Quarantining From Professional Identity: How Did COVID-19 Impact Professional Identity Formation in Undergraduate Medical Education?

Introduction: Professional Identity Formation (PIF) entails the integration of a profession's core values and beliefs with an individual's existing identity and values. Within undergraduate medical education (UGME), the cultivation of PIF is a key objective. The COVID-19 pandemic brought about substantial sociocultural challenges to UGME. Existing explorations into the repercussions of COVID-19 on PIF in UGME have predominantly adopted an individualistic approach. We sought to examine how the COVID-19 pandemic influenced PIF in UGME from a sociocultural perspective. This study aims to provide valuable insights for effectively nurturing PIF in future disruptive scenarios. Methods: Semi structured interviews were conducted with medical students from the graduating class of 2022 (n = 7) and class of 2023 (n = 13) on their medical education experiences during the pandemic and its impact on their PIF. We used the Transformation in Medical Education (TIME) framework to develop the interview guide. Direct content analysis was used for data analysis. Results: The COVID-19 pandemic significantly impacted the UGME experience, causing disruptions such as an abrupt shift to online learning, increased social isolation, and limited in-person opportunities. Medical students felt disconnected from peers, educators, and the clinical setting. In the clerkship stage, students recognized knowledge gaps, producing a "late blooming" effect. There was increased awareness for self-care and burnout prevention. Discussion: Our study suggests that pandemic disruptors delayed PIF owing largely to slower acquisition of skills/knowledge and impaired socialization with the medical community. This highlights the crucial role of sociocultural experiences in developing PIF in UGME. PIF is a dynamic and adaptable process that was preserved during the COVID-19 pandemic.

Three-Year Outcomes Following Permissive Cardiotoxicity in Patients on Trastuzumab.

INTRODUCTION: Cardiotoxicity, manifest by reduced left ventricular ejection fraction (LVEF), is the most common reason for the premature discontinuation of trastuzumab. While permissive cardiotoxicity (where mild cardiotoxicity is accepted to enable ongoing trastuzumab) has been shown feasible, the longer-term outcomes are unknown. We aimed to study the intermediate-term clinical outcomes of patients who underwent permissive cardiotoxicity. MATERIALS AND METHODS: We performed a retrospective cohort study of patients referred to the cardio-oncology service at McMaster University from 2016 to 2021 for LV dysfunction following trastuzumab administration. RESULTS: Fifty-one patients underwent permissive cardiotoxicity. The median (25th-75th percentile) follow-up time from cardiotoxicity onset was 3 years (1.3-4 years). Forty-seven (92%) patients completed trastuzumab; 3 (6%) developed severe LV dysfunction or clinical heart failure (HF) while on trastuzumab and prematurely discontinued therapy. One discontinued trastuzumab by patient choice. At final follow-up after therapy completion, 7 (14%) patients still had mild cardiotoxicity, including 2 who had clinical heart failure and stopped trastuzumab early. Among those with recovered LV function, 50% had normalized LVEF or GLS by 6 and 3 months, respectively, after initial cardiotoxicity. There was no difference in characteristics between those who did or did not recover their LV function. CONCLUSIONS: Among patients exposed to permissive trastuzumab cardiotoxicity for HER2-positive breast cancer, 6% were unable to complete planned trastuzumab due to severe LV dysfunction or clinical HF. Although most patients recover their LV function after trastuzumab discontinuation or completion, 14% still have persistent cardiotoxicity by 3-year follow-up.

High-Dose Thiamine Supplementation in Older Patients With Heart Failure: A Pilot Randomized Controlled Crossover Trial (THIAMINE-HF).

