Randomized Evaluation of a Remote Management Program to Improve Guideline-Directed Medical Therapy: The DRIVE Trial.

BACKGROUND: Several SGLT2i (sodium-glucose transport protein 2 inhibitors) and GLP1-RA (glucagon-like peptide-1 receptor agonists) reduce cardiovascular events and improve kidney outcomes in patients with type 2 diabetes; however, utilization remains low despite guideline recommendations. METHODS: A randomized, remote implementation trial in the Mass General Brigham network enrolled patients with type 2 diabetes with increased cardiovascular or kidney risk. Patients eligible for, but not prescribed, SGLT2i or GLP1-RA were randomly assigned to simultaneous virtual patient education with concurrent prescription of SGLT2i or GLP1-RA (ie, Simultaneous) or 2 months of virtual education followed by medication prescription (ie, Education-First) delivered by a multidisciplinary team driven by nonlicensed navigators and clinical pharmacists who prescribed SGLT2i or GLP1-RA using a standardized treatment algorithm. The primary outcome was the proportion of patients with prescriptions for either SGLT2i or GLP1-RA by 6 months. RESULTS: Between March 2021 and December 2022, 200 patients were randomized. The mean age was 66.5 years; 36.5% were female, and 22.0% were non-White. Overall, 30.0% had cardiovascular disease, 5.0% had cerebrovascular disease, and 1.5% had both. Mean estimated glomerular filtration rate was 77.9 mL/(min‧1.73 m2), and mean urine/albumin creatinine ratio was 88.6 mg/g. After 2 months, 69 of 200 (34.5%) patients received a new prescription for either SGLT2i or GLP1-RA: 53.4% of patients in the Simultaneous arm and 8.3% of patients in the Education-First arm (P<0.001). After 6 months, 128 of 200 (64.0%) received a new prescription: 69.8% of patients in the Simultaneous arm and 56.0% of patients in Education-First (P<0.001). Patient self-report of taking SGLT2i or GLP1-RA within 6 months of trial entry was similarly greater in the Simultaneous versus Education-First arm (69 of 116 [59.5%] versus 37 of 84 [44.0%]; P<0.001) Median time to first prescription was 24 (interquartile range [IQR], 13-50) versus 85 days (IQR, 65-106), respectively (P<0.001). CONCLUSIONS: In this randomized trial, a remote, team-based program identifies patients with type 2 diabetes and high cardiovascular or kidney risk, provides virtual education, prescribes SGLT2i or GLP1-RA, and improves guideline-directed medical therapy. These findings support greater utilization of virtual team-based approaches to optimize chronic disease management. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06046560.

Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination: A systematic review and meta-analysis.

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

Randomized adaptive selection trial of cryotherapy, compression therapy, and placebo to prevent taxane-induced peripheral neuropathy in patients with breast cancer.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of taxane therapy. Small non-randomized studies in patients with early-stage breast cancer (ESBC) suggest both cryotherapy and compression therapy may prevent CIPN. It is unknown which is more effective. METHODS: We conducted a randomized phase IIB adaptive sequential selection trial of cryotherapy vs. compression therapy vs. placebo ("loose" gloves/socks) during taxane chemotherapy. Participants were randomized in triplets. Garments were worn for 90-120 min, beginning 15 min prior and continuing for 15 min following the infusion. The primary goal was to select the best intervention based on a Levin-Robbins-Leu sequential selection procedure. The primary endpoint was a < 5-point decrease in the Functional Assessment of Cancer Therapy Neurotoxicity (FACT-NTX) at 12 weeks. An arm was eliminated if it had four or more fewer successes than the currently leading arm. Secondary endpoints included intervention adherence and patient-reported comfort/satisfaction. RESULTS: Between April 2019 and April 2021, 63 patients were randomized (cryotherapy (20); compression (22); placebo (21)). Most patients (60.3%) were treated with docetaxel. The stopping criterion was met after the 17th triplet (n = 51) was evaluated; success at 12 weeks occurred in 11 (64.7%) on compression therapy, 7 (41.1%) on cryotherapy, and 7 (41.1%) on placebo. Adherence to the intervention was lowest with cryotherapy (35.0%) compared to compression (72.7%) and placebo (76.2%). CONCLUSION: Compression therapy was the most effective intervention in this phase IIB selection trial to prevent CIPN and was well tolerated. Compression therapy for the prevention of CIPN should be evaluated in a phase III study. CLINICAL TRIAL REGISTRATION: ClinicaTrials.gov Identifier: NCT03873272.

