Autophagy suppresses tumorigenesis through elimination of p62.

Allelic loss of the essential autophagy gene beclin1 occurs in human cancers and renders mice tumor-prone suggesting that autophagy is a tumor-suppression mechanism. While tumor cells utilize autophagy to survive metabolic stress, autophagy also mitigates the resulting cellular damage that may limit tumorigenesis. In response to stress, autophagy-defective tumor cells preferentially accumulated p62/SQSTM1 (p62), endoplasmic reticulum (ER) chaperones, damaged mitochondria, reactive oxygen species (ROS), and genome damage. Moreover, suppressing ROS or p62 accumulation prevented damage resulting from autophagy defects indicating that failure to regulate p62 caused oxidative stress. Importantly, sustained p62 expression resulting from autophagy defects was sufficient to alter NF-kappaB regulation and gene expression and to promote tumorigenesis. Thus, defective autophagy is a mechanism for p62 upregulation commonly observed in human tumors that contributes directly to tumorigenesis likely by perturbing the signal transduction adaptor function of p62-controlling pathways critical for oncogenesis.

International Analgesia and Sedation Weaning and Withdrawal Practices in Critically Ill Adults: The Adult Iatrogenic Withdrawal Study in the ICU.

OBJECTIVES: Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population. DESIGN: International, multicenter, observational, point prevalence study. SETTING: Adult ICUs. PATIENTS: All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day. CONCLUSIONS: This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients.

The Validity of Vital Signs for Pain Assessment in Critically Ill Adults: A Narrative Review.

OBJECTIVES: Pain assessment in the intensive care unit (ICU) is challenging because many patients are unable to self-report or exhibit pain-related behaviors. In such situations, vital signs (VS) through continuous monitoring are alternative cues for pain assessment. This review aimed to describe the reliability and validity of VS for ICU pain assessment. DESIGN: Narrative review of the literature. DATA SOURCES: Medline, Embase, CINAHL, Cochrane. REVIEW/ANALYSIS METHODS: A narrative review was conducted with a comprehensive search in four databases. Search terms included VS, pain assessment, and ICU. RESULTS: Out of 1,359 results, 30 studies from 17 countries were included. Heart rate, blood pressure, and respiratory rate were most used for ICU pain assessment. Assessments were performed at rest before procedures, during nociceptive and non-nociceptive procedures, and after procedures. Increases in respiratory rate were clinically significant by more than 25% during nociceptive procedures (e.g., endotracheal suctioning, turning) compared with rest/pre-procedures in five studies. Correlations of VS with self-reported pain (reference standard measure) and behavioral pain scores (alternative measure) were absent or weak. CONCLUSIONS: VS are not valid indicators for ICU pain assessment. Increases of respiratory rate may be a cue for the detection of pain. However, fluctuations in respiratory rate can be influenced by opioids or controlled ventilation mode. Our results dissuade the use of VS for pain assessment because of the lack of association with ICU pain reference standards. Other physiologic measures of pain in critically ill adults should be explored.

Prediction of acute postoperative pain based on intraoperative nociception level (NOL) index values: the impact of machine learning-based analysis.

The relationship between intraoperative nociception and acute postoperative pain is still not well established. The nociception level (NOL) Index (Medasense, Ramat Gan, Israel) uses a multiparametric approach to provide a 0-100 nociception score. The objective of the ancillary analysis of the NOLGYN study was to evaluate the ability of a machine-learning aglorithm to predict moderate to severe acute postoperative pain based on intraoperative NOL values. Our study uses the data from the NOLGYN study, a randomized controlled trial that evaluated the impact of NOL-guided intraoperative administration of fentanyl on overall fentanyl consumption compared to standard of care. Seventy patients (ASA class I-III, aged 18-75 years) scheduled for gynecological laparoscopic surgery were enrolled. Variables included baseline demographics, NOL reaction to incision or intubation, median NOL during surgery, NOL time-weighted average (TWA) above or under manufacturers' recommended thresholds (10-25), and percentage of surgical time spent with NOL > 25 or < 10. We evaluated different machine learning algorithms to predict postoperative pain. Performance was assessed using cross-validated area under the ROC curve (CV-AUC). Of the 66 patients analyzed, 42 (63.6%) experienced moderate to severe pain. NOL post-intubation (42.8 (31.8-50.6) vs. 34.8 (25.6-41.3), p = 0.05), median NOL during surgery (13 (11-15) vs. 11 (8-13), p = 0.027), percentage of surgical time spent with NOL > 25 (23% (18-18) vs. 20% (15-24), p = 0.036), NOL TWA < 10 (2.54 (2.1-3.0) vs. 2.86 (2.48-3.62), p = 0.044) and percentage of surgical time spent with NOL < 10 (41% (36-47) vs. 47% (40-55), p = 0.022) were associated with moderate to severe PACU pain. Corresponding ROC AUC for the prediction of moderate to severe PACU pain were 0.65 [0.51-0.79], 0.66 [0.52-0.81], 0.66 [0.52-0.79], 0.65 [0.51-0.79] and 0.67 [0.53-0.81]. Penalized logistic regression achieved the best performance with a 0.753 (0.718-0.788) CV-AUC. Our results, even if limited by the small number of patients, suggest that acute postoperative pain is better predicted by a multivariate machine-learning algorithm rather than individual intraoperative nociception variables. Further larger multicentric trials are highly recommended to better understand the relationship between intraoperative nociception and acute postoperative pain.Trial registration Registered on ClinicalTrials.gov in October 2018 (NCT03776838).

