Sleep quality with WHO Step III opioid use for cancer pain

Peer reviewedPostprin

Physical function endpoints in cancer cachexia clinical trials: Systematic Review 1 of the cachexia endpoints series

In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia

Physical Function Endpoints in Cancer Cachexia Trials; Systematic Review 1 of the Cachexia Endpoints Series

Abstract In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990–2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6‐min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group‐Performance Status [ECOG‐PS]) or patient‐reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ‐C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise‐based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG‐PS (16 vs. 9 trials), and patient‐reported EORTC QLQ‐C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia

Vann, juss og samfunn

Society’s use and management of water relies on professional expertise spanning diverse fields: from biology and technology to economics and law. This book examines current issues related to regulating water through chapters summarizing various sets of regulation as well as chapters that take a scientific deep dive into selected themes. The diversity of professional expertise is also reflected in the law aspect. We explore such subjects as surface runoff, natural disasters, drinking water, groundwater, salmon, hydropower, and human rights, as well as general impact assessment requirements and duty of knowledge in environmental law administration. A key objective of the book has been to provide an interdisciplinary understanding of the legal circumstances associated with water, and in addition, deliberate the pros and cons of some of the current regulations. This book will be particularly useful for those who in various ways support and facilitate procedures within the public sector at both the national and municipal levels. It will also be useful for private sector actors seeking familiarity with legal questions that can arise in relation to public administration and other private actors. From a broader perspective, we hope the book can help to throw light on conflicts between different interests and groups within society that occur, for example, when introducing fees, special injunctions against private actors, and requirements for knowledge basis. This book project is the result of legal research conducted at the Norwegian University of Life Sciences (NMBU) and is supplemented by national expertise in several areas. It has been edited by Steinar Taubøll, a professor at NMBU’s Department of Property and Law. Taubøll has a background in both law and the natural sciences, and extensive experience with interdisciplinary work.Håndtering og bruk av vann i samfunnet krever et faglig mangfold fra biologi og teknikk til økonomi og juss. Denne boken drøfter aktuelle temaer knyttet til rettslig regulering av vann, både i form av oversiktskapitler om ulike regelsett og gjennom vitenskapelige dypdykk i utvalgte temaer. Den faglige spennvidden gjenspeiler seg også innen det juridiske. I boken finner man stoff om overvannshåndtering, naturfare, drikkevann, grunnvann, villaks, kraftutbygging, menneskerettigheter, samt om generelle utredningskrav og kunnskapsplikter i miljørettsforvaltning. Et sentralt siktemål er å bygge opp tverrfaglig forståelse av gjeldende juridiske forhold knyttet til vann, og dessuten sette noen av dagens reguleringer under debatt. Boken retter seg særlig til de ressurspersonene som på ulike måter støtter saksbehandlingen i stat og kommune. Boken antas også å være nyttig for private aktører som vil gjøre seg mer kjent med rettsspørsmål som kan oppstå i forhold til forvaltningen og til andre private aktører. I et bredere perspektiv er det dessuten ønskelig at boken kan bidra til å belyse konflikter mellom ulike hensyn og grupper i samfunnet, for eksempel ved innføring av gebyrer, pålegg rettet mot private, innføring av tyngende vilkår og krav til kunnskap og faktagrunnlag. Bokprosjektet springer ut av den juridiske forskningen ved Norges miljø- og biovitenskapelige universitet, og har i tillegg knyttet til seg nasjonal spisskompetanse på mange temaer. Bokas redaktør er dosent Steinar Taubøll ved Institutt for eiendom og juss ved NMBU, som har naturfaglig og juridisk utdannelse, samt lang erfaring med tverrfaglig arbeid

