The Underuse of Clozapine and Long-Acting Injectable Antipsychotics.

Schizophrenia is among the most devastating and costly human diseases. The public face of the failure to appropriately treat schizophrenia includes approximately 100,000 homeless individuals with schizophrenia and related psychoses and 200,000 incarcerated individuals with similar diagnoses. Clozapine and long-acting injectable antipsychotics are among the most effective treatments, but both are markedly underused. The following organizations should take responsibility for fixing this problem: National Institute of Mental Health, Patient-Centered Outcomes Research Institute, Substance Abuse and Mental Health Services Administration, Centers for Medicare and Medicaid Services, U.S. Food and Drug Administration, American Psychiatric Association, and patient and family advocacy groups.

Introducing new antibiotics for multidrug-resistant bacteria: obstacles and the way forward.

BACKGROUND: Following intense efforts to revive the dry antibiotic research and development pipeline, a few highly awaited antibiotics with activity against multidrug-resistant (MDR) bacteria were recently approved. OBJECTIVES: We aim to highlight gaps in the evidence generated for new antibiotics by the time of their approval and to review the consequent limitations of treatment guidelines for priority MDR bacteria. We also report on availability of the new antibiotics, reimbursement strategies allowing use of these antibiotics in hospitals and antibiotic stewardship efforts. SOURCES: We searched PubMed for phase 3 randomized controlled trials that assessed antibiotics approved for use against MDR bacteria between 2013-2023. Other sources included governmental and professional documents regarding policies for reimbursement and use of the new antibiotics. CONTENT: Several gaps in the evidence available regarding the new antibiotics are described related to the trials' target populations, comparators, management algorithm within the trial, non-inferiority hypotheses and assessment of resistance development within the studies. We highlight the risk of current guidelines to increase usage of new antibiotics and consequently accelerate resistance development. Updated mapping of antibiotic availability reveals critical inequality in access to the new antibiotics. Finally, strategies used nationally in Europe to provide access to the new antibiotics are not sufficiently balanced by antibiotic stewardship efforts to calibrate judicious use of the new antibiotics. IMPLICATIONS: Antibiotic resistance is an immediate threat. The present review highlights areas where more systematic and uniform strategies across countries and geographical regions are warranted to improve evidence, availability and use of new broad-spectrum antibiotics.

ASTCT Consensus Recommendations on Testing and Treatment of Patients with Donor-specific Anti-HLA Antibodies.

Donor-specific anti-HLA antibodies (DSA) are an important cause of engraftment failure and may negatively impact survival outcomes of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using an HLA-mismatched allograft. The incidence of DSA varies across studies, depending on individual factors, detection or identification methods and thresholds considered clinically relevant. Although DSA testing by multiplex bead arrays remains semiquantitative, it has been widely adopted as a standard test in most transplant centers. Additional testing to determine risk of allograft rejection may include assays with HLA antigens in natural conformation, such as flow cytometric crossmatch, and/or antibody binding assays, such as C1q testing. Patients with low level of DSA (<2,000 mean fluorescence intensity; MFI) may not require treatment, while others with very high level of DSA (>20,000 MFI) may be at very high-risk for engraftment failure despite current therapies. By contrast, in patients with moderate or high level of DSA, desensitization therapy can successfully mitigate DSA levels and improve donor cell engraftment rate, with comparable outcomes to patients without DSA. Treatment is largely empirical and multimodal, involving the removal, neutralization, and blocking of antibodies, as well as inhibition of antibody production to prevent activation of the complement cascade. Desensitization protocols are based on accumulated multicenter experience, while prospective multicenter studies remain lacking. Most patients require a full intensity protocol that includes plasma exchange, while protocols relying only on rituximab and intravenous immunoglobulin may be sufficient for patients with lower DSA levels and negative C1q and/or flow cytometric crossmatch. Monitoring DSA levels before and after HSCT could guide preemptive treatment when high levels persist after stem cell infusion. This paper aims to standardize current evidence-based practice and formulate future directions to improve upon current knowledge and advance treatment for this relatively rare, but potentially serious complication in allogeneic HSCT recipients.

Quality of care provided to patients with type 2 diabetes mellitus in Tshwane, South Africa.

