Sulphasalazine in ankylosing spondylitis: a double blind controlled study in 60 patients.

Sulphasalazine has been reported to be effective in ankylosing spondylitis with peripheral arthritis, but its efficacy in spondylitis is unknown. Thus 60 patients with active ankylosing spondylitis without peripheral arthritis or gastrointestinal symptoms were randomly allocated to one of two therapeutic groups. One group received 2 g sulphasalazine daily for six months and the other a placebo. Thirteen patients (six given placebo and seven given sulphasalazine) dropped out of the trial and were considered to be treatment failures. After six months'' follow up efficacy was rated as good or very good by 15 of the 30 patients given sulphasalazine and by only six of the 30 given placebo (p less than 0.02). Furthermore, in the patients given sulphasalazine the daily consumption of non-steroidal anti-inflammatory drugs, functional index, and plasma IgG concentrations had fallen significantly. These data suggest that sulphasalazine may be a safe and effective treatment for spondylitis in ankylosing spondylitis.     

Efficacy of a small single dose of oral dexamethasone for outpatient croup: a double blind placebo controlled clinical trial.

OBJECTIVE--To assess the efficacy of a single dose of oral dexamethasone 0.15 mg/kg in children with mild croup not admitted to hospital. DESIGN--Double blind, randomised, placebo controlled clinical trial. SETTING--The emergency department of a tertiary paediatric hospital. SUBJECTS--100 children aged 4-122 months presenting with mild croup. INTERVENTION--A single oral dose of dexamethasone 0.15 mg/kg or placebo. MAIN OUTCOME MEASURE--Return to medical care with ongoing croup. RESULTS--Baseline characteristics of the two treatment groups were similar. Eight children (all from the placebo group) returned to medical care with ongoing croup, one being admitted. There was no reported difference in duration of croup symptoms, duration of viral symptoms, or rate of return to medical care for other reasons. CONCLUSION--Oral dexamethasone in a dose of 0.15 mg/kg is effective in reducing return to medical care with ongoing croup in children with mild croup.     

Importance of hypovolaemic shock and endoscopic signs in predicting recurrent haemorrhage from peptic ulceration: a prospective evaluation.

The incidence of rebleeding was studied prospectively in 177 patients with acute gastrointestinal haemorrhage from peptic ulceration with reference to the degree of haemodynamic insult on admission and the presence of endoscopic signs of recent haemorrhage on initial endoscopy. Rebleeding occurred in two (2%) of 114 patients without shock, in seven (18%) of 38 with tachycardia (pulse rate greater than 100 beats/min, systolic blood pressure greater than 100 mm Hg), and in 12 (48%) of 25 with shock (systolic blood pressure less than 100 mm Hg). A similar gradient was noted with the presence of endoscopic signs alone. Rebleeding occurred in four (5%) of 79 patients with no endoscopic signs, in none of 40 with black spot only, in 11 (23%) of 48 with a clot, and in five (50%) of 10 with a visible vessel on endoscopy. When the incidence of rebleeding was assessed in shocked patients, however, it was significantly higher in those with important signs (clot or visible vessel), in 11 (79%) out of 14 patients, than in those with no signs, in one (9%) out of 11 (p less than 0.001). These data suggest that the association of shock with important endoscopic signs is a stronger predictor of rebleeding than either shock or important signs alone. More aggressive treatment may be warranted in this small group of patients.     

Double blind comparative study of omeprazole 10 mg and 30 mg daily for healing duodenal ulcers.

Healing of duodenal ulcers was assessed in 66 patients who received omeprazole either 10 mg or 30 mg daily for four weeks in a double blind study. Healing was rapid in both groups. At two weeks the ulcers in 15 of the 30 patients taking 10 mg daily had healed compared with 28 of the 36 (78%) taking 30 mg daily (p less than 0.03). At four weeks the respective proportions had risen to 83% (25/30) and 94% (33/35) (p greater than 0.05). In non-smokers the proportion of ulcers healed did not differ significantly with the two doses, although there was a trend for less healing at two weeks with 10 mg daily; in smokers significantly fewer ulcers (p less than 0.05) were healed with 10 mg than 30 mg daily at two weeks (7/16 (44%) v 17/21 (81%] and at four weeks (12/16 (75%) v all 21 (100%]. Adverse reactions were few and transient and were considered unlikely to be due to omeprazole.     

