Recurrent aphthous ulceration or stomatitis (RAS) is a common condition characterised by painful recurring oral ulcers, typically commencing in childhood. These ulcers classically present as round or oval lesions, and have a yellow or grey base and a surrounding erythematous inflammatory halo. Although ‘aphthous-like ulcers’ can be associated with a number of systemic diseases, ‘recurrent aphthous ulceration’ is a term that should strictly be reserved for recurring ulcers arising in the absence of associated systemic disease.
The authors of this...]]>
There is some evidence for the role of inflammation and insulin resistance in the pathophysiology of plaque psoriasis. Thiazolidinediones are antidiabetic drugs that act by improving insulin sensitivity and also possess anti-inflammatory effects. Evidence from in vitro, animal and human studies has accumulated suggesting that these drugs may be of use in psoriasis.
This systematic review and meta-analysis was performed to assess the efficacy of thiazolidinediones on psoriasis severity.
Randomised, open-label or single blind or double blind, published as well as unpublished, studies of thiazolidinedione administration compared with placebo, given to patients with plaque psoriasis for at least 8 weeks were considered for inclusion in this review. The primary outcomes were as follows: mean or mean percent change in Psoriasis Area and Severity Index (PASI) from baseline to end of treatment with pioglitazone, proportion of patients showing >75% improvement in PASI score, and proportion of patients showing >50% improvement in PASI score. Data analysis was done using Revman 5.
Twenty-seven relevant citations were identified. Two studies each for pioglitazone and rosiglitazone were included in the meta-analysis. There was a significantly greater mean decrease in PASI scores from baseline to end of treatment (–4.24 (95% CI –5.35 to –3.12)) in the pioglitazone group as compared to placebo. There was a non-significant improvement in PASI50/70 in the pooled analysis of rosiglitazone trials.
Pioglitazone appears to have efficacy for the treatment of psoriasis. The clinical significance of the effect and role in management of psoriasis deserve further study.
Early cord clamping (ECC) has been practiced intermittently for over 100 years. However, it did not enter standard care until it was included, for convenience, as part of the package of active management of the third stage of labour (AMTSL). Since the 1980s, when the total package (oxytocic, controlled cord traction and early cord clamping) was shown to be effective at preventing postpartum haemorrhage (PPH,
It is only in the last decade that the AMSTL package has been unpacked and it is becoming clear that it is only the oxytocic drug that reduces PPH – the controlled cord traction2 and early cord clamping (ECC)3 appear to have no maternal benefits. But might ECC actually cause harm to the baby? In preterm births, there is evidence from a small number of randomised babies (n=297) that ECC causes...]]>
Post-thrombotic syndrome (PTS) can be a debilitating consequence of acute deep venous thrombosis (DVT). The subset of patients with iliofemoral DVT represents a particularly high-risk cohort of patients likely to develop PTS.
Treatment strategies which eliminate clot and restore unobstructed venous drainage to the vena cava have resulted in better quality of life and reduced PTS
The stated purpose of the CaVenT study...]]>
Depression is two to three times more common in people with chronic physical disease. When combined with other chronic diseases, depression is associated with significantly greater decrements in functioning than one or more chronic physical illness, or depression alone.
The TEAMcare study randomised 214 patients with depression and poorly controlled diabetes and/or coronary heart...]]>
Chest pain (CP) in children is a common complaint, though cardiac causes are rare. The study by Saleeb et al aims to determine whether any children diagnosed initially with CP in the cardiology clinic of a children's hospital subsequently died as a result of a cardiac condition.
Medical records were reviewed for all clinic patients >6 years of age with an International Classification of Diseases-9 (ICD-9) code for initial CP assessment who were seen at Children's Hospital Boston over 10 years. The authors suggest that usual coding practice in the clinic would be to use such codes for patients not considered to have cardiac disease. Demographic features, history and exam findings, tests performed and presumed diagnoses were abstracted. The vital status of all patients, and cause of death of deceased patients, were ascertained from the National Death Index and the Social Security Death Index.
The primary outcome was death related...]]>
Mild traumatic brain injuries (TBIs) are common in children and the vast majority of children with mild TBI have normal head CT scans. However, even when the initial scan is normal, some patients are reimaged and/or hospitalised for observation. There is little data regarding the value or harm of a second scan or hospitalisation and one would like to avoid the radiation and costs of these interventions if they are not beneficial. The study by Holmes et al is a secondary analysis of a large study of mild paediatric TBI designed to identify children who do not need a head CT.
This was a planned secondary analysis of data from a...]]>
Acute infective conjunctivitis is the commonest ocular problem encountered in general practice. Traditionally most patients were prescribed topical antibiotics, essentially to cover for bacterial causes. Despite some evidence of improved clinical and microbiological remission rates with antibiotic use in bacterial conjunctivitis, most patients with acute infective conjunctivitis will get better without antibiotics.
The authors conducted an individual patient level meta-analysis of data from three randomised clinical trials. Studies were identified by literature search and selected for inclusion, by two independent assessors, if the following criteria were met: (i)...]]>
Due to decreased vascular compliance, hypertension in older patients is commonly limited to systolic blood pressure; pulse pressures are wider than for younger patients. Decades ago, physicians commonly withheld treatment for older patients with isolated systolic hypertension due to a belief that this was a ‘normal’ or acceptable consequence of ageing that carried no excess morbidity. Since the early 1990's, multiple large-scale treatment trials disproved this hypothesis. These included the Syst-Eur and Syst-China trials of nitrendipine, and the MRC(Medical Research Council) trial of hydrochlorothiazide plus amiloride.