BACKGROUND:  Type 2 diabetes mellitus (T2D) is a public health challenge, affecting 90% of all patients with diabetes, globally. Compliance to treatment guidelines among healthcare professionals (HCPs) is low, thus resulting in inadequate quality of patient care and poor health outcomes among patients. AIM:  To examine the availability of equipment, guidelines, screening and education offered to patients with T2D and compare between clinics and community health centres (CHCs). SETTING:  Tshwane Metropolitan Municipality, Gauteng Province, South Africa. METHODS:  A cross-sectional descriptive study utilised a self-administered questionnaire to collect data from nurses and doctors responsible for treating patients with T2D, from May to June 2022. About 250 eligible HCPs were recruited during routine morning meetings in 22 clinics and six CHCs. RESULTS:  More than 80% of HCPs reported having basic equipment except for ophthalmoscopes, Snellen charts (67%), tuning forks (64%), electrocardiograms (ECG) (46%) and monofilaments (12%). SEMDSA guidelines were reported by 16% of the participants, Diabetic Foot Care Guidelines were reported by 54% and Dietary Guidelines for Diabetic Patients by 55%. Furthermore, 91%, 71% and 69% of HCPs reported that ECG, microalbumin-creatinine and foot examinations were not always performed, respectively. About 66% and 17% always offered individual educational and group sessions, respectively. CONCLUSION:  Equipment availability and compliance with treatment guidelines, patient education and screening of chronic complications are inadequate.Contribution: The study highlights the poor adherence to treatment guidelines and inadequate equipment in health facilities. These shortcomings could lead to missed opportunities for early diagnosis of complications and ultimately poorer patient outcomes.

Chinese guidelines on the management of ascites in cirrhosis : Chinese Society of Hepatology, Chinese Medical Association.

In 2023, Chinese Society of Hepatology of Chinese Medical Association convened a panel of experts to update the Chinese guidelines on the management of ascites and associated complications in cirrhosis which was launched in 2017 and renamed this guidelines as "Guidelines on the Management of Ascites in Cirrhosis." This comprehensive resource offers essential recommendations for the diagnosis and treatment of cirrhotic ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome.

Assessing the state of obesity care: Quality, access, guidelines, and standards.

Background: An international panel of obesity medicine experts from multiple professional organizations examined patterns of obesity care and current obesity treatment guidelines to identify areas requiring updating in response to emerging science and clinical evidence. Aims: The panel focused on multiple medical health and societal issues influencing effective treatment of obesity and identified several unmet needs in the definition, assessment, and care of obesity. Methods: The panel was held in Leesburg, Virginia in September 2019. Results: The panelists recommended addressing these unmet needs in obesity medicine through research, education, evaluation of delivery and payment of care, and updating clinical practice guidelines (CPG) to better reflect obesity's pathophysiological basis and heterogeneity, as well as the disease's health, sociocultural, and economic complications; effects on quality of life; need for standards for quantitative comparison of treatment benefits, risks, and costs; and the need to more effectively integrate obesity treatment guidelines into routine clinical practice and to facilitate more direct clinician participation to improve public understanding of obesity as a disease with a pathophysiological basis. The panel also recommended that professional organizations working to improve the care of people with obesity collaborate via a working group to develop an updated, patient-focused, comprehensive CPG establishing standards of care, addressing identified needs, and providing for routine, periodic review and updating. Conclusions: Unmet needs in the definition, assessment and treatment of obesity were identified and a blueprint to address these needs developed via a clinical practice guideline that can be utilized worldwide to respond to the increasing prevalence of obesity.

SNO-EANO-EURACAN consensus on management of pineal parenchymal tumors.

Pineal parenchymal tumors are rare neoplasms for which evidence-based treatment recommendations are lacking. These tumors vary in biology, clinical characteristics, and prognosis, requiring treatment that ranges from surgical resection alone to intensive multimodal antineoplastic therapy. Recently, international collaborative studies have shed light on the genomic landscape of these tumors, leading to refinement in molecular-based disease classification in the 5th edition of the World Health Organization (WHO) classification of tumors of the central nervous system. In this review, we summarize the literature on diagnostic and therapeutic approaches, and suggest pragmatic recommendations for the clinical management of patients presenting with intrinsic pineal region masses including parenchymal tumors (pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma), pineal cyst, and papillary tumors of the pineal region.

