Using thresholds based on risk of cardiovascular disease to target treatment for hypertension: modelling events averted and number treated

ObjectiveTo estimate the impact of using thresholds based on absolute risk of cardiovascular disease to target drug treatment to lower blood pressure in the community.DesignModelling of three thresholds of treatment for hypertension based on the absolute risk of cardiovascular disease. 5 year risk of disease was estimated for each participant using an equation to predict risk. Net predicted impact of the thresholds on the number of people treated and the number of disease events averted over 5 years was calculated assuming a relative treatment benefit of one quarter.SettingAuckland, New Zealand.Participants2158 men and women aged 35-79 years randomly sampled from the general electoral rolls.Results46 374 (12%) Auckland residents aged 35-79 receive drug treatment to lower their blood pressure, averting an estimated 1689 disease events over 5 years. Restricting treatment to individuals with blood pressure ⩾170/100 mm Hg and those with blood pressure between 150/90-169/99 mm Hg who have a predicted 5 year risk of disease ⩾10% would increase the net number for whom treatment would be recommended by 19 401. This 42% relative increase is predicted to avert 1139/1689 (68%) additional disease events overall over 5 years compared with current treatment. If the threshold for 5 year risk of disease is set at 15% the number recommended for treatment increases by <10% but about 620/1689 (37%) additional events can be averted. A 20% threshold decreases the net number of patients recommended for treatment by about 10% but averts 204/1689 (12%) more disease events than current treatment.ConclusionsImplementing treatment guidelines that use treatment thresholds based on absolute risk could significantly improve the efficiency of drug treatment to lower blood pressure in primary care.     

Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study

ObjectiveTo determine the relation between systolic blood pressure over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes.DesignProspective observational study.Setting23 hospital based clinics in England, Scotland, and Northern Ireland.Participants4801 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk.ResultsThe incidence of clinical complications was significantly associated with systolic blood pressure, except for cataract extraction. Each 10 mm Hg decrease in updated mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes (95% confidence interval 10% to 14%, P<0.0001), 15% for deaths related to diabetes (12% to 18%, P<0.0001), 11% for myocardial infarction (7% to 14%, P<0.0001), and 13% for microvascular complications (10% to 16%, P<0.0001). No threshold of risk was observed for any end point.ConclusionsIn patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised blood pressure. Any reduction in blood pressure is likely to reduce the risk of complications, with the lowest risk being in those with systolic blood pressure less than 120 mm Hg.     

A randomised controlled trial and economic evaluation of a referrals facilitator between primary care and the voluntary sector

ObjectivesTo compare outcome and resource utilisation among patients referred to the Amalthea Project, a liaison organisation that facilitates contact between voluntary organisations and patients in primary care, with patients receiving routine general practitioner care.DesignRandomised controlled trial with follow up at one and four months.Setting26 general practices in Avon.Participants161 patients identified by their general practitioner as having psychosocial problems.ResultsThe Amalthea group showed significantly greater improvements in anxiety (average difference between groups after adjustment for baseline −1.9, 95% confidence interval −3.0 to −0.7), other emotional feelings (average adjusted difference −0.5, −0.8 to −0.2), ability to carry out everyday activities (−0.5, −0.8 to −0.2), feelings about general health (−0.4, −0.7 to −0.1), and quality of life (−0.5, −0.9 to −0.1). No difference was detected in depression or perceived social support. The mean cost was significantly greater in the Amalthea arm than the general practitioner care arm (£153 v £133, P=0.025).ConclusionReferral to the Amalthea Project and subsequent contact with the voluntary sector results in clinically important benefits compared with usual general practitioner care in managing psychosocial problems, but at a higher cost.     

Associations of serum 25-hydroxyvitamin D, parathyroid hormone and calcium with cardiovascular risk factors: analysis of 3 NHANES cycles (2001-2006)

Background

Increasing evidence suggests a role for mineral metabolism in cardiovascular disease risk. 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), and calcium may be directly associated with cardiovascular risk factors or mediated by each other.