Patch: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre,randomised, controlled trial

Background  

Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect.     

Yoga for bronchial asthma: a controlled study.

Fifty three patients with asthma underwent training for two weeks in an integrated set of yoga exercises, including breathing exercises, suryanamaskar, yogasana (physical postures), pranayama (breath slowing techniques), dhyana (meditation), and a devotional session, and were told to practise these exercises for 65 minutes daily. They were then compared with a control group of 53 patients with asthma matched for age, sex, and type and severity of asthma, who continued to take their usual drugs. There was a significantly greater improvement in the group who practised yoga in the weekly number of attacks of asthma, scores for drug treatment, and peak flow rate. This study shows the efficacy of yoga in the long term management of bronchial asthma, but the physiological basis for this beneficial effect needs to be examined in more detail.     

Diagnostic utility of flumazenil in coma with suspected poisoning: a double blind,randomised controlled study.

OBJECTIVE--To assess the diagnostic value and safety of the benzodiazepine antagonist flumazenil in patients with coma of unclear origin with suspected poisoning. DESIGN--Double blind, placebo controlled, randomised study. SETTING--Intensive care unit at a major teaching hospital. PATIENTS--105 Unconscious adults admitted consecutively with suspected drug overdosage during 18 months from a total of 362 cases of poisoning. Exclusion criteria were pregnancy, epilepsy, obvious poisoning with drugs identified unequivocally from information from relatives or others as other than benzodiazepines, and coma score greater than 10 on a scale graded from 4 to 20. Patients were allocated randomly to receive flumazenil (21 men and 32 women) or placebo (25 men and 27 women). INTERVENTIONS--Intravenous injection of flumazenil (10 ml, 0.1 mg/ml) or placebo (10 ml vehicle alone) given double blind over three minutes. MAIN OUTCOME MEASURES--Serum and urine concentrations of benzodiazepines, antidepressants, and several other agents; blood gas tensions; standardised evaluation on admission and five minutes after the injection by means of coma scale score and urgent diagnostic or therapeutic interventions indicated according to the history and clinical examination; standardised interview after the injection to try to ascertain further information; and adverse reactions. RESULTS--Benzodiazepines were found in the serum in 36 of the 53 patients in the flumazenil group and in 37 of the 52 who received placebo. The average coma scale score increased significantly after injection in the flumazenil group (6.4 v 12.1, p less than 0.001) but not in the placebo group. In the flumazenil group several interventions were rendered unnecessary by the injection: gastric lavage and urinary catheterisation (19 patients each), intubation (21), artificial ventilation and computed tomography of the brain (three patients each), blood culture and lumbar puncture (one patient each), and electroencephalography (two). In the placebo group the indications for these procedures did not change in any patient after injection. The 95% confidence interval for the difference in reduction of the frequency of indications for gastric lavage after injection between the two groups was 21% to 51%, that for intubation 25% to 55%, and that for urinary catheterisation 21% to 51%. In the flumazenil group 21 patients gave valuable information on their drug ingestion within 10 minutes after injection compared with only one in the placebo group (p less than 0.001). Nine adverse reactions were recorded in the flumazenil group, eight of which were graded as mild and one severe. The safety of the antagonist was acceptable, even though 60% of the patients in the flumazenil group had multiple drug poisoning including benzodiazepine. No epileptic seizures or arrhythmias were recorded. CONCLUSION--Flumazenil is a valuable and safe differential diagnostic tool in unclear cases of multiple drug poisoning.     

Reversal of postmenopausal vertebral bone loss by oestrogen and progestogen: a double blind placebo controlled study

Because of uncertainty about the place of hormones in the treatment of postmenopausal bone loss vertebral and forearm bone loss was measured by absorptiometry in early post-menopausal women before and after continuous or sequential treatment with combined oestrogen and progestogen in a double blind placebo controlled trial. Treatment with hormones significantly reversed the vertebral bone loss. The net gain in vertebral bone density amounted to 6·4% a year with continuous supplementation and 5·4% a year with sequential supplementation; the net gain in forearm bone density was lower (3·6% with continuous and 3·7% with sequential supplementation).Before a policy of supplementation with hormones can be recommended to all postmenopausal women with the aim of reducing the incidence of vertebral crush fractures further studies with different doses and combinations of hormones, administered over several years, are needed.     

