Beyond Early- and Late-onset Neonatal Sepsis Definitions: What are the Current Causes of Neonatal Sepsis Globally? A Systematic Review and Meta-analysis of the Evidence.

Sepsis remains a leading cause of neonatal mortality, particularly in low- and lower-middle-income countries (LLMIC). In the context of rising antimicrobial resistance, the etiology of neonatal sepsis is evolving, potentially making currently-recommended empirical treatment guidelines less effective. We performed a systematic review and meta-analysis to evaluate the contemporary bacterial pathogens responsible for early-onset sepsis (EOS) and late-onset neonatal sepsis (LOS) to ascertain if historical classifications-that guide empirical therapy recommendations based on assumptions around causative pathogens-may be outdated. We analyzed 48 articles incorporating 757,427 blood and cerebrospinal fluid samples collected from 311,359 neonates across 25 countries, to evaluate 4347 significant bacteria in a random-effects meta-analysis. This revealed gram-negative bacteria were now the predominant cause of both EOS (53%, 2301/4347) and LOS (71%, 2765/3894) globally. In LLMICs, the predominant cause of EOS was Klebsiella spp. (31.7%, 95% CI: 24.1-39.7%) followed by Staphylococcus aureus (17.5%, 95% CI: 8.5 to 28.4%), in marked contrast to the Streptococcus agalactiae burden seen in high-income healthcare settings. Our results reveal clear evidence that the current definitions of EOS and LOS sepsis are outdated, particularly in LLMICs. These outdated definitions may be guiding inappropriate empirical antibiotic prescribing that inadequately covers the causative pathogens responsible for neonatal sepsis globally. Harmonizing sepsis definitions across neonates, children and adults will enable a more acurate comparison of the epidemiology of sepsis in each age group and will enhance knowledge regarding the true morbidity and mortality burden of neonatal sepsis.

Validity of Patient-Reported Outcome Measures in Evaluating Nerve Damage Following Chemotherapy.

Importance: Chemotherapy-induced peripheral neuropathy (CIPN) is a substantial adverse effect of anticancer treatments. As such, the assessment of CIPN remains critically important in both research and clinic settings. Objective: To compare the validity of various patient-reported outcome measures (PROMs) with neurophysiological and sensory functional measures as the optimal method of CIPN assessment. Design, Setting, and Participants: This cohort study evaluated participants treated with neurotoxic chemotherapy across 2 cohorts using a dual-study design. Participants commencing treatment were assessed prospectively at beginning of neurotoxic treatment, midtreatment, and at the end of treatment. Participants who completed treatment up to 5 years prior were assessed cross-sectionally and completed a single assessment time point. Participants were recruited from oncology centers in Australia from August 2015 to November 2022. Data analysis occurred from February to November 2023. Exposures: Neurotoxic cancer treatment including taxanes, platinums, vinca-alkaloids, proteasome inhibitors, and thalidomide. Main Outcomes and Measures: CIPN was assessed via PROMs (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-CIPN20], Functional Assessment of Cancer Therapy/Gynecological Cancer Group Neurotoxicity Questionnaire (FACT/GOG-Ntx), and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE]), neurological and neurophysiological assessment (Total Neuropathy Score and sural and tibial compound nerve amplitudes), and sensory measures (Grating orientation, Von Frey monofilament, and 2-point discrimination tasks). Core measurement properties of CIPN outcome measures were evaluated. Convergent and known-groups validity was assessed cross-sectionally following treatment completion, and responsiveness was evaluated prospectively during treatment. Neurological, neurophysiological, and sensory outcome measure scores were compared between those who reported high and low levels of CIPN symptoms using linear regressions. Results: A total of 1033 participants (median [IQR] age, 61 [50-59] years; 676 female [65.4%]) were recruited to this study, incorporating 1623 assessments. PROMs demonstrated best ability to accurately assess CIPN (convergent validity), especially the PRO-CTCAE composite score (r = 0.85; P < .001) and EORTC-CIPN20 (r = 0.79; P < .001). PROMS also demonstrated the best ability to discriminate between CIPN severity (known-groups validity) and to detect changes at onset of CIPN development (responsiveness), especially for EORTC-CIPN20 (d = 0.67; 95% CI, 0.52-0.83), FACT/GOG-Ntx (d = 0.65; 95% CI, 0.49-0.81) and the PRO-CTCAE (d = 0.83; 95% CI, 0.64-1.02). Other measures did not achieve threshold for convergent validity (α < 0.7). Neurophysiological and sensory measures did not demonstrate acceptable responsiveness. In regression models, neurological, neurophysiological, and sensory outcome measures were significantly impaired in participants who reported high levels of CIPN symptoms compared with those who reported low levels of CIPN symptoms. Conclusions and Relevance: In this cohort study of 1033 cancer patients, PROMs were the only measures to satisfy all 3 core measurement property criteria (convergent validity, known-groups validity, and responsiveness). These findings suggest that adoption of PROMs in clinical practice can equip clinicians with valuable information in assessing CIPN morbidity.