One of the largest and most influential trials was the Systolic Hypertension in the Elderly Program (SHEP) study.
Pharmacological thromboprophylaxis has been proven effective for preventing venous thromboembolic events (VTE) in both surgical and acutely ill medical patients.
This study is an international multi-centre double-blind, placebo-controlled, randomised trial comparing enoxaparin 40 mg daily for 10±4 days compared with placebo in 8392 patients mainly from Asia. All patients received knee-high elastic stockings with graduated compression. Inclusion criteria were an age of at least 40 years and hospitalisation for acute decompensated heart failure, severe systemic infection with at least one risk factor for VTE, or active cancer. The primary...]]>
Although oral anticoagulation with vitamin K antagonists reduces major thromboembolism in high-risk patients, it requires frequent laboratory monitoring to prevent over-anticoagulation which can result in serious bleeding or under anticoagulation which increases the risk for thromboembolism. This monitoring typically occurs in clinical settings, but with marketing of accurate and reliable portable devices, it can now be done more conveniently by the patient at home. Several clinical trials have evaluated the safety and efficacy of patient self-monitoring: either patient self-management (patient tests and adjusts the dose as needed) or patient self-testing with clinical dosing (dosing changes determined by clinicians). Heneghan et al present a systematic review and meta-analysis of individual patient data from 11 of these trials.
A systematic review of published and unpublished sources identified 21 trials published in any language that randomised adults to either usual care or patient self-monitoring. Ten studies were excluded because individual patient level...]]>
Osteoarthritis of the finger joints is present in about 10% of individuals aged 40 to 49, rising to 92% in individuals over 70 years of age.
Gabay and colleagues conducted a single-centre, randomised, double-blind, placebo-controlled clinical trial of 162 patients with radiographic evidence of hand osteoarthritis and moderate to...]]>
Effective pharmacological prophylaxis reduces venous thromboembolism (VTE) in high-risk medically-ill patients.
Lederle et al conducted a comprehensive meta-analysis of available clinical trials. Articles were identified by searching MEDLINE from 1950 through April 2011 and the Cochrane Library. A comprehensive search strategy was provided including details of searches for unpublished material, with good attention to study quality and a data extraction protocol. Studies providing separate data for medical patients or stroke patients in acute or intermediate care, healthcare facilities were included. The analysis included data from randomised trials that provided clinical outcomes and evaluated therapy with heparins or mechanical devices. Studies were included if they compared these treatments to no treatment, or to other active interventions. The principal outcome was 120-day total mortality. Secondary outcomes included symptomatic deep vein thrombosis (DVT), symptomatic pulmonary...]]>
With the licensing and subsequent roll-out of female vaccination against human papillomavirus (HPV) in many, mainly high-resource settings, there has emerged a chorus of voices advocating vaccination for males. The interest in male vaccination has intensified with the publication of early observational data from Australia heralding the effectiveness of vaccination when high coverage is achieved
A previously described
WHO recommends that all babies should be exclusively breastfed for the first 6 months after birth.
The authors analysed 522 women with recent GDM recruited between September 2008 and March 2011, who underwent...]]>
Our commentary was a comparison between the paper by Hoberman, Paradise et al, and one by Tahtinen et al in the same issue of the New England Journal of Medicine. Because of space limitations, we focused only on the primary outcomes of both studies. The primary outcome of the study by Hoberman et al was symptomatic response.
In their letter, Hoberman and Paradise suggest that overall clinical response, which in their study differed more between groups but was largely based on otoscopic findings, is more important. We disagree. In assessing the magnitude of benefit of antibiotics for acute otitis media (AOM) in studies such as this one, we feel that clinicians should consider symptomatic response as the most important outcome, for three reasons: (1) shortened symptom duration...]]>
Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal (GI) tract characterised by abdominal pain or discomfort, associated with a change in either frequency, or form of stool. The condition is chronic, with a relapsing and remitting natural history,
Ruepert et al searched MEDLINE, EMBASE, the Cochrane Library, CINAHL and PsycInfo between 1966 and March 2009 to identify randomised controlled trials (RCTs) published in full that recruited IBS sufferers aged over 12 years, and compared efficacy of soluble and insoluble fibre, antispasmodics (including peppermint oil), or antidepressants with placebo. Studies...]]>
A total of 1.2 million cases of colorectal cancer (CRC) and nearly 609 000 related deaths will occur worldwide this year.
Colonoscopy is often considered the preferred CRC screening test. Many countries including Austria recommend initiating screening colonoscopy in average risk individuals at age 50, one decade earlier than the typical onset of CRC.
The objective of this study by Frelitsch et al is to determine the prevalence of adenomas, advanced adenomas (AA) and CRC detected on screening colonoscopy and the number needed to screen (NNS) by 5 year age groups and by gender....]]>
Pharmacotherapies directly targeted towards the pathophysiology of erectile dysfunction (ED) are efficacious. But whether lifestyle modification and other pharmacotherapies that target one of the main underlying risks for ED, cardiovascular (CV) risk factors and disease can improve ED remains unclear.
