Randomised, double-blind, placebo-controlled, parallel-group, multicentric, phase IIA clinical trial for evaluating the safety, tolerability, and therapeutic efficacy of daily oral administration of NFX88 to treat neuropathic pain in individuals with spinal cord injury.

STUDY DESIGN: Double-blind, randomized, placebo-controlled, parallel-group multicentric phase IIA clinical trial. OBJECTIVE: To assess the safety and tolerability of oral administration of NFX-88 in subjects with chronic spinal cord injury (SCI) and explore its efficacy in pain control. SETTING: A total of 7 spinal cord injury rehabilitation units in Spain. METHODS: A total of 61 adult with traumatic complete or incomplete spinal cord injury (C4-T12 level), were randomised 1:1:1:1 to a placebo, NFX88 1.05 g, 2.1 g, 4.2 g/day for up to 12 weeks. The placebo or NFX-88 was administered as add-on therapy to pre-existing pregabalin (150-300 mg per day). Safety and tolerability were evaluated, and the Visual Analogue Scale (VAS) was the primary measure to explore the efficacy of NFX-88 in pain control. RESULTS: No severe treatment-related adverse effects were reported for any of the four study groups. 44 SCI individuals completed the study and were analysed. The data obtained from the VAS analysis and the PainDETECT Questionnaire (PD-Q) suggested that the combination of NFX88 with pregabalin is more effective than pregabalin with placebo at reducing neuropathic pain (NP) in individuals with SCI and that the dose 2.10 g/day causes the most dramatic pain relief. CONCLUSIONS: NFX88 treatment was found to be highly safe and well tolerated, with the dose of 2.10 g/day being the most effective at causing pain relief. Thus, the promising efficacy of this first-in-class lipid mediator deserves further consideration in future clinical trials.

Preventive treatment with alendronate of loss of bone mineral density in acute traumatic spinal cord injury. Randomized controlled clinical trial.

STUDY DESIGN: Randomized controlled clinical trial of two parallel groups. OBJECTIVES: Analyse the efficacy of primary prevention with alendronate on the loss of bone mass which occurs during the first year of traumatic SCI, measured by double-energy X-ray bone densitometry (DXA). SETTING: National Hospital for Paraplegics (HNP), Toledo, Spain. METHODS: We included 52 people admitted to the HNP with traumatic SCI Grade A and B on the ASIA Impairment Scale and less than 8 weeks of progression, which were randomized to one of the two treatment groups. Both groups received calcifediol and a calcium-enriched diet for 52 weeks. Only one group was administered alendronate 70 mg weekly. The dose of alendronate was adjusted according to changes in serum ß-CTX. RESULTS: 52 Participants were randomized. Of the 26 assigned to each group, 4 patients were lost in the alendronate group and 3 in the control group. The random distribution of women was asymmetrical, so we analysed the effect of treatment on men. In the total left hip, the mean (SD) decrease in bone mass was -22.791% (10.768) in the control group compared to the mean (SD) decrease of -2.693% (6.283) in the same location in the alendronate group (p < 0.0001). No patient presented related adverse events. CONCLUSION: Alendronate administered for one year in the first 8 weeks after traumatic SCI decreases bone loss in the hip in men. This treatment is well tolerated.

Increased number of deaths within 24 h of admission during a period of social restriction related to the COVID-19 pandemic: A retrospective service evaluation in a metropolitan palliative care unit.