Vann, juss og samfunn

Society’s use and management of water relies on professional expertise spanning diverse fields: from biology and technology to economics and law. This book examines current issues related to regulating water through chapters summarizing various sets of regulation as well as chapters that take a scientific deep dive into selected themes. The diversity of professional expertise is also reflected in the law aspect. We explore such subjects as surface runoff, natural disasters, drinking water, groundwater, salmon, hydropower, and human rights, as well as general impact assessment requirements and duty of knowledge in environmental law administration. A key objective of the book has been to provide an interdisciplinary understanding of the legal circumstances associated with water, and in addition, deliberate the pros and cons of some of the current regulations. This book will be particularly useful for those who in various ways support and facilitate procedures within the public sector at both the national and municipal levels. It will also be useful for private sector actors seeking familiarity with legal questions that can arise in relation to public administration and other private actors. From a broader perspective, we hope the book can help to throw light on conflicts between different interests and groups within society that occur, for example, when introducing fees, special injunctions against private actors, and requirements for knowledge basis. This book project is the result of legal research conducted at the Norwegian University of Life Sciences (NMBU) and is supplemented by national expertise in several areas. It has been edited by Steinar Taubøll, a professor at NMBU’s Department of Property and Law. Taubøll has a background in both law and the natural sciences, and extensive experience with interdisciplinary work

Appetite and dietary intake endpoints in cancer cachexia clinical trials: Systematic Review 2 of the cachexia endpoints series

There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The aim of this systematic review was to summarize and evaluate endpoints used to assess appetite and dietary intake in cancer cachexia clinical trials. A search for studies published from 1 January 1990 until 2 June 2021 was conducted using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Eligible studies examined cancer cachexia treatment versus a comparator in adults with assessments of appetite and/or dietary intake as study endpoints, a sample size ≥40 and an intervention lasting ≥14 days. Reporting was in line with PRISMA guidance, and a protocol was published in PROSPERO (2022 CRD42022276710). This review is part of a series of systematic reviews examining cachexia endpoints. Of the 5975 articles identified, 116 were eligible for the wider review series and 80 specifically examined endpoints of appetite (65 studies) and/or dietary intake (21 studies). Six trials assessed both appetite and dietary intake. Appetite was the primary outcome in 15 trials and dietary intake in 7 trials. Median sample size was 101 patients (range 40–628). Forty-nine studies included multiple primary tumour sites, while 31 studies involved single primary tumour sites (15 gastrointestinal, 7 lung, 7 head and neck and 2 female reproductive organs). The most frequently reported appetite endpoints were visual analogue scale (VAS) and numerical rating scale (NRS) (40%). The appetite item from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30/C15 PAL (38%) and the appetite question from North Central Cancer Treatment Group anorexia questionnaire (17%) were also frequently applied. Of the studies that assessed dietary intake, 13 (62%) used food records (prospective registrations) and 10 (48%) used retrospective methods (24-h recall or dietary history). For VAS/NRS, a mean change of 1.3 corresponded to Hedge's g of 0.5 and can be considered a moderate change. For food records, a mean change of 231 kcal/day or 11 g of protein/day corresponded to a moderate change. Choice of endpoint in cachexia trials will depend on factors pertinent to the trial to be conducted. Nevertheless, from trials assessed and available literature, NRS or EORTC QLQ C30/C15 PAL seems suitable for appetite assessments. Appetite and dietary intake endpoints are rarely used as primary outcomes in cancer cachexia. Dietary intake assessments were used mainly to monitor compliance and are not validated in cachexia populations. Given the importance to cachexia studies, dietary intake endpoints must be validated before they are used as endpoints in clinical trials

Quality of life endpoints in cancer cachexia clinical trials: systematic review 3 of the cachexia endpoints series

