflected higher costs for hospital stay (p < 0.01), total inpatient care (p < 0.01), and primary care drugs (p < 0.01). CONCLUSION: Despite routine use of antenatal steroids and postnatal surfactant, certain patients with CLD, particularly those who receive home oxygen treatment, show high rates of utilisation of health service resources after discharge from the neonatal care unit.

Impact of the Australian Measles Control Campaign on immunity to measles and rubella.

To evaluate the impact of the 1998 Australian Measles Control Campaign on immunity to measles and rubella, 4400 opportunistically-collected sera, submitted to diagnostic laboratories across Australia from subjects aged 1-49 years, and 3000 from subjects aged 1-18 years, were tested before and after the campaign, respectively. The proportion of individuals aged 1-18 years who were immune to measles rose from 85% before, to 90% after, the campaign (P < 0.001). The greatest increase was in preschool (7%, P < 0.001) and primary school (10%, P < 0.001) children, who were actively targeted by the campaign. Rubella immunity in 1-18 year-olds rose from 83% to 91% (P < 0.0001), again with significant increases in preschool (4%, P = 0.002) and primary school (16%, P < 0.001) children. 94% of individuals aged 19-49 years were immune to rubella. These serosurveys confirm other evidence of the effectiveness of the Australian Measles Control Campaign and demonstrate the value of serosurveillance using opportunistically collected sera.

Health care utilisation of infants with chronic lung disease, related to hospitalisation for RSV infection.

AIMS: To compare the use of health care resources and associated costs between infants with chronic lung disease (CLD) who had or had not an admission with a proven respiratory syncytial virus (RSV) infection. METHODS: Review of community care, outpatient attendances, and readmissions in the first two years after birth. PATIENTS: 235 infants (median gestational age 27 weeks) evaluated in four groups: 45 infants with a proven RSV admission (RSV proven); 24 with a probable bronchiolitis admission; 60 with other respiratory admissions; and 106 with non-respiratory or no admissions. RESULTS: The RSV proven compared to the other groups required more frequent and longer admissions to general paediatric wards and intensive care units, more outpatient attendances and GP consultations for respiratory related disorders, and had a higher total cost of care. CONCLUSION: RSV hospitalisation in patients with CLD is associated with increased health service utilisation and costs in the first two years after birth.

The Australian Measles Control Campaign, 1998.

The 1998 Australian Measles Control Campaign had as its aim improved immunization coverage among children aged 1-12 years and, in the longer term, prevention of measles epidemics. The campaign included mass school-based measles-mumps-rubella vaccination of children aged 5-12 years and a catch-up programme for preschool children. More than 1.33 million children aged 5-12 years were vaccinated at school: serological monitoring showed that 94% of such children were protected after the campaign, whereas only 84% had been protected previously. Among preschool children aged 1-3.5 years the corresponding levels of protection were 89% and 82%. During the six months following the campaign there was a marked reduction in the number of measles cases among children in targeted age groups.

A randomized trial of two acellular pertussis vaccines (dTpa and pa) and a licensed diphtheria-tetanus vaccine (Td) in adults.

A single blinded randomized controlled trial to compare the reactogenicity and immunogenicity of adult formulated dTpa and monovalent pa vaccines with a licensed Td vaccine. Five hundred and forty-eight healthy adults aged 19-70 years received a single injection of dTpa or separate injections of pa or Td (with the alternate vaccine 1 month later). Local and systemic reactions were monitored for 15 days after each vaccination. Serum antibody levels were measured immediately prior to and 1 month after vaccination. Antibody levels were measured 12 months after vaccination in 100 subjects. There was no difference in the total frequency of symptoms and signs between subjects receiving any of the three vaccines. There was a significantly lower incidence of local reactions following pa (60%) than dTpa (80%, P=0.002) or Td (93%, P=0.0008). The incidence of clinically significant (Grade 2 or 3) swelling (> or =20 mm) was higher for Td (20%, P=0.002) than for dTpa (11%) or for pa (2%), however, there were no other significant differences in the incidence of Grade 2 or 3 reactions between the vaccines. A high anti-pertussis seroconversion rate (>97%) against all the studied pertussis antigens was seen 1 month after vaccination with dTpa and pa. A total of 96 and 99% of subjects receiving dTpa and Td, respectively, had anti-diphtheria titres > or =0.01 IU/ml, and all but one subject had anti-tetanus titres > or =0.1 IU/ml after 1 month. Twelve months after vaccination the majority (90-100%) of the subjects were still seropositive for each antigen and although GMTs had decreased they were substantially higher than pre-vaccination levels. The dTpa vaccine was well tolerated and capable of eliciting an immune response against all the antigens in a broad spectrum of the adult population and could potentially replace Td for routine boosters in adults.