Barrier films or dressings for the prevention of acute radiation dermatitis in breast cancer: a systematic review and network meta-analysis.

BACKGROUND: Barrier films or dressings were reported to be effective in preventing radiation dermatitis (RD) in breast cancer patients, but their comparative efficacy is unknown. METHODS: A systematic literature search was performed on Embase, MEDLINE and Cochrane CENTRAL Registry of Clinical Trials from inception to October 20, 2023. Randomised controlled trials (RCTs) comparing barrier films or dressings to the standard of care (SOC) or other interventions were included. We estimated summary odds ratios and mean differences using network meta-analysis with random effects. This study was registered with PROSPERO (ID: CRD42023475021). RESULTS: Fourteen RCTs met inclusion criteria. Six interventions were analysed: 3M™ Moisturizing Double Barrier Cream (MDBC), 3M™ No Sting Barrier Film (BF), Hydrofilm® (HF), Mepitel® Film (MF), Silver Leaf Nylon Dressing and StrataXRT®. HF, MF and StrataXRT® reduced the incidence of moist desquamation compared to SOC (HF: OR = 0.08; p = 0.02; MF: OR = 0.31 p < 0.01; StrataXRT®: OR = 0.22, p = 0.04). The ranking of agents from most to least effective in preventing moist desquamation according to P-scores was HF (92.5%), MF (78.5%), StrataXRT® (70.1%), BF (46.4%), Silver Leaf Nylon Dressing (24.9%), MDBC (22.9%) and SOC (14.7%). Only four RCTs on HF and MF included patient-reported outcome (PRO) assessments that allowed pooling for analysis. HF and MF were more effective in reducing pain, itchiness and burning sensation compared to SOC (p < 0.01 for all symptoms). CONCLUSION: HF and MF were effective in preventing RD in breast cancer. Future RCTs should compare these interventions to effective cream preparations, such as topical corticosteroids.

Enrollment strategies in the era of digital revolution: Experience from a remote health management program.

We describe the strategies used to identify and enroll participants in a remote health management program aimed at optimizing diabetes care in patients at high cardiovascular and kidney risk. Using a combination of digital and traditional outreach methods, including patient portals, emails, mailed letters, and provider referrals, we successfully enrolled 200 participants. Our experience highlights the effectiveness of a hybrid approach in achieving enrollment targets, addressing the challenges of identification of eligible candidates and engagement while integrating traditional methods for inclusivity.

Dose Individualization for Phase I Cancer Trials With Broadened Eligibility.

Broadening eligibility criteria in cancer trials has been advocated to represent the intended patient population more accurately. The advantages are clear in terms of generalizability and recruitment, however there are some important considerations in terms of design for efficiency and patient safety. While toxicity may be expected to be homogeneous across these subpopulations, designs should be able to recommend safe and precise doses if subpopulations with different toxicity profiles exist. Dose-finding designs accounting for patient heterogeneity have been proposed, but existing methods assume that the source of heterogeneity is known. We propose a broadened eligibility dose-finding design to address the situation of unknown patient heterogeneity in phase I cancer clinical trials where eligibility is expanded, and multiple eligibility criteria could potentially lead to different optimal doses for patient subgroups. The design offers a two-in-one approach to dose-finding by simultaneously selecting patient criteria that differentiate the maximum tolerated dose (MTD), using stochastic search variable selection, and recommending the subpopulation-specific MTD if needed. Our simulation study compares the proposed design to the naive approach of assuming patient homogeneity and demonstrates favorable operating characteristics across a wide range of scenarios, allocating patients more often to their true MTD during the trial, recommending more than one MTD when needed, and identifying criteria that differentiate the patient population. The proposed design highlights the advantages of adding more variability at an early stage and demonstrates how assuming patient homogeneity can lead to unsafe or sub-therapeutic dose recommendations.

Validation of the Skin Symptom Assessment (SSA) questionnaire for the evaluation of radiation dermatitis in breast cancer patients.