Accordance of Registered Drug Packages with Guideline-Recommended Treatment Durations for Community-Acquired Pneumonia-A New Antibiotic Stewardship Target?

In most countries, antibiotics for oral administration are put on the market in fixed packages. When there is no exact unit dispensing of antimicrobials, drug pack size may influence prescribers' choice of treatment duration. The aim of this study was to investigate the accordance of approved antibiotic packages with national guidelines for the treatment of community-acquired pneumonia (CAP). For the purpose of this study, criteria were developed to determine the accordance of approved antibiotic packages for treating CAP (criteria), which are based on recommendations from national guidelines for treating CAP. Subsequently, the accordance of approved antibiotic packages with the number of antibiotic doses resulting from the specified criteria was determined. Of 39 identified therapeutic option-package size combinations, 11 were found to be matched (28.2%), meaning there were no leftover medication units after completing therapy, and 28 were mismatched combinations (71.8%), indicating that there were excess doses of antibiotics remaining at the end of therapy. The results of this research showed a significant non-accordance of the approved antibiotic packages with the national guidelines for the treatment of CAP and, consequently, the creation of a large amount of residues of unit doses of antibiotics in the community.

Concordance of provider chart notation and guideline-based classification of asthma severity.

OBJECTIVE: To evaluate concordance of asthma severity classification via physician chart notation compared with guideline-based criteria in adolescents with diagnosed asthma. METHODS: Of 284 urban primary care and subspecialty clinic patients aged 13-18 years approached through convenience sampling, 203 surveys were completed (RR = 71.5%). We assessed concordance with sensitivity, specificity, and positive predictive values; overall agreement was evaluated with weighted kappa coefficients and McNemar's test. RESULTS: When considering prescribed treatment according to NAEPP guidelines as a gold standard, the sensitivity for chart notation was very good for intermittent (95%) and less for non-intermittent severity ratings (51%, 58%, and 67% for moderate, severe, and mild persistent asthma, respectively). Overall agreement between chart notation and guideline-based asthma criteria ranged from fair-to-good for mild- (k = 0.36), moderate- (k = 0.44), and severe-persistent severity (k = 0.66). Although the agreement for intermittent severity was highest (k = 0.88), it did not significantly differ by between the two classifications (p ≥ 0.05). CONCLUSIONS: Concordance for all non-intermittent asthma severity classifications varied between physician and medication-driven 2007 NAEPP guideline classifications in an ethnically diverse urban adolescent patient sample. Physicians should remain aware of the potential for this discordance and refer to the guidelines to classify and treat adolescents with asthma.

A cost analysis of a simplified model for HCV screening and treatment at a tertiary hospital in Zimbabwe.

BACKGROUND: The treatment of chronic hepatitis C virus (HCV) infection using directly acting antivirals was recently adopted in the treatment guidelines of Zimbabwe. The objectives of this study were to design a simplified model of HCV care and estimate the cost of screening and treatment of hepatitis C infection at a tertiary hospital in Zimbabwe. METHODS: We developed a model of care for HCV using WHO 2018 guidelines for the treatment of HCV infection and expert opinion. We then performed a micro-costing to estimate the costs of implementing the model of care from the healthcare sector perspective. Deterministic and probabilistic sensitivity analyses were performed to explore the impact of uncertainty in input parameters on the estimated total cost of care. RESULTS: The total cost of screening and treatment was estimated to be US$2448 (SD=$290) per patient over a 12-week treatment duration using sofosbuvir/velpatasvir. The cost of directly acting antivirals contributed 57.5% to the total cost of care. The second largest cost driver was the cost of diagnosis, US$819, contributing 34.6% to the total cost of care. CONCLUSION: Screening and treatment of HCV-infected individuals using directly acting antivirals at a tertiary hospital in Zimbabwe may require substantial financial resources.

Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023.

OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.

Clavicle fracture and triathlon performance: a case report.

