14,112 research outputs found
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial
No full textBackground: Throughout the usual LDL cholesterol range in Western populations, lower blood concentrations are associated with lower cardiovascular disease risk. In such populations, therefore, reducing LDL cholesterol may reduce the development of vascular disease, largely irrespective of initial cholesterol concentrations. Methods: 20 536 UK adults (aged 40–80 years) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive 40 mg simvastatin daily (average compliance: 85%) or matching placebo (average non-study statin use: 17%). Analyses are of the first occurrence of particular events, and compare all simvastatin-allocated versus all placebo-allocated participants. These “intention-to-treat” comparisons assess the effects of about two-thirds (85% minus 17%) taking a statin during the scheduled 5-year treatment period, which yielded an average difference in LDL cholesterol of 1·0 mmol/L (about two-thirds of the effect of actual use of 40 mg simvastatin daily). Primary outcomes were mortality (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity. Findings: All-cause mortality was significantly reduced (1328 [12·9%] deaths among 10 269 allocated simvastatin versus 1507 [14·7%] among 10 267 allocated placebo; p=0·0003), due to a highly significant 18% (SE 5) proportional reduction in the coronary death rate (587 [5·7%] vs 707 [6·9%]; p=0·0005), a marginally significant reduction in other vascular deaths (194 [1·9%] vs 230 [2·2%]; p=0·07), and a non-significant reduction in non-vascular deaths (547 [5·3%] vs 570 [5·6%]; p=0·4). There were highly significant reductions of about one-quarter in the first event rate for nonfatal myocardial infarction or coronary death (898 [8·7%] vs 1212 [11·8%]; p<0·0001), for non-fatal or fatal stroke (444 [4·3%] vs 585 [5·7%]; p<0·0001), and for coronary or noncoronary revascularisation (939 [9·1%] vs 1205 [11·7%]; p<0·0001). For the first occurrence of any of these major vascular events, there was a definite 24% (SE 3; 95% CI 19–28) reduction in the event rate (2033 [19·8%] vs 2585 [25·2%] affected individuals; p<0·0001). During the first year the reduction in major vascular events was not significant, but subsequently it was highly significant during each separate year. The proportional reduction in the event rate was similar (and significant) in each subcategory of participant studied, including: those without diagnosed coronary disease who had cerebrovascular disease, or had peripheral artery disease, or had diabetes; men and, separately, women; those aged either under or over 70 years at entry; and—most notably—even those who presented with LDL cholesterol below 3·0 mmol/L (116 mg/dL), or total cholesterol below 5·0 mmol/L (193 mg/dL). The benefits of simvastatin were additional to those of other cardioprotective treatments. The annual excess risk of myopathy with this regimen was about 0·01%. There were no significant adverse effects on cancer incidence or on hospitalisation for any other non-vascular cause. Interpretation: Adding simvastatin to existing treatments safely produces substantial additional benefits for a wide range of high-risk patients, irrespective of their initial cholesterol concentrations. Allocation to 40 mg simvastatin daily reduced the rates of myocardial infarction, of stroke, and of revascularisation by about one-quarter. After making allowance for non-compliance, actual use of this regimen would probably reduce these rates by about one-third. Hence, among the many types of high-risk individual studied, 5 years of simvastatin would prevent about 70–100 people per 1000 from suffering at least one of these major vascular events (and longer treatment should produce further benefit). The size of the 5-year benefit depends chiefly on such individuals' overall risk of major vascular events, rather than on their blood lipid concentrations alone
Progress in prevention of mother-to-child transmission of HIV infection in Ukraine: results from a birth cohort study
No full textBackground: Ukraine was the epicentre of the HIV epidemic in Eastern Europe, which has the most rapidly accelerating HIV epidemic world-wide today; national HIV prevalence is currently estimated at 1.6%. Our objective was to evaluate the uptake and effectiveness of interventions for prevention of mother-to-child transmission (PMTCT) over an eight year period within operational settings in Ukraine, within the context of an ongoing birth cohort study.Methods: The European Collaborative Study (ECS) is an ongoing birth cohort study in which HIV-infected pregnant women identified before or during pregnancy or at delivery were enrolled and their infants prospectively followed. Three centres in Ukraine started enrolling in 2000, with a further three joining in September 2006.Results: Of the 3356 women enrolled, 21% (689) reported current or past injecting drug use (IDU). Most women were diagnosed antenatally and of those, the proportion diagnosed in the first/second trimester increased from 47% in 2000/01 (83/178) to 73% (776/1060) in 2006/07 (p < 0.001); intrapartum