Intranasal midazolam had no clinical benefit over intranasal placebo for the control of dyspnoea. The low level of anxiety at baseline and dose of active drug delivered may have been important factors. Many participants found the SNS bottles to be a challenging mode of drug delivery. This study confirms the importance of placebo-controlled trials for defining best clinical practise.

Arohanui Hospice is a 12-bed specialist palliative care service based in Palmerston North, New Zealand. It serves a population of 180 000 people spread over a wide geographical area, both urban and rural. The Liverpool Care Pathway (LCP) was initially implemented at the hospice inpatient unit in January 2005. Following this, the 'LCP Pilot Project' was developed. This project involved the implementation of the LCP within three aged residential care facilities and two wards within the regional hospital. Included in the project was a research component to enable evaluation of the effectiveness of the LCP in each setting. This article will consider and demonstrate the use of process mapping (Buckman, 2003) as a quality improvement tool to enhance the effective implementation and sustained use of the LCP for the dying patient within aged residential care. Measures are considered that support the implementation of the LCP at an organisational level rather than at a purely clinical level. While this work has been completed within the New Zealand context, it is believed that the principles are transferable to similar settings internationally.

The ecology of 350 strains of group F streptococci isolated from clinical material over a six-year period is described. The respiratory tract, particularly the throat, yielded the largest number of isolates. Wound swabs, mainly appendectomy, ranked second as a source of this organism, followed closely by the genitourinary tract. A significant proportion of strains was recovered from gastrointestinal sites. Dental abscess yielded several strains, often in pure culture, and the external auditory canal was identified as minor locale of the group F streptococcus. A few isolates were also obtained from blood, cerebrospinal fluid, and miscellaneous tissues.

BackgroundNicotine preloading means using nicotine replacement therapy prior to a quit date while smoking normally. The aim is to reduce the drive to smoke, thereby reducing cravings for smoking after quit day, which are the main cause of early relapse. A prior systematic review showed inconclusive and heterogeneous evidence that preloading was effective and little evidence of the mechanism of action, with no cost-effectiveness data.ObjectivesTo assess (1) the effectiveness, safety and tolerability of nicotine preloading in a routine NHS setting relative to usual care, (2) the mechanisms of the action of preloading and (3) the cost-effectiveness of preloading.DesignOpen-label randomised controlled trial with examination of mediation and a cost-effectiveness analysis.SettingNHS smoking cessation clinics.ParticipantsPeople seeking help to stop smoking.InterventionsNicotine preloading comprised wearing a 21 mg/24 hour nicotine patch for 4 weeks prior to quit date. In addition, minimal behavioural support was provided to explain the intervention rationale and to support adherence. In the comparator group, participants received equivalent behavioural support. Randomisation was stratified by centre and concealed from investigators.Main outcome measuresThe primary outcome was 6-month prolonged abstinence assessed using the Russell Standard. The secondary outcomes were 4-week and 12-month abstinence. Adverse events (AEs) were assessed from baseline to 1 week after quit day. In a planned analysis, we adjusted for the use of varenicline (Champix®; Pfizer Inc., New York, NY, USA) as post-cessation medication. Cost-effectiveness analysis took a health-service perspective. The within-trial analysis assessed health-service costs during the 13 months of trial enrolment relative to the previous 6 months comparing trial arms. The base case was based on multiple imputation for missing cost data. We modelled long-term health outcomes of smoking-related diseases using the European-study on Quantifying Utility of Investment in Protection from Tobacco (EQUIPT) model.ResultsIn total, 1792 people were eligible and were enrolled in the study, with 893 randomised to the control group and 899 randomised to the intervention group. In the intervention group, 49 (5.5%) people discontinued preloading prematurely and most others used it daily. The primary outcome, biochemically validated 6-month abstinence, was achieved by 157 (17.5%) people in the intervention group and 129 (14.4%) people in the control group, a difference of 3.02 percentage points [95% confidence interval (CI) –0.37 to 6.41 percentage points; odds ratio (OR) 1.25, 95% CI 0.97 to 1.62;p = 0.081]. Adjusted for use of post-quit day varenicline, the OR was 1.34 (95% CI 1.03 to 1.73;p = 0.028). Secondary abstinence outcomes were similar. The OR for the occurrence of serious AEs was 1.12 (95% CI 0.42 to 3.03). Moderate-severity nausea occurred in an additional 4% of the preloading group compared with the control group. There was evidence that reduced urges to smoke and reduced smoke inhalation mediated the effect of preloading on abstinence. The incremental cost-effectiveness ratio at the 6-month follow-up for preloading relative to control was £710 (95% CI –£13,674 to £23,205), but preloading was dominant at 12 months and in the long term, with an 80% probability that it is cost saving.LimitationsThe open-label design could partially account for the mediation results. Outcome assessment could not be blinded but was biochemically verified.ConclusionsUse of nicotine-patch preloading for 4 weeks prior to attempting to stop smoking can increase the proportion of people who stop successfully, but its benefit is undermined because it reduces the use of varenicline after preloading. If this latter effect could be overcome, then nicotine preloading appears to improve health and reduce health-service costs in the long term. Future work should determine how to ensure that people using nicotine preloading opt to use varenicline as cessation medication.Trial registrationCurrent Controlled Trials ISRCTN33031001.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 22, No. 41. See the NIHR Journals Library website for further project information.

