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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.

Background Current guidelines support family members' participation in care, but little is known regarding their potential contribution to pain assessment using validated behavioral pain scales. Aims This study aimed to describe family members’ observations of pain behaviors with the Critical-Care Pain Observation Tool and their evaluation of the tool and its use, and to understand their experience and perceptions of their potential role in pain management in the intensive care unit. Design A mixed methods cross-sectional explanatory design was used. Setting A medical-surgical intensive care unit in Canada. Participants/Subjects Family members were eligible if they had a loved one admitted in the intensive care unit who was unable to self-report. Methods Family members identified pain behaviors using the Critical-Care Pain Observation Tool after a brief training, completed a self-administered questionnaire, and participated in a follow-up individual interview regarding their experience and perceived potential role in pain management when their loved one is unable to self-report. Results Ten family members participated. A 15-minute training appeared sufficient for family members to be comfortable with observing pain behaviors included in the Critical-Care Pain Observation Tool. The tool allowed them to confirm their observations of pain behaviors, to focus more on the patient, and to advocate for better pain management. Conclusions Future research is needed to explore the views of more family members and to compare their Critical-Care Pain Observation Tool scores to the ones of nurses' for interrater reliability testing.

This review describes family member involvement in intensive care unit pain assessment and management and generates implications for clinical practice, education, and future research. A literature review was performed in MEDLINE, PubMed, EMBASE, Cochrane, and CINAHL databases from their inception until April 30, 2019. Only 11 studies addressing the topic were identified, and the current quality of evidence is low. Family members can be involved in pain assessment by describing patients’ pain behaviors and in pain management by selecting and delivering nonpharmacological interventions tailored to patients’ needs, if the family members feel comfortable with this role. More-rigorous research is required to describe the role of family members in patients’ pain assessment and management. Advancing knowledge in this field could improve patients’ and family members’ experiences with pain assessment and management in the intensive care unit.

Context Multimodal analgesic approaches are recommended for intensive care unit (ICU) pain management. Although music is known to reduce pain in acute and chronic care settings, less is known about its effectiveness in the adult ICU. Objectives Determine the effects of music interventions on pain in the adult ICU, compared with standard care or noise reduction. Methods This review was registered on PROSPERO (CRD42018106889). Databases were searched for randomized controlled trials of music interventions in the adult ICU, with the search terms ["music*" and ("critical care" or "intensive care")]. Pain scores (i.e., self-report rating scales or behavioral scores) were the main outcomes of this review. Data were analyzed using a DerSimonian-Laird random-effects method with standardized mean difference (SMD) of pain scores. Statistical heterogeneity was determined as I2 > 50% and explored via subgroup analyses and meta-regression. Results Eighteen randomized controlled trials with a total of 1173 participants (60% males; mean age 60 years) were identified. Ten of these studies were included in the meta-analysis based on risk of bias assessment (n = 706). Music was efficacious in reducing pain (SMD −0.63 [95% CI −1.02, −0.24; n = 10]; I2 = 87%). Music interventions of 20–30 minutes were associated with a larger decrease in pain scores (SMD −0.66 [95% CI −0.94, −0.37; n = 5]; I2 = 30%) compared with interventions of less than 20 minutes (SMD 0.10 [95% CI −0.10, 0.29; n = 4]; I2 = 0%). On a 0–10 scale, 20–30 minutes of music resulted in an average decrease in pain scores of 1.06 points (95% CI −1.56, −0.56). Conclusion Music interventions of 20–30 minutes are efficacious to reduce pain in adult ICU patients able to self-report.

