What are the views of Quebec and Ontario citizens on the tiebreaker criteria for prioritizing access to adult critical care in the extreme context of a COVID-19 pandemic?

BACKGROUND: The prioritization protocols for accessing adult critical care in the extreme pandemic context contain tiebreaker criteria to facilitate decision-making in the allocation of resources between patients with a similar survival prognosis. Besides being controversial, little is known about the public acceptability of these tiebreakers. In order to better understand the public opinion, Quebec and Ontario's protocols were presented to the public in a democratic deliberation during the summer of 2022. OBJECTIVES: (1) To explore the perspectives of Quebec and Ontario citizens regarding tiebreakers, identifying the most acceptable ones and their underlying values. (2) To analyze these results considering other public consultations held during the pandemic on these criteria. METHODS: This was an exploratory qualitative study. The design involved an online democratic deliberation that took place over two days, simultaneously in Quebec and Ontario. Public participants were selected from a community sample which excluded healthcare workers. Participants were first presented the essential components of prioritization protocols and their related issues (training session day 1). They subsequently deliberated on the acceptability of these criteria (deliberation session day 2). The deliberation was then subject to thematic analysis. RESULTS: A total of 47 participants from the provinces of Quebec (n = 20) and Ontario (n = 27) took part in the online deliberation. A diverse audience participated excluding members of the healthcare workforce. Four themes were identified: (1) Priority to young patients - the life cycle - a preferred tiebreaker; (2) Randomization - a tiebreaker of last resort; (3) Multiplier effect of most exposed healthcare workers - a median acceptability tiebreaker, and (4) Social value - a less acceptable tiebreaker. CONCLUSION: Life cycle was the preferred tiebreaker as this criterion respects intergenerational equity, which was considered relevant when allocating scarce resources to adult patients in a context of extreme pandemic. Priority to young patients is in line with other consultations conducted around the world. Additional studies are needed to further investigate the public acceptability of tiebreaker criteria.

A qualitative study of physicians' conscientious objections to medical aid in dying.

BACKGROUND: Under Quebec's Act respecting end-of-life care, physicians may refuse to provide medical aid in dying because of personal convictions, also called conscientious objections. Before legalisation, the results of our survey showed that the majority of physicians were in favour of medical aid in dying (76%), but one-third (28%) were not prepared to perform it. After 18 months of legalisation, physicians were refusing far more frequently than the pre-Act survey had anticipated. AIM: To explore the conscientious objections stated by physicians so as to understand why some of them refuse to get involved in their patients' medical aid in dying requests. DESIGN/PARTICIPANTS: An exploratory qualitative study based on semi-structured interviews with 22 physicians who expressed a refusal after they received a request for medical aid in dying. Thematic descriptive analysis was used to analyse physicians' motives for their conscientious objections and the reasons behind it. RESULTS: The majority of physicians who refused to participate did not oppose medical aid in dying. The reason most often cited is not based on moral and religious grounds. Rather, the emotional burden related to this act and the fear of psychological repercussions were the most expressed motivations for not participating in medical aid in dying. CONCLUSION: The originality of this research is based on what the actual perception is of doing medical aid in dying as opposed to merely a conceptual assent. Further explorations are required in order to support policy decisions such as access to better emotional supports for providers and interdisciplinary support.

Pulse Pressure Amplification and Arterial Stiffness in Low-Risk, Uncomplicated Pregnancies.

