Tramadol associated with greater risk of hypoglycaemia

Find out about key research findings, of relevance to primary care, which have been published this month in major medical journals.
Tramadol associated with greater risk of hypoglycaemia

Tramadol associated with greater risk of hypoglycaemia
Retrospective analysis suggests significant association in contrast to other opioids

US research published in Scientific Reports, which analysed over 12 million adverse drug reaction reports from the United States FDA Adverse Event Reporting System, found a significant association of tramadol use with hypoglycaemia. The findings show there was a 10-fold greater risk of hypoglycaemia using tramadol than virtually every other opioid. Among eleven opioids, four serotonin and norepinephrine reuptake inhibitors (SNRIs) and five N-methyl-D-aspartate receptors (NMDAR)-antagonists that were analysed, only methadone was associated with hypoglycaemia similarly to tramadol. Recognised adverse drug reactions associated with tramadol include dizziness, nausea, headaches and constipation -- all common side effects of opioids. More serious but rarer adverse drug reactions include serotonin syndrome and increased seizure risk. The link to hypoglycaemia is relatively new, though the authors note it had been previously suggested by case studies and animal model testing. While this study underscores an association between tramadol and hypoglycaemia, a large, randomised, controlled clinical trial would be needed to definitively establish causality.

Vegetarian and pescetarian diets linked to lower risk of CHD
But vegetarians may have higher risk of stroke than meat eaters

People are increasingly turning to vegetarian and vegan diets, and while previous studies suggested vegetarians have a lower risk of coronary heart disease (CHD) than non-vegetarians, little has been reported on stroke risk difference. A prospective cohort study in The BMJ therefore looked at the incidence of CHD in 48,188 participants over 45 years of age, with no history of CHD or stroke, and classified into three diet groups: meat eaters (n=24,428), pescetarians (n=7,506), and vegetarians, including vegans (n=16,254). Over 18.1 years follow-up, and taking into account potentially influential factors, pescetarians and vegetarians had a 13% and 22% lower risk of CHD than meat eaters, respectively, which the authors say is possibly due in part to the lower BMI and lower rates of high blood pressure, high blood cholesterol and diabetes linked with these diets. However, vegetarians and vegans had a 20% higher risk of stroke than meat eaters, which the authors note may be due to the lower circulating cholesterol and levels of several nutrients (e.g. vitamin B12) in the vegetarian/vegan participants. Nevertheless, a linked editorial suggests the study’s stroke risk should be kept in perspective as “it is based on results from just one study and the increase is modest relative to meat eaters”.

H. pylori eradication, vitamins and garlic
Follow-up study suggests potential opportunities for gastric cancer prevention

The extended follow-up of a Chinese randomised intervention trial, including 3,365 participants, and published in The BMJ, has added some weight to the potential role of Helicobacter pylori treatment, vitamin and garlic supplementation in the prevention of gastric cancer. While initial findings at 15 years follow-up only found statistically significant reduction in incidence of gastric cancer with H. pylori treatment with amoxicillin and omeprazole for two weeks, extended follow up to just over 22 years showed that it was also true for vitamin C, E, and selenium supplementation. All three interventions also showed significant reductions in gastric cancer mortality with fully adjusted hazard ratio of 0.62 (95% CI 0.39 to 0.99) for H. pylori treatment, 0.48 (0.31 to 0.75) for vitamin supplementation, and 0.66 (0.43 to 1.00) for garlic supplementation (extract and oil). The authors note further research is now needed to confirm the favourable effects of the interventions and identify any possible risks.

Efficacy and safety profile of anti-VEGFs in retinopathy of prematurity
Ranibizumab 0.2 mg might be superior to laser therapy