Many patients in the intensive care unit (ICU) suffer from pain and are non-communicative. Therefore, alternative pain measures are necessary. Although behavioral pain measures are available, physiological measures are lacking. The Nociception Level index (NOL™) provides a value from combination of multiple physiological parameters to measure pain and its use in the ICU is new.To explore the use of a multiple physiological parameter measure for pain assessment, the NOL™ index, in mechanically ventilated patients able to self-report pain in the ICU.A prospective cohort study was performed. Data were collected before, during, and 15 minutes after a non-nociceptive procedure (noninvasive blood pressure using cuff inflation) and a nociceptive procedure (endotracheal suctioning). NOL index, 0 to 10 pain intensity, and Critical-Care Pain Observation Tool (CPOT) scores were also obtained. Data were analyzed using Friedman and Mann-Whitney tests. Feasibility of study procedures was described.Out of 28 patients who consented, 17 remained eligible and data were analyzed for 15. Technical issues prevented obtaining a NOL signal in 2 patients. NOL values were higher during endotracheal suctioning (median = 41.6) compared with before (median = 11.2) and after the procedure (median = 11.8) and compared with cuff inflation (median = 15.1; Friedman test, p .001). NOL values were associated with pain intensity and CPOT scores (Mann-Whitney tests, p .05).The study procedures with the NOL were found feasible; NOL values could discriminate between nociceptive and non-nociceptive procedures, and values were associated with reference pain measures. Further NOL testing is required in other ICU patient groups and procedures.

To evaluate the use of vital signs for pain detection in brain-injured patients in the intensive care unit.A repeated-measures descriptive-correlational study.Two neurological intensive care units in Montréal, Canada. A total of 101 brain-injured patients were included.This study examined the fluctuations in systolic and diastolic blood pressure, heart and respiratory rates, and oxygen saturation in brain-injured critically ill patients before, during, and 15 minutes after turning and soft touch using a data collection computer. When possible, patients' pain self-reports were obtained using a 0-10 Faces Pain Thermometer.The heart and respiratory rates were higher during turning than soft touch and higher during the procedure compared to prior (p 0.05), but their fluctuation was modest. The systolic blood pressure increased during both turning and soft touch by 2 mmHg, but was 26.6 mmHg higher for those who reported pain versus no pain (Mann-Whitney = 25.00, p = 0.008, n = 28). A moderate correlation was observed between the systolic blood pressure (Spearman's rho = 0.617, p = 0.004, n = 24) and self-reported pain intensity during turning. No significant effects were observed for diastolic blood pressure and oxygen saturation.Only increases in systolic blood pressure were positively associated with pain in this sample and replication studies with larger samples is needed.

Background The evidence shows that brain-injured patients express behaviours that are related to their level of consciousness (LOC), and different from other patients in the intensive care unit (ICU). Therefore, existing behavioural scales should be revised to enhance their content and validity for use in these patients. Objectives The aim was to evaluate the content relevance of behaviours and autonomic responses for pain assessment of brain-injured ICU patients from the perspective of critical care clinicians. Methods A total of 77 clinicians from four adult neuroscience ICUs (three from Canada and one from the United States) participated in this descriptive study. A physician/nurse ratio of 21% (13/61) was reached in this quota sample, and three physiotherapists also participated. They completed a content validation questionnaire of 19 items rated on clarity and relevance based on the patient’s LOC. Item Content Validity Index (I-CVI), and modified kappa (κ*) were calculated. Values higher than 0.78 and 0.75 respectively were considered excellent. Results Regardless of the patient’s LOC, brow lowering, grimacing, and trying to reach the pain site were rated as the most relevant behaviours by clinicians, with excellent values of I-CVI > 0.78 and κ* > 0.75. Eyes tightly closed, moaning and verbal complaints of pain also obtained excellent values in altered LOC and conscious patients. Eye weeping obtained excellent values only in conscious patients. Other items showed fair (0.40–0.59) to good (0.60–0.74) values, while blinking and coughing showed poor values ( Conclusions Facial expressions, movements towards the pain site, and vocalisation of pain were the most relevant pain-related behaviours rated by critical care clinicians. The relevance of some behaviours (e.g., moaning and verbal complaints of pain) varied across LOCs, thereby calling forth adaptations of behavioural pain scales to allow for interpretation in the context of a patient’s LOC and ability to express specific behaviours.