A genetic study of platelet adenylate cyclase activity: evidence for a single major locus effect in fluoride-stimulated activity.

The activity of membrane-bound platelet adenylate cyclase, when stimulated in vitro by several compounds (including fluoride), is significantly reduced in alcoholics compared with control subjects. We have begun a study of the genetics of this enzyme activity. Complex segregation analysis of basal (unstimulated) platelet adenylate cyclase activity in families reveals a mode of inheritance that cannot be accounted for by a simple mixed model of transmission. By contrast, adenylate cyclase activity stimulated by fluoride ion reveals a single major locus effect with a modest multifactorial background. These results suggest that a single factor in the second-messenger pathway may (a) account for the majority of individual differences in stimulation of adenylate cyclase of fluoride and (b) help explain the reduced activities previously observed in alcoholics.     

Cocaine and single ventricle: a population study.

A recent case report by Shepard et al. (Teratology 43:113-117, 1991) suggested that single ventricle may result from maternal cocaine ingestion by inducing coronary occlusion in the developing fetal heart. We used data from the Atlanta Birth Defects Case-Control Study and the Metropolitan Atlanta Congenital Defects Program (MACDP) to investigate the role of maternal cocaine ingestion in the induction of single ventricles. We identified through the MACDP 58 case infants with a single ventricle, 27 who were study subjects in the Atlanta Birth Defects Case-Control Study, and 31 who were not. We conducted a case-control study with the 27 Atlanta Birth Defects Case Control Study infants, frequency-matched to control infants by race, hospital of birth, and calendar quarter of birth. None of the 27 case infants were exposed to cocaine during early pregnancy, but 7 (0.43%) of the control infants were exposed during early pregnancy. Using MACDP data, we conducted an analysis of trends for prevalence of single ventricle in the metropolitan area. No upward trend in single ventricle was detected for 1968 through 1990. Our data suggest that even if maternal cocaine ingestion during pregnancy is a cause of single ventricle, most cases appear to be unrelated to this exposure.     

Platelet monoamine oxidase (MAO) activity: evidence for a single major locus.

Monoamine oxidase (MAO), a mitochondrial enzyme involved in the degradation of biogenic amines, has been associated with psychiatric morbidity. Although twin and family studies have indicated that MAO activity is familial, the exact mode of transmission is unclear. We performed segregation analysis on 154 nuclear families containing 419 individuals using the mixed model, which allows for a single major locus with a polygenic background. We were able to reject a dominant and additive locus with or without a heritable background and a recessive locus without background. The acceptable models were: (1) a codominant model without background where the mean of the heterozygote distribution was 30% of the distance from the low to the high homozygote distributions, and (2) a recessive locus with heritable background. In both cases, the gene frequency for the high-MAO allele is approximately .25--at odds with suggestions that low-MAO represents a genetic marker for a disorder such as schizophrenia with a lifetime risk of only 0.85%. To ensure that results were not artifacts from a familial, skewed distribution, the data were also analyzed after power transformation. In addition, hypotheses were tested using both the joint and conditional likelihoods to examine for possible misspecification of the model with respect to intergenerational differences. Finally, we allowed for non-Mendelian transmission probabilities to provide another class of alternatives against which to test the hypothesis of a major locus. All these approaches provided additional confirmation for the presence of a major locus segregating within these families.     

Removing seasonal confectionery from prominent store locations and purchasing behaviour within a major UK supermarket: Evaluation of a nonrandomised controlled intervention study

