A purified reconstituted bilayer matrix shows improved outcomes in treatment of non-healing diabetic foot ulcers when compared to the standard of care: Final results and analysis of a prospective, randomized, controlled, multi-centre clinical trial.

As the incidence of diabetic foot ulcers (DFU) increases, better treatments that improve healing should reduce complications of these ulcers including infections and amputations. We conducted a randomized controlled trial comparing outcomes between a novel purified reconstituted bilayer membrane (PRBM) to the standard of care (SOC) in the treatment of non-healing DFUs. This study included 105 patients who were randomized to either of two treatment groups (n = 54 PRBM; n = 51 SOC) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n = 47 PRBM; n = 33 SOC). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing, quality of life, and cost to closure. The DFUs that had been treated with PRBM healed at a higher rate than those treated with SOC (ITT: 83% vs. 45%, p = 0.00004, PP: 92% vs. 67%, p = 0.005). Wounds treated with PRBM also healed significantly faster than those treated with SOC with a mean of 42 versus 62 days for SOC (p = 0.00074) and achieved a mean wound area reduction within 12 weeks of 94% versus 51% for SOC (p = 0.0023). There were no adverse events or serious adverse events that were related to either the PRBM or the SOC. In comparison to the SOC, DFUs healed faster when treated with PRBM. Thus, the use of this PRBM is an effective option for the treatment of chronic DFUs.

An initiative to implement a triage and referral system to make exercise and rehabilitation referrals standard of care in oncology.

BACKGROUND: Clinical guidelines suggest that patients should be referred to exercise while undergoing cancer treatment. Oncology clinicians report being supportive of exercise referrals but not having the time to make referrals. Toward the goal of making exercise referrals standard of care, we implemented and evaluated a novel clinical workflow. METHODS: For this QI project, a rehabilitation navigator was inserted in chemotherapy infusion clinics. Patients were offered a validated electronic triage survey. Exercise or rehabilitation recommendations were communicated to patients during a brief counseling visit by the rehabilitation navigator. The implementation approach was guided by the EPIS framework. Acceptability and feasibility were assessed. RESULTS: Initial meetings with nursing and cancer center leadership ensured buy-in (exploration). The education of medical assistants contributed to the adoption of the triage process (preparation). Audit and feedback ensured leadership was aware of medical assistants' performance (implementation). 100% of medical assistants participated in implementing the triage tool. A total of 587 patients visited the infusion clinics during the 6-month period when this QI project was conducted. Of these, 501 (85.3%) were offered the triage survey and 391 (78%) completed the survey (acceptability). A total of 176 (45%) of triaged patients accepted a referral to exercise or rehabilitation interventions (feasibility). CONCLUSIONS: Implementation of a validated triage tool by medical assistants and brief counseling by a rehabilitation navigator resulted in 45% of infusion patients accepting a referral to exercise or rehabilitation. The triage process showed promise for making exercise referrals standard of care for patients undergoing cancer treatment.

Adolescent HIV Screening and Opt-Out Testing as a Standard of Care.

Despite the significant steps made in the diagnosis and treatment of HIV, there is still a notable amount of people living with HIV without being diagnosed, with a fair portion of these infections occurring in adolescents and young adults. For some individuals, by the time they are diagnosed they are living with advanced-staged disease, missing the opportunity for receiving antiretroviral treatment that would have markedly reduced their morbidity, mortality, and risk of transmission to others. Opt-out testing, or notifying the patient the test will be performed unless explicitly declined or deferred, increases the rates of testing while reducing the stigma of the disease. It is a universal recommendation for those between ages 13 and 55 years to have an HIV screening test. It should be standard of care for HIV tests in the adolescent population to be structured as an opt-out screening in both the ambulatory and acute care settings. [Pediatr Ann. 2024;53(4):e111-e113.].

Investigational Approaches for Treatment of Melanoma Patients Progressing After Standard of Care.