Objectives To examine the relationship between levels of the T-cell regulatory cytokine interleukin-7 (IL-7) and CD4 cell counts during immune reconstitution and to assess its prognostic value in advanced HIV-1-infected patients receiving lopinavir/ritonavir-based therapy. Methods Thirty-six HIV-1-infected adults who completed 48 weeks of follow-up visits were included in this prospective study. Patients having failed two or more antiretroviral therapy regimens were treated with lopinavir/ritonavir-based therapy. An enzyme-linked immunosorbent assay was used to determine IL-7 plasma levels, flow cytometry was used to analyse cell surface antigens, and polymerase chain reaction was used to quantify plasma HIV-1. Results Pretreatment IL-7 levels were elevated in all patients (mean 11.0 pg/mL) and were negatively correlated with CD4 cell counts and age (r=−0.59, P

Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS; also known as "B-cell factor belonging to the tumor necrosis factor family" [BAFF]). We have recently shown that, in human immunodeficiency virus (HIV)-infected individuals with rapid and those with classic disease progression, B-cell dysregulations were associated with increased BLyS expression in plasma and by blood myeloid DCs (mDCs), in contrast to aviremic HIV-infected individuals with slow disease progression (also known as "elite controllers"). In previous work with transgenic mice expressing HIV genes, B-cell dysregulations were concomitant with altered mDCs and dependent on HIV negative factor (Nef). We now report that HIV Nef is detected early after infection and despite successful therapy in plasma and BLyS-overexpressing blood mDCs of HIV-infected rapid and classic progressors, whereas it is low to undetectable in aviremic slow progressors. In vitro, HIV Nef drives monocyte-derived DCs toward BLyS overexpression through a process involving STAT1. Importantly, this is counteracted in the presence of all-trans retinoic acid. Nef thus contributes to high BLyS proinflammatory profiles in HIV-infected individuals.

Objectives To determine the severity of injection site reactions (ISRs), patient quality of life (QoL) and preference when enfuvirtide is administered by the Biojector® (Bioject, Medical Technologies, Inc., Tualatin, OR, USA) relative to standard needles. Methods A total of 201 HIV-positive patients on stable enfuvirtide-based therapy (n=184) or initiating such therapy (n=17) were evaluated prospectively after switching from standard needles to the Biojector® system. Patients used needles for a minimum of 2 weeks prior to switching to the Biojector®. Questionnaires to assess the incidence and severity of ISRs (31-item score) and QoL [Medical Outcomes Study HIV Health Survey (MOS-HIV)] were administered at baseline and following a minimum of 14 days of Biojector® use. Results The median changes in ISR score and number of ISRs following a median of 1.0 month [interquartile range (IQR) 0.9, 1.3] of Biojector® use were −3 (IQR −7, 1) and −1 (IQR −3, 1), respectively. The severity of pain (P

Interleukin-7 (IL-7), RANTES (regulated on activation, normal T cell expressed and secreted), stromal cell-derived factor-1 (SDF-1) and transforming growth factor-beta (TGF-beta) appear to share certain biological properties in vitro and all are involved in HIV-1 disease progression. Our earlier observations indicated that IL-7 levels decrease upon CD4 T-cell recovery and represent a new, independent predictor of virological response. Here, we examine associations among circulating levels of IL-7, RANTES, SDF-1 and TGF-beta in hopes of gaining insight into their contribution to the predictive value of IL-7.Levels of IL-7, RANTES, SDF-1 and TGF-beta, and immune and viral parameters were assessed in HIV-1-infected patients.Cross-sectional (n=148) and longitudinal (n=36) analyses showed that levels of IL-7, but not RANTES, SDF-1 or TGF-beta, were increased in HIV-1-infected adults compared with those of healthy controls. In the cross-sectional study, levels of IL-7 were correlated with RANTES (r=0.31, P=0.002) and TGF-beta (r=0.53, P0.001) but not with SDF-1 (r=0.12, P=0.22), and these associations were more pronounced in patients with CD4 T-cell counts200 cells/microL. In contrast to IL-7, levels of RANTES, SDF-1 and TGF-beta were not correlated with CD4 T-cell counts. Longitudinal analysis revealed a marked decline in IL-7 levels accompanied by an increase in CD4 T-cell count following antiretroviral therapy (ART), but no changes in RANTES, SDF-1 or TGF-beta levels. Multivariate regression analysis showed no influence of baseline RANTES, SDF-1 or TGF-beta levels on the value of IL-7 as a predictor of virological response at 48 weeks.Collectively, these results indicate that changes in IL-7 levels did not induce changes in RANTES, SDF-1 or TGF-beta. Furthermore, they indicate that RANTES, SDF-1 or TGF-beta levels do not explain the predictor value of IL-7 in patients receiving ART.

