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On The Pulse – March 2019

On The Pulse

Tertius Lydgate

Friday, 29 March 2019

Diagnosing brain tumours in primary care
Brain tumours are difficult to diagnose in primary care as they are uncommon and often present with non-specific symptoms. A qualitative study in The BJGP explored the experiences of 39 adults recently diagnosed with a primary brain tumour, and their family members, with regards to symptom appraisal, help seeking, and routes to diagnosis. The interviews revealed multiple subtle changes and frequent GP visits often precede brain tumour diagnosis, giving possible diagnostic opportunities for GPs. Few participants (n= 7; 18%) presented as an emergency without having had a previous GP consultation. The subtle ‘changes’, often noticed by others rather than the patient, frequently led to loss of interest or less ability to engage with daily living activities. The most common changes were in cognition (speaking, writing, comprehension, memory, concentration, and multitasking), sleep, and other ‘head feelings’ such as dizziness. Not all patients experienced a seizure, and few seizures were experienced ‘out of the blue’. Quality of communication in GP consultations played a key role in patients’ subsequent symptom appraisal and the timing of their decision to re-consult. The authors conclude that refined community symptom awareness and GP guidance could enable more direct pathways to diagnosis, and potentially improve patient experiences and outcomes.

The risks of testosterone
Testosterone replacement therapy has increased globally, yet evidence of its role in cardiovascular disease is unclear. Researchers writing in The BMJ sought out to determine whether endogenous testosterone had a causal role in thromboembolism, heart failure, and myocardial infarction by conducting a mendelian randomisation study using genetic variants as instrumental variables, randomly allocated at conception, to infer causality as additional randomised evidence. Of the UK Biobank participants, which included 392,038 white British men and women aged 40-69, 13,691 had thromboembolism (6,208 men; 7,483 women), 1,688 heart failure (1,186; 502), and 12,882 myocardial infarction (10,136; 2746). In men, endogenous testosterone genetically predicted by variants in the JMJD1C gene region was positively associated with thromboembolism and heart failure, but not myocardial infarction. Associations were less obvious in women. In the validation study, which included 171,875 participants of about 77% European descent, genetically predicted testosterone was positively associated with myocardial infarction. The results suggest sex hormone related mechanisms have a role in thromboembolism, heart failure, and myocardial infarction, and the authors suggest endogenous testosterone could be a modifiable risk factor for thromboembolism and heart failure.

Postmenopausal hormone therapy and risk of Alzheimer’s disease
So far, clinical data on the association between the use of postmenopausal hormone therapy and the risk of Alzheimer’s disease (AD) have been conflicting. A nationwide case-control study in The BMJ set out to better understand the association by comparing the use of hormone therapy between Finnish postmenopausal women with (n=84,739) and without (matched controls, n=84,739) a diagnosis of AD. 83,688 (98.8%) women were diagnosed at age 60 or more; 47,239 (55.7%) at 80+. Systemic hormone therapy was associated with a 9-17% increased risk of AD. The risk of the disease did not differ significantly between users of oestradiol only and those of oestrogen-progestogen. The risk increases in users of oestrogen-progestogen therapy were not related to different progestogens; but in women younger than 60 at hormone therapy initiation, these risk increases were associated with hormone therapy exposure over 10 years. The age at initiation of systemic hormone therapy was not a decisive determinant for the increase in risk of AD. Of note, the exclusive use of vaginal oestradiol did not affect the risk of the disease. The authors highlight that although the absolute risk increase for AD is small, the data should be implemented into information for present and future users of hormone therapy.

Depression risk higher in primary care patients with inflammatory disorders
Although research suggests a contributory role of inflammation in the initiation of depression and anxiety in patients with chronic inflammatory disorders, evidence has so far been inconsistent. A prospective cohort study in the Annals of Rheumatic Diseases, including 538,707 patients from primary care, revealed a significant increment in the onset of new depression and anxiety events within organ-specific and multisystemic inflammatory disorders. The incidence of depression ranged from 14 per 1,000 person-years (severe psoriasis) to 9 per 1,000 person-years (systemic vasculitis), substantively higher compared with their comparison group (5–7 per 1,000 person-years). Hazard ratios (HR) of multiple depression and anxiety events were 16% higher within inflammatory disorders compared with the matched comparison group. The incidence of depression and anxiety was strongly associated with the age at inflammatory disorder onset. The overall HR estimate for depression was 1.90 (95% CI 1.66 to 2.17) within early-onset disorder (<40 years of age) and 0.93 (95% CI 0.90 to 1.09) within late-onset disorder (≥60 years of age). Although the study does not demonstrate a causal relationship between inflammation and depression and anxiety, the authors recommend clinicians should be vigilant for early symptoms of depression or anxiety in this highly at-risk group of patients.