ABSTRACT: The advent of effective immunotherapy, specifically cytotoxic T-lymphocyte associated protein 4 and programmed cell death 1 inhibitors, as well as targeted therapy including BRAF/MEK inhibitors, has dramatically changed the prognosis for metastatic melanoma patients. Up to 50% of patients may experience long-term survival currently. Despite these advances in melanoma treatment, many patients still progress and die of their disease. As such, there are many studies aimed at providing new treatment options for this population. Therapies currently under investigation include, but are not limited to, novel immunotherapies, targeted therapies, tumor-infiltrating lymphocytes and other cellular therapies, oncolytic viral therapy and other injectables, and fecal microbiota transplant. In this review, we discuss the emerging treatment options for metastatic melanoma patients who have progressed on standard of care treatments.

Toward more accurate preclinical glioblastoma modeling: Reverse translation of clinical standard of care in a glioblastoma mouse model.

Glioblastoma (GBM) is the deadliest of all brain cancers. GBM patients receive an intensive treatment schedule consisting of surgery, radiotherapy and chemotherapy, which only modestly extends patient survival. Therefore, preclinical studies are testing novel experimental treatments. In such preclinical studies, these treatments are administered as monotherapy in the majority of cases; conversely, in patients the new treatments are always combined with the standard of care. Most likely, this difference contributes to the failure of clinical trials despite the successes of the preclinical studies. In this methodological study, we show in detail how to implement the full clinical standard of care in preclinical GBM research. Systematically testing new treatments, including cellular immunotherapies, in combination with the clinical standard of care can result in a better translation of preclinical results to the clinic and ultimately increase patient survival.

Stereotactic body radiation therapy for spinal metastases: A new standard of care.

Advancements in systemic therapies for patients with metastatic cancer have improved overall survival and, hence, the number of patients living with spinal metastases. As a result, the need for more versatile and personalized treatments for spinal metastases to optimize long-term pain and local control has become increasingly important. Stereotactic body radiation therapy (SBRT) has been developed to meet this need by providing precise and conformal delivery of ablative high-dose-per-fraction radiation in few fractions while minimizing risk of toxicity. Additionally, advances in minimally invasive surgical techniques have also greatly improved care for patients with epidural disease and/or unstable spines, which may then be combined with SBRT for durable local control. In this review, we highlight the indications and controversies of SBRT along with new surgical techniques for the treatment of spinal metastases.

Integrating and optimizing tonabersat in standard glioblastoma therapy: A preclinical study.

Glioblastoma (GB), a highly aggressive primary brain tumor, presents a poor prognosis despite the current standard therapy, including radiotherapy and temozolomide (TMZ) chemotherapy. Tumor microtubes involving connexin 43 (Cx43) contribute to glioma progression and therapy resistance, suggesting Cx43 inhibition as a potential treatment strategy. This research aims to explore the adjuvant potential of tonabersat, a Cx43 gap junction modulator and blood-brain barrier-penetrating compound, in combination with the standard of care for GB. In addition, different administration schedules and timings to optimize tonabersat's therapeutic window are investigated. The F98 Fischer rat model will be utilized to investigate tonabersat's impact in a clinically relevant setting, by incorporating fractionated radiotherapy (three fractions of 9 Gy) and TMZ chemotherapy (29 mg/kg). This study will evaluate tonabersat's impact on tumor growth, survival, and treatment response through advanced imaging (CE T1-w MRI) and histological analysis. Results show extended survival in rats receiving tonabersat with standard care, highlighting its adjuvant potential. Daily tonabersat administration, both preceding and following radiotherapy, emerges as a promising approach for maximizing survival outcomes. The study suggests tonabersat's potential to reduce tumor invasiveness, providing a new avenue for GB treatment. In conclusion, this preclinical investigation highlights tonabersat's potential as an effective adjuvant treatment for GB, and its established safety profile from clinical trials in migraine treatment presents a promising foundation for further exploration.

The current standard of care of inflammatory bowel disease.

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Experience on postmortem minimally invasive tissue sampling to ascertain the cause of death determination in South African children: A case for implementing as standard of care.