An online search of peer-reviewed databases was conducted for randomised controlled clinical trials of lifestyle modification or pharmacotherapy of CV risk factors with a minimum intervention period of 6 weeks. Study selection was undertaken with a hierarchical approach by two of the authors acting independently.
Erectile function was assessed with the 5-item International Index of Erectile Function (IIEF-5) questionnaire. Intervention outcome was measured by a change in the IIEF-5 score, and the weighted mean difference with 95% CIs was calculated using a random effects model. Statistical analyses included the assessment of heterogeneity and publication bias.
Of the 1943 references retrieved, six studies satisfied the selection criteria. Four of these involved...]]>
As stated in our report, we ourselves considered the differences in symptomatic response between the amoxicillin-clavulanate and placebo groups to be modest. On the other hand, the differences we found in rates of clinical failure, as manifested by persistence of otoscopic signs of infection, were substantial: at or before day 4–5, 4% versus 23% (absolute difference 19%; 95% CI...]]>
We read with concern the commentary by Binns CW
Our analysis of the data in
The original authors studied obesity rates at 3 years and feeding patterns in the first 6 months of life.
They showed;
Breastfeeding for 4 months or more is associated with low rates of obesity at 3 years. Lower rates of obesity are associated with any proportion of breast milk. The data does not identify infants exclusively breastfed. For babies in whom breastfeeding has ceased by 4 months, starting solids between 4 and 5 months is associated with equally low rates of obesity at 3 years. Ceasing breastfeeding while also commencing solids before 4 months was associated with a significant...]]>
We welcome the publication of Medow and Lucey in the December issue, describing a qualitative approach to Bayes' theorem.
However, the approach proposed by the authors is not new. We reported a didactic model based on a visual representation of Bayesian logic on a logarithmic scale 8 years ago in peer-reviewed journals.
The authors report a major limitation of their model: it applies to the intermediate range of probabilities (10–90), leaving the very high post-test probabilities often at stake in specialist care and the...]]>
Multimodal recovery programmes decrease hospital stay. The objective of this systematic review was to assess how single-modality evidence-based care principles, regarding postoperative analgesia and postoperative nausea and vomiting (PONV) prophylaxis, combine to achieve this.
A systematic review of randomised controlled trials was performed. Relevant trials compared postoperative epidural analgesia/parenteral opioid analgesia/paracetamol/non-steroidal anti-inflammatory drugs (NSAIDs) and postoperative antiemetics. The effect on recovery was evaluated in terms of length of hospital stay, pain intensity, duration of gastrointestinal dysfunction and incidence of PONV.
Twenty-three trials were included. Epidural anaesthesia failed to reduce length of stay or the incidence of PONV when compared to controls. Pain intensity and time to first bowel movement were reduced (p<0.05). Paracetamol did not reduce the incidence of PONV. NSAIDs reduced postoperative opioid consumption and the incidence of PONV (p<0.05). Dexamethasone and 5-HT3 antagonists reduced the incidence of PONV compared to controls.
Epidural anaesthesia appears to not reduce length of hospital stay or incidence of PONV despite reducing pain intensity and ileus. NSAIDs are more effective than paracetamol in reducing postoperative opioid consumption and PONV, while dexamethasone and 5-HT3 antagonists are both effective in reducing PONV.
Recommended revisit intervals for adults with diabetes or other chronic conditions are based largely on expert opinion due to lack of evidence to support specific recommendations. Without randomised trial data, analysis of observational data to assess the association of specific visit interval with care outcomes is a desirable approach.
This retrospective cohort study includes 26 496 adults with diabetes and elevated A1c, blood pressure (BP) or low-density lipoprotein cholesterol (LDL) values who received diabetes care from primary care physicians from 2000 to 2009. The association of primary care contact frequency (any chart note, with or without face-to-face visit) with time to address control of haemoglobin A1c (A1c), BP or LDL was estimated using marginal Cox proportional hazards regression models and other methods.
Mean time to reach A1c <7% was 22.8 months, to reach LDL <100 mg/dl was 25.6 months, and to reach BP <130/85 mm Hg was 8.7 months....]]>
Kangaroo care (KC) is the practice of skin-to-skin contact between a parent and their infant. Although initially introduced for low-birthweight infants in Columbia because of scarce resources and high-neonatal morbidity,
This randomised crossover trial evaluated the analgesic effect of paternal vs maternal KC in 62 preterm (gestational age (GA) of 28–36 weeks) infants undergoing heel lance (HL). Infants were randomised to the order assignment...]]>
Patients with a recent transient ischaemic attack (TIA) or ischaemic stroke attributed to 70–99% intracranial artery stenosis have a 23% of 1-year risk for subsequent stroke. Over the past decade, intracranial angioplasty and stenting (IAS) has increasingly been used, without convincing evidence of efficacy or rigorous assessment of safety. Stenting and aggressive medical management for preventing recurrent stroke in intracranial stenosis (SAMMPRIS) was a clinical trial that sought to determine whether IAS combined with intensive medical management (IMM) was superior to IMM alone in the prevention of stroke and death.