BACKGROUND: Arterial stiffness, a composite indicator of vascular health and predictor of future cardiovascular (CV) disease and events, was assessed in low-risk, uncomplicated pregnancies. METHODS: Women with low-risk pregnancy were recruited consecutively (recruitment across the 3 trimesters). Vessel hemodynamics and arterial stiffness were measured every 4 weeks from recruitment until delivery and at 6.5 weeks postpartum. RESULTS: Sixty-three women (maternal age: 32.7 ± 4.9 years) with low-risk, uncomplicated pregnancy were recruited. Mean arterial pressure (P = .04) and aortic pulse pressure (P = .03) decreased during pregnancy, whereas heart rate gradually increased until delivery (P = .0002) and decreased postpartum (P = .06). Pulse pressure amplification (PPA) and carotid-to-radial pulse wave velocity initially decreased in the second trimester, followed by a steady increase until delivery (P = .01 and P = .04, respectively). Interestingly, PPA sharply decreased postpartum (P = .01). Augmentation index and the subendocardial viability ratio significantly increased postpartum (P = .03 and .02, respectively). CONCLUSION: The PPA increased steadily after the second trimester and was sharply decreased postpartum in low-risk, uncomplicated pregnancy. Longer and larger longitudinal studies will evaluate changes in PPA and its potential as a marker of CV risk later in women's life.

Combined impact of high body mass index and in vitro fertilization on preeclampsia risk: a hospital-based cohort study.

OBJECTIVES: Overweight and obese women may be heavy users of in vitro fertilization (IVF) owing to obesity-related oligo-anovulation. The higher doses of gonadotropins required to achieve pregnancy in obese women may contribute to impaired placentation and the development of preeclampsia. This study was designed to assess the combined effect of high maternal body mass index (BMI) and IVF on risk of preeclampsia and to evaluate for an interaction between the two factors. METHODS: This is a hospital-based cohort study of 10,013 singleton pregnancies that delivered from 2001 to 2008 at a tertiary hospital in Montreal, Canada. The combined effect of high BMI and IVF on preeclampsia versus no risk factors was estimated in multivariate logistic regression models fitted with an interaction term between high BMI (> 25 or > 30 kg/m(2) ) and IVF. RESULTS: IVF pregnancies in obese women had a considerably higher risk of preeclampsia than spontaneous nonobese pregnancies (OR 6.7, 95% CI 3.3-13.8; p interaction 0.03). IVF was not independently associated with preeclampsia (OR 0.6, 95% CI 0.3-1.4). Analyses were similar in subgroup analyses and in analyses correcting for bias. CONCLUSIONS: High BMI is strongly associated with preeclampsia, and this risk is compounded in IVF pregnancies.

Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial.

BACKGROUND: Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS. METHODS: We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov, number NCT00143598, and Current Controlled Trials, number ISRCTN71334751. FINDINGS: From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73-1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings. INTERPRETATION: ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. FUNDING: Canadian Institutes of Health Research.

Gastro-intestinal haemorrhage risks of selective serotonin receptor antagonist therapy: a new look.

AIMS: (i) To determine the effects of selective serotonin reuptake inhibitors (SSRI) and other classes of antidepressants on upper gastro-intestinal (GI) haemorrhage and (ii) to assess the drug-drug interaction effects of antidepressants and warfarin or clopidogrel on the risk of GI haemorrhage. METHODS: This was a population-based case control study in the General Practice Research Database (GPRD). Cases with a first episode of upper GI haemorrhage between 2000 and 2005 were matched with up to 10 controls. Exposure to the study drugs was defined by a prescription issued in the 90 days before the index date. Rate ratios were estimated using conditional logistic regression. RESULTS: Four thousand and twenty-eight cases of GI haemorrhage and 40 171 controls were identified. The excess risk of GI haemorrhage with SSRI use was small (Rate Ratio [RR]: 1.3; 95% confidence interval [CI]: 1.1, 1.6) and null with exposure to tricyclic antidepressants (TCAs) (RR 1.0; 95% CI: 0.8, 1.3). The risk of GI haemorrhage was highest with venlafaxine use (RR: 1.9; 95% CI: 1.3, 2.6). There was no drug-drug interaction between warfarin anticoagulation and antidepressant use. CONCLUSIONS: This study supports a small increased risk of upper GI haemorrhage with the use of SSRI antidepressants compared with the older TCA drugs, but to a lesser extent than previously reported due to confounding by alcohol use. The small elevation in risk of GI haemorrhage with SSRI and venlafaxine should be weighed against the therapeutic benefit of their use.

