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Higher VTE risk with newer combined oral contraceptives
WOMEN taking newer preparations of combined oral contraceptives, with the exception of those containing norgestimate, are at a higher risk of venous thromboembolism (VTE) than those taking second generation drugs, a study has found. The research, published in The BMJ, used data from two UK general practice databases to measure the association between the use of oral contraception and risk of VTE among women aged 15‒49 years. The final analysis included 5062 VTE cases from a clinical practice research database matched to 19 638 controls, and 5500 VTE cases from a primary care research database matched to 22 396 controls. The authors found that current exposure to any combined oral contraceptive was associated with an increased risk of VTE compared with no exposure in the previous year. Women exposed to drospirenone, gestodene, cyproterone and desogestrel within the previous 28 days had a four times increased risk of VTE, while women exposed to levonorgestrel, norethisterone and norgestimate had about a 2.5 times higher VTE risk compared with women not exposed in the past year. Risks for current use of gestodene, drospirenone, cyproterone and desogestrel were 1.5–1.8 times higher than for levonorgestrel, the authors said. The number of extra cases of VTE per year per 10 000 treated women was lowest for levonorgestrel and norgestimate, and highest for desogestrel and cyproterone. The authors said their study had produced the most reliable possible risk estimates based on currently available UK prescription data, and “confirmed results from other recent large scale studies and added new evidence, particularly for newer or less used combined oral preparations, such as those containing drospirenone or norgestimate”. An accompanying editorial said the results clarified inconsistencies in earlier studies and “provide important guidance for the safe prescribing of oral contraceptives”.
Lower level of care for elderly surgical patients
AUSTRALIAN researchers have shown that the oldest surgical patients are treated differently postoperatively than younger patients, receiving lower levels of care. The retrospective cross-sectional study, published in BMJ Open was based on reported deaths of 11 376 surgical patients in 111 public and 61 private hospitals in Australia. It found the oldest patients had more trauma and emergency admissions than patients in medium and youngest age groups. Oldest patients were those aged 80 years and older, medium patients were aged 65‒79 years, and youngest were aged 17‒64 years. Seven of eight measured markers of postoperative care demonstrated “strong and significant” relationships between lower levels of aggressive intervention and resource use and increasing age. The eight markers were fluid balance problems, unplanned return to theatre, unplanned intensive care unit (ICU) admission, treated in ICU, clinical incidents, postoperative complication, infection present at death, and if, retrospectively, the surgeon would have done anything differently when managing the patient. Compared with the medium group the oldest group had decreased rates of: unplanned returns to theatre (11.2% v 20.2%), unplanned intensive care admissions (16.3% v 24.0%) and treatment in ICUs (59.7% v 76.7%). The authors postulated that care in the oldest age group might be less aggressive, or appropriately scaled down because of expected poor outcome, concerns of futility of care or competing comorbidities. Perceived future quality of life issues might also influence decisions by caregivers, especially in the presence of malignancy, they wrote. “These findings may indicate a willingness to offer an operation on presentation, but early withdrawal of treatment if complications occur — rather than initial instigation of palliative care”, the authors wrote. “As a result, surgical costs may increase at a lower rate than expected if older people continue to have fewer complex postoperative interventions.”
Psychotic episodes infrequent in most cases
PSYCHOTIC episodes (PEs) are infrequent for most of the people who experience them, according to research published in JAMA Psychiatry. The researchers, including from Australia, examined data from the WHO World Mental Health Surveys, a coordinated set of community epidemiologic surveys of the prevalence and correlates of mental disorders in representative household samples from 18 countries in 2001‒2009, which included 31 261 adults who were asked about lifetime and 12-month prevalence and frequency of six types of PEs (two hallucinatory experiences and four delusional experiences). They found 32.2% reported one PE episode in their life and 64.0% reported no more than five lifetime occurrences. In the general population, those with two or more types of PEs were also significantly more likely to have more PE episodes. The authors wrote that of those who reported three or more PE types, 24.5% reported 101 or more occurrences. “Our findings provide an empirical foundation on which to investigate factors that influence the persistence of PEs”, the authors wrote. “In the general population, a small subgroup of individuals has multiple types of PEs and experiences these types of PEs more frequently. The research community needs to leverage this fine-grained information to better determine how PEs reflect risk status.” The authors said the study highlighted the subtle and variegated nature of the epidemiologic features of PEs.