Paramedics Providing Palliative Care at Home: A Retrospective Cohort Study Comparing Symptom Management of Breathlessness and Pain in Cancer Versus Non-Cancer Conditions.

Background Palliative care aims to alleviate pain and distressing symptoms, affirm life, and offer support to patients and their caregivers. For many, the expressed preference is to die at home. As a result, there is growing recognition that paramedics can play an integral role at the end of life for symptom relief. Paramedic comfort with symptom management in the palliative care context is suspected, based on past work, to be higher for cancer as opposed to non-cancer life advanced disease. The objective of this study was to explore the paramedic management of patients with cancer and non-cancer advanced disease, using pain and breathlessness as key symptoms. Methods  A retrospective cohort study was conducted. Paramedic electronic patient care records were queried for calls with palliative goals of care between July 1, 2015, and June 30, 2016, in Nova Scotia, Canada, which was the first year of the Paramedics Providing Palliative Care program. A manual chart review of a subgroup of 100 consecutive charts was completed to gain deeper insight. A descriptive analysis was conducted to understand practice variation within this population.  Results The electronic query returned 1909 calls with a palliative approach. A total of 765 (40.1%) had cancer. The most common non-cancer disease category was respiratory. The top chief complaint was respiratory distress in both cancer and non-cancer populations. Medication was administered more often for pain (80%) compared to breathlessness (46.5%). Paramedics were more likely to call Medical Oversight Physicians for pain control advice. Post-treatment pain scores were documented infrequently. In the chart review, symptom management using the patient's own medications occurred in 17% of cases while an additional 5% of cases involved a combination of the patient's medications and paramedic service formulary. Conclusion  The non-cancer population was less likely to have a non-transport outcome. Opportunities for improvement of symptom management were noted for pain and particularly so for breathlessness. Increased comfort with a palliative approach in the non-cancer disease cohort as well as with this key symptom will be a key to the success of the program.

Plasma Lipidomic Profiling Identifies Elevated Triglycerides as Potential Risk Factor in Chemotherapy-Induced Peripheral Neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of cytotoxic cancer treatment, often necessitating dose reduction (DR) or chemotherapy discontinuation (CD). Studies on peripheral neuropathy related to chemotherapy, obesity, and diabetes have implicated lipid metabolism. This study examined the association between circulating lipids and CIPN. METHODS: Lipidomic analysis was performed on plasma samples from 137 patients receiving taxane-based treatment. CIPN was graded using Total Neuropathy Score-clinical version (TNSc) and patient-reported outcome measure European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN (EORTC-QLQ-CIPN20). RESULTS: A significant proportion of elevated baseline lipids were associated with high-grade CIPN defined by TNSc and EORTC-QLQ-CIPN20 including triacylglycerols (TGs). Multivariable Cox regression on lipid species, adjusting for BMI, age, and diabetes, showed several elevated baseline TG associated with shorter time to DR/CD. Latent class analysis identified two baseline lipid profiles with differences in risk of CIPN (hazard ratio, 2.80 [95% CI, 1.50 to 5.23]; P = .0013). The higher risk lipid profile had several elevated TG species and was independently associated with DR/CD when modeled with other clinical factors (diabetes, age, BMI, or prior numbness/tingling). CONCLUSION: Elevated baseline plasma TG is associated with an increased risk of CIPN development and warrants further validation in other cohorts. Ultimately, this may enable therapeutic intervention.

Cyclooxygenase products contribute to the exaggerated exercise pressor reflex evoked by static muscle contraction in male UCD-type 2 diabetes mellitus rats.

Cyclooxygenase (COX) products of arachidonic acid metabolism, specifically prostaglandins, play a role in evoking and transmitting the exercise pressor reflex in health and disease. Individuals with type 2 diabetes mellitus (T2DM) have an exaggerated exercise pressor reflex; however, the mechanisms for this exaggerated reflex are not fully understood. We aimed to determine the role played by COX products in the exaggerated exercise pressor reflex in T2DM rats. The exercise pressor reflex was evoked by static muscle contraction in unanesthetized, decerebrate, male, adult University of California Davis (UCD)-T2DM (n = 8) and healthy Sprague-Dawley (n = 8) rats. Changes (Δ) in peak mean arterial pressure (MAP) and heart rate (HR) during muscle contraction were compared before and after intra-arterial injection of indomethacin (1 mg/kg) into the contracting hindlimb. Data are presented as means ± SD. Inhibition of COX activity attenuated the exaggerated peak MAP (Before: Δ32 ± 13 mmHg and After: Δ18 ± 8 mmHg; P = 0.004) and blood pressor index (BPi) (Before: Δ683 ± 324 mmHg·s and After: Δ361 ± 222 mmHg·s; P = 0.006), but not HR (Before: Δ23 ± 8 beats/min and After Δ19 ± 10 beats/min; P = 0.452) responses to muscle contraction in T2DM rats. In healthy rats, COX activity inhibition did not affect MAP, HR, or BPi responses to muscle contraction. Inhibition of COX activity significantly reduced local production of prostaglandin E2 in T2DM and healthy rats. We conclude that peripheral inhibition of COX activity attenuates the pressor response to muscle contraction in T2DM rats, suggesting that COX products partially contribute to the exaggerated exercise pressor reflex in those with T2DM.NEW & NOTEWORTHY We compared the pressor and cardioaccelerator responses to static muscle contraction before and after inhibition of cyclooxygenase (COX) activity within the contracting hindlimb in decerebrate, unanesthetized type 2 diabetic mellitus (T2DM) and healthy rats. The pressor responses to muscle contraction were attenuated after peripheral inhibition of COX activity in T2DM but not in healthy rats. We concluded that COX products partially contribute to the exaggerated pressor reflex in those with T2DM.