Methodology/Principal Findings

We combined data for adult participants in three cycles of the National Health and Nutrition Examination Survey (2001–2, 2003–4, 2005–6), a representative sample of the civilian, non-institutionalized US population (N = 3,958). Using this data we examined joint associations of 25(OH)D, PTH and calcium with a range of cardiovascular risk factors. 25(OH)D was inversely associated with fasting insulin (mean difference in insulin per 1 standard deviation 25(OH)D: −0.053 (95%CI: −0.091, −0.015)), glucose (−0.046 95%CI: −0.081, −0.012) and systolic blood pressure (SBP) (−0.032 95%CI: −0.062, −0.001), and positively associated with high density lipoprotein cholesterol HDL-c (0.088 95%CI: 0.044, 0.148), after adjustment for ethnicity, smoking, socio-economic status and waist circumference. PTH was positively associated with diastolic blood pressure (0.110, 95%CI: 0.055, 0.164) in confounder adjusted models, but was not associated with other cardiovascular risk factors. Albumin adjusted calcium was associated with triglycerides (0.102 95%CI: 0.063, 0.141), postload glucose (0.078, 95%CI: 0.025, 0.130), fasting insulin (0.074, 95%CI: 0.044, 0.104), HbA1c (0.070, 95%CI: 0.036, 0.105), SBP (0.064, 95%CI: 0.028, 0.100), fasting glucose (0.055, 95%CI: 0.018, 0.092) and low density lipoprotein cholesterol (0.052, 95%CI: 0.014, 0.091). With mutual adjustment for each other, these associations remained essentially unchanged.

Conclusions/Significance

Lower levels of 25(OH)D and higher levels of calcium and PTH appear to be associated with different cardiovascular risk factors and may therefore affect cardiovascular disease risk through different mechanisms.     

Sex differences in step count-blood pressure association: a preliminary study in type 2 diabetes

Background

Walking and cardiovascular mortality are inversely associated in type 2 diabetes, but few studies have objectively measured associations of walking with individual cardiovascular risk factors. Such information would be useful for “dosing” daily steps in clinical practice. This study aimed to quantify decrements in blood pressure and glycated hemoglobin (A1C) per 1,000 daily step increments.

Methodology/Principal Findings

Two hundred and one subjects with type 2 diabetes underwent assessments of step counts (pedometer-measured), blood pressure, A1C and anthropometric parameters. Due to missing data, the final analysis was conducted on 83 women and 102 men, with a mean age of 60 years. Associations of daily steps with blood pressure and A1C were evaluated using sex-specific multivariate linear regression models (adjusted for age, ethnicity, and BMI). Potential sex differences were confirmed in a combined model (women and men) with interaction terms. Mean values for daily steps, blood pressure, A1C and BMI were 5,357 steps/day; 137/80 mm Hg; 7.7% and 30.4 kg/m² respectively. A 1,000 daily step increment among women was associated with a −2.6 (95% CI: −4.1 to −1.1) mm Hg change in systolic and a −1.4 (95% CI: −2.2 to −0.6) mm Hg change in diastolic blood pressure. Among men, corresponding changes were −0.7 (95% CI: −2.1 to 0.7) and −0.6 (95% CI: −1.4 to 0.3) mm Hg, respectively. Sex differences were confirmed in combined models. Step counts and A1C did not demonstrate clinically important associations.

Conclusions/Significance

A 1,000 steps/day increment is associated with important blood pressure decrements among women with type 2 diabetes but the data were inconclusive among men. Targeted “dose increments” of 1,000 steps/day in women may lead to measurable blood pressure reductions. This information may be of potential use in the titration or “dosing” of daily steps. No associations were found between step count increments and A1C.     

Randomised controlled trial of midwife led debriefing to reduce maternal depression after operative childbirth

ObjectiveTo assess the effectiveness of a midwife led debriefing session during the postpartum hospital stay in reducing the prevalence of maternal depression at six months postpartum among women giving birth by caesarean section, forceps, or vacuum extraction.DesignRandomised controlled trial.SettingLarge maternity teaching hospital in Melbourne, Australia.Participants1041 women who had given birth by caesarean section (n= 624) or with the use of forceps (n= 353) or vacuum extraction (n= 64).Results917 (88%) of the women recruited responded to the outcome questionnaire. More women allocated to debriefing scored as depressed six months after birth than women allocated to usual postpartum care (81 (17%) v 65 (14%)), although this difference was not significant (odds ratio=1.24, 95% confidence interval 0.87 to 1.77). They were also more likely to report that depression had been a problem for them since the birth, but the difference was not significant (123 (28%) v 94 (22%); odds ratio=1.37, 1.00 to 1.86). Women allocated to debriefing had poorer health status on seven of the eight SF-36 subscales, although the difference was significant only for role functioning (emotional): mean scores 73.32 v 78.98, t= −2.31, 95% confidence interval −10.48 to −0.84).ConclusionsMidwife led debriefing after operative birth is ineffective in reducing maternal morbidity at six months postpartum. The possibility that debriefing contributed to emotional health problems for some women cannot be excluded.     

Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care

ObjectiveTo determine the cost effectiveness of a strategy of near patient Helicobacter pylori testing and endoscopy for managing dyspepsia.DesignRandomised controlled trial.Setting31 UK primary care centres.Participants478 patients under 50 years old presenting with dyspepsia of longer than four weeks duration.InterventionsNear patient testing for H pylori and open access endoscopy for patients with positive results. Control patients received acid suppressing drugs or specialist referral at general practitioner''s discretion.Results40% of the study group tested positive for H pylori. 45% of study patients had endoscopy compared with 25% of controls. More peptic ulcers were diagnosed in the study group (7.4% v 2.1%, P=0.011). Paired comparison of symptom scores and quality of life showed that all patients improved over time with no difference between study and control groups. No significant differences were observed in rates of prescribing, consultation, or referral. Costs were higher in the study group (£367.85 v £253.16 per patient).ConclusionsThe test and endoscopy strategy increases endoscopy rates over usual practice in primary care. The additional cost is not offset by benefits in symptom relief or quality of life.

What is already known on this topic

Patients younger than 50 without H pylori infection are unlikely to have treatable disease detected at endoscopySuch patients can be managed by acid suppression and reassurance aloneTest and endoscopy (referral of patients testing positive for H pylori in primary care) has been recommended as a way to reduce endoscopic workload

What this paper adds

Applying a test and endoscopy strategy increased the endoscopy referral rate from 25% to 40%The strategy produced no significant differences in symptoms or quality of life compared with usual managementThe increased costs of this strategy cannot be justified     

Coronary and cardiovascular risk estimation for primary prevention: validation of a new Sheffield table in the 1995 Scottish health survey population

ObjectiveTo examine the accuracy of a new version of the Sheffield table designed to aid decisions on lipids screening and detect thresholds for risk of coronary heart disease needed to implement current guidelines for primary prevention of cardiovascular disease.DesignComparison of decisions made on the basis of the table with absolute risk of coronary heart disease or cardiovascular disease calculated by the Framingham risk function. The decisions related to statin treatment when coronary risk is ⩾30% over 10 years; aspirin treatment when the risk is ⩾15% over 10 years; and the treatment of mild hypertension when the cardiovascular risk is ⩾20% over 10 years.SettingThe table is designed for use in general practice.SubjectsRandom sample of 1000 people aged 35-64 years from the 1995 Scottish health survey.Results13% of people had a coronary risk of ⩾15%, and 2.2% a risk of ⩾30%, over 10 years. 22% had mild hypertension (systolic blood pressure 140-159 mm Hg). The table indicated lipids screening for everyone with a coronary risk of ⩾15% over 10 years, for 95% of people with a ratio of total cholesterol to high density lipoprotein cholesterol of ⩾8.0, but for <50% with a coronary risk of <5% over 10 years. Sensitivity and specificity were 97% and 95% respectively for a coronary risk of ⩾15% over 10 years; 82% and 99% for a coronary risk of ⩾30% over 10 years; and 88% and 90% for a cardiovascular risk of ⩾20% over 10 years in mild hypertension.ConclusionThe table identifies all high risk people for lipids screening, reduces screening of low risk people by more than half, and ensures that treatments are prescribed appropriately to those at high risk, while avoiding inappropriate treatment of people at low risk.     