Determining the death burden for prioritising public health interventions necessitates detailed data on the causal pathways to death. Postmortem minimally invasive tissue sampling (MITS), incorporating histology, molecular and microbial culture diagnostics, enhances cause-of-death attribution, particularly for infectious deaths. MITS proves a valid alternative to full diagnostic autopsies, especially in low- and middle-income countries. In Soweto, South Africa (SA), the Child Health and Mortality Prevention Surveillance (CHAMPS) programme has delineated over 1 000 child and stillbirth deaths since 2017. This SA CHAMPS site supports advocating for the use of postmortem MITS as routine practice, for more granular insights into under-5 mortality causes. This knowledge is crucial for SA's pursuit of Sustainable Development Goal 3.2, targeting reduced neonatal and under-5 mortality rates. This commentary explores the public health advantages and ethicolegal considerations surrounding implementing MITS as standard of care for stillbirths, neonatal and paediatric deaths in SA. Furthermore, based on the data from CHAMPS, we present three pragmatic algorithmic approaches to the wide array of testing options for cost-effectiveness and scalability of postmortem MITS in South African state facilities.

Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards). 1st Edition.

These first Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards) have been developed to inform the healthcare requirements for CoHD services and enable all Australian patients, families and carers impacted by CoHD (paediatric CoHD and adult congenital heart disease [ACHD]) to live their best and healthiest lives. The CoHD Standards are designed to provide the clarity and certainty required for healthcare services to deliver excellent, comprehensive, inclusive, and equitable CoHD care across Australia for patients, families and carers, and offer an iterative roadmap to the future of these services. The CoHD Standards provide a framework for excellent CoHD care, encompassing key requirements and expectations for whole-of-life, holistic and connected healthcare service delivery. The CoHD Standards should be implemented in health services in conjunction with the National Safety and Quality Health Service Standards developed by the Australian Commission on Safety and Quality in Health Care. All healthcare services should comply with the CoHD Standards, as well as working to their organisation's or jurisdiction's agreed clinical governance framework, to guide the implementation of structures and processes that support safe care.

Vulvar Carcinoma: Standard of Care and Perspectives.

PURPOSE: Treatment of vulvar carcinoma (VC) is challenging. The objectives of this review were to describe for clinicians the epidemiologic and clinical aspects of VC, the standard of care in terms of primary local treatment and systemic therapies, and the recent innovations and perspectives emerging from translational research in immuno-oncology. DESIGN: We conducted a comprehensive review outlying the clinical aspects and biologic background of vulvar cancer, highlighting modern treatment strategies on the basis of a personalized approach. RESULTS: Epidemiologic data showed a recent rise in incidence of VC, attributed to human papillomavirus. Surgery is the mainstay of primary treatment, but multimodal approaches are frequently required in the presence of adverse prognosis histopathologic factors. Chemoradiation is indicated when organ-sparing surgery is not feasible. However, inability to achieve high locoregional control rates in advanced cases and the morbidity associated with local treatments are still key issues. Recent clinical data showed the benefit of individualized strategies combining organ-sparing surgical strategies, less invasive lymph node staging procedures, and refinement in radiotherapy modalities. Among the most important research area, there is a sound rationale for testing modern systemic approaches such as immune checkpoint inhibitors in selected patients with recurrent and/or metastatic tumors. Although no specific data exist for VC, the role of supportive care and post-treatment rehabilitation strategies is also crucial. CONCLUSION: There are still insufficient studies dedicated to patients with VC. Public health programs for prevention, screening, and early diagnosis are required, and clinical research should be strengthened to provide high-quality clinical evidence and improve patients' oncologic and functional outcomes.

Novel hormonal therapy versus standard of care-A registry-based comparative effectiveness evaluation for mCRPC-patients.

