Scholarly Curriculum at a Psychiatry Residency Program in Canada: 10-Year Outcomes.

PROBLEM: For research in medicine to address needed interventions and produce outcomes relevant to patient care, it is important for physicians to gain hands-on experience in scientific methods during their training. However, the results of recent studies in the United States and Canada indicate low interest in research among residents. APPROACH: In 2011, involvement in a scholarly activity was made mandatory for all residents joining the Western University psychiatry residency program (WUPRP). A faculty member was appointed as a research coordinator who collaborated with research-intensive faculty members and prepared a list of potential projects suitable for resident involvement; organized monthly research meetings to support residents in initiating scholarly activities, monitor their progress, and address challenges; and developed competency-based research objectives, guidelines, and assessment tool. OUTCOMES: Data on all residents enrolled at WUPRP from 2011 to 2017 (the latter graduated in 2022 with completed scholarly requirements) were analyzed with respect to residents' participation in a scholarly project. A total of 54 residents were enrolled during this period. Fifty-two (96%) residents were involved in a scholarly project; of these 52, 38 (73%) completed their project. Of these 38, 32 (84%) had academic achievements, which include poster and oral presentations at a conference, publications, and prizes and awards. Of the 52 residents involved in a scholarly project, 14 (27%) residents could not complete their projects, though they still met scholarly activity requirements and 1 (2%) enrolled in the Western University Clinician Investigator Program with the goal of pursuing research as a career. NEXT STEPS: There is a lack of data on how many WUPRP graduates from 2011 to 2017 are currently pursuing careers in research. The authors plan to perform longer and closer follow-up of residents to evaluate whether a scholarly curriculum makes an impact on residents' career choices.

Toxicokinetic analysis of commonly used pesticides using data on acute poisoning cases from Hyderabad, South India.

Organophosphorus pesticides (OPs) interfere with the activity of acetylcholinesterase (AChE), a vital enzyme that regulates the functioning of the nervous system, resulting in acetylcholine (Ach) accumulation at the synapses and myoneural junctions. It remains unknown whether the commonly used OPs in South India also interfere with the AChE activity and their toxicokinetics in humans remains poorly understood. We collected peripheral blood samples from OP-associated suicide cases (hospitalised) and analysed the pesticide concentration and AChE activity, and the toxicokinetics of six commonly used pesticides. LC-MS/MS was used for the estimation of pesticide concentration. Based on a comparison of six pesticide kinetic profiles and toxicokinetic parameters, we concluded that chlorpyrifos ingestion resulted in the highest concentration of chlopyrifos among the identified pesticides, followed by acephate, triazophos, propanil, while dimethoate exhibited the lowest concentration. Based on a time-course analysis, we observed a faster elimination phase for monocrotophos and dimethoate. We observed that there was a significant decrease in the mean concentration of monocrotophos (64 ng/mL) (P = 0.015), while the mean value of AChE (1.08 unit/mL) increased over time. While monocrotophos and dimethoate elimination phases were remarkable in human subjects, the other pesticides did notdemonstrate similar elimination phases owing to their low rate of metabolism and high stability.

Accumulation of polychlorinated biphenyls in fish and assessment of dietary exposure: a study in Hyderabad City, India.

The objective of this study is to determine the concentrations of polychlorinated biphenyls (PCBs) in different fish species collected from fish outlets in the south Indian city of Hyderabad. The samples of fish extracted by using Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) and concentrations of polychlorinated biphenyls (PCBs, 45 congeners) were determined by gas chromatography-microelectron capture detection (GC-µECD) method. The intake of individual PCB congeners through fish, toxicity equivalence factors (TEFs), hazardous quotient, quantitative assessment, and risk evaluations was estimated in the Indian population. Daily dietary intakes of PCBs at the 95th-percentile-measured concentrations were twice the values of the 50th-percentile-measured concentrations in all socio-economic groups. The dietary intakes of PCBs through fish consumption in middle-income group, low-income group, and industrial laborers (0.023 µg kg(-1) day(-1)), the high-income group (0.031 µg kg(-1) day(-1)), and slum dwellers (0.039 µg kg(-1) day(-1)) exceeded the reference dose. The observed estimated daily intakes (EDIs) of our study for all socio-economic sections (0.0087 µg/kg/day) crossed the cancer benchmark concentration of 0.0003 µg/kg/day. In slum dwellers, the ingestion of fish from freshwater and marine water results in the highest lifetime cancer risks of 4.7 in 100,000 and 7.8 in 100,000, respectively. Ultimately, the concentrations of PCBs were determined high in all of the fish species collected. Risk assessment showed that the fish were highly contaminated with PCBs and may pose health threats to consumers in the city of Hyderabad as well as a lifetime cancer risk.