Lipid concentrations and the use of lipid lowering drugs: evidence from a national cross sectional survey

ObjectiveTo evaluate the prevalence of the use of lipid lowering agents and its relation to blood lipid concentrations in English adults.DesignCross sectional survey.SettingEngland, 1998.ParticipantsNationally representative sample of 13 586 adults (aged ⩾16 years) living in non-institutional households.Results Mean total cholesterol concentrations were 5.47 (SE 0.02) mmol/l in men and 5.59 (0.02) mmol/l in women. Mean HDL cholesterol concentrations were 1.28 (0.01) mmol/l in men and 1.55 (0.01) mmol/l in women. Overall, of 10 569 adults who had a valid cholesterol measurement taken 7133 (67.5%; 95% confidence interval 66.5% to 68.4%) had a total cholesterol concentration ⩾5 mmol/l, 2804 (26.5%; 25.7% to 27.4%) had a ratio of total cholesterol to HDL cholesterol ⩾5 mmol/l, and 237 (2.2%; 1.9% to 2.5%) reported taking lipid lowering drugs. Of 117 participants with no history of cardiovascular disease but whose estimated 10 year risk of coronary heart disease was ⩾30% and whose total cholesterol concentration was ⩾5 mmol/l, four (3%) were taking lipid lowering drugs. Of 385 adults aged 16-75 with a history of coronary heart disease and eligible for lipid lowering treatment, 114 (30%; 25% to 34%) were taking lipid lowering drugs, of whom only 50 (44%; 35% to 53%) had a total cholesterol concentration <5 mmol/l.ConclusionsDespite the high prevalence of dyslipidaemia in English adults, the proportion of adults taking lipid lowering drugs in 1998 was only 2.2%. Rates of treatment were low among high risk patients eligible for primary prevention with lipid lowering drugs, and less than one third of patients with established cardiovascular disease received such treatment.     

Primary prevention of gestational diabetes mellitus and large-for-gestational-age newborns by lifestyle counseling: a cluster-randomized controlled trial

Background

Our objective was to examine whether gestational diabetes mellitus (GDM) or newborns'' high birthweight can be prevented by lifestyle counseling in pregnant women at high risk of GDM.

Method and Findings

We conducted a cluster-randomized trial, the NELLI study, in 14 municipalities in Finland, where 2,271 women were screened by oral glucose tolerance test (OGTT) at 8–12 wk gestation. Euglycemic (n = 399) women with at least one GDM risk factor (body mass index [BMI] ≥25 kg/m², glucose intolerance or newborn''s macrosomia (≥4,500 g) in any earlier pregnancy, family history of diabetes, age ≥40 y) were included. The intervention included individual intensified counseling on physical activity and diet and weight gain at five antenatal visits. Primary outcomes were incidence of GDM as assessed by OGTT (maternal outcome) and newborns'' birthweight adjusted for gestational age (neonatal outcome). Secondary outcomes were maternal weight gain and the need for insulin treatment during pregnancy. Adherence to the intervention was evaluated on the basis of changes in physical activity (weekly metabolic equivalent task (MET) minutes) and diet (intake of total fat, saturated and polyunsaturated fatty acids, saccharose, and fiber). Multilevel analyses took into account cluster, maternity clinic, and nurse level influences in addition to age, education, parity, and prepregnancy BMI. 15.8% (34/216) of women in the intervention group and 12.4% (22/179) in the usual care group developed GDM (absolute effect size 1.36, 95% confidence interval [CI] 0.71–2.62, p = 0.36). Neonatal birthweight was lower in the intervention than in the usual care group (absolute effect size −133 g, 95% CI −231 to −35, p = 0.008) as was proportion of large-for-gestational-age (LGA) newborns (26/216, 12.1% versus 34/179, 19.7%, p = 0.042). Women in the intervention group increased their intake of dietary fiber (adjusted coefficient 1.83, 95% CI 0.30–3.25, p = 0.023) and polyunsaturated fatty acids (adjusted coefficient 0.37, 95% CI 0.16–0.57, p<0.001), decreased their intake of saturated fatty acids (adjusted coefficient −0.63, 95% CI −1.12 to −0.15, p = 0.01) and intake of saccharose (adjusted coefficient −0.83, 95% CI −1.55 to −0.11, p  =  0.023), and had a tendency to a smaller decrease in MET minutes/week for at least moderate intensity activity (adjusted coefficient 91, 95% CI −37 to 219, p = 0.17) than women in the usual care group. In subgroup analysis, adherent women in the intervention group (n = 55/229) had decreased risk of GDM (27.3% versus 33.0%, p = 0.43) and LGA newborns (7.3% versus 19.5%, p = 0.03) compared to women in the usual care group.

