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Abstract Decades of research have demonstrated that a variety of cognitive biases can affect our judgment and ability to make rational decisions in personal and professional environments. The lengthy, risky, and costly nature of pharmaceutical research and development (R&D) makes it vulnerable to biased decision‐making. Moreover, cognitive biases can play a role in regulatory and clinical decision‐making, the latter impacting diagnostic and treatment decisions in the therapeutic use of medicines. These inherent and/or institutionalized biases (e.g., in assumptions, data, or decision‐making practices) could conceivably contribute to health inequities. In this mini‐review, we provide a broad perspective on how cognitive biases can affect pharmaceutical R&D, regulatory evaluation, and therapeutic decision‐making. Example approaches to mitigate the effect of common biases in the development, approval, and use of new therapeutics, such as quantitative decision criteria, multidisciplinary reviews, regulatory and treatment guidelines, and evidence‐based clinical decision support systems are illustrated. Mitigating the impact of cognitive biases could increase pharma R&D efficiency, change the perspective and prioritization of unmet medical needs, increase representativeness and quality of evidence generated through clinical trials and real‐world research, leading to higher quality insights and more effective medication use, and as such could eventually contribute to more equitable healthcare.

HIV-1 tropism assays play a crucial role in determining the response to CCR5 receptor antagonists. Initially, phenotypic tests were used, but limited access to these tests prompted the development of alternative strategies. Recently, genotyping tropism has been validated using a Canadian technology in clinical trials investigating the use of maraviroc in both experienced and treatment-naive patients. The present guidelines review the evidence supporting the use of genotypic assays and provide recommendations regarding tropism testing in daily clinical management.

The management and treatment of HIV and hepatitis B virus (HBV)-coinfected patients present specific challenges for clinicians. The morbidity and mortality related to these concomitant infections are growing concerns, while the use of antiviral drugs effective against both viruses complicates therapeutic decision making. The present document provides guidelines for physicians regarding care and treatment of patients coinfected with HIV and HBV. Primary prevention of HBV in HIV-positive patients is achieved through appropriate vaccination schedules. Follow-up before treatment of HBV may include liver biopsy, screening for hepatocellular carcinoma and testing for esophageal varicies in cases of cirrhosis. In HBV-infected patients requiring treatment, recommendations regarding initiation, duration and choice of first-line drugs are made. Finally, in the case of resistance, appropriate alternative therapies are necessary.

The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients’ comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication.

BACKGROUND: In patients chronically infected with the hepatitis C virus (HCV), it is not established whether viral outcomes or health-related quality of life (HRQoL) differ between individuals treated at academic or community centres.

BACKGROUND AND OBJECTIVES: A Canadian group, consisting of six physicians and an HIV researcher with significant experience and knowledge in HIV management, reviewed the available data and developed guidelines for Canadian health care providers (who treat HIV infection) on the appropriate use of maraviroc (UK-427,857) in HIV-infected adults.

Concomitant HIV and hepatitis C virus (HCV) is a common yet complex coinfection. The present document is a practical guide for treating HCV infection in people coinfected with HIV. Effective antiretroviral therapies have prolonged survival rates for HIV-infected people over the past decade, which have made latent complications of HCV major causes of morbidity and mortality in these patients. Advances in the treatment of HCV (eg, combined pegylated interferon and ribavirin) offer the possibility of eradicating HCV infection in coinfected persons. The treatment of HCV must be considered in all cases. Intensive management of the adverse effects of HCV treatment is one of the factors for the success of these therapies. HCV eradication is predicted to decrease the mortality associated with coinfection and reduce the toxicity of HIV treatment.

Liver transplantation is a life-saving procedure with demonstrated utility. There are accumulating data indicating that this procedure is helpful in HIV-infected patients as well. Liver transplantation is currently largely unavailable to those living with HIV in Canada. Understanding the obstacles to this procedure is the first step to increasing access. Between August 2005 and November 2005, HIV physicians, one from each Canadian HIV Trials Network site, were asked to complete a quantitative questionnaire on adult liver transplant access and need. Forty-six per cent (16 of 35) of sites responded. A median 20% of the nearly 12,700 HIV patients followed at these sites had concurrent liver disease (20% caused by hepatitis C virus, 5% caused by hepatitis B virus and 5% were alcohol-related). On average, two patients per site were thought to be appropriate candidates for liver transplant evaluation. Eighty per cent of respondents anticipated increased need for liver transplantation over the next five years. Organ supply was universally identified as the chief obstacle to transplantation in patients with HIV. Other key issues included risk of hepatitis C virus reinfection and transplant surgical team willingness. Based on these data, it is believed that these issues should be the focus of efforts designed to increase access to transplantation in Canadians with end-stage liver disease and concurrent HIV.