Quantification of organophosphate insecticides and herbicides in vegetable samples using the "Quick Easy Cheap Effective Rugged and Safe" (QuEChERS) method and a high-performance liquid chromatography-electrospray ionisation-mass spectrometry (LC-MS/MS) technique.

A Quick Easy Cheap Effective Rugged and Safe (QuEchERS) extraction was developed and followed by selective analysis using a liquid chromatography-mass spectrometry method for the quantification of eighteen pesticides in vegetable samples. This method was accurate (⩾99.5%), and it exhibited limits of detection and quantification values in the 0.006-0.091 and 0.020-0.314µgkg-1 ranges, respectively. Furthermore, the coefficients of variations (⩾0.9999) were less than 1% at the low µgkg-1 end of the method. Mean recoveries ranged between 94% and 102%, and relative standard deviations were below 10%. Based on these results, the methodology was proven to be highly efficient, robust, and suitable for monitoring the maximum residue limits (MRL) compliance of a wide range of commodity/pesticide combination. This method was successfully applied to the analysis of vegetable samples that were collected from different government farmers' markets and street shops in urban areas. The presence of target pesticides was found in the range of 0.016 and 50.85µgkg-1.

Adverse drug reaction monitoring: knowledge, attitude and practices of medical students and prescribers.

BACKGROUND: Adverse drug reactions (ADRs) contribute to excessive health care costs through increased patient morbidity and mortality. Thus, there is an urgent need to create awareness among physicians towards ADR monitoring. The present study was designed to assess the knowledge, attitude and practices of fifth semester undergraduate students and prescribers (interns, junior residents and senior residents) towards the recording and reporting of ADRs. METHODS: The fifth semester MB,BS undergraduate students (n=107) and prescribers (n=l 17) working in different disciplines of Lady Hardinge Medical College and associated hospitals were given a questionnaire to answer. The responses of the undergraduate students were compared with those of prescribers. RESULTS: Knowledge about definition, classification, objectives and methods of ADR monitoring was found to be comparable in both groups. Spontaneous and intensive methods of ADR monitoring were known to the majority of participants of both groups. Attitude and practices of the prescribers were significantly (p<0.01 ) better with regard to the status of ADR monitoring in the institute. A significantly higher (p<0.001) proportion of prescribers (82%) as compared to the undergraduate students (64.5%), felt that ADRs should be reported both when it causes inconvenience to the patient as well as death. ADRs were encountered by both undergraduates (46%) and prescribers (66%) during their clinical project exercises and patient care, respectively. Commonly encountered ADRs were allergic reactions, symptoms of upper gastrointestinal irritation, extrapyramidal symptoms and hepatitis. The common offending groups of drugs causing these ADRs were non-steroidal anti-inflammatory drugs, antidopaminergics and chemotherapeutic agents. A majority of ADRs were suspected and subsided on their own by either stopping the drug or reducing its dose. CONCLUSIONS: The knowledge, attitude and practices of both undergraduates and prescribers were comparable but need further improvement. This suggests the need for suitable changes in the undergraduate teaching curriculum. Further, the prescribers also need periodic reinforcement regardingADR monitoring.

Pharmacokinetics of valproic acid in patients with bipolar disorder.