Subjects were adults with 30–80 years of age, and had suffered a TIA or non-disabling stroke within 30 days of enrolment, attributed to an intracranial stenosis of 70–99% as documented by angiography or non-invasive study. Those <50 years old had to have ≥1 additional criteria (vascular risk factor, ischaemic event, revascularisation procedure or evidence of atherosclerosis in another arterial...]]>
Cutaneous warts are highly prevalent benign papillomas of the skin, of which plantar warts (verrucae plantaris) are the most common type. Most warts disappear spontaneously, but plantar warts can also be persistent and frequently cause discomfort. In the UK, almost 2 million people visit their general practitioner (GP) for cutaneous warts at a cost of £40M per year.
Patients aged 12 years and above with one or more plantar warts were recruited from 16 sites (podiatry outpatient clinics or GP practices). This pragmatic, multi-centred, randomised controlled trial compared liquid nitrogen cryotherapy each 14–21...]]>
Asthma is a growing medical and public health concern, and is the most frequent respiratory disorder complicating pregnancy. Estimates from 2001 to 2003 National Health Interview Survey indicate that 8.8% of pregnant women had current asthma.
Murphy et al conducted a systematic review of articles published in English during the period 1975 and 2009. Only prospective or retrospective cohort studies that enrolled pregnant women with asthma as study subjects, and pregnant women without asthma as controls...]]>
Few patients with acute ischaemic stroke receive intravenous recombinant tissue plasminogen activator (rtPA), with the main exclusion criterion being hospital arrival after 41/2 h.
Patients from Get with the Guidelines Stroke Program (a registry of stroke patients admitted to participating hospitals in the USA) between 2003 and...]]>
Atrial fibrillation (AF) significantly increases the risk of thromboembolism. Until recently, thromboprophylaxis in high-risk AF patients has been limited to vitamin K antagonists. Emerging, novel oral anticoagulants are more selective, targeting specific steps in the coagulation cascade. These agents include direct thrombin inhibitors such as dabigatran and Factor Xa inhibitors such as rivaroxaban, and apixaban. These medications bring the potential for decreased monitoring and improved risk profiles with regard to bleeding and drug-drug interactions.
Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) was an international, multicentre, event-driven non-inferiority trial comparing rivaroxaban versus dose-adjusted warfarin for the prevention of stroke and systemic embolism (primary efficacy endpoint). ROCKET AF enrolled 14264 patients with non-valvular AF at moderate to high risk of stroke and randomised them in a double-blind, double-dummy fashion, administering placebo pills and...]]>
Language is a robust developmental phenomenon, characterised by rapid and prodigious growth and change in the first 3 years of life. It is a universal capability that is acquired effortlessly by most children. Adult input is essential to acquiring language so that children learn the languages spoken to them. Predictable milestones observed in early language development are the onset of first words followed by combining single words in simple sentences. Across cultures, child rearing practices and childhood experiences suggest that powerful neurodevelopmental mechanisms guide the onset and timing of these milestones.
An important counterfactual observation is that language acquisition is not robust for all children. An estimated 7% of 5-year-old children have specific language impairment (SLI).
Interpersonal violence is regarded as a global public health problem by the WHO,
Recent evidence about the effect of antenatal anxiety in women on the development of subsequent emotional and behavioural problems in their children, while important in identifying need for effective early interventions, has paid less attention to causes. Home is optimally a haven, in which there is physical and psychological safety. The possibility that...]]>
The need for comparative effectiveness (CE) data continues to grow, fuelled by market demand as well as health reform. There may be an assumption that new drugs result in improved efficacy compared with the standard of care, therefore warranting premium prices. Gout treatment has recently become controversial, as expensive new drugs enter the market with limited CE data.
The authors reviewed published clinical trials and conducted a cost effectiveness analysis on a new drug (febuxostat) versus the standard (allopurinol) to illustrate the limitations in using these data to inform evidence-based decision-making.
Although febuxostat trials included allopurinol as a comparator, methodological limitations make comparative effectiveness evaluations difficult. However, when available trial data were input to a decision analytic model, the authors found that a significant reduction in febuxostat cost would be required in order for it to dominate allopurinol in cost effectiveness analysis. This case exemplifies the challenges of using clinical trial data in comparative and cost effectiveness analyses.
In the 1970s and 1980s, randomised controlled trials of lung cancer screening with chest radiography and sputum cytology found no lung cancer mortality reduction among high-risk patients.
The Mayo Lung Study, for example, compared screening with chest radiography and sputum cytology every 4 months to no screening among male, chronically heavy smokers over a 6-year period. Although screening was associated with higher incidence of lung cancer, no benefits in lung cancer mortality were observed, and the extra incidence was most likely attributable to overdiagnosis.
Early trials, however, may have been underpowered, and modern radiography may be more sensitive for resectable lung cancers. The National Lung Screening Trial (NLST) recently reported a 20% lung cancer mortality reduction among high-risk patients receiving annual low-dose CT screening compared...]]>
Studies have been inconsistent in showing a protective effect of breast feeding on the risk of sudden infant death syndrome (SIDS). Therefore, the meta-analysis by Hauck et al is timely as it aims to quantify and evaluate the protective effect of breast feeding against SIDS, and provide recommendations on the utility of breast feeding as a strategy for reducing the risk of SIDS.
Data on breast feeding and its association with SIDS published from January 1966 to December 2009 were collected from the MEDLINE database. Twenty-four original case-control studies that provided data on the relationship between breast feeding and SIDS risk were identified. Two teams of two reviewers independently evaluated the studies.
