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The healthcare of people with HIV is transitioning from specialty care to the primary healthcare (PHC) system. However, many of the performance indicators used to measure the quality of HIV care pre-date this transition. The goal of this work was to examine how existing HIV care performance indicators measure the comprehensive and longitudinal care offered in a PHC setting. A scoping review consisting of peer-reviewed and grey literature searches was performed. Two reviewers evaluated study eligibility and indicators in documents meeting inclusion criteria were extracted into a database. Indicators were matched to a PHC performance measurement framework to determine their applicability for evaluating quality of care in the PHC setting. The literature search identified 221 publications, of which 47 met inclusion criteria. 1184 indicators were extracted and removal of duplicates left 558 unique indicators. A majority of the 558 indicators fell under the ‘secondary prevention’ (12%) and ‘care of chronic conditions’ (33%) domains when indicators were matched to the PHC performance framework. Despite the imbalance, nearly all performance domains in the PHC framework were populated by at least one indicator with significant concentrations in domains such as patient-provider relationship, patient satisfaction, population and community characteristics, and access to care. Existing performance frameworks for the care of people with HIV provide a comprehensive set of indicators that align well with a PHC performance framework. Nonetheless, some important elements of care, such as patient-reported outcomes, are poorly covered by existing indicators. Advancing our understanding of how the experience of care for people with HIV is impacted by changes in health services delivery, specifically more care within the PHC system, will require performance indicators to capture this aspect of HIV care.

ObjectivesTo assess consistency in the format and content, and overlap of subject and timing, of medication safety letters issued by regulatory health authorities to healthcare providers in Canada, the USA and the UK.DesignA cross-sectional study comparing medication safety letters issued for the purpose of alerting healthcare providers to newly identified medication problems associated with medications already on the market.SettingOnline databases operated by Health Canada, the US Food and Drug Administration and the UK Medicines and Healthcare products Regulatory Agency were searched to select medication safety letters issued between 1 January 2010 and 31 December 2014. Format, content and timing of each medication safety letter were assessed using an abstraction tool comprising 21 characteristics deemed relevant by consensus of the research team.Main outcome measuresMain outcome measures included, first, characteristics (format and content) of medication safety letters and second, overlap of subject and release date across countries.ResultsOf 330 medication safety letters identified, 227 dealt with unique issues relating to medications available in all three countries. Of these 227 letters, 21 (9%) medication problems were the subject of letters released in all three countries; 40 (18%) in two countries and 166 (73%) in only one country. Only 13 (62%) of the 21 letters issued in all three countries were released within 6 months of each other.ConclusionsSignificant discrepancies in both the subject and timing of medication safety letters issued by health authorities in three countries (Canada, the USA and the UK) where medical practice is otherwise comparable, raising questions about why, how and when medication problems are identified and communicated to healthcare providers by the authorities. More rapid communication of medication problems and better alignment between authorities could enhance patient safety.

Huntington’s disease (HD) is a neurodegenerative disorder caused by the inheritance of one mutant copy of the huntingtin gene. Mutant huntingtin protein (mHtt) contains an expanded polyglutamine repeat region near the N-terminus. Cleavage of mHtt releases an N-terminal fragment (N-mHtt) which accumulates in the nucleus. Nuclear accumulation of N-mHtt has been directly associated with cellular toxicity. Decreased transcription is among the earliest detected changes that occur in the brains of HD patients, animal and cellular models of HD. Transcriptional dysregulation may trigger many of the perturbations that occur later in disease progression. An understanding of the effects of mHtt may lead to strategies to slow the progression of HD. Current models of N-mHtt-mediated transcriptional dysregulation suggest that abnormal interactions between N-mHtt and transcription factors impair the ability of these transcription factors to associate at N-mHtt-affected promoters and properly regulate gene expression. We tested various aspects of the current models using two N-mHtt-affected promoters in two cell models of HD using overexpression of known N-mHtt-interacting transcription factors, promoter deletion and mutation analyses and in vitro promoter binding assays. Consequently, we proposed a new model of N-mHtt-mediated transcriptional dysregulation centered on the presence of N-mHtt at promoters. In this model, N-mHtt interacts with multiple partners whose presence and affinity for N-mHtt influence the severity of gene dysregulation. We concluded that simultaneous interaction of N-mHtt with multiple binding partners within the transcriptional machinery would explain the gene-specificity of N-mHtt-mediated transcriptional dysregulation, as well as why some genes are affected early in disease progression while others are affected later. Our model explains why alleviating N-mHtt-mediated transcriptional dysregulation through overexpression of N-mHtt-interacting proteins has proven to be difficult and suggests that the most realistic strategy for restoring gene expression across the spectrum of N-mHtt affected genes is by reducing the amount of soluble nuclear N-mHtt.

IntroductionPotentially inappropriate prescribing (PIP) is frequent and problematic in older patients. Identifying PIP is necessary to improve prescribing quality; ideally, this should be performed at the population level. Screening Tool of Older Persons’ potentially inappropriate Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) and Beers criteria were developed to identify PIP in clinical settings and are useful at the individual patient level; however, they are time-consuming and costly to apply. Only a subset of these criteria is applicable to routinely collected population-level health administrative data (HAD) because the clinical information necessary to implement these tools is often missing from databases. The performance of subsets of STOPP/START and Beers criteria in HAD compared with clinical data from the same patients is unknown; furthermore, the performance of the updated 2014 STOPP-START and 2012 Beers criteria compared with one another is also unknown.Methods and analysisA cross-sectional study of linked HAD and clinical data will be conducted to validate the subsets of STOPP/START and Beers criteria applicable to HAD by comparing their performance when applied to clinical and HAD for the same patients. Eligible patients will be 66 years and over and recently admitted to 1 of 6 long-term care facilities in Ottawa, Ontario. The target sample size is 275, but may be less if statistical significance can be achieved sooner. Medication, diagnostic and clinical data will be collected by a consultant pharmacist. The main outcome measure is the proportion of PIP missed by the subset of STOPP/START and Beers criteria applied to HAD when compared with clinical data.Ethics and disseminationThe study was approved by the Ottawa Health Services Network Research Ethics Board, the Bruyère Continuing Care Research Ethics Board and the ethics board of the City of Ottawa Long Term Care Homes. Dissemination will occur via publication, national and international conference presentations, and exchanges with regional, provincial and national stakeholders.Trial registration numberNCT02523482.