BACKGROUND: This paper presents results from one of the few comparative effectiveness evaluations of novel antiandrogen medications (NHT) against standard of care (SoC) for patients suffering from metastatic castrate-resistant prostate cancer (mCRPC). METHODS: The design and the analysis are published in a protocol before accessing outcome data. Two groups of patients are balanced on hundreds of important covariates measured before the prostate cancer diagnosis and up to the date of the prescription. While the design yields balance on the observed covariates, one cannot discard the possibility that unobserved confounders are not balanced. The unconfoundedness assumption is assessed by estimating placebo regressions on two health measures, not included in the design but added together with the outcome data after protocol publication. RESULTS: We find a substantial (64 percent) increase in mortality for patients prescribed with NHT rather than SoC. However, based on the results from one of the two placebo regressions, we cannot rule out that the difference in mortality may be due to confounding. Using a bounding strategy of the effect, we can, however, rule out that NHT reduces mortality compared to SoC. Under an empirical valid assumption that most mCRPC patients who die suffer from bone metastases, we have a strong indication of increased skeleton-related events in patients if prescribed NHT against SoC. CONCLUSIONS: Generally, the SoC for this group of patients is docetaxel. Given the substantially higher costs of many of the NHT, the finding of no positive effects from NHT on both mortality and SRE is important. More comparative studies, including studies analysing quality of life outcomes, are thus needed.

Immunotherapy Combined With Standard Therapies in Head and Neck Squamous Cell Carcinoma - A Meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) is a deadly disease with a poor prognosis due to late diagnosis and limited treatment options. Immunotherapy (IT) is emerging as a promising approach, especially after the failure of standard of care therapies (STs). The objective of this systematic review and meta-analysis was to evaluate whether the addition of IT to STs improves outcomes for patients with HNSCC, including overall survival (OS), progression-free survival (PFS), and quality of life (QoL). This review employed the Population Intervention Comparison and Outcome (PICO) framework to identify relevant search terms in electronic databases, and also included supplementary hand searches. Six primary research articles were selected using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) flow chart, and were critically appraised. Data extraction from these studies was conducted, and a meta-analysis was performed to aid in the generation of forest plots. The addition of IT to standard anticancer therapies was found to enhance patient outcomes, such as OS, PFS, and QoL. The toxicity profile of IT was acceptable, with minimal treatment-related deaths. The most frequently observed adverse events (AE) were related to the skin, followed by hematological toxicities. Based on our analysis, the addition of IT to STs is a suitable treatment option and is supported by current research. However, further studies are needed to investigate factors that influence treatment effectiveness and to develop optimal therapies. To achieve this, we recommend a comprehensive treatment approach that involves the multidisciplinary team (MDT) and patient assessment tools.

Standards of care and determinants of women's satisfaction with delivery services in Nepal: a multi-perspective analysis using data from a health facility-based survey.

BACKGROUND: Compliance with standards of care is required for sustained improvement in the quality of delivery services. It thus represents a key challenge to improving maternal survival and meeting the Sustainable Development Goal (SDG) target of reducing the maternal mortality ratio to 70 deaths per 100,000 live births. This study examines the extent to which normal low-risk health facility deliveries in Nepal meet the standards of quality of care and assesses the effect of the standards of quality of care and various contextual factors on women's satisfaction with the services they receive. METHODS: Drawing on the 2021 Nepal Health Facility Survey, the sample comprised 320 women who used health facilities for normal, low-risk delivery services. A weighted one-sample t-test was applied to examine the proportion of deliveries meeting the eight standards of care. Women's overall satisfaction level was computed from seven satisfaction variables measured on a Likert scale, using principal component analysis. The composite measure was then dichotomized. Binary logistic regression was used to analyze the determinants of women's satisfaction with delivery care services. RESULTS: Deliveries complying with the eight standards of care and its 53 indicators varied widely; output indicators were more frequently met than input indicators. Of the eight standards of care, the "functional referral system" performed highest (92.0%), while "competent, motivated human resources" performed the least (52.4%). Women who were attended by a provider when they called for support (AOR: 5.29; CI: 1.18, 23.64), who delivered in health facilities that displayed health statistics (AOR 3.16; CI: 1.87, 5.33), who experienced caring behaviors from providers (AOR: 2.59; CI: 1.06, 6.30) and who enjoyed audio-visual privacy (AOR 2.13; CI: 1.04, 4.38) had higher satisfaction levels compared to their counterparts. The implementation of the Maternity Incentive Scheme and presence of a maternal waiting room in health facilities, however, were associated with lower satisfaction levels. CONCLUSIONS: Nepal performed moderately well in meeting the standards of care for normal, low-risk deliveries. To meet the SDG target Nepal must accelerate progress. It needs to focus on people-centered quality improvement to routinely assess the standards of care, mobilize available resources, improve coordination among the three tiers of government, and implement high-impact programs.