The authors analysed the following; (1) breast feeding of any amount (partial or exclusive) or duration, including breast feeding at discharge from the hospital, (2) breast feeding of any amount at the age of 2 months or older...]]>
To determine how often clinical research from doctoral degree programmes is unpublished and to see if one can characterise differences between those researchers who do or do not publish their work or between the institutions where they studied.
Secondary research with data in the public domain: combining a national dataset of healthcare doctoral theses with related publications traceable in two widely accessible databases.
The Index to Theses was searched for UK doctoral theses and the databases Web of Knowledge and SCOPUS searched by author name for literature derived from each thesis. Confirmatory details about student names or their doctoral programmes were obtained from university websites, if required.
Search terms were chosen to identify only projects directly related to human health. Thesis records included ‘clinical trials’ or ‘clinical research’. The awards were all doctorate-level degrees between 2000 and 2010. ‘Related’ publication in the Web of Knowledge or SCOPUS was interpreted very broadly to include publications with any research commonality with the degree project as recorded in the Index to Theses.
A sample of 82 theses from 39 universities provided the initial material for a literature search. The Web of Knowledge contained more publications from more students than SCOPUS held. Of the doctoral research samples, 39 out of 82 theses (47.6%) produced no discernable publications. The 43 students whose research was published typically began publishing before completing their degree (mean time 1.3 years preceding their award). Not all types of doctorates were associated equally with publication: all 11 MD theses in our sample had related publications (100%).
Research evidence associated with doctoral degrees is often left unpublished, across many settings. Sharing such evidence is a scientific and ethical duty. Supporting students in publishing preliminary work while they are still in doctoral programmes may be the most productive response. The large number of doctorates awarded in ‘medical’ disciplines every year represents a substantial investment in training and a resource for evidence-based medicine that should not be squandered.
Trimethoprim–sulfamethoxazole (TMP–SMX) is a combination antibiotic used for a number of infectious diseases and organisms.
The authors completed a population-based, nested case-control study with the objective of characterising the association between hospitalisation for hyperkalaemia and TMP–SMX use in an older population treated with spironolactone. Older subjects aged 66 years or greater, treated with spironolactone, were potentially eligible for inclusion. Within a group of continuous...]]>
After the introduction of digital mobile phone systems in the 1990s, a growing number of people were using these devices that raised concerns about possible health consequences because even small risks could be of public health relevance if the number of exposed were large. A surge of controversy about possible health effects of radio frequency electromagnetic fields occurred and, although the majority of scientists maintained the view that mobile phone use was safe, possible health effects began to be studied in epidemiological, animal experimental and in vitro investigations. In this context the Danish cohort study was initiated in the mid-1990s.
The original study was a retrospective cohort study with 420 095 subscribers selected from 723 421 records from mobile phone companies from 1982 to 1995. A total of 200 507 corporate subscribers were excluded. The present study by Frei et al included only subscribers who were present in a...]]>
The Selenium and vitamin E Cancer Prevention Trial (SELECT)
The effect of selenium and vitamin E on the risk of prostate cancer was studied in 35 151 study subjects. Men were eligible if they were at least 55 years old (50 years old for African–American men), had a normal digital rectal exam (DRE), prostate specific antigen (PSA) <4 ng/ml and no history of prostate cancer. Men were randomly and equally distributed in a double blinded fashion among the four study groups: selenium daily, vitamin E daily, selenium plus...]]>
Lipids are typically measured after an 8–12 h fast. Most patients are not fasting when they are initially evaluated by their providers, meaning that a repeat visit is necessary if a fasting blood draw is required. However, if postprandial effects do not substantially alter lipid levels, then a non-fasting blood draw has many practical advantages for clinical practice, particularly in paediatrics where fasting is a challenge. Recent studies in adults have suggested that non-fasting lipids may suffice for initial screening of cardiovascular risk,
The study participants were 12 744 children aged 3–17 (mean=11) years from the National Health and Nutrition Examination Surveys (1999–2008). Information on time since last food or drink was available...]]>
People on long-term haemodialysis are dialysed three times-weekly such as on Mondays, Wednesdays and Fridays. Accumulation of volume and toxins over the longer 2-day interdialytic interval (eg, Friday–Monday) may provoke excess deaths. The cohort study by Foley et al asked the question whether compared with other days, morbidity and mortality is increased during the long interdialytic interval.
The participants were 32 065 adults in the USA who participated in the End-Stage Renal Disease (ESRD) Clinical Performance Measures Project at the end of calendar years 2004 through 2007. Patients were excluded if they were not receiving haemodialysis three times weekly. The outcomes were various causes of morbidity and mortality and their relationship with the day of dialysis. The mean follow-up was 2.2 years. Existing United States Renal Data System Standard Analytical Files were used to determine dates of hospitalisations, deaths and their causes. Poisson regression was used to calculate event...]]>
Previously, many non-evidence-based recommendations have been made regarding delayed introduction of so-called allergenic foods such as cow's milk protein, eggs, peanuts, tree nuts, soy and gluten. Tromp et al examined whether the timing of introduction of these foods in infancy is associated with eczema and wheezing in children 4 years of age or younger in a comprehensive population-based prospective cohort study of newborns followed up to 4 years of age.
Recently, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a commentary on complementary feeding that recommends delaying introduction of solid foods until the child is 4–6 months of age; the introduction of complementary food should not be delayed beyond the age of 61/2 months based on the results from recent birth cohort studies.