Diffuse hyperplasia of the parathyroid glands is a rare condition in infancy, and both the clinical picture and the histologic structure of the parathyroid glands differ somewhat from those of the comparable disorder in adults. As far as we can ascertain, two previous fatal cases1,2 have been reported with both clinical and postmortem descriptions. In addition, a probable further example of this condition, with apparently successful surgical intervention, has been reported by Landon.3 In these three cases the disease process was present in early infancy, and in two of the cases it proved fatal. The present report describes a further example of infantile hyperparathyroidism resulting from diffuse hyperplasia of the parathyroid glands. Report of CaseThe patient was born in May, 1960, the first child of a deaf and dumb, severely mentally retarded mother. At birth he weighed 5 lb. 4\m=1/4\oz. (about 2,388 gm.). He was admitted to hospital where he was described as having an "elflike" face with a narrow head and a sharp nose. The occipitofrontal circumference was 12¡^in., and the circumference of the chest was 11 in.During this initial stay in hospital crepitations were audible in all areas of the chest ; but the baby was not in any distress, and the chest x-ray was clear. The main problem was the baby's failure to make satisfactory progress, and on discharge at eight weeks of age his weight was still only 6 lb. 2i^oz. (about 2,792 gm.). During this time he received 2^3 oz. of Carnation milk in his formula and one teaspoonful of Infantai * daily. No other vitamin D supplements were given.He was readmitted at three months of age, weighing 7 lb. (about 3,175 gm.). No history of vitamin D intake at home was available, and on his second admission his only addition to his formula was one teaspoonful of Infantai daily. At this time he was described as a miserable, scrawny, pale, and underweight baby. The head circumference was 14 in., and the skull was elongated, soft to palpation, and could be indented like a Ping-pong ball over the occiput.No adventitious chest sounds were now present, and no cardiac murmurs were heard. The abdomen was markedly distended, and the liver was slightly enlarged. The spleen was not felt, and there were no masses.The hemoglobin was 11.3 gm. with 12,050 leu¬ kocytes, of which 30% were neutrophils, 68% lymphocytes, and 2% eosinophils. The BUN was 12 mg. per milliliter. The serum calcium was 9 mEq. per liter and the inorganic phosphate 2.3 mEq. per liter. The alkaline phosphatase was 7.7 Bodansky units. The serum sodium was 118 mEq. per liter and the potassium 5.2 mEq. per liter. The total protein was 7.5 gm/100 ml with 3.5 gm. albumin and 4.0 gm. globulin. Urinalysis was negative for sugar and albumin.A tuberculin patch test was negative, and the electrocardiograph pattern was within normal limits.When the baby was four months of age the serum calcium was 10 mEq. per liter, but several determi-A polyvitamin supplement (Horner) containing 0.00014 vitamin D in 5 cc.