French-Canadian Translation and Cultural Adaptation of the Clinical Opiate Withdrawal Scale: The COWS-FC.

OBJECTIVE: The main objective of the present study was to develop a French-Canadian translation and adaptation of the COWS (i.e., the COWS-FC) for the assessment of opioid withdrawal symptoms in clinical and research settings. METHODS: The French-Canadian translation and cultural adaptation of the COWS was performed following guidelines for the translation and cross-cultural adaptation of self-report measures. The steps consisted of (1) initial translation from English to French, (2) synthesis of the translation, (3) back-translation from French to English, (4) expert committee meeting, (5) test of the prefinal version among healthcare professionals and (6) review of final version by the expert committee. The expert committee considered four major areas where the French-Canadian version should achieve equivalence with the original English-version of the COWS. These areas were (1) semantic equivalence; (2) idiomatic equivalence; (3) experiential equivalence and (4) conceptual equivalence. RESULTS: Rigorous steps based on the guidelines for the translation and cultural adaptation of assessment tools were followed, which led to a semantically equivalent version of the COWS. After a pretest among healthcare professionals, members from the expert committee agreed upon slight modifications to the French-Canadian version of the COWS to yield a final COWS-FC version. CONCLUSIONS: A French-Canadian translation and adaptation of the COWS (i.e., the COWS-FC) was developed. The COWS-FC could be used for the assessment of opioid withdrawal symptoms in clinical and research settings.

French Translation, Adaptation, and Initial Validation of the Nurses' Attitudes and Perceptions of Pain Assessment in Neonatal Intensive Care Questionnaire (NAPPAQ).

PURPOSE: The purpose of this study was to translate, adapt and conduct initial psychometric validation of the French version of the Nurses' Attitudes and Perceptions of Pain Assessment in neonatal intensive care Questionnaire (NAPPAQ) developed by Polkki in 2010. BACKGROUND: Assessing nurses' perceptions, attitudes and knowledge about pain management in preterm infants is important to improve neonatal practices. METHODS: A sample of French-speaking nurses (n = 147) from Quebec and France working in neonatal intensive care was selected to validate the 46-item questionnaire. A French translation of the NAPPAQ, which includes Part I and II, was undertaken prior to its administration. The FIPM questionnaire was added as a Part III. Internal consistency and instrument structure were examined using Cronbach's alphas, inter-item and inter-scale correlations and exploratory factor analysis. RESULTS: The NAPPAQ-FIPM is divided into three parts. Part I of the French version had a Cronbach's alpha of 0.64 and was composed of five factors. Part II had good total internal consistency (0.79) and adequate structure, established by inter-item correlations. Part III had good total internal consistency (0.76), and factor analysis findings suggested the presence of five factors. CONCLUSIONS: The NAPPAQ-FIPM can be used for research purposes. Parts II and III obtained adequate psychometrics results. However, further refinement of Part I could improve its content and internal structure.

Description of the validity of the Analgesia Nociception Index (ANI) and Nociception Level Index (NOL) for nociception assessment in anesthetized patients undergoing surgery: a systematized review.