Overweight and obesity is one of the most important public health issues in many parts of the world today. As reported by Jolly et al, the WHO has referred to the current situation as a global epidemic. Others have suggested that the rise in levels of obesity will cause a decline in life expectancy in the USA in the 21st century.
The investigators evaluated eight weight loss programmes. Three programmes were commercially provided (ie, Weight Watchers, Slimming World and Rosemary Conley) though participants paid with vouchers provided by investigators, two were ‘one to one’ counselling (General Practice led or Pharmacy led)...]]>
Until recently, the standard of care for hepatitis C virus (HCV) infection has been pegylated interferon and ribavirin for 48 weeks for genotype 1 and 24 weeks for genotype 3 infection, with overall sustained virological response (SVR), which equates to cure, of 50% and 80%, respectively. With the recent licensing of the protease inhibitors telaprevir and boceprevir, first generation direct acting antivirals (DAAs), we are at the dawn of a new era of HCV therapy. The ILLUMINATE study explores response-guided therapy in HCV treatment naïve individuals using telaprevir in combination with pegylated interferon and ribavirin.
ILLUMINATE is a phase 3 non-inferiority study exploring shorter course therapy for HCV infection using triple therapy with telaprevir 750 mg orally every 8 h, pegylated interferon α-2a 180 mcg subcutaneously weekly and ribavirin 1000–1200 mg daily. All patients were treated with telaprevir for 12 weeks and at least 24 weeks of pegylated interferon...]]>
Type 2 diabetes is a preventable disease. As with cervical cancer and colon cancer, every new case of type 2 diabetes is evidence of a failure of our public health and medical care systems to address and mitigate the risk factors for this common and costly chronic illness.
The Diabetes Prevention Program (DPP) study demonstrated that in high-risk individuals, a lifestyle intervention targeting modest weight loss, a healthy lower fat diet and physical activity equivalent to about 30 min of walking a day can reduce the RR of developing type 2 diabetes by 58%.
The use of stents in percutaneous coronary intervention (PCI) increases procedural success and decreases restenosis, but it complicates subsequent surgical procedures in these patients.
Albaladejo et al studied 1134 consecutively enrolled French patients with coronary stents who underwent subsequent surgical procedures. Patients were enrolled from 47 different centres...]]>
Intravenous therapy is a common intervention in paediatric medicine. Its uses include the delivery of fluids, nutrition, medication and venous blood sampling. Patient anxiety and difficulty with intravenous placement are common. Patients who require frequent peripheral intravenous placement can have progressive difficulty with intravenous access and can also experience increased anxiety related to the procedure. Obesity or growth retardation can make intravenous insertion more difficult.
Topical anaesthetic applied to the skin over an intravenous insertion site has been shown to decrease pain and anxiety related to the procedure.
A total of 90 children were studied prospectively. Of these, 60 were obese and 30 were growth...]]>
Preterm birth, delivery before 37 weeks gestation, is a leading cause of perinatal morbidity and mortality worldwide.
In order to examine the association between gestational age and mortality in young adulthood, Crump et al used the Swedish Birth Registry to analyse singleton infants...]]>
Type 2 diabetes has its origins in obesity-associated insulin resistance compounded by a progressive inability to secrete adequate amounts of insulin in compensation. Clinical trials have shown that non-pharmacological strategies can reduce the risk of progression of glucose intolerance to diabetes in obese glucose-intolerant individuals. All too often however, clinical practice exposes the difficulties that many people have in achieving and sustaining lifestyle changes. Alternative strategies for diabetes prevention have therefore been sought.
In this meta-analysis, Phung et al identified randomised controlled studies (placebo or active comparator) of at least 3 months duration that each enrolled at least 20 participants. In addition to a conventional meta-analysis, the authors performed a mixed-treatment comparison. The aim of the latter analysis was to determine the comparative efficacy of three classes of oral glucose-lowering drugs via indirect between-trial comparisons. A number of prespecified subgroup sensitivity analyses were also performed. The study was funded...]]>
Antiemetic use is common in children. The majority of paediatric practitioners prescribe antiemetics for intractable vomiting due to gastroenteritis.
This is an update of a review done initially in 2005, 2006 and 2008. The review includes randomised controlled studies of children aged less than 18 years, who received antiemetics orally, intravenously or rectally for vomiting as a result of gastroenteritis. The primary outcome of the review was the time from first administration of the treatment until cessation of vomiting. The secondary outcomes were parenteral satisfaction, number of patients requiring hospitalisation or intravenous rehydration during an emergency department (ED) stay and up to 72 h after discharge, mean number of episodes...]]>
Although Systolic Hypertension in Europe
In an open-label study, 448 patients from a single centre with Type 2 diabetes and hypertension were randomised to receive all antihypertensive medications in the morning (control...]]>
Parenting behaviours clearly have an effect on children but how they impact adult behaviour has received less attention. Johnson et al aimed to determine the association between parenting behaviours and the coping skills, interpersonal skills and personality traits of children that persist into adulthood. They examined this issue by conducting longitudinal research with mothers and children. Prior meta-analyses show positive parenting programmes work for improving children's behaviours.