Background: Thiamine supplementation may improve cardiac function in older adults with heart failure (HF). Our objectives were to determine the following: (i) the feasibility of conducting a large trial of thiamine supplementation in HF; and (ii) the effects of thiamine on clinical outcomes. Methods: We conducted a double-blinded randomized placebo-controlled 2-period crossover feasibility study from June 2018 to April 2021. Adults aged ≥ 60 years with symptomatic HF and reduced ejection fraction (≤ 45%) were included. Participants were randomized to thiamine mononitrate 500 mg, or placebo, for 90 days and were switched to the opposite treatment for 90 days after a 6-week washout period. The primary feasibility outcome was recruitment of 24 participants in 11 months. Results: We screened 330 patients over 21 months to recruit 24 patients. Participants' mean age was 73.4 years. The targets for refusal rate, retention rate, and adherence rate were met. Nonsignificant improvements occurred in left ventricular ejection fraction and N-terminal pro-brain natriuretic peptide (NT-proBNP) level with thiamine. A total of 13 serious adverse events occurred in 7 patients; none were related to the study drug. Conclusions: Although we did not reach our recruitment target, we found high-dose thiamine supplementation to be well tolerated, with potential improvements in biomarker outcomes. A larger trial of thiamine supplementation is warranted.

Introduction: La supplémentation en thiamine peut améliorer la fonction cardiaque chez les personnes âgées atteintes d'insuffisance cardiaque (IC). Nos objectifs visaient à déterminer : (i) la faisabilité d'un essai de grande envergure sur la supplémentation en thiamine lors d'IC ; (ii) les effets de la thiamine sur les résultats cliniques. Méthodes: Nous avons réalisé une étude de faisabilité croisée à double insu et à répartition aléatoire contre placebo sur deux périodes de juin 2018 à avril 2021. Nous avons retenu les adultes de ≥ 60 ans qui avaient une IC symptomatique et une fraction d'éjection réduite (≤ 45 %). Nous avons réparti les participants de façon aléatoire pour recevoir 500 mg de mononitrate de thiamine ou le placebo durant 90 jours, et avons inversé le traitement durant 90 jours après une période de lavage de 6 semaines. Le principal critère de faisabilité était le recrutement de 24 participants en 11 mois. Résultats: Nous avons recruté 24 patients sur les 330 patients sélectionnés durant 21 mois. L'âge moyen des participants était de 73,4 ans. Les cibles des taux de refus, des taux de rétention et des taux d'adhésion ont été atteintes. Avec la thiamine, nous avons observé des améliorations non significatives de la fraction d'éjection ventriculaire gauche et de la concentration de propeptide natriurétique de type B N-terminal (NT-proBNP). Parmi les 13 événements indésirables sérieux qu'ont subis sept patients, aucun n'a été associé au médicament étudié. Conclusions: Bien que nous n'ayons pas atteint notre cible de recrutement, nous avons observé que la supplémentation en thiamine à dose élevée était bien tolérée et qu'il y avait des améliorations potentielles des résultats des biomarqueurs. Un essai de plus grande envergure sur la supplémentation en thiamine est justifié.

Pulmonary artery catheterization in patients with cardiogenic shock: a systematic review and meta-analysis.

PURPOSE: Cardiogenic shock carries high morbidity and mortality. The purpose of this review was to determine the safety and efficacy of pulmonary artery catheterization (PAC) in adult patients hospitalized with cardiogenic shock. SOURCE: We performed a systematic review and meta-analysis of observational studies and randomized controlled trials comparing PAC vs no PAC in cardiogenic shock. We searched MEDLINE, EMBASE, Cochrane CENTRAL, and grey literature. We screened articles, abstracted data, and evaluated risk of bias in duplicate. We pooled data using a random-effects model and evaluated the quality of evidence using the GRADE framework. Outcomes of interest were mortality, length of stay, and procedural complications. PRINCIPAL FINDINGS: We identified 19 eligible observational studies (≥ 2,716,287 patients) and no randomized controlled trials; 14 studies were at high risk of bias (lack of adjustment for prognostic variables and/or co-interventions). When pooling adjusted results, PAC was associated with improved survival to hospital discharge (relative risk [RR], 0.77; 95% confidence interval [CI], 0.64 to 0.91, I2 = 98%; very low-quality evidence) and at longest available follow-up (RR, 0.72; 95% CI, 0.60 to 0.87; I2 = 99%; very low-quality evidence). Unadjusted length of stay was 3.5 days longer (95% CI, 1.49 to 5.54; I2 = 100%; very low-quality evidence) with PAC. Procedural complications were inconsistently reported. CONCLUSIONS: Very low-quality observational evidence suggests PAC use in patients with cardiogenic shock is associated with lower mortality. Overall, these results support consideration of PAC for hemodynamic assessment in cardiogenic shock. Prospective randomized clinical trials are needed to further characterize the role of PAC in this population.