Lifestyle variables and the risk of myocardial infarction in the general practice research database.

BACKGROUND: The primary objective of this study is to estimate the association between body mass index (BMI) and the risk of first acute myocardial infarction (AMI). As a secondary objective, we considered the association between other lifestyle variables, smoking and heavy alcohol use, and AMI risk. METHODS: This study was conducted in the general practice research database (GPRD) which is a database based on general practitioner records and is a representative sample of the United Kingdom population. We matched cases of first AMI as identified by diagnostic codes with up to 10 controls between January 1st, 2001 and December 31st, 2005 using incidence density sampling. We used multiple imputation to account for missing data. RESULTS: We identified 19,353 cases of first AMI which were matched on index date, GPRD practice and age to 192,821 controls. There was a modest amount of missing data in the database, and the patients with missing data had different risks than those with recorded values. We adjusted our analysis for each lifestyle variable jointly and also for age, sex, and number of hospitalizations in the past year. Although a record of underweight (BMI <18.0 kg/m2) did not alter the risk for AMI (adjusted odds ratio (OR): 1.00; 95% confidence interval (CI): 0.87-1.11) when compared with normal BMI (18.0-24.9 kg/m2), obesity (BMI > or =30 kg/m2) predicted an increased risk (adjusted OR: 1.41; 95% CI: 1.35-1.47). A history of smoking also predicted an increased risk of AMI (adjusted OR: 1.81; 95% CI: 1.75-1.87) as did heavy alcohol use (adjusted OR: 1.15; 95% CI: 1.06-1.26). CONCLUSION: This study illustrates that obesity, smoking and heavy alcohol use, as recorded during routine care by a general practitioner, are important predictors of an increased risk of a first AMI. In contrast, low BMI does not increase the risk of a first AMI.

The intention-to-treat approach in randomized controlled trials: are authors saying what they do and doing what they say?

BACKGROUND: Intention-to-treat (ITT) is an approach to the analysis of randomized controlled trials (RCT) in which patients are analyzed as randomized regardless of the treatment actually received. PURPOSE: To ascertain the proportion of RCT reporting the use of intention-to-treat and the accuracy of that report and to examine the distribution and analysis of missing data for the studies reporting an ITT analysis. METHOD: We conducted a cross-sectional literature review of RCTs reported in 10 medical journals in 2002. All articles were assessed using a standardized form. Two evaluators independently reviewed a 10% sample of articles to assess reliability. Subsequently, one evaluator reviewed the remaining articles. The proportion of articles reporting the use of ITT was calculated. Among these, the proportion of articles that ;analyzed patients as randomized' and the proportion and analysis of missing data were evaluated using standardized definitions. RESULTS: Of the 403 articles, 249 (62%) reported the use of ITT. Among these, available patients were clearly analyzed as randomized in 192 (77%). Authors used a modified ITT in 23 (9%); clearly violated a major component of ITT in 17 (7%), and the approach used was unclear in 17 (7%). More than 60% of articles had missing data in their primary analysis. Few articles reported a strategy for missing data. The main reason for missing data was loss to follow-up. LIMITATIONS: A single evaluator evaluated most articles, but the high concordance obtained during the inter-rater evaluation suggests that the assessments were consistent. In addition, the small spectrum of journals limits generalizability. Finally, there could be a difference between what was reported and what was performed. CONCLUSIONS: This study emphasizes that authors use the label ;intention-to-treat' quite differently. The most common use refers to the analysis of all available subjects as randomized regardless of the missing data aspect.

Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding.