Mothers and offspring of the 669 families who participated reported on positive parenting (eg, affection, praise and communication) and child behaviours when the offspring were around 16 years of age. At follow-up, adaptive functioning (eg, optimism, insight/warmth, productivity and being assertive or expressing oneself skilfully) and personality disorder symptoms were measured. Mothers reported on their own and the father's psychiatric symptoms. Mothers and offspring reported on the father's parenting. While 10...]]>
Epidural steroid injections are commonly used for the treatment of lumbar radiculopathies which have failed other conservative measures such as physical therapy or non-steroidal anti-inflammatories. Although the use of such injections has risen considerably over recent years, their efficacy remains unclear. This randomised trial compared disability following epidural steroids, epidural saline or sham injections.
Of 461 patients presenting with chronic radiculopathy (duration >12 weeks), 116 patients met the inclusion criteria and were enrolled in the study. Among several exclusion criteria were patients with secondary gain issues who would be unlikely to respond favourably, prior surgery, pregnancy, deformity, morbid obesity, cauda equina syndrome, severe weakness and severe pain (referred for surgery).
Two control groups were used, one of which received a sham subcutaneous injection (n=40) and another that underwent epidural saline injection (n=39). The treatment group underwent caudal epidural injection of saline plus 40 mg triamcinolone (n=37). The primary outcome measure...]]>
Hepatitis B (HBV) remains a global health concern with 350 million people chronically infected, and transmission still occurs despite the widely available and efficacious vaccine. Mother-to-child transmission (MTCT) is an ongoing problem in many countries, and in countries with high prevalence of HBV (>8%), only 44% have birth dose vaccine implemented into the infant vaccine schedule.
Breastfeeding the newborn of an infected HBV mother has been controversial as it has been shown that...]]>
Efficacy of varenicline for tobacco cessation has been attributed to its partial agonist activity at selective nicotinic acetylcholine receptors.
Most clinical trials of varenicline initiated therapy 1 week prior to target quit date (TQD).
A total of 101 adult volunteers enrolled at a...]]>
The majority of patients with diabetes continue to die from cardiovascular causes. The degree to which improved glucose control could help to address this risk has been examined in recent large trials
Boussageon et al conducted a pooled analysis using published data from 13 trials selected on the basis of having an intensive glucose-lowering treatment arm compared with either a ‘standard’ treatment, less intensive glycaemic lowering or placebo. The authors used a comprehensive search strategy and extraction methods to identify relevant published data. The authors also calculated absolute risk reductions and assessed the impacts of trial quality.
The...]]>
The reduction of HIV-1 transmission remains one of the highest global health priorities. The use of established antiretroviral drugs for preventing HIV-1 transmission was first considered in 1994, after an observational clinical study showed reduced HIV-1 infection rates in partners of HIV-1 infected persons treated with zidovudine monotherapy.
HPTN 052 is a phase III, randomised-controlled clinical trial designed to determine if early initiation of antiretroviral therapy could reduce transmission of HIV-1 in serodiscordant partners, compared with delayed treatment (after a decline in CD4 counts or the onset of HIV symptoms). The principal outcome measures were (i) the rates of new HIV-1 infections in partners of infected subjects, (ii) the frequency of...]]>
Clinical practice guidelines (CPG) for the management of stable chronic obstructive pulmonary disease (COPD) recommend the addition of long-acting bronchodilators for patients who remain symptomatic despite use of short-acting bronchodilators.
If symptoms persist despite the use of tiotropium, CPGs recommend adding a LABA. In practice, the LABA added usually includes inhaled corticosteroid (ICS) as a combination inhaler (LABA/ICS: salmeterol/fluticasone or formoterol/budesonide). Occasionally, a LABA/ICS is used instead of tiotropium as initial therapy, although this is not recommended by evidence-based CPGs. Finally, although commonly used for moderate-to-severe COPD, there has been little research into the effectiveness of so-called ‘triple therapy’, namely a LABA/ICS plus LAMA. This commentary examines two recent studies that have attempted to...]]>
Cardiovascular disease is the leading cause of death in industrialised nations and is associated with high costs. Hence, identifying cost-effective measures to prevent such a disease and its risk factors that are palatable remains a top priority for public health. Modifiable lifestyle factors including dietary habits have been recognised as a cornerstone in the prevention of cardiovascular disease. Among healthy food groups, beneficial effects of whole grains, fruits and vegetables, nuts and low sodium intake on heart disease have been well documented, perhaps, partially due to a high content of flavonoids of those foods. Cocoa and dark chocolate are a natural source of flavonoids and consumption of dark chocolate may confer cardiovascular benefits. However, there are limited and inconsistent data on the effects of chocolate consumption on cardiovascular disease.
Buitrago-Lopez et al completed a systematic review and meta-analysis to synthesise current evidence on the association between chocolate consumption and...]]>
Prior studies show mixed results regarding the harms and benefits of smoking cessation prior to surgery. In one study, cigarette smoking demonstrated an increased risk of peri- and postoperative complications compared with not smoking.
A systematic review with meta-analysis included studies through May 2010 that assessed postoperative complications in patients who had quit smoking 8 weeks or less before surgery, and included a...]]>
Osteoporotic vertebral compression fractures (VCF) are a significant public health concern worldwide. Percutaneous vertebral augmentation or vertebroplasty was introduced to alleviate the pain and reduce the disability associated with VCF in patients failing conservative therapy, but were at very high-risk for open surgery. Due to the apparent success and low morbidity of vertebroplasty, these indications were expanded and widespread use ensued until several randomised trials evaluated the efficacy of vertebroplasty in VCF.