PURPOSE: Radiation dermatitis (RD) is a painful side effect of radiation therapy (RT). The objective of this analysis was to investigate the validity and reliability of the Skin Symptom Assessment (SSA) questionnaire in evaluating the severity of patient- and clinician-reported outcomes for RD in breast cancer patients by comparing it to a validated assessment tool, the Radiation-Induced Skin Reaction Assessment Scale (RISRAS) questionnaire. METHODS: This study compared patient and clinician-reported outcomes for RD from previous clinical trials conducted in a Canadian cancer centre. The analysis included 376 and 38 patients in the two trials using Mepitel Film (doi.org/10.1200) and StrataXRT (clinicaltrials.gov identifier: NCT05594498), respectively. Patients in both studies completed the SSA and RISRAS questionnaires at baseline, 2-weeks post-RT, and 3 months after completion of RT. Clinician SSA and RISRAS assessments were collected at baseline and 2-weeks post-RT. These time points were analyzed longitudinally to investigate the SSA's validity in RD symptom assessment. RESULTS: The majority of patient-reported items on the SSA and RISRAS assessments demonstrated positive significant associations between symptoms of itchiness, between pain/soreness and pain/discomfort, and between blistering or erythema with burning sensation items. All items in the clinician-reported SSA and clinician component of RISRAS showed positive statistical significance between items measuring erythema, pigmentation or edema with dry desquamation, and blistering/peeling with moist desquamation. CONCLUSIONS: The SSA has been validated for assessing patient- and clinician-reported symptoms of RD accurately as outcomes correlate well with the previously validated RISRAS assessment.

StrataXRT for the prevention of acute radiation dermatitis in breast cancer: a pilot study.

PURPOSE: Previous literature has produced heterogeneous results on StrataXRT for prevention of acute radiation dermatitis (RD) in breast cancer. This pilot study aimed to assess the feasibility and efficacy of StrataXRT in a cancer center. METHODS: The study consisted of five cohorts: (1) patients with large breasts treated with local radiation therapy (RT) either in the supine position or (2) the prone position, (3) patients receiving locoregional breast RT with any breast size, and (4) patients receiving chest wall RT, either locally or (5) locoregionally. The primary endpoint of the study was RD grade as assessed using the Common Terminology Criteria for Adverse Events. Secondary endpoints included incidence of moist desquamation (MD), patient- and clinician-reported skin assessments, patient quality of life as assessed by the Skindex-16, and patient satisfaction. These outcomes were compared with those from a published trial from the same institution assessing standard of care and Mepitel Film (MF) as prevention of breast RD. RESULTS: Forty-five patients receiving RT to the breast or chest wall were enrolled. Two withdrew, leaving 43 evaluable patients. Overall, two (4.7%) patients had grade 3 RD, 14 (32.6%) had grade 2 RD, and 27 (62.8%) had grade 1 RD. Ten patients (23.3%) developed MD during/after RT. CONCLUSION: StrataXRT is effective in preventing grade 3 RD in patients, and the most promising results were observed within the prone cohort. Further research includes evaluating the efficacy of StrataXRT against the standard of care for the prophylaxis of RD. TRIAL REGISTRATION: The study protocol was registered at ClinicalTrials.gov (identifier: NCT05594498) on October 13, 2022.

2020 ASCO, 2023 NCCN, 2023 MASCC/ESMO, and 2019 CCO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in cancer patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common toxicity that may impair the quality of life of patients with various malignancies ranging from early to end stages. In light of frequent changes to the guidelines for optimal management of CINV, we undertook this narrative review to compare the most recent guidelines published by ASCO (2020), NCCN (2023), MASCC/ESMO (2023), and CCO (2019). The processes undertaken by each organization to evaluate existing literature were also described. Although ASCO, NCCN, MASCC/ESMO, and CCO guidelines for the treatment and prevention of CINV share many fundamental similarities, the literature surrounding low and minimal emetic risk regimens is lacking. Current data regarding adherence to these guidelines is poor and warrants further investigation to improve care.

Quality of life issues in patients with ductal carcinoma in situ: a systematic review.