BACKGROUND: COVID-19 has led to implementation of wide-ranging social restriction measures with consequent impact on health care utilisation in many domains. There is little published data on the experience of palliative care services catering to a population with low case numbers of COVID-19. AIM: This study aimed to consider the impact of COVID-19 on utilisation of inpatient palliative care in the context of low community transmission, and low numbers of cases in hospital. DESIGN: A retrospective service evaluation examining differences in number of admissions, diagnoses, number of deaths and time from admission to death, across three discrete 8-week time periods spanning the early COVID-19 pandemic. SETTING/PARTICIPANTS: All admissions (n = 194) to a metropolitan tertiary hospital inpatient palliative care unit in Melbourne during the study period. RESULTS: An initial 16.9% fall in admissions was followed by a return to baseline admission numbers, with a 46.7% increase in number of deaths compared to baseline. The number of deaths within 24 h rose from 10.8% to 37.3% (p < 0.01). The number of patients with non-malignant diagnoses increased from 32.4% to 52%, and those with non-malignant diagnoses were more likely to die rapidly (p < 0.01). There were no patients with COVID-19 infection. CONCLUSION: Increased numbers of deaths within 24 h of admission occurred on the palliative care unit despite low COVID-19 case numbers in the wider community, and in the setting of widespread social restriction measures. More research is needed examining the health-related consequences of such restrictions for individuals not infected with COVID-19.

Genetic diversity, structure, and admixture in Mayans from Guatemala and Mexico based on 15 short tandem repeats.

OBJECTIVE: To analyze the genetic origin, relationships, structure, and admixture in Mayan Native American groups from Guatemala and Mexico based on 15 autosomal short tandem repeats (STRs) loci commonly used in human identification (HID). METHODS: We genotyped 513 unrelated Mayan samples from Guatemala based on 15 STR loci (AmpFlSTR® Identifiler kit). Moreover, we included 4408 genotypes previously reported, as following: Mayas from Guatemala and Mexico (n = 1666) and from Latin American, European, and African (n = 2742) populations. Forensic parameters, genetic distances, admixture, and population structure were assessed. RESULTS: Forensic parameters of the 15 STRs in different Mayan groups from Guatemala were reported. Low (Fst = 0.78%; p = 0.000) and non-significant differentiation (Fst = 1.8%; p = 0.108) were observed in Mayas from Guatemala and Mexico, respectively. The relative homogeneity observed among Mayan groups supported theories of extensive pre-Columbian gene flow and trade throughout the Mayan Empire. The distribution of the three Native American ancestries among these Mayan groups did not support the presumable Guatemalan origin of Tojolabal and Lacandon people (South, Mexico). The nonsignificant differentiation between Ladinos and Mayas suggests a relative panmixia in Guatemala. Mestizos from southeastern Mexico and Guatemala constitute a core of Native American ancestry in Latin America related to the Mayan Empire in Central America. CONCLUSIONS: The higher European admixture and homogeneity in Mexican Mayas of the Yucatan Peninsula suggest more intensive post-Columbian gene flow in this region than in Guatemalan Mayas.

Phase II/III placebo-controlled randomized trial of safety and efficacy of growth hormone treatment in incomplete chronic traumatic spinal cord injury.

STUDY DESIGN: This is a double blind phase II/III placebo-controlled randomized trial of the safety and efficacy of GH treatment in incomplete chronic traumatic spinal cord injury. OBJECTIVE: The aim of this study was to investigate the possibility to use exogenous GH administration for motor recovery in chronic traumatic incomplete human SCI. The objectives were to establish safety and efficacy of a combined treatment of subcutaneous GH (or placebo) and rehabilitation in this population. SETTING: Hospital Nacional de Parapléjicos METHODS: The pharmacological treatment was a subcutaneous daily dose of growth hormone (GH, Genotonorm 0.4 mg, Pfizer Pharmaceuticals) or placebo for one year. The pharmacological treatment was performed, during the first six months under hospitalization and supervised rehabilitation. RESULTS: The main findings were that the combined treatment of GH plus rehabilitation treatment is feasible and safe, and that GH but not placebo increases the ISNCSCI motor score. On the other hand, the motor-score increment was marginal (after one-year combined treatment, the mean increment of the motor-score was around 2.5 points). Moreover, we found that intensive and long-lasting rehabilitation program per se increases the functional outcome of SCI individuals (measured using SCIM III and WISCI II). CONCLUSIONS: It is important to highlight that our aim was to propose GH as a possible treatment to improve motor functions in incomplete SCI individuals. At least with the doses we used, we think that the therapeutic effects of this approach are not clinically relevant in most subjects with SCI.