Maintaining optimum analgesia in anesthetized patients is challenging due to the inability to self-report pain or exhibit pain-related behaviours. The Analgesia Nociception Index (ANI) (based on heart rate variability [HRV]) and the Nociception Level Index (NOL) (based on HRV, photoplethysmography, skin conductance, and temperature) both include HRV and provide continuous index monitoring for nociception assessment. The research question was: "What are the validation strategies of the NOL and ANI for nociception assessment in anesthetized patients?". The objectives were to describe and analyze the validation strategies and results. A systematized review was conducted using a comprehensive search with keywords under three concepts (nociception/pain, ANI/NOL, and validity) in four databases. A quality assessment using an adapted GRADE approach for measurement tools, and a risk of bias assessment using QUADAS-2 tool were performed by two reviewers. Out of 525 results, 15 validation studies were included. Strategies included hypothesis testing, discriminative, and criterion validation. Significant changes in ANI/NOL values were found in response to nociceptive stimuli at different opioid concentrations (hypothesis testing). Higher ANI/NOL values were observed during nociceptive stimuli (discriminative). AUCs ranging from 0.83 to 0.99 were obtained to detect nociceptive stimuli (criterion). Both technologies performed superiorly in detecting nociceptive stimuli compared to individual monitoring of HR and blood pressure. Although the aforementioned validation strategies are deemed appropriate, in the absence of a gold standard, criterion validation findings should be interpreted with caution. Moreover, reliability could be examined using test-retest with consistent ANI/NOL values during a stable time-interval.

Influence of caring for COVID-19 patients on nurse's turnover, work satisfaction and quality of care.

AIM: This study aims to examine, through the lens of the Job Demands-Resources model, the influence of caring for COVID-19 patients on nurse's perception of chronic fatigue, quality of care, satisfaction at work and intention to leave their organisation and the profession. BACKGROUND: Studies have examined how fear of COVID-19 contributes to the mental, physical and work adjustment among nurses. To date, few studies have been conducted examining how caring for patients with COVID-19 contributes to work outcomes among nurses. METHODS: This is a cross-sectional survey involving 1705 frontline nurses and licensed practical nurses in Quebec, Canada. From these, 782 reported caring for COVID-19 patients. RESULTS: High chronic fatigue, poor quality of care, lower work satisfaction and higher intention to leave their organisation were found for nurses caring for COVID-19 patients. Poorly prepared and overwhelmed nurses showed higher turnover intention than those well prepared and in control. CONCLUSIONS: There is an urgent need to provide support to nurses during the pandemic, with a long-term strategy to increase their retention. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse administrators play an important role in supporting their nurses during a pandemic in the form of education, training and policy development to positively impact quality of care and retention.

Validation of the Critical-Care Pain Observation Tool-Neuro in brain-injured adults in the intensive care unit: a prospective cohort study.

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 < 0.001). CPOT-Neuro scores were not different across LOC groups. Moderate correlations between CPOT-Neuro and self-reported pain intensity scores were found at rest and during nociceptive procedures (Spearman rho > 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.

Determinants of pain assessment documentation in intensive care units.

PURPOSE: The underassessment of pain is a major barrier to effective pain management, and the lack of pain assessment documentation has been associated with negative patient outcomes. This study aimed to 1) describe the contextual factors related to pain assessment and management in five Québec intensive care units (ICUs); 2) describe their pain assessment documentation practices; and 3) identify sociodemographic and clinical determinants related to pain assessment documentation. METHODS: A descriptive-correlational retrospective design was used. Sociodemographic data (i.e., age, sex), clinical data (i.e., diagnosis, mechanical ventilation, level of consciousness, severity of illness, opioids, sedatives), and pain assessments were extracted from 345 medical charts of ICU admissions from five teaching hospitals between 2017 and 2019. Descriptive statistics and multiple linear regression were performed. RESULTS: All sites reported using the 0-10 numeric rating scale, but the implementation of a behavioural pain scale was variable across sites. A median of three documented pain assessments were performed per 24 hr, which is below the minimal recommendation of eight to 12 pain assessments per 24 hr. Overall, pain assessment was present in 70% of charts, but only 20% of opioid doses were followed by documented pain reassessment within one hour post-administration. Higher level of consciousness (ß = 0.37), using only breakthrough doses (ß = 0.24), and lower opioid doses (ß = -0.21) were significant determinants of pain assessment documentation (adjusted R2 = 0.25). CONCLUSION: Pain assessment documentation is suboptimal in ICUs, especially for patients unable to self-report or those receiving higher opioid doses. Study findings highlight the need to implement tools to optimize pain assessment and documentation.

