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On The Pulse - August 2019

On The Pulse

Tertius Lydgate

Friday, 30 August 2019

Childhood antibiotic exposure predictor for subsequent response failure
But not necessarily because of antibiotic treatment failure

Childhood antibiotic exposure has important clinically relevant implications, including disruption to the microbiome, antibiotic resistance, and clinical workload manifesting as treatment ‘failure’. An observational cohort study, in the BJGP, of 114,329 UK preschool children in primary care, examined the relationship between the number of antibiotic courses prescribed for acute respiratory tract infections (RTI), in the preceding year, and subsequent RTIs that failed to respond to antibiotic treatment, i.e. there was subsequent antibiotic prescription, referral, hospital admission, or death up to 14 days after index antibiotic prescription; or an emergency department attendance within three days. The findings suggest that when children receive more antibiotics for acute RTIs their likelihood of re-consulting a health professional is affected and increases clinical workload. Children receiving ≥ 2 antibiotics in the preceding year were most likely to be affected. The adjusted odds ratio for response failure after one and two antibiotic courses was 1.03 (95% CI= 0.88 to 1.21) and 1.32 (CI= 1.04 to 1.66), respectively. The authors say incorporating antibiotic exposure data into clinical decision-support systems might prompt clinicians to implement strategies to support a non-antibiotic strategy, for example, informing parents about the anticipated recovery period of common RTIs in children.

Did NICE guidelines increase the use of SSRIs in children?
Maybe…

A population-based study in BMJ Open looked at antidepressant prescription rates in children and adolescents within the UK primary care service after the release of the Committee on Safety of Medicines (CSM) warning in December 2003 and the National Institute for Health and Care Excellence (NICE) guidance in September 2005. It found that prescription of NICE cited antidepressants (fluoxetine, citalopram and sertraline) in the UK increased significantly between 2005 and 2010, following the publication of guidance for children and adolescents with depression, following an initial decrease after the CSM was issued. The rate of non-NICE recommended SSRIs and tricyclics prescriptions before and after publication remained low. The authors conclude that despite the guidelines strongly emphasising the role of psychosocial interventions for child and adolescent depression, it may be that the release of the NICE publication inadvertently encouraged higher rates of antidepressant prescribing, and in particular that of sertraline and citalopram. Although the guidelines gave cautions and caveats for the use of antidepressants, practitioners may have interpreted these recommendations as endorsing their use in young people with depression and related conditions.

Should methylphenidate be avoided in patients with psychosis history?
Research challenges existing concerns

Methylphenidate is the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), however there have been ongoing clinical concerns that it might increase the risk of psychotic events, particularly in young people with a history of psychosis. A population-based cohort study in The Lancet Psychiatry challenges the widely held view that methylphenidate should be avoided, or its use restricted in individuals with a history of psychosis. A history of psychosis was reported in 2% of the 23,898 eligible participants (median age at methylphenidate initiation: 17 years). The incidence rate ratios of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1·04 (95% CI 0·80–1·34) in adolescents and young adults without a history of psychosis and 0·95 (0·69–1·30) among those with a history of psychosis. However, the authors stress the need to confirm the findings regarding the immediate risk of psychotic events following methylphenidate initiation in other sample populations and with other study designs. That includes examining the effect of concomitant antipsychotic medication use in those with a history of psychosis. Dr Lydgate agrees this could indeed be an important moderating factor.

NSAIDs linked to higher cardiovascular risks in patients with OA
Study highlights importance of discussing risks and benefits with patients

Non-steroidal anti-inflammatory drugs (NSAIDs) can help to control the pain and inflammation in individuals with osteoarthritis (OA), but a longitudinal study in Arthritis & Rheumatology suggests NSAIDs contribute to cardiovascular side effects in these patients. The study matched 7,743 OA patients with 23,229 non-OA controls. The risk of developing cardiovascular disease among people with OA was 23% higher compared with people without OA. Among secondary outcomes assessed in the study, the risk of congestive heart failure was 42% higher among people with OA compared with people without OA, followed by a 17% greater risk of ischemic heart disease and a 14% greater risk of stroke. Investigators found that approximately 41% of the increased risk of cardiovascular disease among people with OA was mediated through their NSAID use. NSAIDs also played a substantial role in developing the study’s secondary outcomes. The results therefore emphasise the importance of discussing the risks and benefits of taking NSAIDs with people who have OA.