Conclusions

The intervention was effective in controlling birthweight of the newborns, but failed to have an effect on maternal GDM.

Trial registration

Current Controlled Trials ISRCTN33885819 Please see later in the article for the Editors'' Summary     

Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery

ObjectivesTo determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery, and to determine whether the inotropes, adrenaline and dopexamine, used to enhance oxygen delivery influence outcome.DesignRandomised controlled trial with double blinding between inotrope groups.SettingYork District Hospital, England.Subjects138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions.InterventionsPatients were randomised into three groups. Two groups received invasive haemodynamic monitoring, fluid, and either adrenaline or dopexamine to increase oxygen delivery. Inotropic support was continued during surgery and for at least 12 hours afterwards. The third group (control) received routine perioperative care.ResultsOverall, 3/92 (3%) preoptimised patients died compared with 8/46 controls (17%) (P=0.007). There were no differences in mortality between the treatment groups, but 14/46 (30%) patients in the dopexamine group developed complications compared with 24/46 (52%) patients in the adrenaline group (difference 22%, 95% confidence interval 2% to 41%) and 28 patients (61%) in the control group (31%, 11% to 50%). The use of dopexamine was associated with a decreased length of stay in hospital.ConclusionRoutine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care.

Key messages

• Major elective surgery in UK general hospitals still carries significant mortality and morbidity
• Preoperative administration of fluid and inotropes, guided by invasive monitoring, can significantly reduce mortality, morbidity, and length of hospital stay
• The choice of inotrope may influence the extent of improvements in outcome
• Routine preoperative optimisation would require initial investment in high dependency care facilities but is likely to be cost effective by reducing complications and length of hospital stay

     

The psychosocial impact of bilateral prophylactic mastectomy: prospective study using questionnaires and semistructured interviews

ObjectivesTo investigate the psychosocial impact of bilateral prophylactic mastectomy for women with increased risk of breast cancer and to identify, preoperatively, risk factors for postoperative distress.DesignProspective study using interviews and questionnaire assessments.SettingParticipants'' homes throughout the United Kingdom.Participants143 women with increased risk of developing breast cancer who were offered bilateral prophylactic mastectomy and who accepted or declined the surgery; a further 11 were offered surgery but deferred making a decision.ResultsPsychological morbidity decreased significantly over time for the 79 women who chose to have surgery (accepters): 58% (41/71) preoperatively v 41% (29/71) 6 months postoperatively (difference in percentages 17%, 95% confidence interval 2% to 32%; P=0.04) and 60% (39/65) preoperatively v 29% (19/65) 18 months postoperatively (31%, 15% to 47%; P<0.001). Psychological morbidity in the 64 women who declined surgery (decliners) did not decrease significantly: 57% (31/54) at baseline v 43% (23/54) at 6 months (14%, 0% to 29%; P=0.08) and 57% (29/52) at baseline v 41% (21/52) at 18 months (16%; −2% to 33%; P=0.11). Greater than normal proneness to anxiety was more common in the decliners than in the accepters: 78% (45/58) v 56% (41/73) (22%, 6% to 38%; P=0.006). Accepters were more likely than decliners to believe it inevitable that they would develop breast cancer (32% (24/74) v 10% (6/58) (difference in percentages 22%, 9% to 35%; P=0.003)), and decliners were more likely to believe that screening could help (92% (55/60) v 74% (55/74) (18%, 5% to 31%; P=0.007)). Level of sexual discomfort and degree of sexual pleasure did not change significantly over time in either of the two groups.ConclusionsBilateral prophylactic mastectomy may provide psychological benefits in women with a high risk of developing breast cancer.     

Cost-effectiveness of Internet-based self-management compared with usual care in asthma

Background

Effectiveness of Internet-based self-management in patients with asthma has been shown, but its cost-effectiveness is unknown. We conducted a cost-effectiveness analysis of Internet-based asthma self-management compared with usual care.