The use of patient‐reported outcomes (PROMs) of quality of life (QOL) is common in cachexia trials. Patients' self‐report on health, functioning, wellbeing, and perceptions of care, represent important measures of efficacy. This review describes the frequency, variety, and reporting of QOL endpoints used in cancer cachexia clinical trials. Electronic literature searches were performed in Medline, Embase, and Cochrane (1990–2023). Seven thousand four hundred thirty‐five papers were retained for evaluation. Eligibility criteria included QOL as a study endpoint using validated measures, controlled design, adults (>18 years), ≥40 participants randomized, and intervention exceeding 2 weeks. The Covidence software was used for review procedures and data extractions. Four independent authors screened all records for consensus. Papers were screened by titles and abstracts, prior to full‐text reading. PRISMA guidance for systematic reviews was followed. The protocol was prospectively registered via PROSPERO (CRD42022276710). Fifty papers focused on QOL. Twenty‐four (48%) were double‐blind randomized controlled trials. Sample sizes varied considerably (n = 42 to 469). Thirty‐nine trials (78%) included multiple cancer types. Twenty‐seven trials (54%) featured multimodal interventions with various drugs and dietary supplements, 11 (22%) used nutritional interventions alone and 12 (24%) used a single pharmacological intervention only. The median duration of the interventions was 12 weeks (4–96). The most frequent QOL measure was the EORTC QLQ‐C30 (60%), followed by different FACIT questionnaires (34%). QOL was a primary, secondary, or exploratory endpoint in 15, 31 and 4 trials respectively, being the single primary in six. Statistically significant results on one or more QOL items favouring the intervention group were found in 18 trials. Eleven of these used a complete multidimensional measure. Adjustments for multiple testing when using multicomponent QOL measures were not reported. Nine trials (18%) defined a statistically or clinically significant difference for QOL, five with QOL as a primary outcome, and four with QOL as a secondary outcome. Correlation statistics with other study outcomes were rarely performed. PROMs including QOL are important endpoints in cachexia trials. We recommend using well‐validated QOL measures, including cachexia‐specific items such as weight history, appetite loss, and nutritional intake. Appropriate statistical methods with definitions of clinical significance, adjustment for multiple testing and few co‐primary endpoints are encouraged, as is an understanding of how interventions may relate to changes in QOL endpoints. A strategic and scientific‐based approach to PROM research in cachexia trials is warranted, to improve the research base in this field and avoid the use of QOL as supplementary measures

An Update on Prevalence, Assessment, and Risk Factors for Sleep Disturbances in Patients with Advanced Cancer—Implications for Health Care Providers and Clinical Research

Patients with advanced cancer experience multiple symptoms, with fluctuating intensity and severity during the disease. They use several medications, including opioids, which may affect sleep. Sleep disturbance is common in cancer patients, decreases the tolerability of other symptoms, and impairs quality of life. Despite its high prevalence and negative impact, poor sleep quality often remains unrecognized and undertreated. Given that sleep is an essential aspect of health-related quality of life, it is important to extend both the knowledge base and awareness among health care providers in this field to improve patient care. In this narrative review, we provide recommendations on sleep assessment in patients with advanced cancer and highlight cancer-related factors that contribute to insomnia. We also present direct implications for health care providers working in palliative care and for future research

Antibiotic Therapy in Integrated Oncology and Palliative Cancer Care: An Observational Study

Decision-making for antibiotic therapy in palliative cancer care implies avoiding futile interventions and to identify patients who benefit from treatment. We evaluated patient-reported outcome-measures (PROMs), physiological findings, and survival in palliative cancer care patients hospitalized with an infection. All acute admissions during one year, directly to a University Hospital unit that provided integrated services, were included. Serious infection was defined as a need to start intravenous antibiotics. PROMs, clinical and paraclinical variables, and survival were obtained. Sixty-two of 257 patients received intravenous antibiotic treatment. PROMs were generally similar in the infection group and the non-infection group, both in respect to intensities at admission and improvements during the stay. There were more physiological and paraclinical deviations at admission in patients in the infection group. These deviations improved during the stay. Survival was not poorer in the infection group compared to the non-infection group. Patients in integrated cancer care were as likely to be put on intravenous antibiotics but had longer survival. In integrated oncology and palliative cancer services, patients with an infection had similar outcomes as those without an infection. This argues that the use of intravenous antibiotics is appropriate in many patients admitted to palliative care