RéSUMé: OBJECTIF: Le choc cardiogénique entraîne une morbidité et une mortalité élevées. Le but de cette revue était de déterminer la sécurité et l'efficacité de l'utilisation d'un cathétérisme de l'artère pulmonaire (CAP) chez des patients adultes hospitalisés en choc cardiogénique. SOURCES: Nous avons réalisé une revue systématique et une méta-analyse d'études observationnelles et d'études randomisées contrôlées comparant l'utilisation vs la non-utilisation de CAP pour le traitement d'un choc cardiogénique. Nous avons effectué des recherches dans les bases de données MEDLINE, EMBASE, Cochrane CENTRAL et dans la littérature grise. Nous avons examiné les articles, résumé les données et évalué le risque de biais à deux reprises. Nous avons regroupé les données à l'aide d'un modèle à effets aléatoires et évalué la qualité des données probantes en nous appuyant sur le système GRADE. Les issues d'intérêt étaient la mortalité, la durée de séjour et les complications procédurales. CONSTATATIONS PRINCIPALES: Nous avons identifié 19 études observationnelles admissibles (≥ 2 716 287 patients) et aucune étude randomisée contrôlée; 14 études comportaient un risque élevé de biais (absence d'ajustement sur les variables pronostiques et/ou les interventions concomitantes). En regroupant les résultats ajustés, le CAP a été associé à une meilleure survie jusqu'au congé de l'hôpital (risque relatif [RR], 0,77; intervalle de confiance [IC] à 95 %, 0,64 à 0,91, I2 = 98 %; données probantes de très faible qualité) et jusqu'au point de suivi disponible rapporté le plus lointain dans le temps (RR, 0,72; IC 95 %, 0,60 à 0,87; I2 = 99 %; données probantes de très faible qualité). La durée de séjour non ajustée était 3,5 jours plus longue (IC 95 %, 1,49 à 5,54; I2 = 100 %; données probantes de très faible qualité) avec un CAP. Les complications procédurales n'étaient par rapportées de manière uniforme. CONCLUSION: Des données observationnelles de très faible qualité suggèrent que l'utilisation d'un CAP chez des patients en choc cardiogénique est associée à une réduction de la mortalité. Dans l'ensemble, ces résultats suggèrent de considérer le CAP pour l'évaluation hémodynamique en cas de choc cardiogénique. Des études cliniques randomisées prospectives sont nécessaires pour mieux caractériser le rôle du CAP dans cette population.

Cardiogenic shock in the context of newly diagnosed anomalous origin of the right coronary artery originating from the pulmonary artery: a case report.

BACKGROUND: Anomalous right coronary artery (RCA) from the pulmonary artery (ARCAPA) is a rare congenital heart abnormality with varying clinical presentations, for which multiple imaging modalities are often required for diagnosis. CASE SUMMARY: We present a case of a 76-year-old female presenting with 2 weeks of palpitations and shortness of breath who was found to be in rapid atrial fibrillation (AF) with congestive heart failure. Despite initial medical management, the patient developed cardiogenic shock with anuric renal failure. Emergent right and left heart catheterization did not demonstrate any significant obstructive coronary artery disease but showed severe right ventricular (RV) failure and raised the possibility of an ARCAPA. This diagnosis was further corroborated by findings on a subsequent transoesophageal echocardiogram. In view of profound decline and limited anticipated improvement, the patient ultimately decided to pursue comfort measures in a hospice setting. DISCUSSION: We postulate that the underlying aetiology of our patient's shock state was multifactorial, notably progressive RCA-territory ischaemia and RV failure, sepsis, and new-onset uncontrolled AF. In adults, unrecognized congenital heart disease can uncommonly cause cardiogenic shock. In our case, echocardiography and invasive angiography were integrated for the diagnosis of ARCAPA given the clinical circumstances that limited the use of cardiac computed tomography angiography.

Characterization of Listeria monocytogenes isolates from lactating dairy cows in a Wisconsin farm: Antibiotic resistance, mammalian cell infection, and effects on the fecal microbiota.