PURPOSE: Ductal carcinoma in situ (DCIS) of the breast is one of the most common pre-invasive cancers diagnosed in women. Quality of life (QoL) is extremely important to assess in studies including these patients due to the favorable prognosis of the disease. The primary objective of this systematic review was to compile a comprehensive list of QoL issues, all existing QoL assessment tools, and patient-reported outcome measures used to assess DCIS. METHODS: A search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases from inception to August 2023, using keywords such as "ductal carcinoma in-situ", "quality of life", and "patient-reported outcomes." QoL issues and QoL tools in primary research studies were extracted. RESULTS: A total of 67 articles identified issues pertaining to patients with DCIS spanning physical, functional, and psychosocial QoL domains. Physical and functional issues observed in patients included pain, fatigue, and impaired sexual functioning. Psychosocial issues such as anxiety, depression, and confusion about one's disease were also common. QoL tools included those that assessed general QoL, breast cancer-specific tools, and issue-specific questionnaires. CONCLUSION: The current instruments available to assess QoL in patients with DCIS do not comprehensively capture the issues that are pertinent to patients. Thus, the modification of existing tools or the creation of a DCIS-specific QoL tool is recommended to ensure that future research will be sensitive towards challenges faced by patients with DCIS.

Dose optimization for cancer treatments with considerations for late-onset toxicities.

Given that novel anticancer therapies have different toxicity profiles and mechanisms of action, it is important to reconsider the current approaches for dose selection. In an effort to move away from considering the maximum tolerated dose as the optimal dose, the Food and Drug Administration Project Optimus points to the need of incorporating long-term toxicity evaluation, given that many of these novel agents lead to late-onset or cumulative toxicities and there are no guidelines on how to handle them. Numerous methods have been proposed to handle late-onset toxicities in dose-finding clinical trials. A summary and comparison of these methods are provided. Moreover, using PI3K inhibitors as a case study, we show how late-onset toxicity can be integrated into the dose-optimization strategy using current available approaches. We illustrate a re-design of this trial to compare the approach to those that only consider early toxicity outcomes and disregard late-onset toxicities. We also provide proposals going forward for dose optimization in early development of novel anticancer agents with considerations for late-onset toxicities.

The patient perspective on dose optimization for anticancer treatments: A new era of cancer drug dosing-Challenging the "more is better" dogma.

The Patient-Centered Dosing Initiative, a patient-led effort advocating for a paradigm shift in determining cancer drug dosing strategies, pioneers a departure from traditional oncology drug dosing practices. Historically, oncology drug dosing relies on identifying the maximum tolerated dose through phase 1 dose escalation methodology, favoring higher dosing for greater efficacy, often leading to higher toxicity. However, this approach is not universally applicable, especially for newer treatments like targeted therapies and immunotherapies. Patient-Centered Dosing Initiative challenges this "more is better" ethos, particularly as metastatic breast cancer patients themselves, as they not only seek longevity but also a high quality of life since most metastatic breast cancer patients stay on treatment for the rest of their lives. Surveying 1221 metastatic breast cancer patients and 119 oncologists revealed an evident need for flexible dosing strategies, advocating personalized care discussions based on patient attributes. The survey results also demonstrated an openness toward flexible dosing and a willingness from both patients and clinicians to discuss dosing as part of their care. Patient-centered dosing emphasizes dialogue between clinicians and patients, delving into treatment efficacy-toxicity trade-offs. Similarly, clinical trial advocacy for multiple dosing regimens encourages adaptive strategies, moving away from strict adherence to maximum tolerated dose, supported by recent research in optimizing drug dosages. Recognizing the efficacy-effectiveness gap between clinical trials and real-world practice, Patient-Centered Dosing Initiative underscores the necessity for patient-centered dosing strategies. A focus on individual patient attributes aligns with initiatives like Project Optimus and Project Renewal, aiming to optimize drug dosages for improved treatment outcomes at both the pre- and post-approval phases. Patient-Centered Dosing Initiative's efforts extend to patient education, providing tools to initiate dosage-related conversations with physicians. In addition, it emphasizes physician-patient dialogues and post-marketing studies as essential in determining optimal dosing and refining drug regimens. A dose-finding paradigm prioritizing drug safety, tolerability, and efficacy benefits all stakeholders, reducing emergency care needs and missed treatments for patients, aligning with oncologists' and patients' shared goals. Importantly, it represents a win-win scenario across healthcare sectors. In summary, the Patient-Centered Dosing Initiative drives transformative changes in cancer drug dosing, emphasizing patient well-being and personalized care, aiming to enhance treatment outcomes and optimize oncology drug delivery.

Contribution of Aerobic Cellulolytic Gut Bacteria to Cellulose Digestion in Fifteen Coastal Grapsoid Crabs Underpins Potential for Mineralization of Mangrove Production.

