Non-steroidal anti-inflammatory drugs (NSAIDs) are a common cause of adverse drug events (ADEs), but renal risks of NSAIDs are less well quantified than gastrointestinal and cardiac risks. This paper ...reports a systematic review of published population-based observational studies examining the risk of acute kidney injury (AKI) associated with NSAIDs in community-dwelling adults and those with pre-existing chronic kidney disease (CKD).
MEDLINE and EMBASE databases were searched until June 2016, and 3789 papers screened. Ten studies reporting NSAID risk of AKI in the general population were included in random effects meta-analysis, of which five additionally reported NSAID risk in people with CKD.
In the general population, the pooled odds ratio (OR) of AKI for current NSAID exposure was 1.73 (95%CI 1.44 to 2.07), with somewhat higher risk observed in older people (OR 2.51, 95%CI 1.52 to 2.68). In people with CKD, individual study OR of AKI due to current NSAID exposure ranged from 1.12 to 5.25, with pooled estimate OR 1.63 (95% CI 1.22 to 2.19).
No study reported baseline risk of AKI in different populations meaning absolute risks could not be estimated, but baseline risk and therefore the absolute risk of NSAID exposure is likely to be higher in people with CKD and older people. Large population based studies measuring AKI using current definitions and estimating the absolute risk of harm are needed in order to better inform clinical decision making.
Cognitive impairment of various kinds is common in older people admitted to hospital, but previous research has usually focused on single conditions in highly-selected groups and has rarely examined ...associations with outcomes. This study examined prevalence and outcomes of cognitive impairment in a large unselected cohort of people aged 65+ with an emergency medical admission.
Between January 1, 2012, and June 30, 2013, admissions to a single general hospital acute medical unit aged 65+ underwent a structured specialist nurse assessment (n = 10,014). We defined 'cognitive spectrum disorder' (CSD) as any combination of delirium, known dementia, or Abbreviated Mental Test (AMT) score < 8/10. Routine data for length of stay (LOS), mortality, and readmission were linked to examine associations with outcomes.
A CSD was present in 38.5% of all patients admitted aged over 65, and in more than half of those aged over 85. Overall, 16.7% of older people admitted had delirium alone, 7.9% delirium superimposed on known dementia, 9.4% known dementia alone, and 4.5% unspecified cognitive impairment (AMT score < 8/10, no delirium, no known dementia). Of those with known dementia, 45.8% had delirium superimposed. Outcomes were worse in those with CSD compared to those without - LOS 25.0 vs. 11.8 days, 30-day mortality 13.6% vs. 9.0%, 1-year mortality 40.0% vs. 26.0%, 1-year death or readmission 62.4% vs. 51.5% (all P < 0.01). There was relatively little difference by CSD type, although people with delirium superimposed on dementia had the longest LOS, and people with dementia the worst mortality at 1 year.
CSD is common in older inpatients and associated with considerably worse outcomes, with little variation between different types of CSD. Healthcare systems should systematically identify and develop care pathways for older people with CSD admitted as medical emergencies, and avoid only focusing on condition-specific pathways such as those for dementia or delirium alone.
E-cigarette (EC) use is increasing exponentially worldwide. The early cardiovascular effects of switching from tobacco cigarettes (TC) to EC in chronic smokers is unknown. Meta-analysis of ...flow-mediated dilation (FMD) studies indicate 13% lower pooled, adjusted relative risks of cardiovascular events with every 1% improvement in FMD.
This study sought to determine the early vascular impact of switching from TC to EC in chronic smokers.
The authors conducted a prospective, randomized control trial with a parallel nonrandomized preference cohort and blinded endpoint of smokers ≥18 years of age who had smoked ≥15 cigarettes/day for ≥2 years and were free from established cardiovascular disease. Participants were randomized to EC with nicotine or EC without nicotine for 1 month. Those unwilling to quit continued with TC in a parallel preference arm. A propensity score analysis was done to adjust for differences between the randomized and preference arms. Vascular function was assessed by FMD and pulse wave velocity. Compliance with EC was measured by carbon monoxide levels.
Within 1 month of switching from TC to EC, there was a significant improvement in endothelial function (linear trend β = 0.73%; 95% confidence interval CI: 0.41 to 1.05; p < 0.0001; TC vs. EC combined: 1.49%; 95% CI: 0.93 to 2.04; p < 0.0001) and vascular stiffness (−0.529 m/s; 95% CI: −0.946 to −0.112; p = 0.014). Females benefited from switching more than males did in every between-group comparison. Those who complied best with EC switch demonstrated the largest improvement. There was no difference in vascular effects between EC with and without nicotine within the study timeframe.