BackgroundThe proportion of energy from free sugars and saturated fat currently exceeds the UK-recommended intake across all age groups. Recognising the limits of reformulation programmes, the government in England has announced their intention to introduce legislation to restrict the promotion of foods high in free sugars, salt, and saturated fats in prominent store locations. Here, we evaluated a grocery store intervention to remove seasonal confectionery from prominent locations within a major UK supermarket.Methods and findingsA nonrandomised controlled intervention study with interrupted time series (ITS) analysis was used. Data were analysed from 34 intervention stores located in 2 London boroughs and 151 matched control stores located elsewhere in the UK owned by the same retailer. Stores were matched based on store size and overall sales during the previous year. Between 15 February 2019 and 3 April 2019 (before Easter), stores removed free-standing promotional display units of seasonal confectionery from prominent areas, although these products were available for purchase elsewhere in the store.Store-level weekly sales (units, weight (g), and value (£)) of seasonal chocolate confectionery products were used in primary analyses, with data from 1 January 2018 to 24 November 2019. Secondary outcomes included total energy, fat, saturated fat, and sugars from all in-store purchases. Multivariable hierarchical models were used to investigate pre/post differences in weekly sales of confectionery in intervention versus control stores. ITS analyses were used to evaluate differences in level and trends after intervention implementation.Over a preintervention baseline period (15 February 2018 to 3 April 2018), there were no significant differences in sales (units, weight, and value) of all chocolate confectionery between intervention versus control stores. After intervention implementation, there was an attenuation in the seasonal increase of confectionery sales (units) in intervention stores compared to control (+5% versus +18%; P < 0.001), with similar effects on weight (g) (+12% versus +31%; P < 0.001) and value (£) (−3% versus +10%; P < 0.001). ITS analyses generally showed statistically significant differences in the level at the point of intervention (P ranges 0.010 to 0.067) but also in the trend afterwards (P ranges 0.024 to 0.053), indicating that the initial difference between intervention and control stores reduced over time. There was a significant difference in level change in total energy sold, adjusted for the total weight of food and drink (kcal/g, P = 0.002), and total fat (fat/g) (P = 0.023), but no significant changes in saturated fat or sugars from total sales in ITS models. There was no evidence that the main results varied across store deprivation index. The limitations of this study include the lack of randomisation, residual confounding from unmeasured variables, absolute differences in trends and sales between intervention versus control stores, and no independent measures of intervention fidelity.ConclusionsRemoval of chocolate confectionery from prominent locations was associated with reduced purchases of these products, of sufficient magnitude to observe a reduction in the energy content of total food purchases. These results from a “real-world” intervention provide promising evidence that the proposed legislation in England to restrict promotions of less healthy items in prominent locations may help reduce overconsumption.Trial registrationhttps://osf.io/br96f/.

Carmen Piernas and team evaluate purchasing behaviour associated with a grocery store intervention to remove seasonal confectionery from prominent locations within a major UK supermarket.     

Cellular versus acellular matrix devices in treatment of diabetic foot ulcers: study protocol for a comparative efficacy randomized controlled trial

Background

The referral letter plays a key role both in the communication between primary and secondary care, and in the quality of the health care process. Many studies have attempted to evaluate and improve the quality of these referral letters, but few have assessed the impact of their quality on the health care delivered to each patient.

Methods

A cluster randomized trial, with the general practitioner office as the unit of randomization, has been designed to evaluate the effect of a referral intervention on the quality of health care delivered. Referral templates have been developed covering four diagnostic groups: dyspepsia, suspected colonic malignancy, chest pain, and chronic obstructive pulmonary disease. Of the 14 general practitioner offices primarily served by University Hospital of North Norway Harstad, seven were randomized to the intervention group. The primary outcome is a collated quality indicator score developed for each diagnostic group. Secondary outcomes include: quality of the referral, health process outcome such as waiting times, and adequacy of prioritization. In addition, information on patient satisfaction will be collected using self-report questionnaires. Outcome data will be collected on the individual level and analyzed by random effects linear regression.

Discussion

Poor communication between primary and secondary care can lead to inappropriate investigations and erroneous prioritization. This study’s primary hypothesis is that the use of a referral template in this communication will lead to a measurable increase in the quality of health care delivered.