New therapies for immunoglobulin A nephropathy: what's the standard of care in 2023?

PURPOSE OF REVIEW: As the most common primary glomerulonephritis, immunoglobulin A (IgA) nephropathy (IgAN) is an important cause of kidney failure and mortality. Until recently, therapeutic options were limited. Fortunately, there have been numerous recent clinical trials demonstrating efficacy of new therapies in slowing chronic kidney disease (CKD) progression at varying stages of disease. RECENT FINDINGS: The TESTING trial has provided high-quality evidence for slowing estimated glomerular filtration rate (eGFR) decline with a reduced-dose glucocorticoid regimen, while demonstrating an improved safety profile. Targeted-release budesonide represents a well tolerated therapy for reducing eGFR decline. Mycophenolate mofetil may reduce CKD progression in some populations, while hydroxychloroquine is efficacious in reducing proteinuria. Sodium-glucose cotransporter (SGLT2) inhibitors and sparsentan are effective therapies for CKD due to IgAN, but should not be used in lieu of disease-modifying immunosuppressive therapy. Many new therapies are approaching readiness for clinical use. SUMMARY: Numerous therapeutic options now exist and include disease-modifying and nephroprotective drugs. Identifying the right treatment for the right patient is now the clinical challenge and, with new drugs on the horizon, represents the primary unmet research need in this rapidly-developing field.

Oral and middle ear delivery of otitis media standard of care antibiotics, but not biofilm-targeted antibodies, alter chinchilla nasopharyngeal and fecal microbiomes.

Otitis media (OM) is one of the most globally pervasive pediatric conditions. Translocation of nasopharynx-resident opportunistic pathogens like nontypeable Haemophilus influenzae (NTHi) assimilates into polymicrobial middle ear biofilms, which promote OM pathogenesis and substantially diminish antibiotic efficacy. Oral or tympanostomy tube (TT)-delivered antibiotics remain the standard of care (SOC) despite consequences including secondary infection, dysbiosis, and antimicrobial resistance. Monoclonal antibodies (mAb) against two biofilm-associated structural proteins, NTHi-specific type IV pilus PilA (anti-rsPilA) and protective tip-region epitopes of NTHi integration host factor (anti-tip-chimer), were previously shown to disrupt biofilms and restore antibiotic sensitivity in vitro. However, the additional criterion for clinical relevance includes the absence of consequential microbiome alterations. Here, nine chinchilla cohorts (n = 3/cohort) without disease were established to evaluate whether TT delivery of mAbs disrupted nasopharyngeal or fecal microbiomes relative to SOC-OM antibiotics. Cohort treatments included a 7d regimen of oral amoxicillin-clavulanate (AC) or 2d regimen of TT-delivered mAb, AC, Trimethoprim-sulfamethoxazole (TS), ofloxacin, or saline. Fecal and nasopharyngeal lavage (NPL) samples were collected before and several days post treatment (DPT) for 16S sequencing. While antibiotic-treated cohorts displayed beta-diversity shifts (PERMANOVA, P < 0.05) and reductions in alpha diversity (q < 0.20) relative to baseline, mAb antibodies failed to affect diversity, indicating maintenance of a eubiotic state. Taxonomic and longitudinal analyses showed blooms in opportunistic pathogens (ANCOM) and greater magnitudes of compositional change (P < 0.05) following broad-spectrum antibiotic but not mAb treatments. Collectively, results showed broad-spectrum antibiotics induced significant fecal and nasopharyngeal microbiome disruption regardless of delivery route. Excitingly, biofilm-targeting antibodies had little effect on fecal and nasopharyngeal microbiomes.