Methodology and Principal Findings

Cost-effectiveness analysis alongside a randomized controlled trial, with 12 months follow-up. Patients were aged 18 to 50 year and had physician diagnosed asthma. The Internet-based self-management program involved weekly on-line monitoring of asthma control with self-treatment advice, remote Web communications, and Internet-based information. We determined quality adjusted life years (QALYs) as measured by the EuroQol-5D and costs for health care use and absenteeism. We performed a detailed cost price analysis for the primary intervention. QALYs did not statistically significantly differ between the Internet group and usual care: difference 0.024 (95% CI, −0.016 to 0.065). Costs of the Internet-based intervention were $254 (95% CI, $243 to $265) during the period of 1 year. From a societal perspective, the cost difference was $641 (95% CI, $−1957 to $3240). From a health care perspective, the cost difference was $37 (95% CI, $−874 to $950). At a willingness-to-pay of $50000 per QALY, the probability that Internet-based self-management was cost-effective compared to usual care was 62% and 82% from a societal and health care perspective, respectively.

Conclusions

Internet-based self-management of asthma can be as effective as current asthma care and costs are similar.

Trial Registration

Current Controlled Trials ISRCTN79864465     

Endpiece: Hospital league tables 1830

ObjectiveTo assess the long term effects of advice to restrict dietary sodium in adults with and without hypertension.DesignSystematic review and meta-analysis of randomised controlled trials.OutcomesMortality, cardiovascular events, blood pressure, urinary sodium excretion, quality of life, and use of antihypertensive drugs.ResultsThree trials in normotensive people (n=2326), five trials in those with untreated hypertension (n=387), and three trials in people being treated for hypertension (n=801) were included, with follow up from six months to seven years. The large high quality (and therefore most informative) studies used intensive behavioural interventions. Deaths and cardiovascular events were inconsistently defined and reported. There were 17 deaths, equally distributed between intervention and control groups. Systolic and diastolic blood pressures were reduced (systolic by 1.1 mm Hg, 95% confidence interval 1.8 to 0.4 mm Hg; diastolic by 0.6 mm Hg, 1.5 to −0.3 mm Hg) at 13 to 60 months, as was urinary 24 hour sodium excretion (by 35.5 mmol/24 hours, 47.2 to 23.9). Degree of reduction in sodium intake and change in blood pressure were not related.ConclusionsIntensive interventions, unsuited to primary care or population prevention programmes, provide only small reductions in blood pressure and sodium excretion, and effects on deaths and cardiovascular events are unclear. Advice to reduce sodium intake may help people on antihypertensive drugs to stop their medication while maintaining good blood pressure control.

What is already known on this topic

Restricting sodium intake in people with hypertension reduces blood pressureLong term effects (on blood pressure, mortality, and morbidity) of reduced salt intake in people with and without hypertension are unclear

What this study adds

Few deaths and cardiovascular events have been reported in salt reduction trialsMeta-analysis shows that blood pressure was reduced (systolic by 1.1 mm Hg, diastolic by 0.6 mm Hg) at 13 to 60 months, with a reduction in sodium excretion of almost a quarter (35.5 mmol/24 hours)The interventions used were highly intensive and unsuited to primary care or population prevention programmesLower salt intake may help people on antihypertensive drugs to stop their medication while maintaining good control of blood pressure, but there are doubts about effects of sodium reduction on overall health     

Computer support for interpreting family histories of breast and ovarian cancer in primary care: comparative study with simulated cases

ObjectivesTo evaluate the potential effect of computer support on general practitioners'' management of familial breast and ovarian cancer, and to compare the effectiveness of two different types of computer program.DesignCrossover experiment with balanced block design.ParticipantsOf a random sample of 100 general practitioners from Buckinghamshire who were invited, 41 agreed to participate. From these, 36 were selected for a fully balanced study.InterventionsDoctors managed 18 simulated cases: 6 with computerised decision support system Risk Assessment in Genetics (RAGs), 6 with Cyrillic (an established pedigree drawing program designed for clinical geneticists), and 6 with pen and paper.ResultsRAGs resulted in significantly more appropriate management decisions (median 6) than either Cyrillic (median 3) or pen and paper (median 3); median difference between RAGs and Cyrillic 2.5 (95% confidence interval 2.0 to 3.0; P<0.0001). RAGs also resulted in significantly more accurate pedigrees (median 5) than both Cyrillic (median 3.5) and pen and paper (median 2); median difference between RAGs and Cyrillic 1.5 (1.0 to 2.0; P<0.0001). The time taken to use RAGs (median 178 seconds) was 51 seconds longer per case (95% confidence interval 36 to 65; P<0.0001) than pen and paper (median 124 seconds) but was less than Cyrillic (median 203 seconds; difference 23. (5 to 43; P=0.02)). 33 doctors (92% (78% to 98%)) preferred using RAGs overall. The most important elements of an “ideal computer program” for genetic advice in primary care were referral advice, the capacity to create pedigrees, and provision of evidence and explanations to support advice.ConclusionsRAGs could enable general practitioners to be more effective gatekeepers to genetics services, empowering them to reassure the majority of patients with a family history of breast and ovarian cancer who are not at increased genetic risk.     