RéSUMé: OBJECTIF: La sous-évaluation de la douleur constitue un obstacle majeur à une gestion efficace de la douleur, et le manque de documentation de l'évaluation de la douleur a été associé à des conséquences défavorables pour les patients. Cette étude visait à : 1) décrire les facteurs contextuels liés à l'évaluation et à la gestion de la douleur dans cinq unités de soins intensifs (USI) du Québec; 2) décrire leurs pratiques de documentation de l'évaluation de la douleur; et 3) identifier les déterminants sociodémographiques et cliniques liés à la documentation de l'évaluation de la douleur. MéTHODE: Un devis de recherche rétrospectif descriptif-corrélationnel a été utilisé. Les données sociodémographiques (c.-à-d. l'âge, le sexe), les données cliniques (c.-à-d. le diagnostic, la ventilation mécanique, le niveau de conscience, la gravité de la maladie, les opioïdes, les sédatifs) et les évaluations de la douleur ont été extraites de 345 dossiers médicaux avec admissions à l'USI de cinq hôpitaux universitaires entre 2017 et 2019. Des statistiques descriptives et une régression linéaire multiple ont été effectuées. RéSULTATS: Tous les sites ont déclaré utiliser l'échelle d'évaluation numérique de 0 à 10, mais l'implantation d'une échelle de douleur comportementale variait d'un site à un autre. Une médiane de trois évaluations de douleur étaient documentées par 24 heures, ce qui est inférieur à la recommandation minimale de huit à 12 évaluations de douleur par 24 heures. Dans l'ensemble, l'évaluation de la douleur était présente dans 70 % des dossiers, mais seulement 20 % des doses d'opioïdes étaient suivies d'une réévaluation documentée de la douleur dans l'heure suivant leur'administration. Un niveau de conscience plus élevé (ß = 0,37), l'utilisation exclusive d'entredoses d'opioïdes pour les percées de douleur (ß = 0,24) et des doses d'opioïdes plus faibles (ß = -0,21) ont constitué les déterminants significatifs dans la documentation de l'évaluation de la douleur (R2 ajusté = 0,25). CONCLUSION: La documentation de l'évaluation de la douleur est sous-optimale dans les USI, en particulier pour les patients incapables de s'exprimer ou ceux qui reçoivent des doses plus élevées d'opioïdes. Les résultats de cette étude soulignent l'importance d'implanter des outils pour optimiser l'évaluation et la documentation de la douleur.

Initial testing of the use of the Safer Nursing Care Tool in a Canadian acute care context.

AIM: Initial testing of England's Safer Nursing Care Tool for adult in-patient acute care wards in a university-affiliated Canadian hospital. BACKGROUND: Safe-nursing staffing decisions have significant impacts on patients' safety and quality of care. The Safer Nursing Care Tool was developed in England to provide managers with a validated formula for making appropriate nursing staffing decisions. The tool has been widely used and studied in the UK but has yet to be tested in a Canadian context. METHOD: Ten high service quality acute care wards from a university-affiliated Canadian hospital tested the use of the Safer Nursing Care Tool. Service quality, patients' dependency/acuity and staff activity data were benchmarked against information collected in 726 comparable UK wards. RESULTS: Higher bed occupancy and patient dependency/acuity mix were found in the 10 Canadian wards compared to their UK counterparts. Overall staff activity was comparable between UK and Canadian wards. CONCLUSION: The Safer Nursing Care Tool can be applied in this Canadian hospital, and further testing in other hospitals and specialties is required. IMPLICATION FOR NURSING MANAGEMENT: The Safer Nursing Care Tool is a valid staffing tool to use that, when combined with professional judgement, can help managers to properly establish nursing staff in acute care wards.

The FCR-1: Initial validation of a single-item measure of fear of cancer recurrence.

