Toronto General & Western Hospital Foundation

In the 24-year period since it was first proposed that this lesion arose from the alveolar epithelium in multicentric fashion and, therefore, carried an unfavorable prognosis, a continuing assessment has revealed a spectrum of disease essentially similar to that of other lung cancers. Arising peripherally, localized lesions may have a favorable prognosis, although tumors associated with a hilar adenopathy or those developing in multinodular fashion are of aggressive biologic type. A further series of 74 cases has now been reviewed. All met the specific criteria of primary bronchiolo-alveolar carcinoma, and all have been followed longer than 5 years after diagnosis and treatment. A relatively high proportion proved to be localized, biologically favorable, and amenable to curative treatment by lobectomy. On the basis of this additional experience, it would appear logical to: 1. Consider bronchiolo-alveolar carcinoma a specific entity; 2. Urge prompt treatment of operable disease in an attempt to forestall endo-bronchial or lymphatic spread; 3. Advise lobectomy as the treatment of choice for localized peripheral disease, and 4. Insist that potentially cured patients stop smoking in order to avoid the development of multicentric foci resulting from continuing exposure to external carcinogenic agents.

When disease impairs clearance of drugs, multiple-dose therapy may result in cumulation. The disposition of chlordiazepoxide (CDX), 50 mg infused intravenously over 10 min, was studied in 14 normal subjects and in 11 patients with biopsy-proven cirrhosis. In the normal subjects, mean (+/- SE) kinetic parameters were: t 1/2 beta, 10.0 (+/- 0.9) hr; Vd, 0.38 (+/- 0.04) l/kg; clearance, 0.54 (+/- 0.13) ml/min/kg. Clearance of total drug correlated inversely with serum albumin concentration in normal subjects (r = -0.63). Values in cirrhotic patients were: t 1/2 beta, 34.9 (+/- 8.7) hr; Vd, 0.34 (+/- 0.024) 1/kg; and clearance, 0.185 (+/- 0.34) ml/min/kg. Desmethylchlordiazepoxide (DMCDX), the major metabolite of CDX, appeared in blood of cirrhotic patients less rapidly than in normal subjects. Severity of liver disease did not indicate the impairment of CDX clearance. In 5 of the same cirrhotic patients, mean t 1/2 beta for oxazepam (7.1 +/- 1.0 hr) was 27% longer than in control subjects (5.6 +/- 0.7 hr); the difference is not significant. On kinetic grounds oxazepam may be preferable to chlordiazepoxide in cirrhotic patients since its elimination kinetics are not greatly altered in cirrhosis.

The disposition of chlordiazepoxide (50 mg, intravenously), diazepam (0.143 mg/kg, orally), and oxazepam (0.429 mg/kg, orally) were studied in normal and alcoholic men before and after chronic disulfiram administration. Decreases in the plasma clearance of chlordiazepoxide (54%, p < 0.05), diazepam (41%, p < 0.05), and their active N‐desmethyl metabolites were observed. Oxazepam has no important active metabolites and its net disposition is minimally altered by disulfiram. Oxazepam disposition is unaffected by age and liver disease. These considerations together with that of the short half‐life of oxazepam (median, 6.1 hr) suggest that oxazepam may be the drug of choice if benzodiazepine therapy is used for patients taking disulfiram.

Resistance by Plasmodium falciparum to almost all clinically used antimalarial drugs requires the development of new classes of antimalarials. 6-Iodouridine (15), a novel and potent inhibitor of orotidine 5'-monophosphate decarboxylase (ODCase), exhibited efficacy in a mouse model infected by P. chabaudi chabaudi. Compound 15 exhibited promising antimalarial activity against P. falciparum, including drug-resistant isolates, and no rapid drug-resistant populations of the parasite were observed when challenged with 15. Uridine provided options to overcome any toxicity in the host but still suppressing the parasite load when treated with 15. In drug combination studies, compound 15 showed good efficacy in vivo with artemisinin and azithromycin. The propionyl ester of 15 exhibited superior antimalarial efficacy. Antimalarial activities of 15 and its prodrugs and potential for combination therapy are discussed in the context of novel strategies.

OBJECTIVE: To determine whether the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) is valid in identifying patients who had a clinically important overall improvement with no worsening in other descriptors/systems. METHODS: Consecutive patients with systemic lupus erythematosus with active disease who attended the Lupus Clinic between 2000 and 2012 were studied. Based on the change in the total SLEDAI-2K scores on last visit, patients were grouped as improved, flared/worsened, and unchanged. Patients showing improvement were evaluated for the presence of new active descriptors at last visit compared with baseline visit. RESULTS: Of the 158 patients studied, 109 patients had improved, 38 remained unchanged, and 11 flared/worsened at last visit. In the improved group, 11 patients had a new laboratory descriptor that was not present at baseline visit. In those 11 patients, this new laboratory descriptor was not clinically significant and did not require a change in disease management. CONCLUSION: The SLEDAI-2K identifies improvement in disease activity overall without concealing clinically important worsening.

Alcohol-related liver disease (ARLD) is a common indication for liver transplantation yet it is considered ethically controversial in academic, clinical and public discourses. Various social groups consider people with ARLD as personally responsible for their condition and question whether they should have access to a scarce resource. How the news media constructs responsibility for ARLD may influence public opinions toward those who are ill as well as related healthcare policies. Since the organ transplantation system relies on the willingness of individuals to donate organs, understanding how the media portrays controversial issues is a matter of vital importance for public health and health policy. We investigated how responsibility for ARLD requiring liver transplantation is presented for public consumption in the news media. Using a keyword search of two online news databases, we selected 81 articles from the United Kingdom, Canada and the United States. We analyzed the articles using a discursive psychological approach. We found that the news media ascribed responsibility for ARLD to three main actors: individuals with ARLD, biological predisposition, and policy and industry representatives. How responsibility for ARLD requiring liver transplantation is presented in the news media may have implications for people diagnosed with other substance-related disorders who present for transplant candidacy or are on the transplant waiting list. Investigating how responsibility for ARLD is constructed in news media may provide insights into how responsibility is understood in other stigmatized health conditions and its potential implications for population health equity.

BACKGROUND: Higher-weight individuals report lower rates of physical activity behavior and poorer physical activity experiences compared with their normative-weight counterparts, likely owing to the pervasiveness of weight stigma in physical activity contexts. Employing weight-inclusive strategies may improve physical activity outcomes, though little is known about the practical application of weight-inclusive principles in physical activity contexts. Furthermore, given the prominence of virtual methods of information dissemination, exploring online weight-inclusive resources is valuable. METHODS: Using Google, Instagram, and snowball searches, a virtual environmental scan was conducted to collect publicly available weight-inclusive physical activity resources. Two independent coders applied an a priori codebook to all eligible resources to evaluate the application of weight-inclusive principles. RESULTS: N = 80 weight-inclusive physical activity resources were identified, offering a range of educational materials (40%) and/or provision of physical activity services (76.3%). Virtual resources generally adhered to weight-inclusive principles by showcasing diversity in body size, using weight-inclusive language, and centering physical activity that honors the body's signals and cues; however, some also included weight-normative content. Provisional physical activity resources primarily targeted diverse-bodied end users, offered a range of physical activity types (eg, yoga, weight training, and dance), were membership-based, and offered asynchronous access. CONCLUSIONS: This study utilizes a systematic approach to collect and evaluate virtual, publicly available, and weight-inclusive physical activity resources. Virtual physical activity resources that adhere to weight-inclusive principles may be important for increasing accessible physical activity opportunities for higher-weight individuals.