A Simple Clinical Tool for Stratifying Risk of Clinically Significant CKD after Nephrectomy: Development and Multinational Validation.

BACKGROUND: Clinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed. METHODS: To develop a tool for stratifying patients' risk of CKD arising after surgery for kidney cancer, we tested models in a population-based cohort of 699 patients with kidney cancer in Queensland, Australia (2012-2013). We validated these models in a population-based cohort of 423 patients from Victoria, Australia, and in patient cohorts from single centers in Queensland, Scotland, and England. Eligible patients had two functioning kidneys and a preoperative eGFR ≥60 ml/min per 1.73 m2. The main outcome was incident eGFR <45 ml/min per 1.73 m2 at 12 months postnephrectomy. We used prespecified predictors-age ≥65 years old, diabetes mellitus, preoperative eGFR, and nephrectomy type (partial/radical)-to fit logistic regression models and grouped patients according to degree of risk of clinically significant CKD (negligible, low, moderate, or high risk). RESULTS: Absolute risks of stage 3b or higher CKD were <2%, 3% to 14%, 21% to 26%, and 46% to 69% across the four strata of negligible, low, moderate, and high risk, respectively. The negative predictive value of the negligible risk category was 98.9% for clinically significant CKD. The c statistic for this score ranged from 0.84 to 0.88 across derivation and validation cohorts. CONCLUSIONS: Our simple scoring system can reproducibly stratify postnephrectomy CKD risk on the basis of readily available parameters. This clinical tool's quantitative assessment of CKD risk may be weighed against other considerations when planning management of kidney tumors and help inform shared decision making between clinicians and patients.

Measuring the spatial deformation of a liquid-crystal on silicon display with a self-interference effect.

We present a simple technique to characterize the spatial non-uniformity of a liquid-crystal on silicon (LCOS) spatial light modulator (SLM). It is based on illuminating the display with a wavelength out of the operation range, so there is a significant reflection at the output surface. As a consequence, a Gires-Tournois interferometer is directly created, without any alignment requirement and insensitive to vibrations. The beam reflected at the output surface is the reference beam, while the beam reflected at the silicon backplane is modulated with the addressed gray level in order to quantitatively derive its deformation. We provide an experimental demonstration using a LCOS-SLM designed to operate in the near-infrared range but illuminated with visible light.

Lung Ultrasound in COVID-19 Pneumonia: Correlations with Chest CT on Hospital admission.

BACKGROUND: Lung ultrasound (LUS) is an accurate, safe, and cheap tool assisting in the diagnosis of several acute respiratory diseases. The diagnostic value of LUS in the workup of coronavirus disease-19 (COVID-19) in the hospital setting is still uncertain. OBJECTIVES: The aim of this observational study was to explore correlations of the LUS appearance of COVID-19-related pneumonia with CT findings. METHODS: Twenty-six patients (14 males, age 64 ± 16 years) urgently hospitalized for COVID-19 pneumonia, who underwent chest CT and bedside LUS on the day of admission, were enrolled in this observational study. CT images were reviewed by expert chest radiologists, who calculated a visual CT score based on extension and distribution of ground-glass opacities and consolidations. LUS was performed by clinicians with certified competency in thoracic ultrasonography, blind to CT findings, following a systematic approach recommended by ultrasound guidelines. LUS score was calculated according to presence, distribution, and severity of abnormalities. RESULTS: All participants had CT findings suggestive of bilateral COVID-19 pneumonia, with an average visual scoring of 43 ± 24%. LUS identified 4 different possible -abnormalities, with bilateral distribution (average LUS score 15 ± 5): focal areas of nonconfluent B lines, diffuse confluent B lines, small subpleural microconsolidations with pleural line irregularities, and large parenchymal consolidations with air bronchograms. LUS score was significantly correlated with CT visual scoring (r = 0.65, p < 0.001) and oxygen saturation in room air (r = -0.66, p < 0.001). CONCLUSION: When integrated with clinical data, LUS could represent a valid diagnostic aid in patients with suspect COVID-19 pneumonia, which reflects CT findings.