TC smokers, particularly females, demonstrate significant improvement in vascular health within 1 month of switching from TC to EC. Switching from TC to EC may be considered a harms reduction measure. (Vascular Effects of Regular Cigarettes Versus Electronic Cigarette Use VESUVIUS; NCT02878421; ISRCTN59133298)
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Summary Background The prevalence of male obesity is increasing but few men take part in weight loss programmes. We assessed the effect of a weight loss and healthy living programme on weight loss in ...football (soccer) fans. Methods We did a two-group, pragmatic, randomised controlled trial of 747 male football fans aged 35–65 years with a body-mass index (BMI) of 28 kg/m2 or higher from 13 Scottish professional football clubs. Participants were randomly assigned with SAS (version 9·2, block size 2–9) in a 1:1 ratio, stratified by club, to a weight loss programme delivered by community coaching staff in 12 sessions held every week. The intervention group started a weight loss programme within 3 weeks, and the comparison group were put on a 12 month waiting list. All participants received a weight management booklet. Primary outcome was mean difference in weight loss between groups at 12 months, expressed as absolute weight and a percentage of their baseline weight. Primary outcome assessment was masked. Analyses were based on intention to treat. The trial is registered with Current Controlled Trials, number ISRCTN32677491. Findings 374 men were allocated to the intervention group and 374 to the comparison group. 333 (89%) of the intervention group and 355 (95%) of the comparison group completed 12 month assessments. At 12 months the mean difference in weight loss between groups, adjusted for baseline weight and club, was 4·94 kg (95% CI 3·95–5·94) and percentage weight loss, similarly adjusted, was 4·36% (3·64–5·08), both in favour of the intervention (p<0·0001). Eight serious adverse events were reported, five in the intervention group (lost consciousness due to drugs for pre-existing angina, gallbladder removal, hospital admission with suspected heart attack, ruptured gut, and ruptured Achilles tendon) and three in the comparison group (transient ischaemic attack, and two deaths). Of these, two adverse events were reported as related to participation in the programme (gallbladder removal and ruptured Achilles tendon). Interpretation The FFIT programme can help a large proportion of men to lose a clinically important amount of weight; it offers one effective strategy to challenge male obesity. Funding Scottish Government and The UK Football Pools funded delivery of the programme through a grant to the Scottish Premier League Trust. The National Institute for Health Research Public Health Research Programme funded the assessment (09/3010/06).
Bell's palsy is an acute unilateral facial paralysis of unknown aetiology and should only be used as a diagnosis in the absence of any other pathology. As the proposed pathophysiology is swelling and ...entrapment of the nerve, some surgeons suggest surgical decompression of the nerve as a possible management option; this is ideally performed as soon as possible after onset. This is an update of a review first published in 2011, and last updated in 2013. This update includes evidence from one newly identified study.
To assess the effects of surgery in the early management of Bell's palsy.
On 20 March 2020, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO ICTRP. We handsearched selected conference abstracts for the original version of the review.
We included all randomised controlled trials (RCTs) or quasi-RCTs involving any surgical intervention for Bell's palsy. Trials compared surgical interventions to no treatment, later treatment (beyond three months), sham treatment, other surgical treatments or medical treatment.
Three review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. We used standard methodological procedures expected by Cochrane. The primary outcome was complete recovery of facial palsy at 12 months. Secondary outcomes were complete recovery at three and six months, synkinesis and contracture at 12 months, psychosocial outcomes at 12 months, and side effects and complications of treatment.
Two trials with 65 participants met the inclusion criteria; one was newly identified at this update. The first study randomised 25 participants into surgical or non-surgical (no treatment) groups using statistical charts. One participant declined surgery, leaving 24 evaluable participants. The second study quasi-randomised 53 participants; however, only 41 were evaluable as 12 declined the intervention they were allocated. These 41 participants were then divided into early surgery, late surgery or non-surgical (no treatment) groups using alternation. There was no mention on how alternation was decided. Neither study mentioned if there was any attempt to conceal allocation. Neither participants nor outcome assessors were blinded to the interventions in either study. There were no losses to follow-up in the first study. The second study lost three participants to follow-up, and 17 did not contribute to the assessment of secondary outcomes. Both studies were at high risk of bias. Surgeons in both studies used a retro-auricular/transmastoid approach to decompress the facial nerve. For the outcome recovery of facial palsy at 12 months, the evidence was uncertain. The first study reported no differences between the surgical and no treatment groups. The second study fully reported numerical data, but included no statistical comparisons between groups for complete recovery. There was no evidence of a difference for the early surgery versus no treatment comparison (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.05 to 11.11; P = 0.84; 33 participants; very low-certainty evidence) and for the early surgery versus late surgery comparison (RR 0.47, 95% CI 0.03 to 6.60; P = 0.58; 26 participants; very low-certainty evidence). We considered the effects of surgery on facial nerve function at 12 months very uncertain (2 RCTs, 65 participants; very low-certainty evidence). Furthermore, the second study reported adverse effects with a statistically significant decrease in lacrimal control in the surgical group within two to three months of denervation. Four participants in the second study had 35 dB to 50 dB of sensorineural hearing loss at 4000 Hz, and three had tinnitus. Because of the small numbers and trial design we also considered the adverse effects evidence very uncertain (2 RCTs, 65 participants; very low-certainty evidence).