Mucinous ovarian carcinoma: A survey of practice in Australia and New Zealand.

BACKGROUND: Mucinous ovarian carcinoma (MOC) is a rare ovarian cancer with limited evidence to support clinical care. AIMS: We undertook a clinician survey to better understand current practice in treating MOC in Australia and New Zealand, and to determine any features associated with variation in care. In addition, we aimed to understand future research priorities. METHODS: A RedCap survey was distributed to clinician members of the Australia New Zealand Gynaecological Oncology Group (ANZGOG). Questions included respondent demographics, three case studies and future research priorities. Clinicians were asked questions specific to their speciality. RESULTS: Respondents (n = 47) were commonly experienced gynae-oncology specialists, most often surgical (38%) or medical (30%) oncologists. There was good consensus for surgical approaches for stage I disease; however, variation in practice was noted for advanced or recurrent MOC. Variation was also observed for medical oncologists; in early-stage disease there was no clear consensus on whether to offer chemotherapy, or which regimen to recommend. For advanced and recurrent disease a wide range of chemotherapy options was considered, with a trend away from an ovarian-type toward gastrointestinal (GI)-type regimens in advanced MOC. This practice was reflected in future research priorities, with 'Is a GI chemotherapy regimen better than an ovarian regimen?' the most highly ranked option, followed by 'Should stage 1C patients receive chemotherapy?' CONCLUSIONS: Although the number of respondents limited the analyses, it was clear that chemotherapy selection was a key point of divergence for medical oncologists. Future research is needed to establish well-evidenced guidelines for clinical care of MOC.

Impact of Pain on Symptom Burden in Chemotherapy-Induced Peripheral Neurotoxicity.

BACKGROUND: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects the quality of life of cancer survivors. However, the impact of pain on symptom burden remains undefined. This study aimed to define differences in the clinical symptom profile of patients with painful and nonpainful CIPN. PATIENTS AND METHODS: A total of 579 participants (median age, 59 years [IQR, 19 years]; F=66%) were assessed cross-sectionally 6 months posttreatment. CIPN severity was graded using multiple methods, including patient-reported outcome measures, a clinically graded scale (NCI-CTCAE), and a neurologic examination score. Participants were classified into subgroups based on patient symptom report, with painful CIPN characterized by the presence of shooting/burning pain, and nonpainful CIPN characterized by the presence of numbness or tingling without shooting/burning pain. Behavioral changes were assessed via structured patient interview regarding symptom impact on sleep, exercise, and treatment-seeking. RESULTS: Among 579 participants, 24% (n=140) reported painful CIPN, 48% (n=280) reported nonpainful CIPN, and 28% (n=159) had no CIPN. Participants with painful CIPN demonstrated higher CIPN severity than those with nonpainful CIPN across multiple measures, including NCI-CTCAE, neurologic grading, and patient report (all P<.05). Participants with painful CIPN were more likely to report that their symptoms affected their ability to exercise (P=.007), produced sleep impairment, and increased treatment-seeking behavior due to their symptoms (both P<.001) compared with participants with nonpainful CIPN. CONCLUSIONS: Overall, participants with painful CIPN reported higher scores across all CIPN severity measures, including behavioral changes. This study underlines the need for accurate identification of different CIPN subgroups in hopes of informing better treatment and rehabilitation options for cancer survivors with painful CIPN.

Upper-limb dysfunction in cancer survivors with chemotherapy-induced peripheral neurotoxicity.

INTRODUCTION: Upper-limb symptoms are often reported in the context of chemotherapy-induced peripheral neurotoxicity (CIPN), but objective quantification of functional deficits is often lacking. We examined and compared a range of neurophysiological and functional assessments of the upper-limb in the assessment of CIPN severity. METHODS: Cross-sectional assessment of neurotoxic chemotherapy-treated patients was undertaken using patient-reported and clinically-graded CIPN measures. Upper-limb functional assessments comprised of assessing fine motor skills, sensory perception, and neurophysiological measures of the median nerve. Group comparisons between participants who reported absence or presence of upper-limb functional deficits were investigated. RESULTS: 60 participants who were 11.5 (IQR = 4.0-26.0) months post-neurotoxic chemotherapy treatment reported CIPN. 65% (n = 39) reported upper-limb CIPN symptoms. Reduction in fine motor skills, sensory perception and median nerve SNAP amplitudes were associated with higher CIPN severity. Participants who self-reported presence of upper-limb functional deficits had worse CIPN severity across all measures, compared to participants who reported no upper-limb functional deficits. CONCLUSIONS: Participants who reported upper-limb symptoms and functional deficits had worse CIPN severity and quality-of-life. There is a high burden of upper-limb dysfunction long after neurotoxic chemotherapy treatment cessation. Focus on research into supportive care and rehabilitation options to improve upper-limb function is warranted to improve patient quality-of-life.