Grapsoid crabs (Decapoda: Grapsoidea) inhabiting along the land-sea transition provided various amounts and quality of vascular plant carbon (e.g., fresh mangrove leaf, leaf litter, and mangrove-derived organic carbon) and perform differing levels of herbivory. Other than endogenous cellulase, symbiotic cellulolytic bacteria could also contribute to the crabs' vascular plant carbon assimilation and mineralization. In this study, we isolated culturable cellulolytic bacteria from three gut regions (i.e., stomach, midgut, and hindgut) of 15 species of grapsoid crabs that inhabit in various coastal habitats (i.e., land margin, mangrove forest, tidal flat, and subtidal area). Bacillus, which was isolated from 11 out of the 15 grapsoid crabs, was the most common genus of culturable prominently cellulolytic bacteria among the target species. Seventy to ninety nine percent of culturable cellulolytic bacteria were removed, and the endoglucanase activity of five species was significantly reduced by 14.4-27.7% after antibiotic treatment. These results suggest that cellulolytic bacteria play a role in assisting mangrove carbon utilization in coastal grapsoid crabs, especially those inhabiting mangrove, mudflat, and subtidal areas. The significantly higher abundance of cellulolytic bacteria and the generally higher hydrolytic capacity of the bacteria in mangrove crab species suggest that they receive more contribution from symbionts for mangrove carbon utilization, while semi-terrestrial crabs seem to depend little on symbiotic cellulase due to the lower abundances.

"Using dried blood spots beyond newborn screening - is Hong Kong ready?": navigating the intersection of innovation readiness, privacy concerns, and Chinese parenting culture.

BACKGROUND: Newborn screening programmes offer an opportunity to obtain dried blood spots (DBS) cards that contain a wealth of biological information that can be stored for long periods and have potential benefits for research and quality assurance. However, the storage and secondary uses of DBS cards pose numerous ethical, clinical, and social challenges. Empirical research exploring public attitudes is central to public policy planning as it can indicate whether or not there is broad public support, define public concerns, and ascertain the circumstances required to alleviate concerns and ensure support. This study aims to describe the clinical experience and attitudes towards newborn screening and investigate the perceptions and expectations of Hong Kong parents and healthcare providers regarding the retention of DBS cards and their usage for research. METHODS: We conducted semi-structured in-person interviews with 20 parents and healthcare providers in Hong Kong. Thematic analysis was conducted. RESULTS: Awareness of the significant research value of secondary uses of dried blood spot cards is low. Parents and healthcare providers support the storage and secondary uses of DBS cards with some concerns, including privacy and confidentiality breaches, the risk of discrimination or stigmatisation based on genetic information, and their inability to oversee the use of their child's biospecimen. Parents, however, prioritise their child's health over privacy concerns and support identifiable storage using pseudonymity to gain more information about their children's health. CONCLUSION: Child information takes precedence over potential concerns over privacy, underscoring the significance of engaging patients and the public in shaping public policy related to biobanking and healthcare research, in line with cultural and social values.

A functional analysis reveals extremely low redundancy in global mangrove invertebrate fauna.

Deforestation results in habitat fragmentation, decreasing diversity, and functional degradation. For mangroves, no data are available on the impact of deforestation on the diversity and functionality of the specialized invertebrate fauna, critical for their functioning. We compiled a global dataset of mangrove invertebrate fauna comprising 364 species from 16 locations, classified into 64 functional entities (FEs). For each location, we calculated taxonomic distinctness (Δ+), functional richness (FRi), functional redundancy (FRe), and functional vulnerability (FVu) to assess functional integrity. Δ+ and FRi were significantly related to air temperature but not to geomorphic characteristics, mirroring the global biodiversity anomaly of mangrove trees. Neither of those two indices was linked to forest area, but both sharply decreased in human-impacted mangroves. About 60% of the locations showed an average FRe < 2, indicating that most of the FEs comprised one species only. Notable exceptions were the Eastern Indian Ocean and west Pacific Ocean locations, but also in this region, 57% of the FEs had no redundancy, placing mangroves among the most vulnerable ecosystems on the planet. Our study shows that despite low redundancy, even small mangrove patches host truly multifunctional faunal assemblages, ultimately underpinning their services. However, our analyses also suggest that even a modest local loss of invertebrate diversity could have significant negative consequences for many mangroves and cascading effects for adjacent ecosystems. This pattern of faunal-mediated ecosystem functionality is crucial for assessing the vulnerability of mangrove forests to anthropogenic impact and provides an approach to planning their effective conservation and restoration.

