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On The Pulse - December 2018

On The Pulse

Tertius Lydgate

Friday, 14 December 2018

How to jingle all the weight this Christmas?
Festive periods such as the Christmas holiday season are likely to result in weight gain for many of us. But if these weight gains are not fully lost in the following months, researchers writing in The BMJ suggest this can lead to a 5-10 kg increase in body weight over 10 years. Against a backdrop of global obesity epidemic, they conducted a randomised controlled trial in the UK to assess the effectiveness of a brief behavioural intervention involving regular self-weighing, weight management advice, and information about the amount of physical activity required to expend the calories in festive foods and drinks, to prevent weight gain over the Christmas holiday period. Participants in the intervention group (n=136) and comparator group (which only received a leaflet on healthy living, n=136) had a mean weight change of −0.13kg (95% CI −0.4 to 0.15) and 0.37 kg (0.12 to 0.62) respectively. The adjusted mean difference in weight (intervention−comparator) was −0.49 kg (95% CI −0.85 to −0.13). The authors call on policy makers to consider these results to prevent weight gain in the population during high risk periods such as holidays.

December holiday period: vulnerable time for discharged patients?
Following research on the so-called “weekend effect”, a Canadian cohort study in The BMJ set out to determine whether patients discharged from hospital during the December holiday period have fewer outpatient follow-ups and higher rates of death or readmission than patients discharged at other times. Participants included 217,305 children and adults discharged home after an urgent admission, during the two-week December holiday period, compared with 453,641 children and adults discharged during two control periods in late November and January. The baseline characteristics of both patient groups did not differ meaningfully. Yet, patients discharged during the December holiday period had an increased risk of death or readmission within seven days (13.2% v 11.7%), 14 days (18.6% v 17.0%), and 30 days (25.9% v 24.7%). Patients discharged during the holiday period were less likely to have an outpatient follow-up visit with a physician within seven or 14 days of discharge (36.3% v 47.8% and 59.5% v 68.7%, respectively). The authors point out that the relation between discharge from hospital during the holiday period and death or readmission might be explained in several ways and that their study did not test if differences in follow-up explain the association between discharge during the holiday period and death or readmission.

Effectiveness of the Epley manoeuvre in primary care
The Epley manoeuvre is commonly performed in a primary care setting, but the evidence for its effectiveness is limited. A group of researchers from Spain attempted to evaluate outcomes for patients in a multicentre, double-blind randomised controlled trial in the BJGP. They studied 134 patients, who were over 18, with subjective or objective benign paroxysmal positional vertigo. One group received the standard Epley manoeuvre and the other received a sham manoeuvre with both groups then prescribed betahistine. Dix Hallpike testing (DHT) stratified the groups into negative (neither vertigo or nystagmus) or positive. Positive results were further divided into a positive result for both vertigo and nystagmus (positive DHT with nystagmus), and a positive result for vertigo only (positive DHT without nystagmus). In addition, patients were given a rating scale to complete on resolution or severity of vertigo. The intervention group showed better results in the unadjusted analyses at one week, with a lower rate of positive DHT with nystagmus. The group with a positive baseline DHT with nystagmus was associated with a reduction in vertigo severity and better positive DHT rates in the intervention group (adjusted OR 0.09, 95% CI 0.01 to 0.92). Thus, the authors concluded that the Epley manoeuvre seems more effective if patients have a positive DHT or baseline nystagmus, suggesting this is of key importance prior to commencing treatment.

New scoring system for bleeding risk with NOACs
Oral anticoagulation is an important treatment to reduce the risk of strokes in patients with atrial fibrillation. Many patients are now treated with non-vitamin K oral anticoagulants (NOACs) which have gradually replaced vitamin K antagonists as drugs of choice. However, clinicians are cautious due to the risk of bleeding, and risk scores are routinely checked. But these scoring systems have not been derived from patients solely taking NOACs. Researchers writing in OpenHeart considered whether a simplified tool for assessing bleeding score may be of clinical use. They followed up 21,248 patients for a median time of 183 days looking at different numbers of independent risk factors. Ten independent risk factors for bleeding were identified, which when included in a risk prediction model achieved a C-index of 0.68 (95% CI 0.66 to 0.70). However, a three-variable simplified score based on age, history of bleeding and non-bleeding related hospitalisation in the last 12 months yielded similar results with a c-index of 0.66 (95% CI 0.65 to 0.68). Therefore, the authors propose that a more simplified bleeding risk score could provide much faster estimation for clinicians in practice.