diagnosis was associated with IDU (Adjusted odds ratio 4.38; 95% CI 3.19-6.02). The percentage of women not receiving any antiretroviral prophylaxis declined from 18% (36/205) in 2001 to 7% in 2007 (61/843) p < 0.001). Use of sdNVP alone substantially declined after 2003, with a concomitant increase in zidovudine prophylaxis. Median antenatal zidovudine prophylaxis duration increased from 24 to 72 days between 2000 and 2007. Elective caesarean section (CS) rates were relatively stable over time and 34% overall. Mother-to-child transmission (MTCT) rates decreased from 15.2% in 2001 (95% CI 10.2-21.4) to 7.0% in 2006 (95% CI 2.6-14.6). In adjusted analysis, MTCT risk was reduced by 43% with elective CS versus vaginal delivery and by 75% with zidovudine versus no prophylaxis.Conclusion: There have been substantial improvements in use of PMTCT interventions in Ukraine, including earlier diagnosis of HIV-infected pregnant women and increasing coverage with antiretroviral prophylaxis and the initial MTCT rate has more than halved. Future research should focus on hard-to-reach populations such as IDU and on missed opportunities for further reducing the MTCT rate
Pulse oximetry adoption and oxygen orders at paediatric admission over 7 years in Kenya: a multihospital retrospective cohort study
No full textObjectives To characterise adoption and explore specific clinical and patient factors that might influence pulse oximetry and oxygen use in low-income and middle-income countries (LMICs) over time; to highlight useful considerations for entities working on programmes to improve access to pulse oximetry and oxygen.
Design A multihospital retrospective cohort study.
Settings All admissions (n=132 737) to paediatric wards of 18 purposely selected public hospitals in Kenya that joined a Clinical Information Network (CIN) between March 2014 and December 2020.
Outcomes Pulse oximetry use and oxygen prescription on admission; we performed growth-curve modelling to investigate the association of patient factors with study outcomes over time while adjusting for hospital factors.
Results Overall, pulse oximetry was used in 48.8% (64 722/132 737) of all admission cases. Use rose on average with each month of participation in the CIN (OR: 1.11, 95% CI 1.05 to 1.18) but patterns of adoption were highly variable across hospitals suggesting important factors at hospital level influence use of pulse oximetry. Of those with pulse oximetry measurement, 7% (4510/64 722) had hypoxaemia (SpO2 <90%). Across the same period, 8.6% (11 428/132 737) had oxygen prescribed but in 87%, pulse oximetry was either not done or the hypoxaemia threshold (SpO2 <90%) was not met. Lower chest-wall indrawing and other respiratory symptoms were associated with pulse oximetry use at admission and were also associated with oxygen prescription in the absence of pulse oximetry or hypoxaemia.
Conclusion The adoption of pulse oximetry recommended in international guidelines for assessing children with severe illness has been slow and erratic, reflecting system and organisational weaknesses. Most oxygen orders at admission seem driven by clinical and situational factors other than the presence of hypoxaemia. Programmes aiming to implement pulse oximetry and oxygen systems will likely need a long-term vision to promote adoption, guideline development and adherence and continuously examine impact
Prior events predict cerebrovascular and coronary outcomes in the PROGRESS trial
No full text<p><b>Background and Purpose:</b> The relationship between baseline and recurrent vascular events may be important in the targeting of secondary prevention strategies. We examined the relationship between initial event and various types of further vascular outcomes and associated effects of blood pressure (BP)–lowering.</p>
<p><b>Methods:</b> Subsidiary analyses of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial that established the benefits of BP–lowering in 6105 patients (mean age 64 years, 30% female) with cerebrovascular disease, randomly assigned to either active treatment (perindopril for all, plus indapamide in those with neither an indication for, nor a contraindication to, a diuretic) or placebo(s).</p>
<p><b>Results:</b> Stroke subtypes and coronary events were associated with 1.5- to 6.6-fold greater risk of recurrence of the same event (hazard ratios, 1.51 to 6.64; P=0.1 for large artery infarction, P<0.0001 for other events). However, 46% to 92% of further vascular outcomes were not of the same type. Active treatment produced comparable reductions in the risk of vascular outcomes among patients with a broad range of vascular events at entry (relative risk reduction, 25%; P<0.0001 for ischemic stroke; 42%, P=0.0006 for hemorrhagic stroke; 17%, P=0.3 for coronary events; P homogeneity=0.4).</p>
<p><b>Conclusions:</b> Patients with previous vascular events are at high risk of recurrences of the same event. However, because they are also at risk of other vascular outcomes, a broad range of secondary prevention strategies is necessary for their treatment. BP–lowering is likely to be one of the most effective and generalizable strategies across a variety of major vascular events including stroke and myocardial infarction.</p>