Reduction in mortality after inappropriate early discharge from intensive care unit: logistic regression triage model

ObjectiveTo develop a predictive model to triage patients for discharge from intensive care units to reduce mortality after discharge.DesignLogistic regression analyses and modelling of data from patients who were discharged from intensive care units.SettingGuy''s hospital intensive care unit and 19 other UK intensive care units from 1989 to 1998.Participants5475 patients for the development of the model and 8449 for validation.ResultsMortality after discharge from intensive care was up to 12.4%. The triage model identified patients at risk from death on the ward with a sensitivity of 65.5% and specificity of 87.6%, and an area under the receiver operating curve of 0.86. Variables in the model were age, end stage disease, length of stay in unit, cardiothoracic surgery, and physiology. In the validation dataset the 34% of the patients identified as at risk had a discharge mortality of 25% compared with a 4% mortality among those not at risk.ConclusionsThe discharge mortality of at risk patients may be reduced by 39% if they remain in intensive care units for another 48 hours. The discharge triage model to identify patients at risk from too early and inappropriate discharge from intensive care may help doctors to make the difficult clinical decision of whom to discharge to make room for a patient requiring urgent admission to the unit. If confirmed, this study has implications on the provision of resources.

What is already known on this topic

In the United Kingdom, the mortality of patients who die on the ward after discharge from intensive care is unacceptably high (9% to 27%)Indirect evidence has shown that this is due to too early and inappropriate discharge from intensive care that has increased over the past 10 years

What this study adds

A triage model identifies patients at risk from inappropriate discharge from intensive careMortality after discharge from intensive care may be reduced by 39% if these patients were to stay in intensive care for another 48 hoursAn estimated 16% more beds are required if mortality after discharge from intensive care is to be reduced     

Analysing the large decline in coronary heart disease mortality in the Icelandic population aged 25-74 between the years 1981 and 2006

Background

Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s. We examined how much of the decrease between 1981 and 2006 could be attributed to medical and surgical treatments and how much to changes in cardiovascular risk factors.

Methodology

The previously validated IMPACT CHD mortality model was applied to the Icelandic population. The data sources were official statistics, national quality registers, published trials and meta-analyses, clinical audits and a series of national population surveys.

Principal Findings

Between 1981 and 2006, CHD mortality rates in Iceland decreased by 80% in men and women aged 25 to 74 years, which resulted in 295 fewer deaths in 2006 than if the 1981 rates had persisted. Incidence of myocardial infarction (MI) decreased by 66% and resulted in some 500 fewer incident MI cases per year, which is a major determinant of possible deaths from MI. Based on the IMPACT model approximately 73% (lower and upper bound estimates: 54%–93%) of the mortality decrease was attributable to risk factor reductions: cholesterol 32%; smoking 22%; systolic blood pressure 22%, and physical inactivity 5% with adverse trends for diabetes (−5%), and obesity (−4%). Approximately 25% (lower and upper bound estimates: 8%–40%) of the mortality decrease was attributable to treatments in individuals: secondary prevention 8%; heart failure treatments 6%; acute coronary syndrome treatments 5%; revascularisation 3%; hypertension treatments 2%, and statins 0.5%.

Conclusions

Almost three quarters of the large CHD mortality decrease in Iceland between 1981 and 2006 was attributable to reductions in major cardiovascular risk factors in the population. These findings emphasize the value of a comprehensive prevention strategy that promotes tobacco control and a healthier diet to reduce incidence of MI and highlights the potential importance of effective, evidence based medical treatments.     