LABA, LAMA, LABA/LAMA, LABA/ICS: which is most effective?
The Cochrane library has conducted a systematic review and network meta‐analysis to compare the efficacy and safety of available formulations from four different groups of inhalers: long‐acting β‐agonist (LABA)/long‐acting muscarinic antagonist (LAMA) combination, LABA/inhaled corticosteroid (ICS) combination, LAMA and LABA, in people with moderate to severe COPD. The study, which included a total of 101,311 participants from 99 studies, showed that the LABA/LAMA combination was the best treatment, followed by LAMA, in preventing flare‐ups, although there was some uncertainty in the results. Combination inhalers (LABA/LAMA and LABA/ICS), are more effective for controlling symptoms than single‐agent therapies (LAMA and LABA), in general. The LABA/LAMA combination was better than LABA/ICS combination, especially in people with a prior episode of flare‐ups. The LABA/ICS combination had a higher incidence of severe pneumonia compared to the others. The authors say that research and development of a new therapy, such as triple combination therapy, which would have a greater impact on controlling symptoms and preventing exacerbations, are much desired.

Incretin-based drugs and cholangiocarcinoma risk
Although a useful group of drugs for the management of diabetes, the incretin-based therapies have biological evidence that suggests they may be implicated in the development of the rare cancer, cholangiocarcinoma. A population-based study in The BMJ looked at 154,162 adults treated with this group of medicines over a 10-year period. Results showed that the use of DPP-4 inhibitors was associated with a 77% increased hazard of cholangiocarcinoma (HR 1.77, 95% CI 1.04 to 3.01). In addition, the use of GLP-1 receptor agonists was associated with an increased hazard with a wide confidence interval (HR 1.97, 0.83 to 4.66). When compared to sulfonylureas or thiazolidinediones using a post hoc pharmacovigilance analysis, there was an increased odd ratio for cholangiocarcinoma with both DPP-4 inhibitors and GLP-1 receptor agonists. The authors therefore conclude that there may be an increased risk of the development of this rare cancer in patients treated with this class of medicines.

Novel immunotherapies and adverse reactions
An observational study in The Lancet set out to provide a comprehensive report of the haematological immune-related adverse events (haem-irAEs) induced by the novel immunotherapies for cancer: anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies. Out of 948 patients screened, 35 patients (21 men and 14 women) with haem-irAEs related to anti-PD-1 or anti-PD-L1 were included in the study. The most common tumour types were melanoma (43%), non-small-cell lung cancer (34%), and lymphoma (11%). 57% of patients received nivolumab, 40% pembrolizumab, and 3% atezolizumab. Neutropenia, autoimmune haemolytic anaemia, and immune thrombocytopenia were the most common types of haem-irAE (26%), followed by pancytopenia or aplastic anaemia (14%), bicytopenia (6%), and pure red cell aplasia (3%). Haem-irAEs resolved in 60% of the 35 patients. 6% of patients died from febrile neutropenia during haem-irAE related to anti-PD-1. The authors conclude that haem-irAEs induced by PD-1 or PD-L1 inhibitors are rare but potentially life-threatening events and say investigations into earlier detection and better management are warranted.

A comparison of the most effective measures to reverse frailty
The prevalence of frailty is growing in the population with this group utilising significant amounts of healthcare budget. Identification with early warning risk tools have been used to find the cohort that would be best served by practical interventions. However, there is little data on the most effective measures in this group. A systematic review of frailty interventions in primary care, published in the BJGP, looked at 925 studies including a total of 15,690 participants. Effectiveness was scored in terms of change of frailty status or frailty indicators and ease of implementation in terms of human resources, marginal costs, and time requirements. A significant improvement of frailty status was demonstrated in 71% of studies and of frailty indicators in 69% of studies where measured. Interventions with both muscle strength training and protein supplementation were consistently placed highest for effectiveness and ease of implementation. The authors conclude that techniques to improve this were most likely to delay or reverse frailty and importantly, straightforward to put into clinical practice. 

Glycosylated haemoglobin: a false sense of security
The BMJ Case Reports describes the unusual case of a 37-year-old woman found to have a low glycosylated haemoglobin (HbA1c) despite having recently been diagnosed with diabetes mellitus type 2. The patient, who was not anaemic, with no symptoms or family history of haematological conditions, was subsequently found to have an elevated reticulocyte count, inferring increased red cell turnover as the culprit for the discordant HbA1c result. A diagnosis of hereditary spherocytosis was made based on characteristic peripheral blood film appearances and confirmed by eosin-5-maleimide binding test. Exposure of an undiagnosed haemolytic anaemia by virtue of a low HbA1c is uncommon. However, conditions that distort HbA1c measurements are not infrequent. The authors say that this case should serve to remind clinicians of the limitations of HbA1c in specified situations, and to remain vigilant when interpreting results.

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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