Development of consensus-driven SPIRIT and CONSORT extensions for early phase dose-finding trials: the DEFINE study.

BACKGROUND: Early phase dose-finding (EPDF) trials are crucial for the development of a new intervention and influence whether it should be investigated in further trials. Guidance exists for clinical trial protocols and completed trial reports in the SPIRIT and CONSORT guidelines, respectively. However, both guidelines and their extensions do not adequately address the characteristics of EPDF trials. Building on the SPIRIT and CONSORT checklists, the DEFINE study aims to develop international consensus-driven guidelines for EPDF trial protocols (SPIRIT-DEFINE) and reports (CONSORT-DEFINE). METHODS: The initial generation of candidate items was informed by reviewing published EPDF trial reports. The early draft items were refined further through a review of the published and grey literature, analysis of real-world examples, citation and reference searches, and expert recommendations, followed by a two-round modified Delphi process. Patient and public involvement and engagement (PPIE) was pursued concurrently with the quantitative and thematic analysis of Delphi participants' feedback. RESULTS: The Delphi survey included 79 new or modified SPIRIT-DEFINE (n = 36) and CONSORT-DEFINE (n = 43) extension candidate items. In Round One, 206 interdisciplinary stakeholders from 24 countries voted and 151 stakeholders voted in Round Two. Following Round One feedback, one item for CONSORT-DEFINE was added in Round Two. Of the 80 items, 60 met the threshold for inclusion (≥ 70% of respondents voted critical: 26 SPIRIT-DEFINE, 34 CONSORT-DEFINE), with the remaining 20 items to be further discussed at the consensus meeting. The parallel PPIE work resulted in the development of an EPDF lay summary toolkit consisting of a template with guidance notes and an exemplar. CONCLUSIONS: By detailing the development journey of the DEFINE study and the decisions undertaken, we envision that this will enhance understanding and help researchers in the development of future guidelines. The SPIRIT-DEFINE and CONSORT-DEFINE guidelines will allow investigators to effectively address essential items that should be present in EPDF trial protocols and reports, thereby promoting transparency, comprehensiveness, and reproducibility. TRIAL REGISTRATION: SPIRIT-DEFINE and CONSORT-DEFINE are registered with the EQUATOR Network ( https://www.equator-network.org/ ).

Response of macrophyte litter decomposition in global blue carbon ecosystems to climate change.

Blue carbon ecosystems (BCEs) are important nature-based solutions for climate change-mitigation. However, current debates question the reliability and contribution of BCEs under future climatic-scenarios. The answer to this question depends on ecosystem processes driving carbon-sequestration and -storage, such as primary production and decomposition, and their future rates. We performed a global meta-analysis on litter decomposition rate constants (k) in BCEs and predicted changes in carbon release from 309 studies. The relationships between k and climatic factors were examined by extracting remote-sensing data on air temperature, sea-surface temperature, and precipitation aligning to the decomposition time of each experiment. We constructed global numerical models of litter decomposition to forecast k and carbon release under different scenarios. The current k averages at 27 ± 3 × 10-2 day-1 for macroalgae were higher than for seagrasses (1.7 ± 0.2 × 10-2 day-1 ), mangroves (1.6 ± 0.1 × 10-2 day-1 ) and tidal marshes (5.9 ± 0.5 × 10-3 day-1 ). Macrophyte k increased with both air temperature and precipitation in intertidal BCEs and with sea surface temperature for subtidal seagrasses. Above a temperature threshold for vascular plant litter at ~25°C and ~20°C for macroalgae, k drastically increased with increasing temperature. However, the direct effect of high temperatures on k are obscured by other factors in field experiments compared with laboratory experiments. We defined "fundamental" and "realized" temperature response to explain this effect. Based on relationships for realized temperature response, we predict that proportions of decomposed litter will increase by 0.9%-5% and 4.7%-28.8% by 2100 under low- (2°C) and high-warming conditions (4°C) compared to 2020, respectively. Net litter carbon sinks in BCEs will increase due to higher increase in litter C production than in decomposition by 2100 compared to 2020 under RCP 8.5. We highlight that BCEs will play an increasingly important role in future climate change-mitigation. Our findings can be leveraged for blue carbon accounting under future climate change scenarios.