There is very low-certainty evidence from RCTs or quasi-RCTs on surgery for the early management of Bell's palsy, and this is insufficient to decide whether surgical intervention is beneficial or harmful. Further research into the role of surgical intervention is unlikely to be performed because spontaneous or medically supported recovery occurs in most cases.
High-risk prescribing and preventable drug-related complications are common in primary care. We evaluated whether the rates of high-risk prescribing by primary care clinicians and the related ...clinical outcomes would be reduced by a complex intervention.
In this cluster-randomized, stepped-wedge trial conducted in Tayside, Scotland, we randomly assigned participating primary care practices to various start dates for a 48-week intervention comprising professional education, informatics to facilitate review, and financial incentives for practices to review patients' charts to assess appropriateness. The primary outcome was patient-level exposure to any of nine measures of high-risk prescribing of nonsteroidal antiinflammatory drugs (NSAIDs) or selected antiplatelet agents (e.g., NSAID prescription in a patient with chronic kidney disease or coprescription of an NSAID and an oral anticoagulant without gastroprotection). Prespecified secondary outcomes included the incidence of related hospital admissions. Analyses were performed according to the intention-to-treat principle, with the use of mixed-effect models to account for clustering in the data.
A total of 34 practices underwent randomization, 33 of which completed the study. Data were analyzed for 33,334 patients at risk at one or more points in the preintervention period and for 33,060 at risk at one or more points in the intervention period. Targeted high-risk prescribing was significantly reduced, from a rate of 3.7% (1102 of 29,537 patients at risk) immediately before the intervention to 2.2% (674 of 30,187) at the end of the intervention (adjusted odds ratio, 0.63; 95% confidence interval CI, 0.57 to 0.68; P<0.001). The rate of hospital admissions for gastrointestinal ulcer or bleeding was significantly reduced from the preintervention period to the intervention period (from 55.7 to 37.0 admissions per 10,000 person-years; rate ratio, 0.66; 95% CI, 0.51 to 0.86; P=0.002), as was the rate of admissions for heart failure (from 707.7 to 513.5 admissions per 10,000 person-years; rate ratio, 0.73; 95% CI, 0.56 to 0.95; P=0.02), but admissions for acute kidney injury were not (101.9 and 86.0 admissions per 10,000 person-years, respectively; rate ratio, 0.84; 95% CI, 0.68 to 1.09; P=0.19).
A complex intervention combining professional education, informatics, and financial incentives reduced the rate of high-risk prescribing of antiplatelet medications and NSAIDs and may have improved clinical outcomes. (Funded by the Scottish Government Chief Scientist Office; ClinicalTrials.gov number, NCT01425502.).
Study question What is the predicted risk of acute kidney injury after orthopaedic surgery and does it affect short term and long term survival? Methods The cohort comprised adults resident in the ...National Health Service Tayside region of Scotland who underwent orthopaedic surgery from 1 January 2005 to 31 December 2011. The model was developed in 6220 patients (two hospitals) and externally validated in 4395 patients from a third hospital. Several preoperative variables were selected for candidate predictors, based on literature, clinical expertise, and availability in the orthopaedic surgery setting. The main outcomes were the development of any severity of acute kidney injury (stages 1-3) within the first postoperative week, and 90 day, one year, and longer term survival. Study answer and limitations Using logistic regression analysis, independent predictors of acute kidney injury were older age, male sex, diabetes, number of prescribed drugs, lower estimated glomerular filtration rate, use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and American Society of Anesthesiologists grade. The model’s predictive performance for discrimination was good (C statistic 0.74 in development cohort, 0.70 in validation cohort). Calibration was good in the development cohort and after recalibration in the validation cohort. Only the highest risks were over-predicted. Survival was worse in patients with acute kidney injury compared with those without (adjusted hazard ratio 1.53, 95% confidence interval 1.38 to 1.70). This was most noticeable in the short term (adjusted hazard ratio: 90 day 2.36, 1.94 to 2.87) and diminished over time (90 day-one year 1.40, 1.10 to 1.79; >1 year 1.28, 1.10 to 1.48). The model used routinely collected data in the orthopaedic surgery setting therefore some variables that could potentially improve predictive performance were not available. However, the readily available predictors make the model easily applicable. What this study adds A preoperative risk prediction model consisting of seven predictors for acute kidney injury was developed, with good predictive performance in patients undergoing orthopaedic surgery. Survival was significantly poorer in patients even with mild (stage 1) postoperative acute kidney injury. Funding, competing interests, data sharing SB received grants from Tenovus Tayside, Chief Scientist Office, and the Royal College of Physicians and Surgeons of Glasgow; PT receives grants from Novo Nordisk, GlaxoSmithKline, and the New Drugs Committee of the Scottish Medicines Consortium. No additional data are available.