BACKGROUND AND OBJECTIVES: An eight-member group consisting of Canadian infectious disease and immunology specialists and a family physician with significant experience in HIV management was convened to update existing recommendations, specifically intended for use by Canadian HIV-treating physicians, on the appropriate use of enfuvirtide in HIV/AIDS patients with resistance to other antiretroviral drugs.

We studied HIV genetic diversity in a cohort of 127 pregnant, HIV-infected women who received prenatal care at Sainte-Justine Hospital in Montreal, Canada, between 1999 and 2003. Clade assignments were derived by phylogenetic analysis of amplified pol sequences. Genotyping was successful in 103 of 127 women, 59 (57.3%) of whom were infected with clade B HIV-1, and 44 (42.7%) with nonclade B viruses, including subtypes A, C, D, F, G, and H. Four sequences remained unassigned. Forty-three of 44 women infected with non-clade B viruses were newcomers from sub-Saharan Africa, and subtype identity was consistent with those circulating in their countries of origin. These results highlight the epidemiologic importance of non-B HIV-1 in antenatal populations in a large North American urban center, underscore the influence of population movements on clade intermixing, and identify a group of patients who could be targeted for surveillance and drug therapy followup.

Approximately two years after the introduction of highly active antiretroviral therapy for the treatment of HIV infection, body shape changes and metabolic abnormalities were increasingly observed. Initially, these were ascribed to protease inhibitors, but it is now clear that nucleoside reverse transcriptase inhibitors also contribute to lipodystrophy syndrome. The syndrome groups together clinical conditions describing changes in body fat distribution that include lipoatrophy, lipoaccumulation or both. However, there does not appear to be a direct link between lipoatrophy and lipoaccumulation that would support a single mechanism for the redistribution of body fat. Currently, there is no clear definition of lipodystrophy, which explains the difficulty in determining its prevalence and etiology. There are no current guidelines for the treatment of fat distribution abnormalities that occur in the absence of other metabolic complications. The present article reviews the current state of knowledge of the definition, symptoms, risk factors, pathogenesis, diagnosis and treatment of the morphological changes associated with lipodystrophy syndrome.

BackgroundMany patients experience pain in the intensive care unit (ICU) despite receiving pain medication. Research has shown that music can help reduce pain. Music interventions studied so far have not used music streaming to generate playlists based on patient preferences while incorporating recommended tempo and duration. Previous research has focused on postoperative ICU patients able to self-report, which is underrepresentative of the ICU population that might benefit from a music intervention for pain management. We developed a new patient-oriented music intervention (POMI) that incorporates features based on theoretical, empirical, and experiential data intended to be used in the ICU. Such a music intervention should consider the expertise of ICU patients, family members, and nursing staff, as well as the practicality of the intervention when used in practice. ObjectiveThe primary objectives of this study are to (1) evaluate the acceptability and feasibility of the POMI to reduce pain in ICU patients and (2) evaluate the feasibility of conducting a crossover pilot randomized controlled trial (RCT) for intervention testing in the ICU. A secondary objective is to examine the preliminary efficacy of the POMI to reduce pain in ICU patients. MethodsA single-blind 2×2 crossover pilot RCT will be conducted. Patients will undergo 1 sequence of 2 interventions: the POMI which delivers music based on patients’ preferences via headphones or music pillow for 20-30 minutes and the control intervention (headphones or pillow without music). The sequence of the interventions will be inverted with a 4-hour washout period. Timing of the interventions will be before a planned bed turning procedure. Each patient will undergo 1 session of music. Twenty-four patients will be recruited. Patients able to self-report (n=12), family members of patients unable to self-report (n=12), and nursing staff (n=12) involved in the bed turning procedure will be invited to complete a short questionnaire on the POMI acceptability. Data will be collected on the feasibility of the intervention delivery (ie, time spent creating a playlist, any issue related to headphones/pillow or music delivery, environmental noises, and intervention interruptions) and research methods (ie, number of patients screened, recruited, randomized, and included in the analysis). Pain scores will be obtained before and after intervention delivery. ResultsRecruitment and data collection began in March 2022. As of July 5, 2022, in total, 22 patients, 12 family members, and 11 nurses were recruited. ConclusionsMethodological limitations and strengths are discussed. Study limitations include the lack of blinding for patients able to self-report. Strengths include collecting data from various sources, getting a comprehensive evaluation of the intervention, and using a crossover pilot RCT design, where participants act as their own control, thus reducing confounding factors. Trial RegistrationClinicalTrials.gov NCT05320224; https://clinicaltrials.gov/ct2/show/NCT05320224 International Registered Report Identifier (IRRID)DERR1-10.2196/40760