OBJECTIVE: Fear of cancer recurrence (FCR) is characterized by the fear, worry or concern that cancer will come back or progress. The negative effects associated with FCR are consistently identified by cancer survivors as one of their most prominent unmet needs. Current measures of FCR can be long, complex and burdensome for survivors to complete. The objective of the present study is to develop and validate a one-item measure of FCR. METHODS: The ability of the FCR-1 to detect change in FCR over time was analyzed using a repeated-measures ANOVA and paired-samples t-tests. Pearson correlations were used to measure the concurrent, convergent and discriminant validity of the FCR-1, and a ROC analysis was conducted to determine an optimal clinical cut-off score. RESULTS: The FCR-1 was found to be responsive to change in FCR over time. It demonstrated concurrent validity with the FCRI (r = .395, P = .010), and convergent validity with the Mishel Uncertainty in Illness Scale (r = .493, P = .001) and the Reassurance Questionnaire (r = .325, P = .044). Discriminant validity was confirmed when the FCR-1 did not significantly correlate with unrelated measures. A ROC analysis pinpointed an optimal clinical cut-off score of 45.0. CONCLUSIONS: The FCR-1 is a promising tool that can be incorporated in clinical and research settings. Due to its brevity, the care needs of highly distressed patients can be met quickly and efficiently. In research settings, the FCR-1 can reduce the cognitive burden experienced by survivors.

Exploration of the Nociception Level (NOL™) Index for Pain Assessment during Endotracheal Suctioning in Mechanically Ventilated Patients in the Intensive Care Unit: An Observational and Feasibility Study.

BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and benzodiazepines in critically Ill neonates, children and adults: A systematic review of clinical studies.

WHAT IS KNOWN AND OBJECTIVE: Many critically ill patients are exposed to opioids and benzodiazepines at high doses for prolonged periods, and upon discontinuation of these drugs, they may be at risk for iatrogenic withdrawal. Although this syndrome was associated with worse outcomes in the critically ill, limited guidance exists regarding its evaluation, prevention and treatment. This systematic review examined the frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and/or benzodiazepines in critically ill neonates, children and adults. METHODS: The literature search was conducted in PubMed, Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane register of systematic reviews, DARE, CINAHL, Trip database, CMA infobase and NICE evidence from inception to February 2018. Grey literature was examined. We included studies reporting frequency, risk factors or symptomatology of iatrogenic withdrawal of opioids, benzodiazepines (or both) in critically ill patients. We considered all study designs except case reports and case series. We excluded studies on neonatal abstinence syndrome, alcohol withdrawal, studies on chronic opioid and/or benzodiazepine users and studies on prevention or treatment of withdrawal in critical care patients. Two independent reviewers applied the inclusion and exclusion criteria. Pairs of reviewers independently abstracted data and evaluated methodological quality using the Cochrane Collaboration Tool, Newcastle-Ottawa or QUADAS-2. Details regarding study design, outcomes, definition, evaluation and type of withdrawal (opioid, benzodiazepine or mixed) were collected. Cumulative doses and duration of opioids and benzodiazepines were collected. RESULTS AND DISCUSSION: We identified 21 866 unique citations and 153 full texts were assessed for eligibility. Thirty-four studies were included; the majority were observational and few included adults. In prospective studies, mixed withdrawal was observed in 7.5%-100% of patients in paediatric studies and ranged from 16.7% to 55% in adults. Symptomatology of withdrawal was not well described. Risk factors included higher cumulative dose and prolonged administration of opioids and benzodiazepines. WHAT IS NEW AND CONCLUSION: Iatrogenic withdrawal appears to be a frequent syndrome in critical care patients who received regular doses of opioids and/or benzodiazepines for ≥72 hours. Larger studies are required, especially in critically ill adults, to better define the syndrome and its symptomatology.

Family Members' Experiences with Observing Pain Behaviors Using the Critical-Care Pain Observation Tool.

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.

Does Hand Massage Have Sustained Effects on Pain Intensity and Pain-Related Interference in the Cardiac Surgery Critically Ill? A Randomized Controlled Trial.

BACKGROUND: Despite the promising short-term pain relief effect of massage, little is known regarding its sustained effects on pain intensity and pain-related interference with functioning. AIMS: To evaluate the sustained effect of hand massage on the pain intensity and pain-related interference with functioning of cardiac surgery patients. DESIGN: A randomized controlled trial. SETTINGS: A medical-surgical intensive care unit in Canada. PARTICIPANTS/SUBJECTS: Adult patients undergoing cardiac surgery and at low risk for postoperative complications were eligible. METHODS: In the intensive care unit, patients were randomly assigned to either 20-minute hand massage, hand holding, or rest. Pain intensity and pain-related interference with functioning were assessed on the second postoperative day. RESULTS: A total of 60 patients were randomly allocated and 46 completed data collection on the second postoperative day. Although no significant differences were identified across groups, the hand massage group reported a maximum pain intensity (median 5.75, range: 2-10) that was lower than the hand-holding (median 6.50, range: 1-10) and standard care groups (median 6.25, range: 0-10). The hand massage group could reach 0 pain intensity throughout a 24-hour period (median 0, range: 0-7), contrary to the hand-holding (median 2, range: 0-5) and standard care groups (median 2, range: 0-4.5). A trend for statistical significance was noted for dichotomized ratings on pain interference with walking (p = .176) and sleep (p = .050). CONCLUSIONS: Hand massage could help patients experience longer periods without pain and lower levels of maximum pain intensity. When coupled with recovery activities, hand massage could reduce pain-related interference with functioning.