Optimal triplicator design applied to a geometric phase vortex grating.

In this work, a geometric phase liquid-crystal diffraction grating based on the optimal triplicator design is realized, i.e., a phase-only profile that generates three diffraction orders with equal intensity and maximum diffraction efficiency. We analyze the polarization properties of this special diffraction grating and then use embedded spiral phases to design geometric phase vortex diffraction gratings. Finally, the fabrication of a two-dimensional version of such a design using a micro-patterned half-wave retarder is demonstrated, where the phase distribution is encoded as the orientation of the fast axis of the retarder. This proof-of-concept element is made of liquid crystal on BK7 substrate where the orientation of the LC is controlled via photoalignment, using a commercially available fabrication facility. Experimental results demonstrate the parallel generation of vortex beams with different topological charge and different states of polarization.

The impact of cancer type, treatment, and distress on health-related quality of life: cross-sectional findings from a study of Australian cancer patients.

PURPOSE: This study examined the mediating effects of cancer type, treatment, and distress on health-related quality of life (HRQoL) for early diagnosis cancer patients. Results were interpreted with respect to established thresholds for clinical meaningfulness. METHODS: A cross-sectional design was used. Patients completed surveys collecting demographics, cancer type, treatment, comorbid conditions, distress (HADS), and HRQoL (FACT-G). Hierarchical multivariate regressions examined associations between cancer type, treatment, and distress on HRQoL. Established minimum differences were used to identify clinically meaningful changes in HRQoL. RESULTS: Of the 1183 patients surveyed, 21% were classified as having elevated anxiety and 13% had elevated depression. Our sample reported significantly lower physical and emotional well-being compared to population norms. Patients with prostate, melanoma, gynaecological, and urological cancers had higher HRQoL scores than those with colorectal cancer. However, when effects for treatment type and distress were considered, differences between cancer types became non-significant. Anxiety and depression were associated with lower HRQoL scores as was chemotherapy. Only depression, anxiety, and chemotherapy were associated with clinically meaningful decreases in HRQoL scores. CONCLUSIONS: While statistically significant differences in HRQoL were found between different cancer types, only chemotherapy, anxiety, and depression produced clinically meaningful poorer HRQoL scores. In practice, clinically meaningful differences could promote a shift in resources toward interventions where a positive effect on patient well-being is appreciated by both the patient and health professional.

Recognising and managing dying patients in the acute hospital setting: can we do better?

Healthcare professionals have limited formal end-of-life care training despite the large proportion of hospital deaths. A retrospective review of 201 acute hospital deaths revealed 166 (82.6%) had documentation to suggest the patient was dying but this was performed late with a median time between documentation and death of 0.84 days. Furthermore, 132 (66%) patients received an intervention in the final 48 h of life. This highlights the need to improve the recognition and management of dying patients in acute hospitals.

Age at diagnosis and the surgical management of small renal carcinomas: findings from a cross-sectional population-based study.

