Conservative versus Interventional Treatment for Spontaneous Pneumothorax.

BACKGROUND: Whether conservative management is an acceptable alternative to interventional management for uncomplicated, moderate-to-large primary spontaneous pneumothorax is unknown. METHODS: In this open-label, multicenter, noninferiority trial, we recruited patients 14 to 50 years of age with a first-known, unilateral, moderate-to-large primary spontaneous pneumothorax. Patients were randomly assigned to immediate interventional management of the pneumothorax (intervention group) or a conservative observational approach (conservative-management group) and were followed for 12 months. The primary outcome was lung reexpansion within 8 weeks. RESULTS: A total of 316 patients underwent randomization (154 patients to the intervention group and 162 to the conservative-management group). In the conservative-management group, 25 patients (15.4%) underwent interventions to manage the pneumothorax, for reasons prespecified in the protocol, and 137 (84.6%) did not undergo interventions. In a complete-case analysis in which data were not available for 23 patients in the intervention group and 37 in the conservative-management group, reexpansion within 8 weeks occurred in 129 of 131 patients (98.5%) with interventional management and in 118 of 125 (94.4%) with conservative management (risk difference, -4.1 percentage points; 95% confidence interval [CI], -8.6 to 0.5; P = 0.02 for noninferiority); the lower boundary of the 95% confidence interval was within the prespecified noninferiority margin of -9 percentage points. In a sensitivity analysis in which all missing data after 56 days were imputed as treatment failure (with reexpansion in 129 of 138 patients [93.5%] in the intervention group and in 118 of 143 [82.5%] in the conservative-management group), the risk difference of -11.0 percentage points (95% CI, -18.4 to -3.5) was outside the prespecified noninferiority margin. Conservative management resulted in a lower risk of serious adverse events or pneumothorax recurrence than interventional management. CONCLUSIONS: Although the primary outcome was not statistically robust to conservative assumptions about missing data, the trial provides modest evidence that conservative management of primary spontaneous pneumothorax was noninferior to interventional management, with a lower risk of serious adverse events. (Funded by the Emergency Medicine Foundation and others; PSP Australian New Zealand Clinical Trials Registry number, ACTRN12611000184976.).

The Porirua Protocol in the Treatment of Clozapine-Induced Gastrointestinal Hypomotility and Constipation: A Pre- and Post-Treatment Study.

BACKGROUND: Clozapine, an antipsychotic used in treatment-resistant schizophrenia, causes slow gastrointestinal transit in 50-80% of patients. Clozapine-induced gastrointestinal hypomotility is both common and serious, and potential complications include severe constipation, ileus, bowel obstruction and related complications, with a higher mortality rate than clozapine-related agranulocytosis. Little evidence exists on its prevention and management. METHOD: Using a well-validated radiopaque marker ('Metcalf') method, we compared colonic transit times (CTTs) of clozapine-treated inpatients not receiving laxatives with their transit times when receiving laxatives, with treatment prescribed according to the Porirua Protocol for clozapine-related constipation (docusate and senna augmented by macrogol 3350 in treatment-resistant cases). RESULTS: The median age of participants was 35 years, and median clozapine dose, plasma level and duration of treatment were 575 mg/day, 506 ng/mL and 2.5 years, respectively. Overall, 14 participants (10 male) were enrolled and all completed the study. Transit times improved markedly with laxative treatment. Median colonic transit without laxatives was 110 h (95% confidence interval [CI] 76-144 h), over four times longer than normative values (p < 0.0001). Median CTT with laxatives was 62 h (95% CI 27-96 h), a 2-day reduction in average transit time (p = 0.009). The prevalence of gastrointestinal hypomotility decreased from 86% pre-treatment to 50% post-treatment (p = 0.061). Severe gastrointestinal hypomotility decreased from 64 to 21% (p = 0.031). Subjective reporting of constipation did not correlate well with objective hypomotility, and did not change significantly with treatment. CONCLUSION: Treating clozapine-treated patients with docusate and senna augmented by macrogol appears effective in reducing CTTs in clozapine-induced constipation. Randomised controlled trials are the next step. Australian New Zealand Clinical Trial Registry ACTRN12616001405404 (registered retrospectively).

Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study.

BACKGROUND: Gastrointestinal side effects are particularly common with clozapine and occur with other antipsychotics, ranging from mild constipation to fatal bowel obstruction and/or ischemia. While this adverse-effect spectrum has been attributed to 'gastrointestinal hypomotility', gastrointestinal transit times in antipsychotic-treated patients have not previously been measured, making this mechanism speculative. METHODS: Using standardized radiopaque marker ('Metcalf') methods we established colonic transit times of antipsychotic-treated psychiatric inpatients and compared them with population normative values. We analyzed results by antipsychotic type, antipsychotic dose equivalent, anticholinergic load, duration of treatment, gender, ethnicity, and age. OUTCOMES: For patients not prescribed clozapine, median colonic transit time was 23 h. For patients prescribed clozapine, median transit time was 104.5 h, over four times longer than those on other antipsychotics or normative values (p < 0.0001). Eighty percent of clozapine-treated patients had colonic hypomotility, compared with none of those prescribed other antipsychotics (olanzapine, risperidone, paliperidone aripiprazole, zuclopenthixol or haloperidol). In the clozapine group, right colon, left colon and rectosigmoid transit times were all markedly abnormal suggesting pan-colonic pathology. Hypomotility occurred irrespective of gender, age, ethnicity, or length of clozapine treatment. Transit times were positively correlated with clozapine plasma level (rho = 0.451, p = 0.045), but not with duration of treatment, total antipsychotic load or demographic factors. INTERPRETATION: Clozapine, unlike the other antipsychotics examined, causes marked gastrointestinal hypomotility, as previously hypothesized. Pre-emptive laxative treatment is recommended when starting clozapine.