Listeria monocytogenes is an invasive foodborne pathogen that is ubiquitously present in the dairy farm environment. Although cattle are a reservoir of L. monocytogenes, most adult animals do not exhibit clinical symptoms, suggesting a homeostasis between this pathogen and the bovine gastrointestinal ecosystem. Nevertheless, substantial prevalence of L. monocytogenes fecal shedding by dairy cattle has been reported in many studies, posing threats of transmission within the herd and contamination of the human food supply. Accordingly, understanding the L. monocytogenes ecology within the bovine gastrointestinal tract is important to prevent clinical illness in the animal host, reduce transmission, and guide intervention strategies. In this study, we conducted a longitudinal sampling of fecal samples from 20 lactating dairy cows in one Wisconsin farm over a 29-d period and found a strikingly high incidence of L. monocytogenes shedding, in 90% of sampled animals. The L. monocytogenes isolates were genetically diverse, representing all common serotypes previously identified from cattle. Additionally, most tested isolates were resistant to ampicillin, and a few were also resistant to gentamicin or trimethoprim/sulfamethoxazole. Most isolates effectively infected human epithelial cells (Caco-2) and murine fibroblasts (L2), suggesting that they are all capable of causing systemic infection if the intestinal barrier is breached. Finally, we investigated the effects of L. monocytogenes colonization on the gastrointestinal tract microbiota by analyzing the fecal bacterial communities of some shedding and nonshedding cows. Whereas L. monocytogenes did not affect the α and ß diversity of tested animals, a subset of shedding cows exhibited different abundances of certain operational taxonomic units within the Bacteroidetes and Firmicutes phyla compared with nonshedding cows. Overall, our findings highlight the threat of antibiotic resistance among some L. monocytogenes isolates, emphasize the need for a strain-specific approach in listeriosis treatment, and suggest the potential negative influence of subclinical L. monocytogenes carriage on animal gut health.

Costs of surgical ablation of atrial fibrillation in Ontario, Canada from 2006 to 2017.

BACKGROUND: International guidelines currently recommend concomitant surgical ablation of atrial fibrillation (AF) in patients with AF undergoing cardiac surgery. However, a systematic review and meta-analysis of 23 randomized controlled trials (RCTs) showed no significant difference in mortality or stroke in patients who underwent surgical AF ablation compared with those who did not (moderate-quality evidence). METHODS: We estimated the Ontario-wide costs of surgical AF ablation between 2006 and 2017 using data from a systematic review and meta-analysis of RCTs, estimates of case volumes from Ontario Health Insurance Plan fee codes, the ongoing left atrial appendage occlusion study III trial (NCT01561651), institutional costs from large academic centers in Ontario, as well as professional fees based on the Ontario fee schedule. Device costs were obtained from Canadian industry data with expert input. RESULTS: We estimated the average extra cost of surgical AF ablation at $4,287 CAD (95% CI $4,113-4,619) per patient. Procedural costs (equipment costs and physician remuneration) comprise 82.2% of this, while smaller portions relate to the increased need for pacemaker (3.9%) and additional hospital length of stay (13.9%). Approximately 2,391 patients underwent surgical AF ablation between 2006 and 2017, corresponding to an estimated $10.2 million in incremental cost during that time span. CONCLUSION: Ontario taxpayers spend significant financial resources on surgical ablation of AF, a procedure lacking high-quality evidence demonstrating benefit in reducing mortality or stroke. Further large prospective studies examining clinically important outcomes are needed to justify its routine use in patient care and to guide allocation of healthcare funds.

Cardiovascular Collapse in COVID-19 Infection: The Role of Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO).