OBJECTIVES: To describe the use of partial nephrectomy (PN) for patients with stage T1a renal cell carcinoma (RCC) by age group (<65 and ≥65 years) in two Australian states. MATERIALS AND METHODS: All adults diagnosed with RCC in 2012 and 2013 were identified through population-based cancer registries in the Australian states of Queensland and Victoria. For each patient, research assistants extracted patient, tumour and treatment data from medical records. Percentages of patients treated by PN were determined for the two age groups. Multivariable logistic regression analyses examined factors associated with PN. Clinicians treating RCC were sent surveys to assess attitudes towards PN. RESULTS: Data were collected on 956 patients (Victoria: n = 548; Queensland: n = 404) with stage T1a RCC. Of those undergoing surgery (n = 865), PN was more common for those aged <65 years (61%) than for those aged ≥65 years (44%), with this difference significant after adjusting for patient, tumour (odds ratio 0.50, 95% confidence interval 0.36-0.70). There were significant interactions between age and treatment centre volume (P < 0.05) and residential state (P < 0.05). PN was less likely for younger patients treated at lower-volume hospitals (<24 patients a year) but hospital volume was not associated with PN for older patients. PN was less likely for older patients in Queensland than Victoria. In multivariable analyses, age was not related to laparoscopic surgery. Queensland clinicians were less likely than those from Victoria to agree that PN was the treatment of choice for most T1aN0M0 tumours (P < 0.001). CONCLUSIONS: In Australia, patients aged > 65 years with small renal cancers were less likely to be treated by PN than younger patients. The variation in the surgical procedure used to treat older T1a RCC patients by state and hospital volume indicates that better evidence is needed to direct practice in this area.

Predictors of new-onset chronic kidney disease in patients managed surgically for T1a renal cell carcinoma: An Australian population-based analysis.

BACKGROUND: New-onset chronic kidney disease (CKD) following surgical management of kidney tumors is common. This study evaluated risk factors for new-onset CKD after nephrectomy for T1a renal cell carcinoma (RCC) in an Australian population-based cohort. METHODS: There were 551 RCC patients from the Australian states of Queensland and Victoria included in this study. The primary outcome was new-onset CKD (eGFR <60 mL/min per 1.73 m2 ) and the secondary outcome was new-onset moderate-severe CKD (<45 mL/min per 1.73 m2 ). Multivariable logistic regression was used to evaluate associations between patient, tumor and health-service characteristics and these outcomes. RESULTS: Forty percent (219/551) of patients developed new-onset CKD, and 12% (68/551) experienced new-onset moderate-severe CKD. Risk factors for new-onset CKD were age, lower preoperative eGFR, tumor size >20 mm, radical nephrectomy, lower hospital caseloads (<20 cases/year), and rural place of residence. The associations between rural place of residence and low center volume were a consequence of higher radical nephrectomy rates. CONCLUSION: Risk factors for CKD after nephrectomy generally relate to worse baseline health, or likelihood of undergoing radical nephrectomy. Surgeons in rural centres and hospitals with low caseloads may benefit from formalized integration with specialist centers for continued professional development and case-conferencing, to assist in management decisions.

Integrating referral to community-based cancer information and support services in a hospital setting.

PURPOSE: To implement and evaluate a hospital-based referral mechanism to increase patient uptake of community-based cancer information and support services. Feasibility and acceptability of the intervention and education program was evaluated. Changes in usage of Cancer Council Victoria's cancer information and support telephone line were investigated. METHODS: A 6-month study was conducted in one metropolitan and one regional cancer treatment hospital. Clinicians attended an education session regarding referral mechanisms to Cancer Council support services. Clinicians completed a questionnaire, and consenting patients participated in a semi-structured telephone interview for the project evaluation. The number of calls made from patients at study sites was monitored. RESULTS: Fifty-two clinicians were trained and referred a total of 430 patients to the cancer information and support service during the study period. Calls from patients increased by up to 100% per month from baseline following the implementation of the referral mechanism. Staff evaluations showed support for the referral mechanism and its incorporation into routine practice. Interviews were conducted with 45 patients; most remembered receiving the referral and were positive towards the intervention. Common reasons patients gave for not acting on the referral included forgetting, lack of need, timing and burden of information. CONCLUSIONS: There is preliminary evidence that this intervention increases awareness and uptake of community-based cancer information and support services. Ongoing clinician education and improvements in patient-clinician communication are important for effective translation from referral to service uptake. Consideration of the most appropriate time in a patients' care trajectory to introduce a referral is warranted.

Trends in the surgical management of stage 1 renal cell carcinoma: findings from a population-based study.