An Australian mainstream genetic testing program: Clinicians views about current and future practices.

PURPOSE: Germline genetic testing results can guide treatment decisions for oncology patients and are now offered to many cancer patients. Mainstream testing refers to genetic testing arranged by a non-genetics specialist. This repeated cross-sectional study aimed: (1) to capture clinician views on the existing mainstreaming genetic testing program for ovarian, breast, prostate, and endometrial cancer patients, and (2) to ascertain the interest of clinicians to consider changing practice to adopt mainstream testing. METHODS: Mainstreaming has occurred since 2015 for patients with ovarian and some breast cancer patients, expanding to include prostate cancer patients in 2019, and endometrial cancer patients in 2020. Two web-based surveys were administered within two health districts, covering seven hospitals in NSW. RESULTS: Fifty-four clinicians (70% response rate) participated. Clinicians who had arranged mainstream genetic testing (n = 30) were overall satisfied (76%), viewed the process as time-efficient and accessible for patients, and desired continuation of the program. Of those clinicians yet to engage in the program (n = 24), 88% expressed an interest in learning about mainstream testing. These clinicians identified time constraints, maintenance of current genetic knowledge, and completing the consenting and counseling process as barriers to mainstreaming. Future mainstreaming models are discussed. CONCLUSION: From the clinician's perspective, the mainstreaming program is considered a desirable pathway for germline testing of oncology patients. Access to ongoing education and resources is needed for the ongoing success of the program.

A phase II trial of nivolumab followed by ipilimumab and nivolumab in advanced non-clear-cell renal cell carcinoma.

OBJECTIVE: To evaluate the efficacy of sequential treatment with ipilimumab and nivolumab following progression on nivolumab monotherapy in individuals with advanced, non-clear-cell renal cell carcinoma (nccRCC). MATERIALS AND METHODS: UNISoN (ANZUP1602; NCT03177239) was an open-label, single-arm, phase 2 clinical trial that recruited adults with immunotherapy-naïve, advanced nccRCC. Participants received nivolumab 240 mg i.v. two-weekly for up to 12 months (Part 1), followed by sequential addition of ipilimumab 1 mg/kg three-weekly for four doses to nivolumab if disease progression occurred during treatment (Part 2). The primary endpoint was objective tumour response rate (OTRR) and secondary endpoints included duration of response (DOR), progression-free (PFS) and overall survival (OS), and toxicity (treatment-related adverse events). RESULTS: A total of 83 participants were eligible for Part 1, including people with papillary (37/83, 45%), chromophobe (15/83, 18%) and other nccRCC subtypes (31/83, 37%); 41 participants enrolled in Part 2. The median (range) follow-up was 22 (16-30) months. In Part 1, the OTRR was 16.9% (95% confidence interval [CI] 9.5-26.7), the median DOR was 20.7 months (95% CI 3.7-not reached) and the median PFS was 4.0 months (95% CI 3.6-7.4). Treatment-related adverse events were reported in 71% of participants; 19% were grade 3 or 4. For participants who enrolled in Part 2, the OTRR was 10%; the median DOR was 13.5 months (95% CI 4.8-19.7) and the median PFS 2.6 months (95% CI 2.2-3.8). Treatment-related adverse events occurred in 80% of these participants; 49% had grade 3, 4 or 5. The median OS was 24 months (95% CI 16-28) from time of enrolment in Part 1. CONCLUSIONS: Nivolumab monotherapy had a modest effect overall, with a few participants experiencing a long DOR. Sequential combination immunotherapy by addition of ipilimumab in the context of disease progression to nivolumab in nccRCC is not supported by this study, with only a minority of participants benefiting from this strategy.

Sleep dysfunction associated with worse chemotherapy-induced peripheral neurotoxicity functional outcomes.

PURPOSE: Sleep problems are commonly reported by cancer survivors; however, knowledge of the impact of chemotherapy-induced peripheral neurotoxicity (CIPN) on sleep quality remains limited. In this study, we explored the impact of CIPN on sleep quality, as well as identified clinical characteristics associated with poor sleep quality. METHODS: Participants were assessed cross-sectionally post-neurotoxic chemotherapy. CIPN severity was graded using a range of questionnaires that assessed CIPN severity and quality of life, as well as neurological grading scales. Sleep quality was assessed using a self-rated questionnaire (Pittsburgh Sleep Quality Index, PSQI). Participants with poor sleep quality were further grouped according to whether sleep impairment was due to CIPN or other factors. RESULTS: Among 77 participants who reported CIPN, 75% (n = 58) reported poor sleep quality. Of those, 41% (n = 24) reported CIPN as contributing to sleep impairment, while 59% (n = 34) reported other causes. Participants with CIPN-induced sleep impairments had higher CIPN severity across all outcome measures, as well as greater neuropathic pain (all p < 0.05). Furthermore, participants with CIPN-induced sleep impairments reported worse impact of neuropathy on physical and social functioning, as well as emotional well-being (all p < 0.05). CONCLUSIONS: Participants with CIPN-induced poor sleep quality reported worse scores across all CIPN severity measures. This emphasises the negative impacts of CIPN symptoms on quality of life of chemotherapy-treated patients and highlights the importance of sleep quality assessment in cancer survivors.