Coronavirus Disease 2019 (COVID-19) has been associated with cardiovascular complications, including acute cardiac injury, heart failure, and cardiogenic shock (CS). The role of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in the event of COVID-19-associated cardiovascular collapse has not been established. We reviewed the existing literature surrounding the role of VA-ECMO in the treatment of coronavirus-related cardiovascular collapse. COVID-19 is associated with a higher incidence of cardiovascular complications compared with previous coronavirus outbreaks (Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus). We found only 1 case report from China in which COVID-19-associated fulminant myocarditis and CS were successfully rescued using VA-ECMO as a bridge to recovery. We identified potential clinical scenarios (cardiac injury, myocardial infarction with and without obstructive coronary artery disease, viral myocarditis, and decompensated heart failure) leading to CS and risk factors for poor/uncertain benefit (age, sepsis, mixed/predominantly vasodilatory shock, prothrombotic state or coagulopathy, severe acute respiratory distress syndrome, multiorgan failure, or high-risk prognostic scores) specific to using VA-ECMO as a bridge to recovery in COVID-19 infection. Additional considerations and proposed recommendations specific to the COVID-19 pandemic were formulated with guidance from published data and expert consensus. A small subset of patients with cardiovascular complications from COVID-19 infection may progress to refractory CS. While accepting that resource scarcity may be the overwhelming concern for healthcare systems during this pandemic, VA-ECMO can be considered in highly selected cases of refractory CS and echocardiographic evidence of biventricular failure. The decision to initiate this therapy should take into consideration the availability of resources, perceived benefit, and risks of transmitting disease.

La maladie à coronavirus 2019 (COVID-19) est associée à des complications cardiovasculaires, y compris des lésions cardiaques aiguës, l'insuffisance cardiaque et le choc cardiogénique (CC). Le rôle de l'oxygénation par membrane extracorporelle (ECMO pour extracorporeal membrane oxygenation) veino-artérielle dans les cas de collapsus cardiovasculaire associé à la COVID-19 n'a pas été établi. Nous avons passé en revue la documentation existante abordant le rôle de l'ECMO veino-artérielle dans le traitement du collapsus cardiovasculaire lié au coronavirus. La COVID-19 est associée à une incidence plus élevée de complications cardiovasculaires comparativement aux éclosions antérieures d'infections à coronavirus (syndrome respiratoire aigu sévère et syndrome respiratoire du Moyen-Orient). Nous n'avons trouvé qu'un seul cas (signalé en Chine) de myocardite fulminante et de CC associés à la COVID-19 où l'ECMO veino-artérielle a permis d'assurer la survie du patient dans l'attente d'une récupération de la fonction cardiaque. Nous avons ciblé divers scénarios cliniques (lésion cardiaque, infarctus du myocarde avec ou sans coronaropathie obstructive, myocardite virale et insuffisance cardiaque décompensée) susceptibles d'aboutir à un CC et cerné des facteurs de risque de bienfaits faibles ou incertains (âge, septicémie, choc vasodilatateur mixte ou prédominant, état prothrombotique ou coagulopathie, syndrome de détresse respiratoire aiguë sévère, défaillance multiviscérale ou scores pronostiques à haut risque) cadrant spécifiquement avec l'utilisation de l'ECMO veino-artérielle dans l'attente d'une récupération de la fonction cardiaque chez le patient atteint de COVID-19. D'autres considérations et recommandations visant spécifiquement la pandémie de COVID-19 ont été énoncées à la lumière des données publiées et d'un consensus d'experts. Au sein d'un petit sous-groupe de patients atteints de COVID-19, les complications cardiovasculaires de l'infection peuvent évoluer vers un CC réfractaire. Tout en acceptant que la pénurie de ressources puisse être la principale préoccupation des systèmes de santé pendant cette pandémie, on peut envisager de recourir à l'ECMO veino-artérielle dans des cas soigneusement sélectionnés de CC réfractaire et en présence de preuves échocardiographiques d'insuffisance biventriculaire. La décision d'instaurer ce traitement doit tenir compte de la disponibilité des ressources, des avantages perçus et des risques de transmission de la maladie.

Suicide Attempt by Self-Dissection of Permanent Pacemaker Leads.

We present the case of a patient with depression who attempted suicide through self-dissection and severing of her permanent pacemaker leads. The case highlights the importance of screening for psychiatric disorders prior to device implantation and continued surveillance for self-harm behaviors. (Level of Difficulty: Beginner.).

It's Time to Talk: Challenges in Providing Integrated Palliative Care in Advanced Congestive Heart Failure. A Narrative Review.