BACKGROUND: Anticoagulants and antiplatelet drugs (e.g., warfarin, clopidogrel and acetylsalicylic acid) are key therapeutic agents in the treatment of cardiovascular diseases. However, drug-drug interactions may lead to a greatly increased risk of gastrointestinal bleeding when these drugs are combined. We assessed whether antithrombotic drug combinations increased the risk of such bleeding in a general practice population. METHODS: We conducted a population-based, retrospective case-control study using records in the United Kingdom General Practice Research Database from 2000 through 2005. Cases were identified as patients over 18 years of age with a first-ever diagnosis of gastrointestinal bleeding. They were matched with controls by physician practice, patient age and index date (date of diagnosis of bleeding). All eligible patients had to have at least 3 years of follow-up data in the database. Drug exposure was considered to be any prescription issued in the 90 days before the index date. RESULTS: There were 4028 cases with a diagnosis of gastrointestinal bleeding and 40 171 matched controls. The prescribing of acetylsalicylic acid with either clopidogrel (adjusted rate ratio [RR] 3.90, 95% confidence interval [CI] 2.78-5.47) or warfarin (adjusted RR 6.48, 95% CI 4.25-9.87) was associated with a greater risk of gastrointestinal bleeding than that observed with each drug alone. The same was true when a nonsteroidal anti-inflammatory drug was combined with either clopidogrel (adjusted RR 2.93, 95% CI 1.74-4.93) or warfarin (RR 4.60, 95% CI 2.77-7.64). INTERPRETATION: Drug combinations involving antiplatelets and anticoagulants are associated with a high risk of gastrointestinal bleeding beyond that associated with each drug used alone. Physicians should be aware of these risks to better assess their patients' therapeutic risk-benefit profiles.

Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis.

OBJECTIVE: To assess the strength of association between recurrent fetal loss (RFL) and presence of antiphospholipid antibodies (aPL) in women without autoimmune disease, and to examine whether magnitude of association varies according to type or titer of antibody and timing of fetal loss. METHODS: We searched Medline and Current Contents for articles published between 1975 and 2003 with terms denoting early (less than 13 weeks) and late (less than 24 weeks) RFL associated with various aPL. Published case-control, cohort, and cross-sectional studies rated moderate or strong were included in our metaanalysis. Pooled odds ratios with 95% CI were generated using the random-effects models with Cochrane Review Manager software. RESULTS: Our analysis included 25 studies. Lupus anticoagulant (LAC) was associated with late RFL (OR 7.79, 95% CI 2.30-26.45); the association of LAC was stronger than that of any other aPL. IgG anticardiolipin antibodies (aCL), when combining all titers, were associated with both early (OR 3.56, 95% CI 1.48-8.59) and late RFL (OR 3.57, 95% CI 2.26-5.65). Restricting analysis to include only women with moderate to high titers increased the strength of association (OR 4.68, 95% CI 2.96-7.40). It was not possible to extract data on isolated low IgG aCL positivity. IgM aCL were associated with late RFL (OR 5.61, 95% CI 1.26-25.03). There was no association found between early RFL and anti-Beta2-glycoprotein I antibodies (OR 2.12, 95% CI 0.69-6.53). CONCLUSION: The magnitude of the association between aPL and RFL varies according to type of aPL. More data on the relationship between recurrent fetal loss and isolated IgM aCL as well as with low titer IgG aCL would be useful. The place of testing for anti-Beta2-glycoprotein I antibodies remains to be determined.

Warfarin use and the risk of motor vehicle crash in older drivers.

AIM: On the basis of a recent report, we assessed whether the use of warfarin by elderly drivers results in an increased risk of motor vehicle crash. METHODS: We used computerized records of Quebec insurance programmes, covering a population of 7 million people, to conduct a case-control study based on 5,579 cases and 12,911 controls. RESULTS: The rate of injurious motor vehicle crash associated with the use of warfarin in the past year was not elevated (rate ratio 0.74; 95% confidence interval 0.55, 1.05). CONCLUSIONS: Warfarin therapy does not appear to increase the risk of motor vehicle accidents in elderly drivers.

High rate of missing vital signs data at triage in a paediatric emergency department.