Does insufficient access to dual-energy X-ray absorptiometry (DXA) stifle the provision of quality osteoporosis care in New Zealand?

UNLABELLED: Access to dual-energy X-ray absorptiometry (DXA) scanning varies significantly throughout New Zealand with the majority of scans funded privately or through the health industry. Barriers to access need to be addressed if osteoporosis guidelines are to be implemented across the country equitably, to reduce the incidence and cost of fragility fractures in New Zealand. PURPOSE: This study aims (1) to estimate the number of dual-energy X-ray absorptiometry scans performed in New Zealand, (2) to determine funding sources of DXA scans and (3) to determine the level of regional variation in access. METHODS: DXA scan providers in New Zealand were accessed through a nationwide database and asked to provide data on DXA scans performed in 2007. The numbers of DXA scans performed in each District Health Board (DHB) region were calculated by using a funding source and compared with DHB population estimates provided by Statistics New Zealand for 2007. RESULTS: In New Zealand in 2007, 33,104 DXA scans were performed, with a population rate of 78.1 DXA scans per annum per 10,000 general population, significantly less than international guidelines. There were important regional differences in access to DXA scanning. Funding for scans was predominately by private and pharmaceutical industry funders. DHBs funded only 31 % of DXA scans during this time period. CONCLUSIONS: Access to DXA scan technology varies significantly throughout New Zealand, with the majority of DXA scans funded by the private sector or health industry. Barriers to access need to be addressed if osteoporosis guidelines are to be implemented across the country in an equitable fashion and so reduce the incidence and cost of fragility fractures to New Zealand.

Incidental findings from lung CT scans: implications for research.

INTRODUCTION: We aimed to evaluate the number and nature of incidental findings in CT chest scans in the context of a study of the pulmonary effects of cannabis. METHODS: Three hundred fifty-seven participants were recruited: 78 cannabis-only smokers, 92 tobacco-only smokers, 106 smokers of cannabis and tobacco and 81 never smokers. All participants underwent a high-resolution CT scan of their thorax. Two radiologists read the scans. Associations between abnormalities and age, sex, tobacco and cannabis smoking status were expressed as odds ratios (OR) with 95% confidence interval. RESULTS: Seventy-six findings requiring referral or further investigations were found in 71/357 (19.9%) of participants. In multivariate analyses, only older age, OR (per decade) 2.1 (1.4 to 3.0), was associated with a respiratory abnormality on the CT scan. A total of 37/76 (48.7%) of the abnormalities detected were extra-pulmonary, with findings observed across a wide range of organ systems. Only older age, OR (per decade) 1.7 (1.2 to 2.5), was associated with a non-respiratory abnormality. CONCLUSION: The common occurrence of abnormal findings requiring referral or further investigations raises practical, ethical and medico-legal issues which need to be carefully considered in research programmes utilising chest CT scanning.

Effects of cannabis on pulmonary structure, function and symptoms.

BACKGROUND: Cannabis is the most widely used illegal drug worldwide. Long-term use of cannabis is known to cause chronic bronchitis and airflow obstruction, but the prevalence of macroscopic emphysema, the dose-response relationship and the dose equivalence of cannabis with tobacco has not been determined. METHODS: A convenience sample of adults from the Greater Wellington region was recruited into four smoking groups: cannabis only, tobacco only, combined cannabis and tobacco and non-smokers of either substance. Their respiratory status was assessed using high-resolution CT (HRCT) scanning, pulmonary function tests and a respiratory and smoking questionnaire. Associations between respiratory status and cannabis use were examined by analysis of covariance and logistic regression. RESULTS: 339 subjects were recruited into the four groups. A dose-response relationship was found between cannabis smoking and reduced forced expiratory volume in 1 s to forced vital capacity ratio and specific airways conductance, and increased total lung capacity. For measures of airflow obstruction, one cannabis joint had a similar effect to 2.5-5 tobacco cigarettes. Cannabis smoking was associated with decreased lung density on HRCT scans. Macroscopic emphysema was detected in 1/75 (1.3%), 15/92 (16.3%), 17/91 (18.9%) and 0/81 subjects in the cannabis only, combined cannabis and tobacco, tobacco alone and non-smoking groups, respectively. CONCLUSIONS: Smoking cannabis was associated with a dose-related impairment of large airways function resulting in airflow obstruction and hyperinflation. In contrast, cannabis smoking was seldom associated with macroscopic emphysema. The 1:2.5-5 dose equivalence between cannabis joints and tobacco cigarettes for adverse effects on lung function is of major public health significance.

Management problems of spontaneous ICH.

The management of spontaneous intracerebral haemorrhage (ICH) can be challenging for hospital doctors. Although the management of ICH is covered in stroke guidelines, many difficult clinical questions remain. In this article the authors suggest approaches to ten common and difficult questions.