OBJECTIVES: To determine whether the use of nephron-sparing surgery (NSS) for treatment of stage 1 renal cell carcinoma (RCC) changed between 2009 and the end of 2013 in Australia. PATIENTS AND METHODS: All adult cases of RCC diagnosed in 2009, 2012 and 2013 were identified through the population-based Victorian Cancer Registry. For each identified patient, trained data-abstractors attended treating hospitals or clinician rooms to extract tumour and treatment data through medical record review. Multivariable logistic regression analyses were carried out to examine the significance of change in use of NSS over time, after adjusting for potential confounders. RESULTS: A total of 1 836 patients with RCC were identified. Of these, the proportion of cases with stage 1 tumours was 64% in 2009, 66% in 2012 and 69% in 2013. For T1a tumours, the proportion of patients residing in metropolitan areas receiving NSS increased from 43% in 2009 to 58% in 2012 (P < 0.05), and 69% in 2013 (P < 0.05). For patients residing in non-metropolitan areas, the proportion receiving NSS increased from 27% in 2009 to 49% in 2012, and 61% in 2013 (P < 0.01). Univariable logistic regression showed patients with moderate (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.35-0.94) or severe comorbidities (OR 0.58, 95% CI 0.33-0.99), residing in non-metropolitan areas (OR 0.65, 95% CI 0.47-0.90), were less likely to be treated by NSS, while those attending high-volume hospitals (≥30 cases/year: OR 1.79, 95% CI 1.21-2.65) and those with higher socio-economic status (OR 1.45, 95% CI 1.02-2.07) were more likely to be treated by NSS. In multivariable analyses, patients with T1a tumours in 2012 (OR 2.00, 95% CI 1.34-2.97) and 2013 (OR 3.15, 95% CI 2.13-4.68) were more likely to be treated by NSS than those in 2009. For T1b tumours, use of NSS increased from 8% in 2009 to 20% in 2013 (P < 0.05). CONCLUSION: This population-based study of the management of T1 renal tumours in Australia found that the use of NSS increased over the period 2009 to 2013. Between 2009 and 2013 clinical practice for the treatment of small renal tumours in Australia has increasingly conformed to international guidelines.

Mind the gap: Multiple events and lengthy delays before presentation with a "first seizure".

OBJECTIVE: Up to half of patients assessed for suspected new-onset epileptic seizures report previous undiagnosed events. This suggests that delay to timely and expert assessment is a major issue. Very little is known about the degree of delay or nature of the undiagnosed events, impacting on our understanding of new-onset epilepsy. In this study we aimed to examine events that occur before presentation, as well as the extent and risk factors for delay to assessment. METHOD: Included in this retrospective study were 220 patients diagnosed at the First Seizure Clinic (Austin Health, Australia) between 2003 and 2006 with an epileptic index seizure. Patients with a prior diagnosis of epileptic seizures were excluded. Chart review was undertaken, including detailed interviews conducted by an epileptologist at first assessment. Logistic regression assessed risk factors for delay from first event to presentation, including event characteristics, socioeconomic disadvantage, employment, and distance to medical facility. RESULTS: Forty-one percent (n = 90) of patients had one or more event before their index seizure. Of these, 50% had multiple or more than five prior events and 28% experienced one or more convulsive event before the index seizure. Of the total 220 patients, 36% had delayed presentation >4 weeks, 21% delayed >6 months, and 14% delayed >2 years. First events without convulsions or features likely to disrupt behaviour were strongly associated with delay (p = <0.001). Relative socioeconomic disadvantage was also associated with delay to presentation (p = 0.04). SIGNIFICANCE: Our findings suggest a gap in early diagnosis and care in a sizable proportion of new-onset cases, despite a "first world" urban environment and the availability of free basic medical care. Delay appears particularly likely when events are nonconvulsive or low-impact, suggesting that these seizure types may be underrepresented in studies of new-onset epilepsy. This has implications for our understanding of the incidence, evolution, impact, and treatment response of new-onset epilepsy.

