Approved but Unavailable: A Mystery-Caller Survey of Mifepristone Access in a Large Ontario City.

OBJECTIVES: Mifepristone/misoprostol (mife/miso) has been approved in Canada since 2017, and is available since 2018. Mife/miso does not require witnessed administration in Canada, and therefore most patients obtain a prescription for home use. We sought to determine the proportion of pharmacies in Hamilton, Ontario, Canada, a city of over 500 000, that had combination mife/miso in stock at any given time. METHODS: A mystery-caller approach was used to survey all pharmacies (n = 218) in Hamilton, Ontario, Canada between June 2022 and September 2022. RESULTS: Of the 208 pharmacies that were successfully contacted, only 13 (6%) pharmacies had mife/miso in stock. The most commonly cited reasons for the medication being unavailable were low patient demand (38%), cost (22%), lack of familiarity with medication (13%), supplier issues (9%), training requirements (8%), and medication expiry (7%). CONCLUSIONS: These findings suggest that while mife/miso has been available in Canada since 2017, significant barriers remain to patients accessing this medication. This study clearly demonstrates a need for further advocacy and clinician education to ensure mife/miso is accessible to the patients who require it.

Assessing the prevalence and correlates of prenatal cannabis consumption in an urban Canadian population: a cross-sectional survey.

BACKGROUND: Recreational cannabis use was legalized in Canada in October 2018. We aimed to determine the prevalence and correlates of cannabis consumption among pregnant individuals in a single Canadian city following national legalization. METHODS: Over the period May to October 2019, we distributed an anonymous cross-sectional survey to pregnant patients attending family practice, midwifery, and low-risk and high-risk obstetrics clinics in Hamilton, Ontario. Eligibility was based on English literacy and current pregnancy. The survey included questions regarding lifetime and in-pregnancy cannabis use, intent for postpartum use and patterns of use. We also collected demographic information. We calculated descriptive statistics and performed logistic regression analyses to explore the relations between cannabis consumption and demographic characteristics. RESULTS: Of 531 pregnant individuals approached, 478 agreed and were able to participate, for a 90% participation rate. Among these 478 respondents, 54 (11%) reported consuming cannabis at some point during the pregnancy and 20 (4%) reported currently consuming cannabis. Among the 460 respondents who intended to breastfeed, 23 (5%) planned to consume cannabis during the postpartum period. Of 20 current users, 13 (65%) reported consuming cannabis at least weekly and 19 (95%) reported nausea, sleep problems or anxiety as reasons for use. Respondents without postsecondary education had 10.0-fold (95% confidence interval [CI] 4.6-23.5) greater odds of prenatal cannabis consumption than university-educated respondents. In addition, respondents who reported that their partners used cannabis had 3.9-fold (95% CI 2.2-7.3) greater odds of prenatal cannabis consumption than those who reported that their partners did not use cannabis. INTERPRETATION: Lower educational attainment and partners' cannabis consumption were associated with greater odds of inpregnancy cannabis use. These results may help to inform early intervention strategies to decrease cannabis consumption during this vulnerable period of fetal and neonatal development.

Pregnant Canadians' Perceptions About the Transmission of Cannabis in Pregnancy and While Breastfeeding and the Impact of Information From Health Care Providers on Discontinuation of Use.

OBJECTIVE: Rates of cannabis use during pregnancy and while breastfeeding are increasing in Canada. Some observational studies have found associations between cannabis use in pregnancy and low birthweight, preterm labour, and admission to the intensive care unit. This study aimed to evaluate women's perceptions about transmission of cannabis to the fetus, and whether receiving information from a health care provider influenced their decision to stop using cannabis during pregnancy. METHODS: Pregnant women presenting to obstetrical, midwifery, and family practice clinics in the greater Hamilton, Ontario area were asked to complete an anonymous survey. Chi-square tests were used to investigate whether patient knowledge was influenced by health care providers or by self-directed learning and if this information influenced their decision to discontinue cannabis use. RESULTS: Of the 478 women surveyed, the vast majority perceived that cannabis is transmitted to the fetus during pregnancy and to the infant while breastfeeding (94.3% and 91.2%, respectively). The majority of women (99%) indicated that the advent of cannabis legalization did not influence their choice to use cannabis in pregnancy. Women who continued to use cannabis during pregnancy were more likely to report receiving information on cannabis from a health care provider (52%) than those who chose to discontinue use in pregnancy (35%) (P = 0.035). CONCLUSIONS: In our study, the proportion of pregnant women who understood that cannabis could be transmitted to the fetus in utero and to the infant via breastmilk was high. Despite this, 4.2% of women reported that they continued to use cannabis in pregnancy. More work is needed to understand why some women continue to use cannabis in pregnancy despite being informed of its risks.