Comparison of guidelines for biological ancillary materials used for the manufacture of gene and cellular therapy products in Asia.

BACKGROUND AIMS: Although biologiocal ancillay materials (AMs) have specific risk associated with their derivations, it plays key role to manufature cell and gene therapy (CGT) products. It is important to understand the regulation relevant to AMs for developers. METHODS: The authors investigated the guidelines and pharmacopeia (hereinafter referred to as "guidelines") for biological AMs used for the manufacture of CGT products in Asia (China, India, Japan, Korea and Taiwan). In addition, the authors benchmarked the relevant guidelines in the United States (US) and European Union (EU). RESULTS AND DISCUSSIONS: The guidelines could be classified into two types based on whether specific AMs are scoped: (i) general guidelines for risk assessment of AMs and (ii) guidelines for specific AMs. The authors compared the risk categories for each type of AM provided in the general guidelines between the US and China and the specific requirements for bovine serum and trypsin in the guidelines of China, Japan, Taiwan, US and EU. The authors further compiled in-depth descriptions of the respective regulations in China, India, Japan, Korea and Taiwan. There is limited availability of some guidelines for specific AMs. Moreover, there are no common requirements established across the surveyed countries and regions. Therefore, the authors suggest a risk assessment approach for AMs with consideration of their biological origin and traceability, production steps applied and ability to control or remove AMs from the final medicinal product over the CGT manufacturing process.

StrataXRT for the prevention and treatment of radiation dermatitis: a critical review.

PURPOSE: The primary objective is to systematically review primary studies, such as randomized control trials (RCTs), feasibility, exploratory, and case studies; and the secondary objective is to evaluate all secondary articles, such as reviews, guidelines, and editorials, relevant to the use of StrataXRT for the prevention and/or management of radiation dermatitis (RD) in cancer patients. METHODS: A literature search was conducted up to February 26, 2023, for articles investigating the use of StrataXRT for the prevention and treatment of RD, in the following databases: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar. The keywords "StrataXRT", "dermatitis", "radiotherapy", and "radiation" were used to identify relevant articles. RESULTS: Twenty-seven articles from 2018 to 2022 were identified to fulfill the inclusion criteria of this review, of which nine are primary studies and 18 are secondary papers. Significant heterogeneity was observed in the current literature studying the effects of StrataXRT, making it difficult to make cross-trial comparisons. There is a suggestion of the efficacy of StrataXRT in the prevention and treatment of RD. CONCLUSION: The findings of this review recommend further adequately powered RCTs with robust methodology including patient and clinician assessments to determine the efficacy of StrataXRT in preventing and treating RD. This is essential to improve the quality of life of patients and identify which groups of patients would benefit most from StrataXRT.

Mepitel film for the prevention and treatment of acute radiation dermatitis in breast cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the efficacy of Mepitel film in preventing or treating acute radiation dermatitis (RD) in patients with breast cancer in randomized controlled trials (RCTs). METHODS: Embase, APA PsychInfo, Journals@Ovid Full Text, Ovid MEDLINE, PubMed, and Cochrane Trials were searched until December 12, 2022, to identify RCTs on the use of Mepitel film for preventing or treating acute RD from breast cancer radiotherapy. Per-protocol analysis was used to compare outcomes, calculate pooled effect sizes, odds ratio (OR), and 95% confidence intervals (CI), and to create forest plots using random effects analysis in RevMan 5.4. RESULTS: Three RCTs were included in this review. Mepitel film significantly reduced the incidence of grade 3 RD (OR 0.15 95% CI 0.06, 0.37, p<0.0001) and grade 2 or 3 RD (OR 0.16 95% CI 0.04, 0.65, p=0.01) as scored on either the CTCAE or the RTOG scale. Additionally, Mepitel film significantly reduced RISRAS mean scores assessed by patients and combined researcher and patient (standardized mean difference (SMD) -7.59, 95% CI -14.42, -0.76, p=0.03; SMD -15.36, 95% CI -30.01, -0.71 p=0.04) but not the researcher component of the assessment tool (SMD -17.55, 95% CI -36.94, 1.84, p=0.08). CONCLUSION: Mepitel film reduced the incidence of acute RD and improved patient-reported outcomes with minimal side effects, the main one being itchiness. Future research should assess the feasibility of Mepitel film with respect to specific patient-reported outcomes such as health-related quality of life issues associated with its use.