Time to undetectable viral load after highly active antiretroviral therapy initiation among HIV-infected pregnant women
No full textBackground. There have been no clinical trials in resource-rich regions that have addressed the question of which highly active antiretroviral therapy (HAART) regimens are more effective for optimal viral response in antiretroviral-naive, human immunodeficiency virus (HIV)-infected pregnant women.Methods. Data on 240 HIV-1-infected women starting HAART during pregnancy who were enrolled in the prospective European Collaborative Study from 1997 through 2004 were analyzed. An interval-censored survival model was used to assess whether factors, including type of HAART regimen, race, region of birth, and baseline immunological and virological status, were associated with the duration of time necessary to suppress viral load below undetectable levels before delivery of a newborn.Results. Protease inhibitor-based HAART was initiated in 156 women (65%), 125 (80%) of whom received nelfinavir, and a nevirapine-based regimen was initiated in the remaining 84 women (35%). Undetectable viral loads were achieved by 73% of the women by the time of delivery. Relative hazards of time to achieving viral suppression were 1.54 (95% confidence interval, 1.05-2.26) for nevirapine-based HAART versus PI-based regimens and 1.90 (95% confidence interval, 1.16-3.12) for western African versus non-African women. The median duration of time from HAART initiation to achievement of an undetectable viral load was estimated to be 1.4 times greater in women receiving PI-based HAART, compared with women receiving nevirapine-based HAART. Baseline HIV RNA load was also a significant predictor of the rapidity of achieving viral suppression by delivery, but baseline immune status was not.Conclusions. In this study, nevirapine-based HAART (compared with PI [mainly nelfinavir]-based HAART), western African origin, and lower baseline viral load were associated with shorter time to achieving viral suppression
The SvO2 Study: General design and results of the feasibility phase of a multicenter, randomized trial of three different hemodynamic approaches and two monitoring techniques in the treatment of critically ill patients
No full textAlthough the attainment of normal hemodynamic values has always been assumed to be the therapeutic target for critically ill patients, recent studies reported increased values in oxygen transport variables in survivors of high-risk surgery. It has been supposed that the higher values observed in survivors might indicate a physiological compensation for the increased metabolic requirements due to disease. We designed a randomized, multicentric trial to evaluate the effect of high values of cardiac index (CI) and oxygen delivery (DO2) in critically ill patients. Patients enrolled in the study are randomized to three different hemodynamic targets: normal values of CI (2.5 or = 4.5 L min-1 m-2), and mixed venous oxygen saturation (SvO2) > or = 70% or (Sat a--Sat v) < or = 20%. Two different monitoring systems are used to maintain the target: conventional Swan-Ganz catheter with scheduled samples of mixed venous O2 saturation, and optical catheter with continuous SvO2 evaluation. The aim of the study is to answer three questions regarding the hypothesis reported above: (1) Are results in postoperative patients applicable to other pathological groups? (2) Does continuous monitoring of SvO2 provide advantages over conventional hemodynamic monitoring? (3) Is a normal SvO2 rather than a supranormal CI a good and predictable therapeutic goal? We report herein the protocol of the study and the results of the pilot phase, which was conducted in 98 critically ill patients enrolled by 56 participating centers to evaluate the safety and feasibility of the proposed trial
Methodological challenges for collaborative learning research
No full textResearch on collaborative learning, both face-to-face and computer-supported, has thrived in the past 10 years. The studies range from outcome-oriented (individual and group learning) to process-oriented (impact of interaction on learning processes, motivation and organisation of collaboration) to mixed studies. Collaborative learning research is multi-disciplinary. This introduces a multitude of theoretical accounts for collaborative learning, accompanied by a broad spectrum of methods to study processes and outcomes of collaboration. This special issue will provide an overview of methods that are at the core of current research effort, but also identifies opportunities and problems to sensibly combine methods into mixed method approaches
Examining which clinicians provide admission hospital care in a high mortality setting and their adherence to guidelines: An observational study in 13 hospitals
No full textBackground:
We explored who actually provides most admission care in hospitals offering supervised experiential training to graduating clinicians in a high mortality setting where practices deviate from guideline recommendations.