BACKGROUND: Congestive heart failure is an increasingly prevalent terminal illness in a globally aging population. Prognosis for this disease remains poor despite optimal therapy. Evidence suggests that a palliative care approach may be beneficial - and is currently recommended - in advanced congestive heart failure but these services remain underutilized. OBJECTIVES: To identify the main challenges to the access and delivery of palliative care in patients with advanced congestive heart failure, and to summarize recommendations for clinical practice based on the available literature. METHODS: MEDLINE and EMBASE were searched for articles published from 1995-2017 pertaining to end of life care in individuals suffering from CHF. Only four randomized controlled trials were found. RESULTS: We identified ten key challenges to access and delivery of palliative care services in this patient population: (1) Prognostic uncertainty, (2) Provider education/training, (3) Ambiguity surrounding coordination of care, (4) Timing of palliative care referral, (5) Inadequate community supports, (6) Difficulty communicating uncertainty, (7) Fear of taking away hope, (8) Insufficient advance care planning, (9) Inadequate understanding of illness, and (10) Discrepant patient/family care goals. Provider and patient education, early discussion about prognosis, and a multidisciplinary team-based approach are recommended as we move towards a model where symptom palliation exists concurrently with active disease-modifying therapies. CONCLUSION: Despite evidence that palliative care may improve symptom control and quality of life in patients with advanced congestive heart failure, a multitude of current challenges hinder access to these services. Education, early discussion of prognosis and advance care planning, and multidisciplinary team-based care may be a helpful initial approach as further targeted work addresses these challenges.

Xanthogranulomatous pyelonephritis presenting as acute pleuritic chest pain: a case report.

BACKGROUND: Xanthogranulomatous pyelonephritis is a rare and serious manifestation of chronic kidney inflammation that can be life-threatening if not recognized and treated appropriately, often with antibiotics and surgery. Affected patients are most commonly females in their fifth or sixth decade of life with a background of obstructive uropathy, nephrolithiasis, or recurrent urinary tract infections who present with vague nonspecific symptoms. CASE PRESENTATION: A 43-year-old woman of Russian ethnicity with a history of nephrolithiasis presented to our emergency department with new left-sided pleuritic chest pain amid a 6-week history of constitutional symptoms including fevers, night sweats, and 7 kg of weight loss. Workup for acute coronary syndrome and pulmonary embolism in our emergency department was negative. Given that she was clinically unwell, she was admitted to internal medicine to expedite workup for the cause of her symptoms. A broad differential diagnosis for various infectious, inflammatory/autoimmune, and neoplastic processes was considered. Based on classic radiographic and histopathologic findings, she was ultimately diagnosed with xanthogranulomatous pyelonephritis of her left kidney, which was a direct consequence of chronic inflammation. This inflammation exhibited spread to local tissues and across her left hemidiaphragm, resulting in a unilateral pleural effusion which explained her chest discomfort. She was treated with antibiotics administered intravenously and urgent total nephrectomy with a good functional outcome. CONCLUSIONS: Our case illustrates an uncommon but clinically important do-not-miss diagnosis that underlies a common clinical presentation of pleuritic chest pain. The case underscores the importance of maintaining a broad differential diagnosis and organized approach when treating patients with undifferentiated clinical presentations.

A bio-enabled maximally mild layer-by-layer Kapton surface modification approach for the fabrication of all-inkjet-printed flexible electronic devices.

A bio-enabled, environmentally-friendly, and maximally mild layer-by-layer approach has been developed to surface modify inherently hydrophobic Kapton HN substrates to allow for great printability of both water- and organic solvent-based inks thus facilitating the full-inkjet-printing of flexible electronic devices. Different from the traditional Kapton surface modification approaches which are structure-compromising and use harsh conditions to target, and oxidize and/or remove part of, the surface polyimide of Kapton, the present Kapton surface modification approach targeted the surface electric charges borne by its additive particles, and was not only the first to utilize environmentally-friendly clinical biomolecules to build up a thin film of protamine-heparin complex on Kapton, but also the first to be conducted under minimally destructive and maximally mild conditions. Besides, for electrically charged ink particles, the present surface modification method can enhance the uniformity of the inkjet-printed films by reducing the "coffee ring effect". As a proof-of-concept demonstration, reduced graphene oxide-based gas sensors, which were flexible, ultra-lightweight, and miniature-sized, were fully-inkjet-printed on surface modified Kapton HN films and tested for their sensitivity to dimethyl methylphosphonate (a nerve agent simulant). Such fabricated sensors survived a Scotch-tape peel test and were found insensitive to repeated bending to a small 0.5 cm radius.