To estimate the cost-effectiveness ratio of highly-active antiretroviral therapy (HAART) in Canada.A before-and-after analysis to calculate incremental cost of life year gained (LYG) between 1991 and 1995 (pre-HAART period) and between 1997 and 2001 (HAART period) for non-AIDS and AIDS groups (CDC stage of HIV infection).For two Quebec HIV hospital clinics, mean inpatient (IP) days, outpatient (OP) visits and direct health care costs per patient-year (PPY) were calculated. Cox's proportional hazards models calculated disease progression, stratified by study periods and adjusted for gender, age at cohort entry, sexual orientation, injecting drug use and baseline CD4 cell count.For non-AIDS patients, mean IP days was 1.6 (pre-HAART period) compared with 0.8 PPY (HAART period); mean OP visits increased from 2.8 to 5.5 PPY. Total cost was US$ 4265 (pre-HAART period) and US$ 9445 PPY (HAART period) of which 66 and 84%, respectively were spent on antiretroviral drugs. Median progression time was 6.3 years in the pre-HAART period compared with 12.5 years in HAART period (log rank chi = 270, P0.0001). Incremental cost per LYG between periods was US$ 14 587. For AIDS patients, mean IP days decreased from 13.3 to 4.4 PPY between periods; OP visits increased from 8.3 to 9.2 PPY. Total costs increased from US$ 9099 to US$ 11 754 PPY, while expenditure on antiretroviral drugs increased from 29 to 72% of total cost. Median progression time was 3.8 years in the pre-HAART period, which increased to 13.3 years in the HAART period (log rank chi = 158, P0.0001); incremental cost per LYG between periods was US$ 12 813.HAART appeared a cost-effective intervention in Canada.

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.METHODS: In the present observational study, adults with chronic HCV were treated with peginterferon alfa-2a 180 μg/week plus ribavirin at 45 Canadian centres (16 academic, 29 community). The primary efficacy end point was sustained virological response (SVR). Other outcome measures included HRQoL (assessed using the 36-item Short-Form Health Survey), heath resource use, and workplace productivity and absences within a 60-day interval.RESULTS: In treatment-naive patients infected with HCV genotype 1, significantly higher SVR rates were achieved in those treated at academic (n=54) compared with community (n=125) centres (52% versus 32% [P=0.01]), although rates of dosage reduction and treatment discontinuation were similar across settings. SVR rates among patients infected with genotype 2/3 were similar between academic (n=59) and community (n=100) centres (64% versus 67% [P=0.73]). Following antiviral therapy, patients with genotype 1 who achieved an SVR (n=67) had significantly higher mean scores on the physical (P=0.005) and mental components of the 36-item Short-Form Health Survey (P=0.043) compared with those without an SVR (n=111). In contrast, HRQoL scores were similar in HCV genotype 2/3 patients with and without an SVR. There were no differences in workplace productivity or absences between patients with and without an SVR. The most frequently used health care resources by all patients were visits and phone calls to hepatitis nurses, and general practice or walk-in clinics.CONCLUSION: Patients infected with HCV genotype 1 achieved higher SVR rates when treated at academic rather than community centres in Canada. The reasons for this difference require additional investigation.