Trial registration

This trial has been registered at ClinicalTrials.gov. The trial registration number is NCT01470963     

The effects of continuous prostacyclin infusion on regional blood flow and cerebral vasospasm following subarachnoid haemorrhage: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: One of the main causes of mortality and morbidity following subarachnoid haemorrhage (SAH) is the development of cerebral vasospasm, a frequent complication arising in the weeks after the initial bleeding. Despite extensive research, to date no effective treatment of vasospasm exists. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. In vitro models have shown a relaxing effect of prostacyclin after induced contraction in cerebral arteries and a recent pilot trial showed positive effect on cerebral vasospasm in a clinical setting. No randomised, clinical trials have been conducted, investigating the possible pharmacodynamic effects of prostacyclin on the human brain following SAH. METHODS: This trial is a single-center, randomised, placebo controlled, parallel group, blinded, clinical, pilot trial. A total of 90 patients with SAH will be randomised to one of 3 intervention arms; epoprostenol 1 ng/kg/min, epoprostenol 2 ng/kg/min or placebo in addition to standard treatment. Trial medication will start day 5 after SAH and continue to day 10. Primary outcome measure is changes in regional cerebral blood flow from baseline in the arterial territories of the anterior cerebral artery, medial cerebral artery and the posterior cerebral artery, measured by CT perfusion scan. The secondary outcomes will be vasospasm measured by CT angiography, ischaemic parameters measured by brain microdialysis, flow velocities in the medial cerebral artery, clinical parameters and outcome (Glasgow Outcome Scale) at 3 months. CONCLUSION: The trial is an explorative, pilot trial designed to investigate the feasibility and possible effects of low-dose prostacyclin on a primary outcome of regional blood flow and vasospasm in the human brain following SAH. Trial registration: Clinicaltrials.gov NCT01447095.     

Comparison of physiotherapy,manipulation, and corticosteroid injection for treating shoulder complaints in general practice: randomised,single blind study.

OBJECTIVE: To compare the efficacy of physiotherapy, manipulation, and corticosteroid injection for treating patients with shoulder complaints in general practice. DESIGN: Randomised, single blind study. SETTING: Seven general practices in the Netherlands. SUBJECTS: 198 patients with shoulder complaints, of whom 172 were divided, on the basis of physical examination, into two diagnostic groups: a shoulder girdle group (n = 58) and a synovial group (n = 114). INTERVENTIONS: Patients in the shoulder girdle group were randomised to manipulation or physiotherapy, and patients in the synovial group were randomised to corticosteroid injection, manipulation, or physiotherapy. MAIN OUTCOME MEASURES: Duration of shoulder complaints analysed by survival analysis. RESULTS: In the shoulder girdle group duration of complaints was significantly shorter after manipulation compared with physiotherapy (P < 0.001). Also the number of patients reporting treatment failure was less with manipulation. In the synovial group duration of complaints was shortest after corticosteroid injection compared with manipulation and physiotherapy (P < 0.001). Drop out due to treatment failure was low in the injection group (17%) and high in the manipulation group (59%) and physiotherapy group (51%). CONCLUSIONS: For treating shoulder girdle disorders, manipulation seems to be the preferred treatment. For the synovial disorders, corticosteroid injection seems the best treatment.     

Albendazole chemotherapy for treatment of diarrhoea in patients with AIDS in Zambia: a randomised double blind controlled trial.

OBJECTIVE--To determine the value of short course, high dose albendazole chemotherapy in the treatment of persistent diarrhoea related to HIV in unselected patients in urban Zambia. DESIGN--A randomised double blind placebo controlled trial of albendazole 800 mg twice daily for two weeks. Patients were monitored intensively for one month and followed for up to six months. SETTING--Home care. AIDS services in Lusaka and Ndola. PATIENTS--174 HIV seropositive patients with persistent diarrhoea (defined as loose but not bloody stools three or more times a day for three weeks or longer). No investigations were undertaken except HIV testing after counselling. MAIN OUTCOME MEASURES--Proportion of time periods during which diarrhoea was experienced after completion of treatment; proportion of patients with full remission after completion of treatment; mortality. RESULTS--The patients taking albendazole had diarrhoea on 29% fewer days than those taking placebo (P < 0.0001) in the two weeks after treatment. The benefit of albendazole was maintained over six months. In patients with a Karnofsky score of 50 to 70 (needing help with activities of daily living and unable to work, but not needing admission to hospital) diarrhoea was reduced by 50%. Remission was obtained in 26% of all patients who received albendazole (P = 0.004 against 9% receiving placebo), and this difference was maintained over six months (log rank test, P = 0.003). Albendazole had no effect on mortality. Minimal adverse effects were noted. CONCLUSIONS--For HIV infected Zambians with diarrhoea of more than three weeks'' duration albendazole offers substantial relief from symptoms and may be used empirically, without prior investigation.