Medical characteristics of the oldest old: retrospective chart review of patients aged 85+ in an academic primary care centre.

BACKGROUND: The population aged 85 + - the "oldest old" - is now the fastest growing age segment in Canada. Although existing research demonstrates high health services utilization and medication burden in this population, little clinically derived evidence is available to guide care. This is a descriptive study in a primary care context seeking to describe the most common health conditions and medications used in the "oldest old". METHODS: We conducted a retrospective chart review of all family practice patients aged 85+ (N = 564; 209 males, 355 females) at Sunnybrook Health Sciences Centre in Toronto, Canada. Electronic medical records were reviewed for all current chronic conditions and medication prescriptions, and then stratified by sex and age subgroup (85-89, 90-94, 95+) for descriptive analysis. RESULTS: On average, patients experienced 6.4 concurrent chronic conditions and took 6.8 medications. Most conditions were related to cardiovascular (79%) and bone health (65%). Hypertension (65%) was the most common condition. Bone-related conditions (e.g. osteoarthritis, osteoporosis) and hypothyroidism predominantly affected women, while coronary artery disease and type 2 diabetes were more prevalent in men. The top two prescribed medications were atorvastatin (33%) and aspirin 81 mg (33%). Males were more likely to be prescribed lipid-lowering medications, while females were more likely to receive osteoporosis therapy. Patients received less lipid-lowering therapy with increasing age. CONCLUSIONS: Multimorbidity and polypharmacy are highly prevalent in patients in the 85+ age group. The most common clinical conditions are related to cardiovascular and bone health, and the most commonly prescribed medications are directed towards risk factors for these illnesses. In the absence of data to guide clinical decision-making, this study provides a first look at the common health concerns and medication profiles in this population and reveals trends that give rise to reflections on how clinical care for these patients can be improved.

Chronic, low concentration exposure to pharmaceuticals impacts multiple organ systems in zebrafish.

Pharmaceuticals are found in both receiving and drinking water due to their persistent release in waste-water effluents, raising concerns for environmental and human health. Chronic, aqueous exposure of zebrafish (Danio rerio) to environmentally relevant concentrations of acetaminophen (ACE), venlafaxaine (VEN) (10µgL(-1)), carbamazepine (CBZ) and gemfibrozil (GEM) (0.5 and 10µgL(-1)) decreased reproductive output. Atretic oocytes and altered ovarian histology were seen in female zebrafish exposed to CBZ and GEM, suggesting a direct effect on oocyte development that may account for the reduced fecundity. Apoptosis within the theca and granulosa cells was identified in exposed female zebrafish with atretic oocytes by TUNEL positive staining. The incidence of follicular apoptosis was nearly 2-fold higher in exposed females than the controls. All compounds significantly altered kidney proximal tubule morphology but there was no difference in the incidence of apoptotic cells within the kidney between control and exposed in either males or females. Liver histology was altered by ACE and GEM exposure. Parental exposure to pharmaceuticals did not increase developmental abnormalities, hatching success, or mortality in embryos. Yet, direct exposure of embryos to ACE increased developmental abnormalities and mortality; exposure to 0.5µgL(-1) of all pharmaceuticals increased mortality. CBZ decreased plasma 11-ketotestosterone concentrations in males and females. Overall, these data suggest that low concentration, chronic exposure of fish to pharmaceuticals impacts fish development as well as multiple organ systems in adult fish, leading to effects on reproduction and histology of liver and kidney. These results are significant in understanding the consequences of chronic, low concentration pharmaceutical exposure to fish and suggest that exposed populations are at risk of negative impacts to reproduction and health.

Isolation and identification of ester impurities in RG7128, an HCV polymerase inhibitor.

RG7128 is a di-ester prodrug of a cytidine analog for the treatment of hepatitis C virus (HCV) infection. The structures of nine low level impurities (0.05-0.10%) in RG7128 drug substance were elucidated. The majority of the impurities were formed during the synthesis of the prodrug from the parent drug. Structural elucidations of the impurities were achieved either by enrichment of the impurities using preparative chromatography followed by spectroscopic techniques or by confirmation with a reference sample. Heart-cut and recycle chromatographic techniques were applied to purify closely eluting isomers of RG7128.