Spontaneous baroreflex sensitivity is attenuated in male UCD-type 2 diabetes mellitus rats: A link between metabolic and autonomic dysfunction.

Patients with type 2 diabetes mellitus (T2DM) have impaired arterial baroreflex function, which may be linked to the co-existence of obesity. However, the role of obesity and its related metabolic impairments on baroreflex dysfunction in T2DM is unknown. This study aimed to investigate the role of visceral fat and adiponectin, the most abundant cytokine produced by adipocytes, on baroreflex dysfunction in T2DM rats. Experiments were performed in adult male UCD-T2DM rats assigned to the following experimental groups (n = 6 in each): prediabetic (Pre), diabetes-onset (T0), 4 weeks after onset (T4), and 12 weeks after onset (T12). Age-matched healthy Sprague-Dawley rats were used as controls. Rats were anesthetized and blood pressure was directly measured on a beat-to-beat basis to assess spontaneous baroreflex sensitivity (BRS) using the sequence technique. Dual-energy X-ray absorptiometry (DEXA) was used to assess body composition. Data are presented as mean ± SD. BRS was significantly lower in T2DM rats compared with controls at T0 (T2D: 3.7 ± 3.2 ms/mmHg vs Healthy: 16.1 ± 8.4 ms/mmHg; P = 0.01), but not at T12 (T2D: 13.4 ± 8.1 ms/mmHg vs Healthy: 9.2 ± 6.0 ms/mmHg; P = 0.16). T2DM rats had higher visceral fat mass, adiponectin, and insulin concentrations compared with control rats (all P < 0.01). Changes in adiponectin and insulin concentrations over the measured time-points mirrored one another and were opposite those of the BRS in T2DM rats. These findings demonstrate that obesity-related metabolic impairments may contribute to an attenuated spontaneous BRS in T2DM, suggesting a link between metabolic and autonomic dysfunction.

Patient navigation models for mental health of parents expecting or caring for an infant or young child: A systematic review.

Patient navigation (PN) aims to improve timely access to healthcare by helping patients to "navigate" complex service provision landscapes. PN models have been applied in diverse healthcare settings including perinatal mental health (PMH). However, the practice models and implementation of PN programs vary widely, and their impact on engagement with PMH services has not been systematically investigated. This systematic narrative review study aimed to (1) identify and describe existing PMH PN models, (2) understand their effectiveness in improving service engagement and clinical outcomes, (3) review patient and provider perceptions, and (4) explore facilitators and barriers to program success. A systematic search of published articles/reports describing PMH PN programs/service delivery models targeting parents in the period from conception to 5 years postpartum was conducted. In total, 19 articles describing 13 programs were identified. The analysis yielded a number of commonalities and differences across program settings, target populations, and the scope of the navigator role. While there was promising evidence to support the clinical efficacy and impact on service utilization of PN programs for PMH, the current evidence base is sparse. Further research evaluating the efficacy of such services, and facilitators and barriers to their success, is warranted.

La meta de Navegación del Paciente (PN) es mejorar el acceso a tiempo a servicios de cuidado de salud por medio de ayudar a los pacientes a "navegar" los complejos esquemas de provisión de servicios. Los modelos PN han sido aplicados en diversos escenarios de cuidados de salud incluyendo la salud mental perinatal (PMH). Sin embargo, los modelos de la práctica e implementación de programas PN varían ampliamente, y su impacto en la participación de los servicios PMH no ha sido sistemáticamente investigada. Este estudio de revisión narrativa sistemática se propuso 1) identificar y describir modelos PMH PN existentes, 2) comprender su eficacia para mejorar la participación en el servicio y resultados clínicos, 3) examinar las percepciones de pacientes y proveedores, y 4) explorar factores facilitadores y barreras al éxito del programa. Se llevó a cabo una sistemática investigación de artículos/reportes publicados que describen modelos que proveen programas/servicios de PMH PN con enfoque en los padres en el período desde la concepción hasta los 5 años posteriores al parto. En total, se identificaron 19 artículos que describían 13 programas. Los análisis dieron como resultado un número de puntos comunes y diferencias a través de la composición de los programas, la población a la cual se dirigían, y el ámbito del papel del navegador. A pesar de que se observó una evidencia prometedora para apoyar la efectividad clínica y el impacto sobre la utilización del servicio de programas PN para PMH, la base actual de la evidencia es escasa. Es necesaria una posterior investigación para evaluar la efectividad de tales servicios, y puntos que los faciliten o barreras al éxito de éstos.