The pharmacokinetics of valproic acid (VPA) were studied in nine patients with bipolar disorder who were receiving VPA as prophylactic therapy, following the full daily dose (400-1500 mg), on which the patients had been maintained for at least the past 3 months. The data from our study showed that the pharmacokinetics of valproate followed a two compartment open model. A time lag of 1-2 h was observed in each patient, followed by rapid absorption, with the peak concentrations being recorded approximately 4 h after drug administration. The average 12 h trough concentration was found to be 54.73+/-11.96 microg/ml. The plasma level decline was biphasic with a terminal half-life of 14.2+/-6.39 h. Total plasma clearance was 0.095+/-0.035 ml/min/kg. The steady-state apparent volume of distribution was found to be 0.11+/-0.05 l/kg. A positive correlation (r = 0.69) was found between the dose (mg/kg) and steady-state serum concentration (Css) of VPA and all patients, except one, had their Css above 50 microg/ml. Most of the pharmacokinetic parameters in this study involving euthymic bipolar patients on long-term VPA monotherapy were found to be in agreement with those reported in literature on seizure disorder patients on similar regime; however, the plasma elimination half-life appears to be prolonged in bipolar patients.

Carbamazepine and valproate monotherapy: feasibility, relative safety and efficacy, and therapeutic drug monitoring in manic disorder.

RATIONALE: Search for alternatives to lithium therapy for mood disorders commenced with anticonvulsants, carbamazepine (CBZ) and valproic acid (VPA), in the late 1970s. The comparative safety and efficacy data of CBZ and VPA monotherapy in patients with bipolar disorder remain to be established. OBJECTIVES: The main objectives of the study were to assess the relative antimanic efficacy and safety of CBZ and VPA; to study the feasibility of using either, as a first line anti-manic agent; to investigate and generate clinically relevant parameters involving therapeutic drug monitoring of the two drugs. METHODS: After a 2-day screening period, suitable patients (n = 30) were randomly assigned to treatment with CBZ or VPA. Both the drugs were started with an average dose of approximately 20 mg/kg body weight per day. Further increment in dose was carried out at weekly intervals, guided by clinical improvement, serum levels and treatment emergent adverse events. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. A favourable clinical response was defined a priori as a decrease of more than 50% from baseline in Young Mania Rating Scale total score. RESULTS: Both CBZ and VPA were found to be efficacious as single first-line anti-manic agents, however VPA proved to be better. Using the intent-to-treat analysis, the VPA group showed a significant fall in YMRS total scores after week 1 while the CBZ group showed a significant fall after week 2. In the primary efficacy analysis, valproate group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the CBZ group. Of the VPA treated patients, 73% showed a favourable clinical response while 53% of the patients on CBZ responded favourably. In the CBZ group, significantly more patients received rescue medication during the week 2 and the requirement was quantitatively more as compared to the VPA group. The steady state serum concentration (Css) of CBZ ranged from 3 to 9 micrograms/ml; however, it did not appear to correlate with the dose or clinical response. The Css of VPA ranged from 50 to 100 micrograms/ml; a linear correlation was found between the dose and serum levels of VPA as well as between weekly rise in serum levels and clinical response. Weekly dose escalations of VPA also correlated positively with corresponding rise in serum levels. Significantly more patients in the CBZ group reported adverse events, including nausea, vomiting and dizziness, than VPA. CONCLUSIONS: The findings from this study suggest that both CBZ and VPA monotherapy is feasible for treatment of acute mania; however, VPA is more efficacious in terms of its early onset of action, lesser requirement for rescue medication and better tolerability. Further work needs to be undertaken to characterise the manic patients in terms of their differential psychopharmacologic response profile.

Malignant hepatic tumours associated with previous exposure to Thorotrast: four cases.