What are the cost and resource implications of voluntary assisted dying and euthanasia?

Objectives Voluntary assisted dying (VAD) legislation has now been passed in all Australian states. Although VAD has been operating in many settings worldwide for a considerable time, the specific costs associated with VAD seem unclear. The aim of this study was therefore to outline the common resource implications associated with VAD. Methods A rapid literature review and grey literature search were undertaken. Results We found a paucity of empirically informed detail regarding the actual costs required to implement VAD. Hence, we tabulated a list of potential costs that could be used for subsequent evaluation and a future research agenda. Conclusions There is a lack of publicly available information related to the costs associated with implementing VAD. Given that this is a significant change in policy and many multidisciplinary practitioners may be directly or indirectly involved in VAD it is important that associated costs are clearly outlined so that appropriate resources can be allocated.

End-of-life care in illicit drug users: mapping medication use.

BACKGROUND: While clinical wisdom has long provided suggested guidance around caring for people who use illicit drugs (referred to as PWUD) at the end of life, there is striking paucity of empirical evidence underpinning these practices. Understanding medications and doses required to manage symptoms at the end of life is essential to provide effective end-of-life care for these patients. This study aimed to examine the type and dose of medications prescribed to hospitalised patients who use illicit drugs at the end of life, compared with patients without previous or current illicit drug use. METHOD: A retrospective medical record review was conducted on consecutive patient deaths between 2012 and 2017 at a metropolitan hospital. PWUD were identified using the International Classification of Diseases 10th Revision codes for illicit drug use. Daily dosage of opioids, benzodiazepines and antipsychotics was documented for the last 3 days of life and compared with a matched comparator group. RESULTS: PWUD patients (n=55) received higher doses of opioids, midazolam and antipsychotics than comparator patients (n=55) for each day, significant for opioids in the last 24 hours (p=0.01). PWUD patients received a significantly higher total opioid dose (median=480.0 mg vs 255.0 mg) and midazolam (median=15.0 mg vs 5.0 mg) (both p<0.05). Rates of dose escalation did not differ. CONCLUSIONS: Results suggest that PWUD require greater doses of symptom-controlling medications, particularly opioids and midazolam, at the end of life but that rates of dose escalation do not differ greatly. This study provides a foundation for future research to inform clinical guidelines for this cohort of palliative care patients.

Prevalence, Severity, and Predictors of Insomnia in Advanced Colorectal Cancer.

CONTEXT: Insomnia is an under-recognized and undertreated symptom in palliative care and advanced cancer cohorts. Insomnia in an advanced colorectal cancer cohort is yet to be investigated despite colorectal cancer being the third commonest cancer worldwide and one with a high symptom burden. OBJECTIVES: To examine the prevalence of insomnia and its associations in a large advanced colorectal cancer cohort. METHODS: A consecutive cohort study of 18,302 patients with colorectal cancer seen by palliative care services across various settings (inpatient, outpatient, and ambulatory) was conducted from an Australia-wide database (2013-2019). The Symptom Assessment Score (SAS) was used to assess the severity of insomnia. Clinically significant insomnia was defined as SAS score ≥3/10, and used to compare associations with other symptoms and functional scores from validated questionnaires. RESULTS: The prevalence of any insomnia was 50.5%, and clinically significant insomnia 35.6%, particularly affecting people who were younger (<45-years-old), more mobile (AKPS score ≥70), or physically capable (RUG-ADL score ≤5). Outpatients and patients living at home had higher prevalence of insomnia. Nausea, anorexia and psychological distress were the commonest concurrent symptoms in patients with clinically significant insomnia. CONCLUSIONS: To our knowledge, this study was the first to investigate the prevalence and associations of insomnia in an advanced colorectal cancer cohort. Our findings demonstrate several groups at greater risk of suffering from insomnia (younger, greater physical capacity, living at home, and those with greater psychological distress). This may guide earlier recognition and management of insomnia to improve overall quality of life in this population.