Long-term risk of recurrent VTE after anticoagulant discontinuation
Study estimating risk variation over time should aid treatment duration decisions

Optimal treatment duration in patients with a first unprovoked venous thromboembolism (VTE) is uncertain, making the decision to give patients indefinite anticoagulation or to stop treatment after the initial three to six months, a challenge. To inform the decision-making process, a systematic review and meta-analysis in The BMJ looked at the long-term risk of recurrent VTE and how it varies over time. The analysis, which included 18 studies involving 7,515 patients, found that in patients with a first episode of unprovoked VTE who completed at least three months of anticoagulant treatment, the risk of recurrent VTE was 10% in the first year after treatment, 16% at two years, 25% at five years, and 36% at 10 years, with 4% of recurrent VTE events resulting in death. The authors say this should inform clinical practice guidelines, enhance confidence in counselling patients of their prognosis, and help guide decision making about long-term management of unprovoked VTE. An accompanying editorial cautions that, while commendable, the research has some limitations and many questions about risk remain. It calls for “a new approach to generating evidence that uses data from every patient to inform safer managements for the next, in a cycle of continuous evidence building”.

Bariatric surgery linked with higher risk of adverse perinatal outcomes
Specialised preconception and antenatal nutritional support may be warranted

Obesity during pregnancy increases the risk of health complications for both mother and baby. While bariatric surgery before pregnancy improves obesity-related problems for the mother, it reduces the absorption of micronutrients that are needed for healthy foetal development. A systematic review and meta-analysis in PLOS Medicine, including 33 studies with 14,880 pregnancies post-bariatric surgery and 3,979,978 controls, investigated whether bariatric surgery was associated with adverse outcomes for the baby. The analysis identified a significant increase in odds of perinatal mortality, congenital anomalies, preterm birth, and neonatal intensive care unit admission but a decrease in odds of post-term birth after bariatric surgery. The odds of small babies were increased and the odds of large babies were decreased after malabsorptive bariatric surgery types. The findings suggest women of reproductive age undergoing bariatric surgery are a high-risk group and require specialised preconception and antenatal nutritional support to achieve the best outcomes for both mothers and babies. The authors call for further research to explore whether restrictive surgery results in better perinatal outcomes, compared to malabsorptive surgery, without compromising maternal outcomes. If so, these may be the preferred surgery for women of reproductive age.

Metformin vs insulin for gestational diabetes: what impact on growth?
Neonates with intrauterine exposure to metformin significantly smaller

Gestational diabetes (GDM) is a common pregnancy complication, affecting around one in seven pregnancies worldwide, and can be associated with adverse outcomes for both mothers and babies. Research in PLOS medicine sought to explore the effects that two of the treatment options, metformin and insulin, may have on foetal growth and also after birth into childhood. The systematic review looked at 28 studies that included 3,976 mothers randomised to metformin or insulin to treat GDM. Babies whose mothers were treated with metformin weighed on average 108 g less at birth than those whose mothers were treated with insulin, and had a lower risk of being born large (>90th centile) for their gestation at delivery. However, metformin-exposed infants were 0.44 kg heavier by 18–24 months than insulin-exposed infants, and they also had higher BMI (by 0.8 kg/m2) by mid-childhood (5–9 years) than insulin-exposed children. As such patterns of low birth weight and postnatal catch-up growth have been reported to be associated with adverse long-term cardio-metabolic outcomes, the authors are calling for further studies examining longitudinal perinatal and childhood outcomes following intrauterine metformin exposure.

The rise of the smart device ECG
What does it mean for clinicians?

While ambulatory ECG has been the cornerstone for the identification of clinically significant paroxysmal arrhythmia, its role with infrequent arrhythmia has been limited. With the emergence of smartphone-based ECG devices, two cardiologists writing in Heart examined the evidence base. They focused on AliveCor Kardia, one or two devices recently rejected by NICE for routine adoption in the NHS due to insufficient evidence. The authors point out that cardiologists are nevertheless more and more likely to see these easily available devices. According to the paper, the evidence seems to indicate that the device, which produces a single-lead rhythm strip comparable to Lead 1 of a standard ECG, would primarily be suitable for the detection of AF, although other significant arrhythmias may also be detected. While highlighting the need for further research, the authors express their optimism regarding the potential of smart device ECG recording and the role it could have in the future.

Author's Image

Tertius Lydgate

Originally from Northumberland, Tertius Lydgate studied medicine in Edinburgh, London and Paris. There he developed a special interest in communicable diseases and hoped to make great advances in treating and preventing them. But, after a promising start in a provincial centre of excellence in middle England, he was forced by circumstances (please, don't inquire) to abandon his high ideals. He now scrapes a living by pouring cold water on the over-enthusiastic at his private cryohydrotherapy clinic. Dreaming of the contributions he once hoped to make himself, he finds consolation in the latest medical journals and is happy to share his discoveries with his readers. He thinks that his creator, George Eliot, would have approved.
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