Adverse events following immunisation associated with the 1998 Australian Measles Control Campaign.

The Measles Control Campaign (MCC) conducted in Australia from August to November 1998 resulted in a total of 1.7 million school children being vaccinated. This article reports on the Adverse Events Following Immunisation (AEFI) associated with measles-mumps-rubella vaccine (MMR) administered as part of the MCC. Reports of adverse events that occurred within 30 days of administration of the MMR vaccine were assessed by an expert panel that assigned a causality rating to each AEFI. Reports with missing onset dates or uncertain causality were excluded. Eighty-nine AEFI were classified as associated with MMR vaccine and the overall rate of adverse events was 5.24 per 100,000 doses of vaccine administered. Of these 46 were thought to be certainly caused by MMR vaccine, 23 were probably and 20 were possibly associated with the vaccine. Although 46 reactions were categorised to be certainly caused by the MMR vaccine, the majority of these were syncopal fits, syncope, local reactions, and allergic reactions that were short-lived, and all of these children recovered. The most commonly occurring adverse reaction was syncopal fit with a rate of 1.24 per 100,000. There was only one anaphylactic reaction, giving a rate of 0.06 per 100,000. The combined rate for anaphylaxis, anaphylactoid and allergic reactions was 1.06 per 100,000 administered doses. The rate of seizures (febrile and afebrile) was 0.30 and encephalopathy was 0.06 per 100,000 doses administered. Of the 89 children who had an AEFI, 43 did not require hospitalisation or medical attention while 13 were seen in an emergency room, 14 were hospitalised and 19 were seen by a doctor. There were no deaths reported resulting from the administration of the MMR vaccine during the period of the campaign. All children who had an AEFI have recovered although 9 children could not be followed up for reasons of confidentiality. The overall rate of adverse events was lower than that observed in the 1994 measles campaign conducted in the United Kingdom. On comparing the risks and benefits of MMR vaccine, the benefits of this MCC far outweigh the incidence of serious adverse events associated with immunisation.

Vaccine preventable diseases and vaccination coverage in Australia, 1993-1998.

BACKGROUND: Since the introduction of childhood vaccination for diphtheria in 1932 and the widespread use of vaccines to prevent tetanus, pertussis (whooping cough) and poliomyelitis in the 1950s, deaths in Australia from vaccine preventable diseases (VPDs) have declined by more than 99%. It is important, however, that the downward trend in morbidity and mortality from VPDs is maintained and carefully monitored, and that changes are interpreted in relation to vaccination coverage. AIM: This report aimed to bring together three national sources of routinely collected data on the morbidity and mortality (notifications, hospitalisations and deaths) from VPDs during the period 1993-1998 for the 8 diseases then on the routine childhood vaccination schedule, and for 4 other diseases potentially preventable by childhood vaccination. It also examined vaccination coverage for the same period. METHODS: Data sources included notifications from the National Notifiable Diseases Surveillance System (NNDSS), hospitalisation data from the Australian Institute of Health and Welfare (AIHW) National Hospital Morbidity Database, deaths from the Australian Bureau of Statistics (ABS) Causes of Death Collection and vaccination coverage according to the Australian Childhood Immunisation Register (ACIR). All data sources were expected to have some limitations, the most important being under-reporting for notifications and vaccination encounters, and coding errors in the hospital morbidity data. RESULTS: Notifications for the 8 diseases covered by the routine schedule declined by 42%, from an average of 11,537 cases each year in 1993-1997 to 6700 in 1998, and hospitalisations fell by 12%, from an average of 1745 per year to 1536 in 1997/1998, while deaths remained unchanged at 7 each year over the period of review (Table 1). Tetanus caused 1 or 2 of the deaths each year. However, 6 of the 7 deaths in 1997 were in infants during a major outbreak of pertussis. Pertussis caused most of the notifications, hospitalisations and deaths during the review period. While most of these were in children, 46% of the notifications and 13% of the hospitalisations occurred in persons aged 15 years or more. There were notable declines in the numbers of notifications of invasive Haemophilus influenzae type b (Hib) disease in children under 5 years of age (77%), measles (87%) and rubella (75%), and there were no notifications of diphtheria or poliomyelitis. Vaccination coverage estimated using ACIR data increased during the review period. Coverage for the first 3 doses of diphtheria, tetanus, pertussis and Hib vaccines, assessed at 1 year of age, increased from 75% to 85%, while coverage for measles-mumps-rubella (MMR) vaccine, assessed at 2 years of age, increased from 83% to 86%. It is likely that these data underestimated coverage by 5-10%, and that the increase in coverage partly reflected better reporting to the ACIR by providers.