Objective:
The aim of the study was to examine the association of tested TSH with age, gender, and diabetes in a large population-based cohort without evidence of thyroid disease.
Design:
...Record-linkage technology was used retrospectively to identify people without evidence of thyroid disease in the general population of Tayside, Scotland, from July 1, 2003, to December 31, 2009.
Cohort:
All Tayside residents who had thyroid function tests performed were identified. Using a unique patient identifier, data linkage enabled a cohort without thyroid disease to be identified by excluding anyone with thyroid or antithyroid prescription, thyroid-related admission or surgery, treatment with radioactive iodine and/or positive thyroid antibodies. Cases below 18 years of age were also excluded.
Outcome Measures:
We measured TSH distribution among different age groups and by gender.
Results:
We identified the latest TSH measurements in 153127 people from the reference population after applying the exclusion criteria. There was a significant increase in median TSH (1.58 mU/L at 31–40 y to 1.86 mU/L at >90 y; P < .001) and 97.5th centile TSH (3.98 to 5.94 mU/L, respectively) with increasing age. The 2.5th centile decreased with age (0.51 to 0.31 mU/L). Patients with diabetes had marginally higher TSH concentration (1.80 vs 1.70 mU/L; P < .001).
Conclusion:
The use of these age-specific reference intervals for TSH, especially in those over 70 years old, would result in the reclassification of many TSH results from “abnormal” to “normal” (within the 95th centile reference interval) and avoid unnecessary treatment.
Chronic rhinosinusitis (CRS) with nasal polyposis is common. The long-term efficacy and safety of approaches to medical management are not well-known.
To evaluate the efficacy and safety of a 2-week ...regimen of oral steroid therapy followed by 26 weeks of sequential topical steroid maintenance therapy.
Parallel randomized trial with computer-generated block randomization and central allocation. Patients and investigators were blinded to group assignment. (ClinicalTrials.gov registration number: NCT00788749)
A specialty rhinology clinic in Tayside, Scotland.
60 adults with CRS and moderate-sized or larger nasal polyps who were referred by their primary physicians for specialty care.
Patients were randomly assigned in a 1:1 ratio to receive oral prednisolone, 25 mg/d, or placebo for 2 weeks, followed in both groups by fluticasone propionate nasal drops, 400 µg twice daily, for 8 weeks and then fluticasone propionate nasal spray, 200 µg twice daily, for 18 weeks.
Polyp grading (primary outcome), hyposmia score, quality of life, symptoms, nasal patency, adrenal function, and bone turnover.
The mean decrease in polyp grade from baseline to 2 weeks was 2.1 units (SD, 1.1) in the prednisolone group and 0.1 unit (SD, 1.0) in the placebo group (mean difference between groups, -1.8 units 95% CI, -2.4 to -1.2 units; P < 0.001). The difference between groups was -1.08 units (CI, -1.74 to -0.42 unit; P = 0.001) at 10 weeks and -0.8 unit (CI, -1.8 to 0.2 unit; P = 0.11) at 28 weeks. The mean decrease in hyposmia score from baseline to 2 weeks was 31.12 mm (SD, 30.1) in the prednisolone group and 1.41 mm (SD, 30.6) in the placebo group (mean difference between groups, -28.33 mm CI, -42.71 to -13.96 mm; P = 0.002). The difference between groups was -16.06 mm (CI, -30.99 to -1.13 mm; P = 0.03) at 10 weeks and -12.13 mm (CI, -30.55 to 6.29 mm; P = 0.19) at 28 weeks. Prednisolone therapy resulted in transient suppression of adrenal function and increase in bone turnover after 2 weeks, with a return to baseline at 10 and 28 weeks.
Patients were referred from primary care to a single-center rhinology clinic, which limits the generalizability of results. Serial measurements of surrogates of nasal inflammation (such as nitric oxide or cytokine levels) were not performed.
Initial oral steroid therapy followed by topical steroid therapy seems to be more effective over 6 months than topical steroid therapy alone in decreasing polyp size and improving olfaction in patients referred for specialty care of CRS with at least moderate nasal polyposis.
Chief Scientist Office, Scotland; National Health Service Tayside Small Grants Scheme; and an Anonymous Trust grant from University of Dundee.
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