Risks–benefits with dual-antiplatelet therapy after stents
EXTENDED use of dual-antiplatelet therapy (DAPT) after drug-eluting stent (DES) placement is associated with about eight fewer cases of myocardial infarction (MI) per 1000 treated patients per year, but six more major bleeding events than shorter duration DAPT, research has found. The systematic review, published in Annals of Internal Medicine, was based on data from nine clinical trials comparing longer and shorter duration DAPT after DES placement, and included more than 28 000 patients. Previous research had shown that DAPT with aspirin and a P2Y12 inhibitor, such as clopidogrel, ticagrelor or prasugrel, effectively prevented stent thrombosis, but the appropriate duration of the therapy remained controversial. Among the trials reviewed in the current study, the difference in duration of therapy between the shorter and longer arms in each study varied from 6 to 24 months, and clopidogrel was the most commonly used thienopyridine. Participating patients were typically men with hypertension and aged in their mid 60s. The authors said the moderate-quality evidence showed that longer duration DAPT decreased risk for MI, while high-quality evidence indicated that it increased the risk for major bleeding. The results also suggested a possible small increase in all-cause mortality among patients who received longer duration DAPT. The authors said their data demonstrated a “trade-off between a small reduction in MI on the one hand and small increase in bleeding and a possibly even smaller increase in mortality on the other”. As a result, decisions regarding DAPT should involve value and preference judgements about the relative aversion to MI and major bleeding, the authors wrote. “Patients who are reluctant to use drugs to achieve small or very small net benefits, those who do not want to risk bleeding events, or those who are risk averse in general are likely to decline use of extended DAPT”, they said.
Role for eGFR and albuminuria in cardiovascular risk prediction
A META-ANALYSIS to assess the addition of creatinine-based estimated glomerular filtration rate (eGFR) and albuminuria to traditional risk factors for prediction of cardiovascular risk has shown they should be taken into account for cardiovascular prediction, especially if they had already been assessed for clinical purpose, or if cardiovascular mortality and heart failure are outcomes of interest. The research, published in The Lancet Diabetes & Endocrinology, included 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4.2–19.0 years) and considered differences and improvements in risk classification for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke and heart failure over a 5-year time frame, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both. It found the addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality and heart failure than for coronary disease and stroke. The risk discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors. “Among clinical populations, in which the assessment of eGFR and albuminuria is already recommended (eg, for individuals with CKD, diabetes, or hypertension), these measures of kidney disease are especially useful for prediction of cardiovascular risk”, the authors wrote. An accompanying commentary said that while the research settled the debate on the predictive value of urinary ACR, it had reignited the questions of the pathophysiological pathways involved and the therapeutic implications.
Neurodevelopmental benefits with delayed cord clamping
A FOLLOW-UP study of a randomised trial of delayed umbilical cord clamping (CC) of children born at full term in low-risk pregnancies has found that optimising the time to clamping might affect neurodevelopment in low-risk children. The research, published in JAMA Pediatrics, assessed the neurodevelopment at 4 years of age of children who participated in a clinical trial comparing delayed (180 seconds or more after delivery) to early (10 seconds or less) CC. The original trial was conducted between 2008 and 2010 in a Swedish county hospital, and 382 children were invited for follow up at 4 years of age. The researchers found full-scale IQ did not differ between the early and delayed CC groups for the mean scores or the proportion of children with a subnormal score of less than 85. The groups also did not differ for verbal IQ, performance IQ, processing-speed quotient and general language composite scores. However, for a task requiring the children to draw within a bicycle trail, the proportion of children with an at-risk score was significantly lower in the delayed CC group than in the early-clamping group (3.8% v 12.9%). This was also the case for immature pencil grip (13.2% vs 25.6%). The delayed group had significantly higher scores leading to significant adjusted mean differences for personal-social and fine-motor domains. “When future guidelines are developed regarding child birth and timing of CC, the effect on fine-motor function shown in our study might be taken into account pending larger studies”, the researchers wrote. An accompanying editorial said the “potential benefit of improving maternal and neonatal care by a simple no cost intervention of delayed CC should be championed by the international community beginning now and leading into the next decade”.
Dyslexia not a vision problem
THE majority of children with dyslexia have normal results for all ophthalmic tests, supporting the consensus that dyslexia is not primarily a vision problem, research published in Pediatrics has found. The authors used data from a UK birth cohort study to assess the link between specific learning disorder with impairment in reading (dyslexia) and ophthalmic abnormalities in children aged 7‒9 years. Data were available for 5822 children and 3% met the criteria for severe reading impairment (SRI). The authors found no association between SRI and strabismus, motor fusion, sensory fusion at a distance, refractive error, amblyopia, convergence, accommodation or contrast sensitivity. In total, four in five children with SRI had normal ophthalmic function in each test used, the authors said. A small minority of children displayed minor anomalies in stereoacuity or fusion of near targets. The slight excess of these children among those with SRI might be a result of their reading impairment, or it might be unrelated, the authors wrote. They said their results did not support the routine referral of children diagnosed with SRI to an ophthalmologist or optometrist, and that “other evidence has not been found in support of ophthalmic therapies as a treatment of SRI or dyslexia”. The data could be helpful for families as reassurance that visual function was unlikely to be contributing to their child’s reading problems, which meant they could pursue other options for supporting their child, the authors wrote. They recommended a detailed synthesis of evidence on “managing specific learning difficulties including SRI, to optimise outcomes for affected children and their families without raising hopes and expectations regarding treatment and outcomes”.