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On The Pulse - August 2018

On The Pulse

Tertius Lydgate

Friday, 31 August 2018

Early detection of multiple myeloma
Myeloma is often difficult to diagnose and patients have the longest intervals from initial symptom reporting to diagnosis of all common cancers, with the most consultations in primary care before referral. A matched case–control study in the BJGP set out to identify which blood tests are useful in suggesting (LR+ = ≥5) or excluding (LR− = ≤0.2) a diagnosis of myeloma. Results from the blood tests of 2,703 cases and 12,157 matched controls, analysed up to five years before diagnosis, showed that plasma viscosity (PV) (LR+ = 2.0) and erythrocyte sedimentation rate (ESR) (LR+ = 1.9) are better for both ruling in and ruling out the disease compared with C-reactive protein (LR+ 1.2). The test combination with the lowest LR− was all normal haemoglobin with calcium and PV, which had an LR− = 0.06, though the LR− for normal haemoglobin and PV together was 0.12. The authors conclude that a combination of a normal ESR or PV and normal haemoglobin is a simple rule-out approach for patients currently being tested in primary care.

ADHD treatments
As controversies remain on the benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD), two systematic reviews published this month looked at treatment profiles. The first, in The Lancet Psychiatry, looked at 133 double-blind randomised controlled trials comparing amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo. Taking into account both efficacy and safety, the authors conclude that the evidence supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred first-choice medications for the short-term treatment of ADHD. But they call for new research to assess the long-term effects of these drugs. The second review, in the Cochrane Library, included 19 studies examining the efficacy and safety of three types amphetamines for adults with ADHD. While the authors caution that overall the evidence generated by the review is of low or very low quality, they concur that amphetamines improved the severity of ADHD symptoms, as assessed by clinicians or patients, in the short term. However, these drugs did not improve retention to treatment and were associated with higher attrition due to adverse events.

ADHD and asthma
A systematic review and meta-analysis in The Lancet Psychiatry aimed to investigate emerging evidence of a possible association between hyperactivity disorder (ADHD) and asthma. The researchers identified 2,649 potentially eligible citations, from which they obtained 49 datasets including a total of 210,363 participants with ADHD and 3,115,168 without. The pooled unadjusted odd ratio (OR) was 1·66 and the pooled adjusted OR was 1·53, indicating a significant association between asthma and ADHD. Possible lack of representativeness of the study population was detected with the Newcastle-Ottawa Scale in 42 of 49 datasets. The population-based study included 1,575,377 individuals of whom 16.5% had asthma and 3·7% had ADHD. Asthma was significantly associated with ADHD (OR 1·60) in the crude model adjusting for sex and year of birth, and this association remained significant after simultaneous adjustment for all covariates. The authors say awareness of this association might help to reduce delay in the diagnosis of both ADHD and asthma.

Acupuncture for menstrual disorders
Menstrual disorders are relatively common problems in adolescent girls. A case and systematic review suggest how acupuncture may help. The BMJ Case Reports describe the case of a 17-year-old girl with a history of dysfunctional uterine bleeding (DUB) and severe dysmenorrhoea who was treated with different conventional hormonal therapies for 16 months without improvement. Treatment with traditional Chinese acupuncture was started while she was taking oral contraceptives. She received a total of 27 treatments in 17 weeks. Her menstrual cycle normalised after four weeks (10 treatments). She continued to be regular during the rest of treatments and to date, six months after the treatment was discontinued. The outcome prompted the author to call for research of carefully controlled trials on irregular bleeding to assess alternative and complementary medicine treatment effectiveness on menstrual heaviness and intervals. A separate Cochrane review looking at benefits of acupuncture and acupressure on premenstrual syndrome (PMS) concludes these may improve both physical and psychological symptoms of PMS when compared to a sham control but that further research is required due to the limited evidence available.

Effects of e-cigarette vapour condensate
Researchers writing in Thorax are cautioning against “the widely held opinion that e-cigarettes are safe”. As controversies on e-cigarettes’ safety remain, the authors point out that much of the current literature has focused on the effect of non-vapourised e-cigarette liquid (ECL) or ECL condensate. So they conducted a small experimental study comparing the effect of unvaped eECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function in an acute in vitro system. Results suggest ECVC is significantly more toxic to AMs than non-vaped ECL. Excessive production of reactive oxygen species, inflammatory cytokines and chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. The researchers say a significant increase in cytotoxicity caused by the vaping process itself and exposure of macrophages to ECVC induced many of the same cellular and functional changes in AM function seen in cigarette smokers and patients with COPD. Authors call for further research to understand the effects of e-cigarette exposure in humans in vivo.

Low 10-year CVD risk
Clinical trials evaluating lipid-lowering therapy for primary prevention of cardiovascular disease (CVD) have typically focused on individuals at moderate or high risk for CVD. An observational study in Circulation looked at the associations of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein-cholesterol (HDL-C) with CVD and coronary heart disease (CHD) mortality in a low 10-year risk cohort of 36,375 participants (72% men, median age 42) who were free of diabetes or CVD and were followed for 27 years. Some 1,086 CVD and 598 coronary heart disease deaths occurred. The findings showed that LDL-C and non–HDL-C ≥160 mg/dL were independently associated with a 50% to 80% increased relative risk of CVD mortality. The authors conclude the findings may have implications for future cholesterol treatment paradigms and recommend that those with low risk should pursue lifestyle interventions, such as diet and exercise, to achieve LDLs levels as low as possible, preferably under 100 mg/dL.

Blood test to detect kidney cancer
Caught early, the five-year survival rate for renal cell carcinoma (RCC) is more than 90%, but rates are much poorer for stages III and IV at 50% and 10% respectively. Researchers writing in Clinical Cancer Research found that plasma kidney injury molecule-1 (KIM-1), which has been shown to be elevated in RCC patients, could represent a means of detecting RCC prior to clinical diagnosis. They measured KIM-1 concentrations in pre-diagnostic plasma from 190 RCC cases and 190 matched controls nested within a population-based prospective cohort study that cases had entered up to five years before diagnosis. They found that the average concentration of KIM-1 was double in those eventually diagnosed with RCC and that, compared with a risk model including known risk factors of RCC, a risk model additionally including KIM-1 approximately doubled the model’s accuracy. The study concludes that plasma KIM-1 concentrations could predict RCC incidence up to five years prior to diagnosis, but the study lead author explains they “don’t expect that KIM-1 will be useful as a screening test, as risk of RCC in the general population is low. KIM-1 is more likely to be relevant in high-risk populations or as an adjunct to other diagnostic procedures.”

Closed-loop insulin delivery in non-critical care
Achieving recommended glycaemic targets in hospitalised diabetic patients can be difficult. Research in the NEJM set out to determine whether a closed-loop delivery system, combining glucose-sensing and insulin-delivery components to provide real-time glucose-responsive insulin administration, could improve control in type 2 diabetes patients in non-critical care. For this randomised, open-label trial, 136 adults with type 2 diabetes who required subcutaneous insulin therapy were assigned to receive either closed-loop insulin delivery (n=70) or conventional subcutaneous insulin therapy, according to local clinical practice (n=66). Closed-loop insulin-delivery system resulted in significantly better glycaemic control than conventional subcutaneous insulin therapy, without a higher risk of hypoglycaemia. The mean (±SD) percentage of time that the sensor glucose measurement was in the target range was 65.8±16.8% in the closed-loop group and 41.5±16.9% in the control group, a difference of 24.3±2.9 percentage points; values above the target range were found in 23.6±16.6% and 49.5±22.8% of the patients, respectively, a difference of 25.9±3.4 percentage points.

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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