Anti-vascular endothelial growth factor agents are increasingly being used for the treatment of retinopathy of prematurity (ROP), yet data on their efficacy and safety are scarce. So, an open-label randomised controlled trial in The Lancet sought to evaluate the profile of intravitreal ranibizumab. Some 225 eligible infants with birthweight less than 1500 g were randomly assigned to either single bilateral intravitreal dose of ranibizumab 0.2 mg, 0.1 mg, or laser therapy. A total of 214 infants were assessed for the primary outcome (n=70, n=76, n=68, respectively). Treatment success occurred in 80% of infants in the ranibizumab 0.2 mg group compared with 75% and 66% in the ranibizumab 0.1 mg and laser therapy groups respectively. Compared with laser therapy, the odds ratio (OR) of treatment success following ranibizumab 0.2 mg was 2.19 (95% Cl 0.99–4.82,), and 1·57 (95% Cl 0.76–3.26) following ranibizumab 0.1 mg; the OR for ranibizumab 0.2 mg compared with 0.1 mg was 1.35 (95% Cl 0.61–2.98). One infant had an unfavourable structural outcome following ranibizumab 0.2 mg, compared with five following ranibizumab 0.1 mg and seven after laser therapy. Ranibizumab 0.2 mg might therefore be superior to laser therapy in the treatment of ROP.

The role of calcium supplementation before or early in pregnancy
The jury is out

While it is established that calcium supplementation in the second half of pregnancy reduces the serious consequences of pre‐eclampsia, it has limited effect on the overall risk of pre‐eclampsia. A Cochrane review sought to determine whether calcium supplementation before, and in early pregnancy (before 20 weeks' gestation) had added benefit not only on pre‐eclampsia and but also other hypertensive disorders, maternal morbidity and mortality, and foetal and neonatal outcomes. The findings from the single eligible study identified (n=1,3555 women) suggest calcium supplementation before and early in pregnancy may reduce the risk of women experiencing the composite outcome pre‐eclampsia or pregnancy loss at any gestational age, but the results are inconclusive for all other outcomes for women and babies. The authors conclude current evidence can neither supports nor refutes the routine use of calcium supplementation before conception and in early pregnancy and further research is therefore required.

Revealing the cause of 35 years of cranial pain
BMJ case report highlights the importance of considering occult oral pathologies

A BMJ Case Report describes the case of a 64-year-old man attending the neurology outpatient clinic for severe chronic migraine headache for the last 35 years without proper response to multiple analgesic agents. During this time, he had several dental extractions and restorations. The patient was eventually diagnosed with a chronic migraine headache without aura that was persistently prolonged by multiple oral facial pathologies that involved the trigeminal nervous system. Relevant treatment included surgical removal of necrotic teeth with dental abscesses and restoration of carious teeth with amalgam/composite. Antibiotic and analgesic therapy was administrated accordingly and successfully. The authors note that the ability of oral pathologies to cause or contribute to the prolongation of the headache was overlooked in this case, highlighting the importance of a multidisciplinary approach.

‘Care navigation’ – what’s behind the buzz word?
If you’re confused, patients may be too

A cross-sectional study in the BJGP defines care navigation as “an avenue to link patients to activities or organisations that can help address non-medical needs affecting health and wellbeing”. While there is a policy steer to engaging patients in social prescribing, using some form of care navigator to help with this, results from the study highlight that, although this type of role is being provided, its implementation is heterogeneous across primary care in England. Responses to a questionnaire sent to clinical commissioning groups (CCGs) showed that over 90% of CCGs had some form of care navigation running in their area, but a total of 75 different titles were used to describe the role. Most services were open to all adult patients, though particular groups may have been targeted; for example, people who are older and those with long-term conditions. Referrals tended to be made by a professional, or people were identified by a receptionist when they presented to a surgery. Evaluation of care navigation services was limited. The authors note that these differences may leave patients unsure about what care navigation is about and how it could help them.

Are we working ‘at scale’?
And how will PCNs integrate with those organisations which are?

Over the last five years, national policy has encouraged general practices to serve populations of > 30,000 people (called ‘working at scale’) by collaborating with other practices. An observational study in the BJGP looked at the available data to determine how many English general practices were. It found that approximately 55% of practices (serving 33.5 million patients) were working at scale, individually or collectively serving populations of > 30,000 people. Organisational models representing close collaboration for the purposes of core general practice services were identifiable for approximately 5% of practices; and approximately 50% of practices were working in looser forms of collaboration, focusing on services beyond core general practice. However, better records of what is happening at practice level are needed to evaluate the effect of working at scale on patient care. The authors also highlight the uncertainty about how Primary Care Networks, which will go beyond general practice and attempt to integrate across community services, will be integrated with existing primary care organisations working at scale, especially when these are not defined by shared geography and links with other parts of the health and social care system.