BACKGROUND: Vital signs measurement is considered standard practice in paediatric emergency department triage assessment, but studies have shown variable incidence of missing data. OBJECTIVES: To evaluate the rate of missing data for vital signs at triage and to determine clinical and environmental predictive factors. METHODS: A retrospective cohort design was used to study a database of consecutive patients registered at a tertiary paediatric emergency department during randomly chosen shifts. Demographic and clinical data were collected. Univariate and multivariate logistic regression analyses were performed to evaluate the determinants of missing data for body temperature, heart rate, respiratory rate, blood pressure and pulse oximetry. RESULTS: There were 2081 patients triaged during the study periods. On multivariate logistic regression analysis, triage level (from 1 = priority to 4 = nonurgent) was an independent predictor of missing data for heart rate, respiratory rate, blood pressure and pulse oximetry (OR 1.48 to 2.05). Patients visiting the emergency department during the day shift (OR 1.08 to 4.72) and the evening shift (OR 1.38 to 9.24) had a higher rate of missing data than those visiting during the night shift. A decreased level of consciousness, an immunocompromised state and referral by a physician did not meet statistical significance as predictive factors. CONCLUSIONS: There was a high rate of missing data for vital signs. Factors related to patients' clinical characteristics, such as acuity of triage level, were associated with a higher rate of vital signs documentation at triage. An environmental factor, shift of presentation, was also independently associated with a higher rate.

Death related to albendazole-induced pancytopenia: case report and review.

Albendazole is a benzimidazole with wide spectrum coverage as an antiparasitic drug. Reported side effects have been minimal. We report the case of a patient who died with severe prolonged pancytopenia beginning during the third week of therapy for a pulmonary echinococcal cyst. This case was a 68-year-old man who presented with a large cystic lung mass. His medical history was significant for Child-Pugh class B cirrhosis. A prolonged course of albendazole was initiated. Two weeks later, the patient presented in septic shock with severe pancytopenia. The patient was initially resuscitated, but died after 10 days with no marrow recovery. Autopsy was consistent with albendazole-induced pancytopenia. This is the third human case of pancytopenia and the first death reported in relation to albendazole-induced pancytopenia. Neutropenia seems to be related more to higher dosage and longer duration of use. Albendazole sulfoxide peak dose and half life are significantly prolonged by liver disease and concomitant administration of certain drugs. The severity and duration of albendazole-induced pancytopenia in this case was likely related to the underlying liver disease. Frequent serial monitoring of blood counts and cessation of medication with any evidence of marrow toxicity in such patients is warranted.

Risk of thrombosis in patients with malignancy and heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a common immunological drug reaction. After exposure to heparin, some patients develop heparin dependent antibodies with no evidence of thrombosis, while others are at risk of thrombocytopenia, thrombosis, limb loss, and death. We conducted a retrospective chart review on all patients serologically positive for HIT by HPIA ELISA in a single tertiary-care hospital, to determine whether patients with malignancy had an increased risk of thrombotic complications. Medical records of 55 patients who tested positive for HIT and met clinical criteria for HIT were analyzed. All patients had been treated with unfractionated heparin. Malignancy was diagnosed in 11 patients, either at surgery or post-mortem examination. A higher rate of venous thrombosis and pulmonary embolism was observed in patients with HIT and malignant disease when compared to patients with no underlying malignancy (odds ratio 13.6, 95% CI 2.9-63.8).

Preeclampsia as a cause of pancreatitis: a case report.

BACKGROUND: Pancreatitis is an uncommon but well-described entity in pregnancy and labour, with most cases attributable to biliary disease. Preeclampsia is not an established cause of pancreatitis. CASE: A 29-year-old woman with preeclampsia and adverse features at 33 weeks' gestation developed pancreatitis during her labour induction. Investigations ruled out known etiologies of pancreatitis. The woman was monitored clinically, biochemically, and radiologically, and underwent a Caesarean delivery of a healthy infant. Both the pancreatitis and preeclampsia resolved rapidly postpartum. Given her benign clinical picture, no specific therapeutic intervention was deemed necessary for the pancreatitis, and she was discharged 5 days postpartum. CONCLUSION: The clinical course and investigations of this woman suggest that preeclampsia should be considered as a cause of pancreatitis.