Pain Assessment in the Patient Unable to Self-Report: Clinical Practice Recommendations in Support of the ASPMN 2019 Position Statement.

Pain is a subjective experience, unfortunately, some patients cannot provide a self-report of pain verbally, in writing, or by other means. In patients who are unable to self-report pain, other strategies must be used to infer pain and evaluate interventions. In support of the ASPMN position statement "Pain Assessment in the Patient Unable to Self-Report", this paper provides clinical practice recommendations for five populations in which difficulty communicating pain often exists: neonates, toddlers and young children, persons with intellectual disabilities, critically ill/unconscious patients, older adults with advanced dementia, and patients at the end of life. Nurses are integral to ensuring assessment and treatment of these vulnerable populations.

ASPMN 2019 Position Statement: Pain Assessment in the Patient Unable to Self-Report.

Managing pain in those vulnerable populations who are unable to self-report or communicate is challenging due to difficulty recognizing pain presence and severity. As no valid and reliable objective measure of pain exists, the ASPMN supports assessment practice recommendations that gather relevant information to infer presence of pain and evaluate response to intervention. Nurses and other healthcare professionals must be advocates for those who are unable to speak for themselves regarding their pain experience.

Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis.

Autophagy is a catabolic pathway used by cells to support metabolism in response to starvation and to clear damaged proteins and organelles in response to stress. We report here that expression of a H-ras(V12) or K-ras(V12) oncogene up-regulates basal autophagy, which is required for tumor cell survival in starvation and in tumorigenesis. In Ras-expressing cells, defective autophagosome formation or cargo delivery causes accumulation of abnormal mitochondria and reduced oxygen consumption. Autophagy defects also lead to tricarboxylic acid (TCA) cycle metabolite and energy depletion in starvation. As mitochondria sustain viability of Ras-expressing cells in starvation, autophagy is required to maintain the pool of functional mitochondria necessary to support growth of Ras-driven tumors. Human cancer cell lines bearing activating mutations in Ras commonly have high levels of basal autophagy, and, in a subset of these, down-regulating the expression of essential autophagy proteins impaired cell growth. As cancers with Ras mutations have a poor prognosis, this "autophagy addiction" suggests that targeting autophagy and mitochondrial metabolism are valuable new approaches to treat these aggressive cancers.

Incidence and Risk Factors of Long-term Opioid Use in Elderly Trauma Patients.

OBJECTIVE: Evaluate the incidence and risk factors of opioid use 1 year after injury in elderly trauma patients. BACKGROUND: The current epidemic of prescription opioid misuse and overdose observed in North America generally concerns young patients. Little is known on long-term opioid use among the elderly trauma population. METHODS: In a retrospective observational multicenter cohort study conducted on registry data, all patients 65 years and older admitted (hospital stay >2 days) for injury in 57 adult trauma centers in the province of Quebec (Canada) between 2004 and 2014 were included. We searched for filled opioid prescriptions in the year preceding the injury, up to 3 months and 1 year after the injury. RESULTS: In all, 39,833 patients were selected for analysis. Mean age was 79.3 years (±7.7), 69% were women, and 87% of the sample was opioid-naive. After the injury, 38% of the patients filled an opioid prescription within 3 months and 10.9% [95% confidence interval (CI) 10.6%-11.2%] filled an opioid prescription 1 year after trauma: 6.8% (95% CI 6.5%-7.1%) were opioid-naïve and 37.6% (95% CI 36.3%-38.9%) were opioid non-naive patients. Controlling for confounders, patients who filled 2 or more opioid prescriptions before the injury and those who filled an opioid prescription within 3 months after the injury were, respectively, 11.4 and 3 times more likely to use opioids 1 year after the injury compared with those who did not fill opioid prescriptions. CONCLUSIONS: These results highlight that elderly trauma patients are at risk of long-term opioid use, especially if they had preinjury or early postinjury opioid consumption.