Bugg et al discuss the important question of whether labour augmentation with oxytocin would decrease the duration of labour. This treatment is part of active management of labour, a concept that also includes objective diagnosis of labour and early amniotomy.
In 1989, the American College of Obstetricians and Gynaecologists suggested that arrest of the first stage of labour cannot be diagnosed until both the latent phases have been completed with the cervix dilated 4 cm or more and a uterine contraction pattern has been present for 2 h without cervical change.
Lifestyle modification is the cornerstone of treatment in type 2 diabetes. Improved nutrition or increased physical activity both improve glycaemic control,
This 52-week multicentre trial in South West England involved 593 patients aged 31 to 80 years with type 2 diabetes diagnosed 5–8 months previously randomised with concealed allocation to three groups: usual care (control group), intensive diet and intensive diet plus physical activity, in a 2:5:5 ratio. Exclusion criteria included HbA1c >10%, blood pressure >180/100 mm Hg, low-density lipoprotein cholesterol >4 mmol/l, body mass index lower than 25 kg/m2 and weight >180 kg. Potential participants were initially screened by phone and 712...]]>
Chronic low back pain continues to be a major socioeconomic problem in most parts of the world. Spinal manipulative therapy is one of the several conservative treatment options, which, based on results from numerous randomised clinical trials, has been included as one of the recommended therapies in several national clinical guidelines.
Rubinstein et al systematically evaluated evidence from randomised, placebo or active comparative clinical trials in which spinal manipulative therapy (spinal manipulation and/or spinal mobilisation) was used to treat chronic low back pain in adults. This represents an update from an earlier Cochrane review and the authors identified the latest trials by searching Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro and the Index to Chiropractic Literature. The primary outcomes were pain, functional status and perceived recovery. Secondary outcomes were return-to-work and quality of life. Studies with patients of >18 years of age from primary, secondary or tertiary care with non-specific...]]>
Inhaled corticosteroids (ICS) are recommended for the management of moderate to severe chronic obstructive pulmonary disease (COPD).
This study evaluated randomised clinical trials (RCTs) of ICS (budesonide or fluticasone) or ICS with a long-acting β agonist (LABA) versus placebo or LABA alone over a follow-up period of at least 24 weeks. The authors also assessed the outcomes of observational studies with respect to...]]>
In 2003,
The HINTS
Cervical intraepithelial neoplasia (CIN) is a common complication in women of reproductive age. Treatment options include excisional treatments, such as cold knife conisation, loop electrosurgical excision procedure, large loop excision of the transformation zone (LLETZ) and laser conisation; and ablative treatments, including cryotherapy, laser ablation, cold coagulation and diathermy. These treatments may have an impact on subsequent pregnancy outcomes. The meta-analysis by Bruinsma and Quinn evaluates the effect of the type of comparison group on the association between treatment for CIN and subsequent preterm birth <37 weeks gestation.
The authors performed a meta-analysis of cohort studies published between 1950 and 2009, evaluating subsequent pregnancy outcome of women who had singleton gestations and who had undergone treatment for CIN. They included both ablative and excisional treatments, but evaluated the treatments separately. Comparisons were of three types: (1) external comparison group of women who gave birth during the same time period...]]>
Symptomatic uterine fibroids may be managed surgically, with hysterectomy or myomectomy, or by radiological therapies, including uterine artery embolisation (UAE) or high-intensity focused ultrasound. The specialty societies in the USA (www.acog.org) and the UK (
This paper reports the 5-year follow-up data from a pragmatic, unblinded randomised controlled trial in 27 centres in the UK, studying women who had ≥1 symptomatic fibroids, complained of menorrhagia or bulk symptoms, and were candidates for surgery (n=157). Randomisation (done centrally and held by a...]]>
Historically, there has been considerable controversy regarding the timing of supplemental parenteral nutrition (PN) in the critical care setting. Guideline recommendations range from continued underfeeding with enteral nutrition (EN) alone for up to 7–10 days
In this large-scale, unblinded, multicentre trial, Casaer et al randomised 4640 seriously ill ICU patients who were not taking oral nutrition to receive early PN or late PN. Both groups received...]]>
Clinical recurrence (CR) of urinary tract infection (UTI) is common in premenopausal women. Practice guidelines recommend 6–12 months of prophylactic antibiotics for CR of UTI. A meta-analysis demonstrated that prophylaxis with antibiotics was 85% (RR 0.15, (0.08 to 0.28)) better than placebo in pre and postmenopausal women. However, antibiotics cause adverse effects (AEs) (RR 1.58 (0.47 to 5.28)) and antimicrobial resistance
In this non-inferiority double blind randomised trial, subjects were community dwelling...]]>
Evidence is accumulating that metformin is a safe alternative to insulin for the treatment of gestational diabetes mellitus (GDM) not adequately controlled by dietary measures alone.
In an open-label prospective study, the Finnish team randomised 100 women (out of a total of 128 eligible women) with singleton pregnancies diagnosed with GDM by oral glucose tolerance test (fasting capillary glucose 5.3 (baseline), 11.0 (1 h) and 9.6 (2 h) mmol/l after 75 g oral glucose) between 12 and 34 weeks of gestation to either...]]>