Cross sectional survey of effectiveness of lipid lowering drugs in reducing serum cholesterol concentration in patients in 17 general practices

ObjectiveTo compare the effectiveness of lipid lowering drugs in lowering serum cholesterol concentrations.DesignCross sectional study.Setting17 practices within 17 primary care groups in Trent region, United Kingdom.ParticipantsPatients aged 35 years or over taking lipid lowering drugs and with at least two serum cholesterol concentrations recorded on computer.Results1353 of 2469 (54.8%) patients receiving lipid lowering treatment had a last recorded serum cholesterol concentration of ⩽5 mmol/l. Significantly more patients taking statins achieved the target value for serum cholesterol (5 mmol/l) than those taking fibrates (1307 (57%) v 46 (26%); P<0.0001). Atorvastatin and simvastatin were the most effective drugs in achieving the target. Significant differences were found between lipid lowering drugs for the pretreatment serum cholesterol concentration, the most recent cholesterol concentration, and the associated percentage reduction. Atorvastatin and simvastatin achieved the greatest percentage reduction in serum cholesterol concentrations (30.1%, 95% confidence interval 28.8% to 31.4%, and 28.0%, 26.7% to 29.3%, respectively). Although the mean serum cholesterol concentrations in this unselected population tended to be higher than those in clinical trials, the percentage reduction was consistent with the trials.ConclusionThe ability of individual statins to lower serum cholesterol concentration varied, with atorvastatin and simvastatin being the most effective. The percentage reductions agreed with those of randomised controlled trials indicating likely benefits in unselected patients in primary care. As the initial serum cholesterol concentrations were higher than those in randomised controlled trials, target serum cholesterol values of ⩽5 mmol/l may be unrealistic even for patients taking the most efficacious drugs. Also, the higher initial levels could mean that the absolute reduction in cardiovascular risk in primary care patients is greater than thought.

What is already known on this topic

Statins in patients with coronary heart disease help reduce further cardiovascular events and improve survivalThis seems to be a class effect of statins, although there may be important differences in effectiveness between themLess than half of patients in the community who take lipid lowering drugs achieve target serum cholesterol values

What this study adds

Statins vary in their ability to lower serum cholesterol concentration, with atorvastatin and simvastatin achieving the best resultsThe percentage reductions agreed with those found in randomised controlled trialsSince the initial serum cholesterol concentrations were higher than in trials, absolute risk reductions in primary care patients may be greater than thoughtTarget values of ⩽5 mmol/l may be unrealistic even for patients on the most efficacious drugs, because the initial mean cholesterol values of primary care patients are higher than those of patients in trials     

Psychological consequences for parents of false negative results on prenatal screening for Down's syndrome: retrospective interview study

ObjectiveTo determine the psychological consequences for parents of children with Down''s syndrome of having received a false negative result on prenatal screening.DesignComparison of adjustment of parents who received a false negative result with that of parents not offered a test and those who declined a test.SettingParents were interviewed in their own homes.ParticipantsParents of 179 children with Down''s syndrome (mean age 4 (range 2-6) years).ResultsOverall, regardless of screening history, parents adjusted well to having a child with Down''s syndrome. Compared with mothers who declined a test, mothers in the false negative group had higher parenting stress (mean score 81.2 v 71.8, P=0.016, 95% confidence interval for the difference 1.8 to 17.0) and more negative attitudes towards their children (124.9 v 134.2, P=0.009, −16.2 to −2.4). Fathers in the false negative group had higher parenting stress test scores (77.8 v 70.0, P=0.046, 1.5 to 14.2) than fathers not offered a test. Mothers in the false negative group were more likely to blame others for the outcome than mothers who had not been offered the test (28% v 13%, P=0.032, 3% to 27%). Mothers and fathers in the false negative group were more likely to blame others for this outcome than parents who had declined a test (mothers 28% v 0%, P=0.001, 19% to 37%; fathers 27% v 0%, P=0.004, 17% to 38%). Blaming others was associated with poorer adjustment for mothers and fathers.ConclusionsA false negative result on prenatal screening seems to have a small adverse effect on parental adjustment evident two to six years after the birth of an affected child.