This report concerns four patients in a district general hospital who died from malignant liver tumours associated with Thorotrast (thorium dioxide) deposits in the liver. Three were known to have had diagnostic angiographic studies performed 36 to 43 years previously using Thorotrast as the contrast agent. In the fourth case no previous relevant information could be obtained. There were two men and one woman with hepatocellular carcinoma and one woman with cholangiocarcinoma. In one of the hepatoma cases there was associated hypercalcaemia of malignancy. Reported latency intervals suggest that cases of Thorotrast-related hepatic malignancy may present up to the second decade of the twenty-first century.

Malignant peripheral nerve sheath tumour with vascular differentiation: a report of four cases.

Four cases of malignant peripheral nerve sheath tumour showing vascular differentiation are described. One case was associated with neurofibromatosis 1 and contained angiosarcomatous, cartilaginous and rhabdomyoblastic elements. The other cases occurred in patients without neurofibromatosis and showed a spectrum of vascular lesions ranging from lobulated, haemangioma-like structures to angiosarcoma. These are the first recorded examples of this phenomenon not associated with neurofibromatosis. Immunohistochemical examination demonstrated the endothelial nature of the lesions in all cases and revealed cells positive for alpha-smooth muscle actin, probably pericytes, closely apposed to the endothelium.

Lipid rich rhabdomyosarcoma.

A lipid rich rhabdomyosarcoma of the paratesticular region was studied by light microscopy, histochemistry, immunohistochemistry and electron microscopy. The tumour was composed of primitive looking, vacuolated, and pleomorphic cells. Lipid was present in varying amounts in all cells but was especially abundant in the vacuolated and pleomorphic cells. Some cells showed eosinophilic fibrillary cytoplasm but cross-striations were not seen. Tumour cells were positive for desmin, muscle specific actin, and vimentin. A few cells were myoglobin positive. At electron microscopy, the presence of lipid was confirmed, while thick and thin filaments, Z disks, lamina and glycogen were observed, thereby confirming striated muscle differentiation. Although moderate amounts of lipid can be expected in almost any tumour, lipid rich rhabdomyosarcomas have received little attention. The present report provides a comprehensively examined case of such a tumour initially presenting diagnostic difficulty because of its possible confusion with liposarcoma.

Hepatic changes in a patient with alpha 1-antitrypsin deficiency (MZ phenotype). Portal tract elastosis and noncirrhotic portal hypertension.

A 57-year-old woman with rheumatoid arthritis and alpha 1-antitrypsin deficiency (PiMZ phenotype), recovering from intraabdominal sepsis in association with gastric ulcer perforation, had portal hypertension. An operative liver biopsy specimen showed a distinctive elastosis of the portal tracts without cirrhosis.

Primary signet ring cell carcinoma of the breast.

Three examples of primary signet ring cell carcinoma of the breast are described. This form of breast carcinoma deserves recognition as an entity because its prognosis may differ from colloid carcinoma of the breast and because of potential difficulty in distinguishing it from metastatic carcinoma.

Mucin-producing carcinomas of the breast: ultrastructural observations.

The ultrastructural characteristics of mucin production in mammary mucoid carcinoma, signet ring cell carcinoma (Harris, Wells & Vasudev 1978), papillary carcinoma and lobular carcinoma are compared. The mucin in lobular carcinoma is confined to intracytoplasmic lumina whereas it is present as membrane bound granules in the other three types, although intracytoplasmic lumina also occur in the latter. A possible origin of intracytoplasmic lumina from distended Golgi cisternae is proposed. Possibly, extracellular mucin acts as a mechanical barrier between tumour cells and lymphatics, thus explaining the good prognosis of typical mucoid carcinomas.

A sarcoma of myofibroblasts: an ultrastructural study.

A low-grade spindle cell sarcoma was shown by electron microscopy to be composed of myofibroblasts. It is suggested that the occurrence of myofibroblasts in spindle cell sarcomas might be of prognostic significance and that a systematic study to elucidate this point would be a valuable exercise.

Squamous carcinoma of the breast.

Two cases of primary squamous carcinoma of the breast are described. One of the tumours appeared to have an origin in an epidermoid cyst and had a pseudosarcomatous stroma. The other tumour arose from metaplastic ductal epithelium. A review of the literature is given.