Introduction: During the COVID-19 pandemic, Quebec has been one of the most affected provinces in Canada. Rising fear of COVID-19 is inevitable among healthcare workers, and a new scale was developed to measure this type of fear, the Fear of COVID-19 Scale (FCV-19S). Aims: To translate the FCV-19S into French-Canadian and English-Canadian, and to validate both versions in the nursing staff from Quebec. Methods: A cross-sectional online survey was sent to approximately 15 000 nursing staff including nurses and licensed practical nurses among those who had consented to their respective Order to be contacted for research. The forward-backward method was used to translate the FCV-19S into French-Canadian and English-Canadian. Both versions along with stress and work-related questionnaires, were used to establish validity. Results: A total of 1708 nursing staff, with a majority of women, completed the survey (1517 and 191 completed the French-Canadian and English-Canadian versions). A unidimensional scale was confirmed for both versions with Cronbach alphas of 0.90 and 0.88. Discriminative values showed higher fear levels in women, and in generation X (40-56 years old). Higher fear levels were also found in nursing staff working in long-term care facilities, provided care to COVID-19 patients who died, and those who felt less prepared to provide safe care. Convergent associations were found between fear levels, stress, work satisfaction, and turnover intention. Discussion and conclusion: A rigorous approach was used to translate the fear of COVID-19 scale into French-Canadian and English-Canadian. Both Canadian versions of the FCV-19S supported a valid unidimensional scale in Quebec nursing staff.

Background & purpose: Pain is prevalent in the ICU at rest and during standard procedures. Clinical practice guidelines recommend a multi-modal approach to pain management, including pharmacological and non-pharmacological interventions. Music has been shown to be efficacious in reducing pain in this clinical setting when played for 20–30 minutes. A preliminary patient-oriented music intervention (preliminary POMI) was developed based on theoretical and empirical knowledge. We aimed to describe the acceptability of the preliminary POMI to critical care experts. Methods & procedures: A descriptive design was used to address the study’s aim. Purposive, snowball sampling was used to recruit participants who were ICU clinicians (i.e., seven nurses, one physician, one respiratory therapist, and one social worker) and music therapists (n = 3). Data were collected via video conference, using a six-item questionnaire and a semi-structured interview guide. Six attributes of acceptability were evaluated (appropriateness, suitability, convenience, effectiveness, risks, and undesirable effects), each rated from 0 (not acceptable) to 4 (most acceptable). Results: Nine women and three men aged 27–68 years with 4–36 years of experience working with critically ill adults participated. All acceptability items had a median score ≥ 3 (range, 1–4). Participants highlighted the importance of taking into consideration the patient’s music preferences and reported the use of streaming services as convenient. The timing of the intervention was more acceptable at rest or before instead of after a painful standard care procedure. Discussion & conclusion: The preliminary POMI was found to be acceptable to critical care experts for ICU patients experiencing pain at rest. Minor modifications to the preliminary POMI are needed prior to testing the intervention for procedural pain in critically ill adults. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to explore the use of a multi-parameter technology, the Nociception Level (NOL) index (Medasense Biometrics Ltd, Ramat Gan, Israel), for pain assessment in postoperative awake patients after cardiac surgery during non-nociceptive and nociceptive procedures in the intensive care unit (ICU). Materials and Methods: A prospective cohort repeated-measures design was used. Patients were included if they were in the ICU after undergoing cardiac surgery and if they could self-report their pain. A non-invasive probe was placed on the patient's finger for the continuous monitoring of the NOL index. Patients' self-reports of pain and anxiety (0– 10 Numeric Rating Scale or NRS), and behavioral scores with the Critical-Care Pain Observation Tool (CPOT) were obtained before and during a non-nociceptive procedure (ie, non-invasive blood pressure [NIBP] using cuff inflation), and before, during and after a nociceptive procedure (ie, chest tube removal [CTR]) for a total of five time points. Non-parametric tests were used to compare scores at different time points, and receiver operating characteristic curve analysis was performed. Results: Fifty-four patients were included in the analysis. The NOL index, pain and anxiety scores were significantly higher during CTR compared to rest and NIBP (p < 0.001). During CTR, the NOL was associated with self-reported pain intensity and unpleasantness but not with anxiety and CPOT scores. The NOL showed a modest performance in detecting pain (NRS ≥ 1 and ≥ 5) in this sample with sensitivity and specificity ranging from 61% to 85%. Conclusion: The NOL index was able to discriminate between a non-nociceptive and a nociceptive procedure and was associated with self-reported pain. Further validation testing of the NOL is necessary in a heterogeneous sample of ICU patients. [ABSTRACT FROM AUTHOR]