La Navigation du Patient (abrégé ici NP en français) a pour but d'améliorer l'accès rapide aux soins de santé en aidant les patients à « naviguer ¼ un paysage complexe d'offre de services. Les modèles NP ont été appliqués dans divers contextes de soins de santé y compris la santé mentale périnatale (SMP en français ici). Cependant les modèles de pratique et de mises en place de programmes NP varient grandement, et leur impact sur l'engagement avec des services SMP n'a pas encore été examiné systématiquement. Cette étude narrative systématique s'est donnée pour but de 1) identifier et décrire les modèles NP existants, 2) comprendre leur efficacité à améliorer d'engagement du service et ses résultats cliniques, 3) passer en revue les perceptions du patient et du prestataire, et 4) explorer ce qui facilite et fait obstacle au succès du programme. Une recherche systématique d'articles/rapports publiés décrivant des modèles de prestation de NP SMP visant des parents dans la période de la conception à 5 ans postpartum a été faite. En tout 19 articles décrivant 13 programmes ont été identifiés. L'analyse a produit un nombre de points communs et de différences au travers des contextes des programmes, des populations ciblées et de la portée du rôle de navigateur. Bien qu'il y ait des preuves promettantes soutenant l'efficacité clinique et l'impact de l'utilisation de services des programmes NP pour la SMP la base de preuves actuelle est éparse. Des recherches supplémentaires évaluant l'efficacité de tels services ainsi que les facteurs de facilitation et les barrières au succès sont nécessaires.

Patient-Reported Outcome Measures in Chemotherapy-Induced Peripheral Neurotoxicity: Defining Minimal and Clinically Important Changes.

BACKGROUND: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common complication of cancer treatment that produces functional disability. Increasingly, patient-reported outcome measures (PROMs) are used to assess CIPN, providing a broader symptom perspective than clinician-graded scales. Understanding when a reported change in CIPN symptoms meets the threshold for clinical significance is challenging. This study aimed to provide interpretation guidelines for validated CIPN PROMs, and thereby enable estimation of thresholds to identify clinically relevant symptoms. METHODS: Patients commencing neurotoxic cancer treatments were assessed at 3 timepoints: baseline, midtreatment, and end-of-treatment. Trajectory of CIPN development was assessed by means of CIPN PROMs, EORTC Quality of Life - Chemotherapy-Induced Peripheral Neuropathy questionnaire (QLQ-CIPN20), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity questionnaire (FACT/GOG-NTX). Thresholds were estimated for CIPN PROMs using the NCI CTCAE sensory neuropathy scale as the clinical anchor by midtreatment and end-of-treatment. Patients were assigned to a clinical change group according to CIPN development: either no development; grade 1 neuropathy (minimally important difference [MID]); or grade 2 neuropathy (clinically important difference). Distribution-based estimates (SD, 0.5) were also evaluated as supportive evidence. RESULTS: In total, 406 patients were recruited to the study, of whom 62% (n=199/320) developed CIPN by midtreatment and 80% (n=274/343) by end-of-treatment. Anchor-based MID estimates by midtreatment were 5.06 (95% CI, 4.26-5.86) for the QLQ-CIPN20 and 3.54 (95% CI, 2.87-4.20) for the FACT/GOG-NTX. End-of-treatment MIDs were estimated to be 7.32 (95% CI, 6.23-8.40) for the QLQ-CIPN20 and 4.84 (95% CI, 3.98-5.70) for the FACT/GOG-NTX. Distribution-based MID estimations yielded lower values than anchor-based methods, at 3.73 for the QLQ-CIPN20 and 2.64 for the FACT/GOG-NTX at midtreatment and 5.52 for the QLQ-CIPN20 and 3.64 for the FACT/GOG-NTX at end-of-treatment. CONCLUSIONS: Findings from the present series aid meaningful interpretation for commonly used validated CIPN PROMs and provide thresholds that serve as guidance on how to interpret score changes, which will be useful for design and evaluation of clinical trials and clinical practice.

Physical activity behaviors in cancer survivors treated with neurotoxic chemotherapy.

AIM: There are many barriers to physical activity among cancer survivors. Survivors treated with neurotoxic chemotherapy may develop chemotherapy-induced peripheral neuropathy (CIPN) and experience additional barriers related to sensorimotor and mobility deficits. This study examined physical activity behaviors, including physical activity predictors, among cancer survivors treated with neurotoxic chemotherapies. METHODS: A cross-sectional study of 252 participants, 3-24 months after neurotoxic chemotherapy, was undertaken. Physical activity was self-reported (IPAQ). CIPN was self-reported (FACT/GOG-Ntx-13), clinically graded (NCI-CTCAE), and objectively measured using neurological grading scales and neurophysiological techniques (tibial and sural nerve conduction studies). Balance (Swaymeter) and fine motor skills (grooved pegboard) were assessed. Regression models were used to identify clinical, demographic and CIPN predictors of walking and moderate-vigorous physical activity. RESULTS: Forty-four percent of participants did not meet recommended physical activity guidelines (≥150 min/week). Sixty-six percent presented with CIPN. Nineteen percent of participants with CIPN reported that symptoms interfered with their ability to be physically active. A lower proportion of survivors aged ≥60, with grade ≥1 CIPN or BMI ≥30, reported meeting physical activity guidelines (all p < .05). Regression models identified older age, higher BMI, and patient-reported CIPN associated with lower walking, while higher BMI and females were associated with lower moderate-vigorous physical activity. Neurologically assessed CIPN did not associate with walking or moderate-vigorous physical activity. CONCLUSION: Cancer survivors exposed to neurotoxic chemotherapy have low physical activity levels. Further work should examine the factors causing physical activity limitations in this cohort and designing interventions to improve physical function and quality of life in survivors.