Symptom management for medically unexplained symptoms
Caring for patient with medically unexplained symptoms (MUS) can be a real challenge in primary care. A qualitative study in the BJGP sought to describe the management strategies used by GPs when confronted with patients with MUS in daily practice. Videos and transcripts of 39 general practice consultations revealed 105 management strategies. Nearly half concerned symptom management; the remainder included medication, referrals, additional tests, follow-up consultations, and watchful waiting. Six themes of symptom management strategies emerged from the data: cognitions and emotions, interaction with health professionals, body focus, symptom knowledge, activity level, and external conditions. Advice on symptom management was often non-specific in terms of content, and ambiguous in terms of communication. Symptom management therefore appears to be a considerable part of the care of MUS in general practice and the authors suggest GPs might benefit from support in how to promote symptom management in specific and unambiguous terms.

Chlorhexidine bathing in non-critical-care units
While universal skin and nasal decolonisation is known to reduce multidrug-resistant pathogens and bloodstream infections in intensive care units, is it more effective than routine bathing in non-critical care units? To answer this question, researchers writing in The Lancet randomised 53 hospital and assigned their participating non-critical-care units (n=194) to either routine care or daily chlorhexidine bathing for all patients plus mupirocin for known methicillin-resistant Staphylococcus aureus (MRSA) carriers. The 21-month intervention period included 339,902 patients: 156,889 and 183,013 in the routine care and decolonisation groups respectively. For the primary outcome of unit-attributable MRSA-positive or vancomycin-resistant enterococcus positive clinical cultures, the hazard ratio (HR) for the intervention period versus the baseline period was 0·79 (0·73–0·87) in the decolonisation group versus 0·87 (95% CI 0·79–0·95) in the routine care group. No difference was seen in the relative HRs. There were 25 (<1%) adverse events, all involving chlorhexidine, among 183,013 patients in units assigned to chlorhexidine, and none were reported for mupirocin. Decolonisation with universal chlorhexidine bathing and targeted mupirocin for MRSA carriers did not therefore appear to significantly reduce multidrug-resistant organisms in non-critical-care patients.

Spinal manipulative therapy for the treatment of chronic low back pain
Low back pain is a common disorder and the role of non-drug interventions for its treatment is not without dispute. The BMJ published a systematic review and meta-analysis of 47 randomised controlled trials, including a total of 9,211 participants (35-60 years), to assess the benefits and harms of spinal manipulative therapy (SMT). It showed SMT produces similar effects to recommended therapies for chronic low back pain and seems to be better than non-recommended interventions for improvement in function in the short term. About half of the studies examined adverse and serious adverse events, but in most of these it was unclear how and whether these events were registered systematically; information is therefore limited. Most of the observed adverse events were musculoskeletal related, transient in nature, and of mild to moderate severity. One study with a low risk of selection bias and powered to examine risk (n=183) found no increased risk of an adverse event or duration of the event compared with sham SMT. However, in one study, the Data Safety Monitoring Board judged one serious adverse event to be possibly related to SMT. The authors conclude clinicians should inform their patients of the potential risks of adverse events associated with SMT.

The effect of the Mediterranean diet on CVD prevention
Observational studies have confirmed the benefits of adherence to a Mediterranean dietary pattern on cardiovascular disease (CVD) risk factors, but clinical trial evidence is more limited. The Cochrane Library reviewed 30 randomised controlled trials (RCTs) (49 papers; 12,461 participants) looking at the effects on CVD prevention of a Mediterranean-style diet, comprising both of the following key components: a high monounsaturated/saturated fat ratio and a high intake of plant‐based foods, including fruits, vegetables and legumes. The authors found that despite the relatively large number of studies included in the review, there is still some uncertainty regarding the effects of a Mediterranean‐style diet on clinical endpoints and CVD risk factors for both primary and secondary prevention. The quality of evidence for the modest benefits on CVD risk factors in primary prevention is low or moderate, with a small number of studies reporting minimal harms. Further adequately powered primary prevention trials are therefore needed to confirm findings on clinical endpoints to date. They also note a paucity of evidence for secondary prevention. However, seven studies that are still ongoing and have been identified and their results may provide more certainty 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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