Influence of chronic barbiturate administration on sleep apnea after hypersomnia presentation: case study

When sleepiness is excessive, undesirable, inappropriate or unexplained, it often indicates a clinical disorder that is generically termed hypersomnia. One of the leading causes of hypersomnia is sleep apnea. We present the case of a 44-year-old woman with a history of bipolar spectrum disorder and epilepsy who initially showed evidence of hypersomnia. The hypersomnia settled with changes to her medication, but the patient was subsequently found to have severe obstructive sleep apnea. The relation between the patient's medication and sleep apnea is discussed, and the possible respiratory-suppressant effects of chronic barbiturate treatment are considered. The role of other evoking factors within the context of this case and the mechanisms by which drug interactions and psychotropic treatment may worsen, obscure or perpetuate sleep apnea are also examined.     

Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration’s RWE Data Working Group

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8–11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration’s Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.     

An interstitial deletion of the long arm of chromosome 21 in a case of a first episode of psychosis

OBJECTIVE: Case of an interstitial deletion of the long arm of chromosome 21 presenting with first episode of psychosis. METHOD: A case report. RESULTS: A 16-year-high school student of Somalian origin presented with a first episode of psychosis, mild mental retardation and dysmorphic features. Chromosome analysis revealed an interstitial deletion in the long arm of chromosome 21, described as 46, XX del (21) (q21q22.1). CONCLUSION: First episode of psychosis occurred in combination with neurobiological vulnerability and a complex genetic inheritance. The occurrence of psychosis in our case may be attributable to genes located within the region 21q21q22.1. The possibility that other loci exist on chromosome 21, which predispose to schizophrenia has to be considered. Identification of susceptibility genes will greatly facilitate investigation of factors that contribute to the disease process and may lead to early intervention and prevention.     

[11C]PBR28 PET imaging is sensitive to neuroinflammation in the aged rat

Neuroinflammation in the aging rat brain was investigated using [¹¹C]PBR28 microPET (positron emission tomography) imaging. Normal rats were studied alongside LRRK2 p.G2019S transgenic rats; this mutation increases the risk of Parkinson''s disease in humans. Seventy [¹¹C]PBR28 PET scans were acquired. Arterial blood sampling enabled tracer kinetic modeling and estimation of V_T. In vitro autoradiography was also performed. PBR28 uptake increased with age, without differences between nontransgenic and transgenic rats. In 12 months of aging (4 to 16 months), standard uptake value (SUV) increased by 56% from 0.44 to 0.69 g/mL, whereas V_T increased by 91% from 30 to 57 mL/cm³. Standard uptake value and V_T were strongly correlated (r=0.52, 95% confidence interval (CI)=0.31 to 0.69, n=37). The plasma free fraction, f_p, was 0.21±0.03 (mean±standard deviation, n=53). In vitro binding increased by 19% in 16 months of aging (4 to 20 months). The SUV was less variable across rats than V_T; coefficients of variation were 13% (n=27) and 29% (n=12). The intraclass correlation coefficient for SUV was 0.53, but was effectively zero for V_T. These data show that [¹¹C]PBR28 brain uptake increases with age, implying increased microglial activation in the aged brain.     

An unmasking phenomenon in an observational post-licensure safety study of adolescent girls and young women

Our recent experience in a post-licensure safety study of autoimmune conditions following the quadrivalent human papillomavirus vaccine in 189,629 girls and young women ages 9-26 years led us to question the adequacy of the exclusion of Day 0 events to prevent the erroneous association of prevalent conditions with vaccination. Of the 18 confirmed cases of Graves' disease diagnosed in days 1-60 following vaccination, only 6 cases appeared to be truly new onset. Among the remaining 12 cases, 2 cases had abnormal thyroid stimulating hormone or thyroxine labs drawn prior to or on Day 0 but had no documented pre-existing symptoms. The other 10 cases had mention of symptoms of hyperthyroidism referencing a period prior to first HPV-4 dose. This 'unmasking' phenomenon, due to health care visits that include vaccination and new workups of preexisting symptoms, may not be adequately controlled through the exclusion of Day 0 events.