Polygenic risk of paclitaxel-induced peripheral neuropathy: a genome-wide association study.

BACKGROUND: Genetic risk factors for chemotherapy-induced peripheral neuropathy (CIPN), a major dose-limiting side-effect of paclitaxel, are not well understood. METHODS: We performed a genome-wide association study (GWAS) in 183 paclitaxel-treated patients to identify genetic loci associated with CIPN assessed via comprehensive neuropathy phenotyping tools (patient-reported, clinical and neurological grading scales). Bioinformatic analyses including pathway enrichment and polygenic risk score analysis were used to identify mechanistic pathways of interest. RESULTS: In total, 77% of the cohort were classified with CIPN (n = 139), with moderate/severe neuropathy in 36%. GWAS was undertaken separately for the three measures of CIPN. GWAS of patient-reported CIPN identified 4 chromosomal regions that exceeded genome-wide significance (rs9846958, chromosome 3; rs117158921, chromosome 18; rs4560447, chromosome 4; rs200091415, chromosome 10). rs4560447 is located within a protein-coding gene, LIMCH1, associated with actin and neural development and expressed in the dorsal root ganglia (DRG). There were additional risk loci that exceeded the statistical threshold for suggestive genome-wide association (P < 1 × 10-5) for all measures. A polygenic risk score calculated from the top 46 ranked SNPs was highly correlated with patient-reported CIPN (r2 = 0.53; P = 1.54 × 10-35). Overlap analysis was performed to identify 3338 genes which were in common between the patient-reported CIPN, neurological grading scale and clinical grading scale GWAS. The common gene set was subsequently analysed for enrichment of gene ontology (GO) and Reactome pathways, identifying a number of pathways, including the axon development pathway (GO:0061564; P = 1.78 × 10-6) and neuronal system (R-HSA-112316; adjusted P = 3.33 × 10-7). CONCLUSIONS: Our findings highlight the potential role of axon development and regeneration pathways in paclitaxel-induced CIPN.

Association of electrochemical skin conductance with neuropathy in chemotherapy-treated patients.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse event of cancer treatment that can affect sensory, motor, or autonomic nerves. Assessment of autonomic neuropathy is challenging, with limited available tools. Accordingly, it is not routinely assessed in chemotherapy-treated patients. In this study, we aimed to examine whether electrochemical skin conductance (ESC) via Sudoscan, a potential measure of autonomic function, associates with subjective and objective measures of CIPN severity and autonomic neuropathy. METHODS: A cross-sectional assessment of patients who completed neurotoxic chemotherapy 3-24 months prior was undertaken using CIPN patient-reported outcomes (EORTC-QLQ-CIPN20), clinically graded scale (NCI-CTCAE), neurological examination score (TNSc), autonomic outcome measure (SAS), and Sudoscan. Differences in CIPN severity between participants with or without ESC dysfunction were investigated. Linear regression analyses were used to identify whether ESC values could predict CIPN severity. RESULTS: A total of 130 participants were assessed, with 93 participants classified with CIPN according to the clinically graded scale (NCI-CTCAE/grade ≥ 1), while 49% demonstrated hands or feet ESC dysfunction (n = 46). Participants with ESC dysfunction did not significantly differ from those with no dysfunction on multiple CIPN severity measures (clinical-grade, patient-report, neurological examination), and no differences on the autonomic outcome measure (SAS) (all p > 0.0063). Linear regression analyses showed that CIPN could not be predicted by ESC values. CONCLUSIONS: The inability of ESC values via Sudoscan to predict clinically-graded and patient-reported CIPN or autonomic dysfunction questions its clinical utility for chemotherapy-treated patients. The understanding of autonomic neuropathy with chemotherapy treatment remains limited and must be addressed to improve quality of life in cancer survivors.

Providing palliative care at home aligns with the professional identity of paramedics: a qualitative study of paramedics and palliative health care providers.