This study aimed to examine the interrater agreement of Critical-Care Pain Observation Tool-Neuro (CPOT-Neuro) scores as a newly developed tool for pain assessment in patients with critical illness and brain injury between raters using two methods of rating (bedside versus video) during standard care procedures (i.e., non-invasive blood pressure and turning). The bedside raters were research staff, and the two video raters had different backgrounds (health and non-health disciplines). Raters received standardized 45 min training by the principal investigator. Video recordings of 56 patient participants with a brain injury at different levels of consciousness were included. Interrater agreement was supported with an Intraclass Correlation Coefficient (ICC) > 0.65 for all pairs of raters and for each procedure. Interrater agreement was highest during turning in the conscious group, with ICCs ranging from 0.79 to 0.90. The use of video recordings was challenging for the observation of some behaviors (i.e., tearing, face flushing), which were influenced by factors such as lighting and the angle of the camera. Ventilator alarms were also challenging to distinguish from other sources for the video rater from a non-health discipline. Following standardized training, video technology was useful in achieving an acceptable interrater agreement of CPOT-Neuro scores between bedside and video raters for research purposes.

Abstract Background Pain assessment in brain-injured patients in the intensive care unit (ICU) is challenging and existing scales may not be representative of behavioral reactions expressed by this specific group. This study aimed to validate the French-Canadian and English revised versions of the Critical-Care Pain Observation Tool (CPOT-Neuro) for brain-injured ICU patients. Methods A prospective cohort study was conducted in three Canadian and one American sites. Patients with a traumatic or a non-traumatic brain injury were assessed with the CPOT-Neuro by trained raters (i.e., research staff and ICU nurses) before, during, and after nociceptive procedures (i.e., turning and other) and non-nociceptive procedures (i.e., non-invasive blood pressure, soft touch). Patients who were conscious and delirium-free were asked to provide their self-report of pain intensity (0–10). A first data set was completed for all participants (n = 226), and a second data set (n = 87) was obtained when a change in the level of consciousness (LOC) was observed after study enrollment. Three LOC groups were included: (a) unconscious (Glasgow Coma Scale or GCS 4–8); (b) altered LOC (GCS 9–12); and (c) conscious (GCS 13–15). Results Higher CPOT-Neuro scores were found during nociceptive procedures compared to rest and non-nociceptive procedures in both data sets (p 0.40 and > 0.60, respectively). CPOT-Neuro cut-off scores ≥ 2 and ≥ 3 were found to adequately classify mild to severe self-reported pain ≥ 1 and moderate to severe self-reported pain ≥ 5, respectively. Interrater reliability of raters’ CPOT-Neuro scores was supported with intraclass correlation coefficients > 0.69. Conclusions The CPOT-Neuro was found to be valid in this multi-site sample of brain-injured ICU patients at various LOC. Implementation studies are necessary to evaluate the tool’s performance in clinical practice.

Introduction: The Critical-Care Pain Observation Tool-Neuro (CPOT-Neuro) was derived from the original CPOT to assess pain in brain-injured patients in the adult intensive care unit (ICU). Objective: This study aimed to describe the nurses’ evaluations of the feasibility and clinical utility of the use of the French and English versions of the CPOT-Neuro in critically ill brain-injured adults. Methods: Fifty-nine ICU nurses from two university affiliated trauma centres (Montreal, Canada) were trained to use the CPOT-Neuro. Those who used it at the bedside during the study were invited to complete a self-administered questionnaire about its feasibility and clinical utility. Results: Twenty-seven of the trained ICU nurses (46 %) used the CPOT-Neuro during the study and completed the questionnaire. Feasibility: All nurses agreed that the training duration was sufficient, that the directives of use were clear, and that the tool content was simple to understand. Some nurses disagreed that the tool was quick to use (11.1 %), and easy to complete (7.7 %). Clinical utility: The tool was found useful by most nurses, but some of them disagreed that it was helpful for practice (7.7 %), that it influenced their practice (15.4 %) and that they would recommend it routinely (11.1 %). Responses did not differ between nurses from the two trauma centres who used either the French or the English version of the CPOT-Neuro (Mann-Whitney U tests, p>.05). Discussion and conclusion: The CPOT-Neuro was found to be feasible and useful by ICU nurses. Its implementation into daily practice could optimize pain assessment in critically ill brain-injured patients.

Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.