The 10,000 PhDs project at the University of Toronto: Using employment outcome data to inform graduate education.

The purpose of the 10,000 PhDs Project was to determine the current (2016) employment status of the 10,886 individuals who graduated from the University of Toronto with a PhD in all disciplines from 2000-2015. Using internet searches, we found that about half (51%) of the PhD graduates are employed in the post-secondary education sector, 26% as tenure-track professors, with an additional 3% as adjunct professors and 2% as full-time teaching-stream professors. Over the time-period 2000-2015 there has been a near doubling in PhD graduates with the biggest increase in graduation numbers for the Physical (2.6-fold) and Life Sciences (2.2-fold). Increasingly, these graduates are finding employment in the private and public sectors providing the highly qualified personnel needed to drive an innovation economy.

Cough Frequency During Treatment Associated With Baseline Cavitary Volume and Proximity to the Airway in Pulmonary TB.

BACKGROUND: Cough frequency, and its duration, is a biomarker that can be used in low-resource settings without the need of laboratory culture and has been associated with transmission and treatment response. Radiologic characteristics associated with increased cough frequency may be important in understanding transmission. The relationship between cough frequency and cavitary lung disease has not been studied. METHODS: We analyzed data in 41 adults who were HIV negative and had culture-confirmed, drug-susceptible pulmonary TB throughout treatment. Cough recordings were based on the Cayetano Cough Monitor, and sputum samples were evaluated using microscopic observation drug susceptibility broth culture; among culture-positive samples, bacillary burden was assessed by means of time to positivity. CT scans were analyzed by a US-board-certified radiologist and a computer-automated algorithm. The algorithm evaluated cavity volume and cavitary proximity to the airway. CT scans were obtained within 1 month of treatment initiation. We compared small cavities (≤ 7 mL) and large cavities (> 7 mL) and cavities located closer to (≤ 10 mm) and farther from (> 10 mm) the airway to cough frequency and cough cessation until treatment day 60. RESULTS: Cough frequency during treatment was twofold higher in participants with large cavity volumes (rate ratio [RR], 1.98; P = .01) and cavities located closer to the airway (RR, 2.44; P = .001). Comparably, cough ceased three times faster in participants with smaller cavities (adjusted hazard ratio [HR], 2.89; P = .06) and those farther from the airway (adjusted HR, 3.61;, P = .02). Similar results were found for bacillary burden and culture conversion during treatment. CONCLUSIONS: Cough frequency during treatment is greater and lasts longer in patients with larger cavities, especially those closer to the airway.

Dynamics of Cough Frequency in Adults Undergoing Treatment for Pulmonary Tuberculosis.

Background: Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load. Methods: We prospectively evaluated human immunodeficiency virus-negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load. Results: The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2-4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0-1.4) and at the end of the study decreased to 0.18 (IQR, 0.0-0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%-41%). Conclusions: Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission.

Pupillary Light Reflexes are Associated with Autonomic Dysfunction in Bolivian Diabetics But Not Chagas Disease Patients.

Autonomic dysfunction is common in Chagas disease and diabetes. Patients with either condition complicated by cardiac autonomic dysfunction face increased mortality, but no clinical predictors of autonomic dysfunction exist. Pupillary light reflexes (PLRs) may identify such patients early, allowing for intensified treatment. To evaluate the significance of PLRs, adults were recruited from the outpatient endocrine, cardiology, and surgical clinics at a Bolivian teaching hospital. After testing for Chagas disease and diabetes, participants completed conventional autonomic testing (CAT) evaluating their cardiovascular responses to Valsalva, deep breathing, and orthostatic changes. PLRs were measured using specially designed goggles, then CAT and PLRs were compared as measures of autonomic dysfunction. This study analyzed 163 adults, including 96 with Chagas disease, 35 patients with diabetes, and 32 controls. PLRs were not significantly different between Chagas disease patients and controls. Patients with diabetes had longer latency to onset of pupil constriction, slower maximum constriction velocities, and smaller orthostatic ratios than nonpatients with diabetes. PLRs correlated poorly with CAT results. A PLR-based clinical risk score demonstrated a 2.27-fold increased likelihood of diabetes complicated by autonomic dysfunction compared with the combination of blood tests, CAT, and PLRs (sensitivity 87.9%, specificity 61.3%). PLRs represent a promising tool for evaluating subclinical neuropathy in patients with diabetes without symptomatic autonomic dysfunction. Pupillometry does not have a role in the evaluation of Chagas disease patients.

Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas.

BACKGROUND: The large airways of the lungs (trachea and bronchi) are lined with a pseudostratified mucociliary epithelium, which is maintained by stem cells/progenitors within the basal cell compartment. Alterations in basal cell behavior can contribute to large airway diseases including squamous cell carcinomas (SQCCs). Basal cells have traditionally been thought of as a uniform population defined by basolateral position, cuboidal cell shape, and expression of pan-basal cell lineage markers like KRT5 and TP63. While some evidence suggests that basal cells are not all functionally equivalent, few heterogeneously expressed markers have been identified to purify and study subpopulations. In addition, few signaling pathways have been identified that regulate their cell behavior. The goals of this work were to investigate tracheal basal cell diversity and to identify new signaling pathways that regulate basal cell behavior. METHODS: We used flow cytometry (FACS) to profile cell surface marker expression at a single cell level in primary human tracheal basal cell cultures that maintain stem cell/progenitor activity. FACS results were validated with tissue staining, in silico comparisons with normal basal cell and lung cancer datasets, and an in vitro proliferation assay. RESULTS: We identified 105 surface markers, with 47 markers identifying potential subpopulations. These subpopulations generally fell into more (~ > 13%) or less abundant (~ < 6%) groups. Microarray gene expression profiling supported the heterogeneous expression of these markers in the total population, and immunostaining of large airway tissue suggested that some of these markers are relevant in vivo. 24 markers were enriched in lung SQCCs relative to adenocarcinomas, with four markers having prognostic significance in SQCCs. We also identified 33 signaling receptors, including the MST1R/RON growth factor receptor, whose ligand MST1/MSP was mitogenic for basal cells. CONCLUSION: This work provides the largest description to date of molecular diversity among human large airway basal cells. Furthermore, these markers can be used to further study basal cell function in repair and disease, and may aid in the classification and study of SQCCs.

Detection and genogrouping of noroviruses from children's stools by Taqman One-step RT-PCR.

Noroviruses (NoVs) are the leading cause of outbreaks of sporadic acute gastroenteritis worldwide in humans of all ages. They are important cause of hospitalizations in children with a public health impact similar to that of Rotavirus. NoVs are RNA viruses of great genetic diversity and there is a continuous appearance of new strains. Five genogroups are recognized; GI and GII with their many genotypes and subtypes being the most important for human infection. However, the diagnosis of these two genotypes remains problematic, delaying diagnosis and treatment. For RNA extraction from stool specimens the most commonly used method is the QIAmp Viral RNA commercial kit from Qiagen. This method combines the binding properties of a silica gel membrane, buffers that control RNases and provide optimum binding of the RNA to the column together with the speed of microspin. This method is simple, fast and reliable and is carried out in a few steps that are detailed in the description provided by the manufacturer. Norovirus is second only to rotavirus as the most common cause of diarrhea. Norovirus diagnosis should be available in all studies on pathogenesis of diarrhea as well as in outbreaks or individual diarrhea cases. At present however norovirus diagnosis is restricted to only a few centers due to the lack of simple methods of diagnosis. This delays diagnosis and treatment. In addition, due to costs and regulated transportation of corrosive buffers within and between countries use of these manufactured kits poses logistical problems. As a result, in this protocol we describe an alternative, economic, in-house method which is based on the original Boom et al. method which uses the nucleic acid binding properties of silica particles together with the anti-nuclease properties of guanidinium thiocyanate. For the detection and genogrouping (GI and GII) of NoVs isolates from stool specimens, several RT-PCR protocols utilizing different targets have been developed. The consensus is that an RT-PCR using TaqMan chemistry would be the best molecular technique for diagnosis, because it combines high sensitivity, specificity and reproducibility with high throughput and ease of use. Here we describe an assay targeting the open reading frame 1 (ORF1)-ORF2 junction region; the most conserved region of the NoV genome and hence most suitable for diagnosis. For further genetic analysis a conventional RT-PCR that targets the highly variable N-terminal-shell from the major protein of the capsid (Region C) using primers originally described by Kojima et al. is detailed. Sequencing of the PCR product from the conventional PCR enables the differentiation of genotypes belonging to the GI and GII genogroups.