BACKGROUND: An innovative program, 'Paramedics Providing Palliative Care at Home,' was implemented in Nova Scotia, Canada in 2015. Roles like this are part of an evolving professional identity; role discordance or lack of clarity not only hinders professionalization but may impair the wellbeing, and career longevity of paramedics. This study explored the alignment of providing palliative support at home with paramedic professional identity. METHODS: Qualitative description was employed, with thematic analysis of focus groups with paramedics and palliative health care providers. Recruitment posters were sent through the professional college (paramedics) and program managers (health care providers). Focus groups followed a semi-structured guide, discussing understanding of and experiences with the role and its alignment with professional identity. Challenges to paramedic palliative support and fit with professional identify were explored. Thematic content analysis was ongoing while focus groups were being conducted, until no new codes were found. Codes were combined, sorted into categories, and ultimately, agreed-upon themes. Saturation of themes was reached. RESULTS: Eleven paramedics and twenty palliative health care providers participated. Four themes reflected paramedic's expanded role: (1) patient centeredness and job satisfaction with provision of palliative support, (2) a bridging role, (3) paramedic as advocate and educator, (4) provision of psychosocial support. Four themes reflected paramedic's professional identity: (1) evolution of paramedicine as a skilled clinical profession, (2) helping people and communities, (3) paramedic skill set aligns with work in palliative care, and (4) changing paramedic mindset. CONCLUSION: Paramedics and palliative health care providers highlighted the provision of palliative care as part of a positive growth of paramedicine as a health profession, and a good fit with professional identity. Novel roles like this are important in the evolution of our health care system faced with increasing pressures to get the right care with the right provider at the right time.

RéSUMé: CONTEXTE: Un programme innovant, " Programme de soins palliatifs paramédicaux à domicile ", a été mis en œuvre en Nouvelle-Écosse, au Canada, en 2015. Les rôles de ce type font partie d'une identité professionnelle en évolution ; la discordance ou le manque de clarté des rôles non seulement entrave la professionnalisation, mais peut aussi nuire au bien-être et à la longévité de la carrière des ambulanciers paramédicaux. Cette étude a exploré l'alignement de la prestation de soutien palliatifs à domicile avec l'identité professionnelle des ambulanciers paramédicaux. MéTHODES: Une description qualitative a été employée, avec une analyse thématique de groupes de discussion avec des ambulanciers paramédicaux et des prestataires de soins palliatifs. Des affiches de recrutement ont été envoyées par le biais du collège professionnel (paramédicaux) et des gestionnaires de programmes (prestataires de soins de santé). Les groupes de discussion ont suivi un guide semi-structuré, discutant de la compréhension et des expériences du rôle et de son alignement avec l'identité professionnelle. Les défis du soutien palliatif paramédical et son adéquation avec l'identité professionnelle ont été explorés. L'analyse du contenu thématique s'est poursuivie pendant la tenue des groupes de discussion, jusqu'à ce qu'aucun nouveau code ne soit trouvé. Les codes ont été combinés, triés en catégories et, finalement, en thèmes convenus. La saturation des thèmes a été atteinte. RéSULTATS: Onze ambulanciers paramédicaux et vingt prestataires de soins palliatifs ont participé. Quatre thèmes reflétaient le rôle élargi des ambulanciers paramédicaux : 1) l'orientation vers le patient et la satisfaction professionnelle à l'égard de la prestation de soutien palliatifs, 2) un rôle de transition, 3) les ambulanciers paramédicaux à titre de défenseurs et d'éducateurs, 4) un soutien psychosocial. Quatre thèmes reflétaient l'identité professionnelle des ambulanciers paramédicaux : 1) l'évolution de la profession paramédicale en tant que profession clinique qualifiée, 2) l'aide aux personnes et aux collectivités, 3) l'ensemble des compétences des ambulanciers paramédicaux s'harmonise avec le travail en soins palliatifs, et 4) l'évolution de l'état d'esprit des ambulanciers paramédicaux. CONCLUSION: Les ambulanciers paramédicaux et les prestataires de soins palliatifs ont souligné que la prestation de soins palliatifs faisait partie d'une croissance positive de la profession paramédicale en tant que profession de la santé et correspondait bien à l'identité professionnelle. Des rôles novateurs comme celui-ci sont importants dans l'évolution de notre système de soins de santé, confronté à des pressions croissantes pour obtenir les bons soins auprès du bon prestataire au bon moment.

An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves.

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.

Essential Elements to Implementing a Paramedic Palliative Model of Care: An Application of the Consolidated Framework for Implementation Research.

Background: Comfort care without transport to hospital was not traditionally a paramedic practice. The novel Paramedics Providing Palliative Care at Home Program includes a new clinical practice guideline, medications, a database to manage and share goals of care, and palliative care training. This study determined essential elements for implementation, scale, and spread of this Program. Methods: Deliberative dialogs, a qualitative method, were held with diverse stakeholders/experts in one province with the Program (Nova Scotia, March 2018) and one without (British Columbia, July 2018). The Consolidated Framework for Implementation Research (CFIR) informed the discussion guide and was used in a framework analysis. Four team members analyzed the data independently; themes were derived by consensus with the broader research team. Results: CFIR constructs framed several key elements. Inter-sectoral communication is critical but challenged by privacy concerns and the siloed structure of the health system. Locally adapted training is an essential characteristic of the intervention; cost is a factor. A shift in mindset away from traditional paramedic roles is required; this can be facilitated by paramedic champions and a positive implementation climate. Early engagement of diverse stakeholders and planning for sustainability is key. Conclusion: This framework analysis using CFIR constructs can guide successful scale and spread of the program. The constructs of Outer setting: Cosmopolitanism; Characteristics of the intervention: Adaptability; Inner Setting: Implementation climate; and Processes: Engagement, and Planning, emerged as essential.