Methods:
We used a large observational data set from 13 Kenyan county hospitals from November 2015 through November 2018 where patients were linked to admitting clinicians. We explored guideline adherence after creating a cumulative correctness of Paediatric Admission Quality of Care (cPAQC) score on a 5-point scale (0–4) in which points represent correct, sequential progress in providing care perfectly adherent to guidelines comprising admission assessment, diagnosis and treatment. At the point where guideline adherence declined the most we dichotomised the cPAQC score and used multilevel logistic regression models to explore whether clinician and patient-level factors influence adherence.
Results:
There were 1489 clinicians who could be linked to 53 003 patients over a period of 3 years. Patients were rarely admitted by fully qualified clinicians and predominantly by preregistration medical officer interns (MOI, 46%) and diploma level clinical officer interns (COI, 41%) with a median of 28 MOI (range 11–68) and 52 COI (range 5–160) offering care per study hospital. The cPAQC scores suggest that perfect guideline adherence is found in ≤12% of children with malaria, pneumonia or diarrhoea with dehydration. MOIs were more adherent to guidelines than COI (adjusted OR 1.19 (95% CI 1.07 to 1.34)) but multimorbidity was significantly associated with lower guideline adherence.
Conclusion:
Over 85% of admissions to hospitals in high mortality settings that offer experiential training in Kenya are conducted by preregistration clinicians. Clinical assessment is good but classifying severity of illness in accordance with guideline recommendations is a challenge. Adherence by MOI with 6 years’ training is better than COI with 3 years’ training, performance does not seem to improve during their 3 months of paediatric rotations
Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer.
No full textBACKGROUND & AIMS:
Germline mutations in four DNA mismatch repair genes are known to cause susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC). The rapidly increasing information about these mutations needs to be collected and appropriately stored to facilitate further studies on the biological and clinical significance of the findings.
METHODS:
The International Collaborative Group on HNPCC has established a database of DNA mismatch repair gene mutations and polymorphisms. In this report, 126 predisposing mutations were analyzed.
RESULTS:
A majority of the mutations affected either the Mut L homologue (MLH) 1 (n = 75) or the Mut S homologue (MSH) 2 (n = 48) and were quite evenly distributed, with some clustering in MSH2 exon 12 and MLH1 exon 16. Most MSH2 mutations consisted of frameshift (60%) or nonsense changes (23%), whereas MLH1 was mainly affected by frameshift (40%) or missense alterations (31%). Although most mutations were unique, a few common recurring mutations were identified. Of the families studied (n = 202), 82% met the Amsterdam criteria and 15% did not; the general mutation profile was similar in both groups.
CONCLUSIONS:
The construction of mutation profiles will facilitate the development of diagnostic strategies in HNPCC
Effectiveness of a multicomponent intervention to reduce social isolation and loneliness in community‐dwelling elders: A randomized clinical trial
No full textAbstract Aims To assess the effect of a multicomponent intervention on reducing social isolation and loneliness and improving the quality of life in community‐dwelling older adults. Design A cluster‐randomized controlled clinical trial. Methods A total of 56 older adults participated in the control group and 63 older adults in the experimental group. The intervention consisted of 6 home‐based face‐to‐face sessions, intercalated with 5 telephone calls and was conducted by nursing students and volunteer staff with experience in the subject. The study was conducted between April 2018 and December 2019. In terms of statistical analysis, several procedures were carried out: a statistical analysis per protocol and intention to treat, considering isolation, loneliness and quality of life as endpoints; a comparison of paired means, to analyse the behaviour of the outcome variables at baseline and the end of the study; and finally, a binary logistic regression analysis, considering social support as a dependent variable. Results The study results do not show the effectiveness of the modified CARELINK programme, analysed as a whole, on the decrease in social isolation or loneliness or the improvement in HRQL. However, a detailed analysis of the behaviour of some of the variables during the study indicates some results that deserve to be commented on. Comparing the mean confidential support scores between the experimental and control group at the initial and final stages shows significant differences in the analysis by protocol, and close to statistical significance in the analysis by intention to treat. Comparing the paired means obtained in the experimental group, an improvement in emotional loneliness scores was found. Finally, the variables associated with the social support of the subjects at the end of the follow‐up period were as follows: having people who help them and mobility. Conclusion Although the results obtained do not allow us to affirm that the intervention programme is effective, these same results point to improved confidential support and emotional loneliness in older adults participating in the intervention. Having people to help them and a greater degree of mobility are factors favouring the decrease in social isolation. Impact This study suggested that modified CARELINK, a multicomponent intervention performed by trained volunteers, could improve confidential support in community‐dwelling older adults. It also reports the importance of considering the level of mobility and support networks as determinants of the improvement caused by the intervention
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