BACKGROUND: Collarbone fracture is a common injury, particularly among athletes involved in contact sports and participating in endurance activities. Conventional treatment requires surgery and postoperative immobilization, resulting in an average return-to-sport timeframe of approximately 13 weeks. This case challenges the established treatment protocols, aiming to expedite recovery and enable a quicker resumption of high-intensity athletic activities. CASE PRESENTATION: A 24-year-old Caucasian athlete completed a Half-Ironman Triathlon (70.3) merely three weeks post-collarbone fracture. Utilizing Extracorporeal Magneto-Transduction Therapy (EMTT) alongside surgical intervention, the patient achieved accelerated healing and remarkable performance outcomes without encountering any adverse effects. CONCLUSIONS: The integration of EMTT into the treatment paradigm for bone fractures alters the traditional understanding of recovery timelines and rehabilitation strategies. This case highlights the potential benefits of electromagnetic wave therapy in expediting the healing process and enabling athletes to resume high-level sports activities at an earlier stage.

Differing Approaches to Pain Management for Intrauterine Device Insertion and Maintenance: A Scoping Review.

Intrauterine devices (IUDs) are considered a reliable contraceptive option for women, but they can come with side effects. There is a disconnect in standard guidelines for IUD insertion within and without the U.S. The objective of this review was to address a gap in the literature regarding official procedures for pain management during IUD implantation. This scoping review was initiated using keywords to extract relevant articles from multiple databases: U.S. National Library of Medicine National Institutes of Health (PubMed), MEDLINE (Ovid), and Excerpta Medica dataBASE (EMBASE, Ovid). Initially, 457 articles were identified and after a rigorous screening and selection process, 37 articles were chosen to be further assessed to ascertain if they met the study's inclusion criteria. Those 37 articles were further evaluated fully to check for relevancy. From that process, 19 articles were chosen for the review, and all passed quality assessment evaluations using the JB Appraisal Tools. To best address the research question, the data from the 19 articles were divided into three categories: 1) circumstantial factors, 2) non-pharmacological methods, and 3) pharmacological methods. Circumstantially, women with previous vaginal deliveries experienced the lowest pain during the procedure, and nulligravid (never pregnant) women experienced the most pain. Lower pain scores were reported by lactating women compared to non-lactating. Black women experienced the most anticipated pain compared to other races. Regarding non-pharmacological methods, different insertion techniques, tools, and the use of a cold compress were found to not affect the level of pain during IUD insertion. Lastly, it was shown that pharmacological methods such as lidocaine gel, lidocaine paracervical block, and lidocaine combined with either diclofenac or prilocaine decreased pain scores at different time stamps of the procedure. Also, oral ketorolac and a vaginal combination of misoprostol and dinoprostone helped reduce pain. Findings from this scoping review revealed a lack of uniformity across practices when performing IUD insertions, possibly due to differences in procedures across circumstantial factors, non-pharmacological methods, and pharmacological methods. More research is needed to investigate the intricacies of pain with IUD insertion. Moving forward, especially following a potential increase in the use of IUDs after the reversal of Roe v. Wade, establishing this gap may lead to a more refined standardized protocol to mitigate pain with IUD insertions.

Audit of essential medicine listing and registration status of medicines on standard treatment guidelines in Kenya, Tanzania and Uganda: Case study of malaria, tuberculosis, hypertension and type 2 diabetes mellitus.

Objectives: To determine alignment between national and World Health Organization (WHO) treatment recommendations, medicines prioritisation in country's essential medicines list (EML), and medicines availability in National drug register. Design: An audit of medicines for malaria, tuberculosis, hypertension and type 2 diabetes mellitus listed in the national standard treatment guidelines (STGs) of Kenya, Tanzania and Uganda, as of March 2021, against WHO treatment guidelines, and respective country EML and National drug register. Setting: Not applicable. Participants: None. Main outcome measures: Proportion of medicine in country's STGs that align with WHO treatment recommendations, country's EML and country's drug register. Results: Some disease areas had two sets of treatment guidelines - national STGs and disease-specific treatment guidelines (DSGs) developed at different times with different recommended medicines. Both STGs and DSGs included medicines not recommended by the WHO or not listed on the country EML and drug register. Non-WHO-recommended medicines accounted for 17/68 (25%), 10/57 (18%) and 3/30 (10%) of all STG medicines in Kenya, Tanzania and Uganda, respectively. For tuberculosis, the numbers and proportion of STG medicines listed on the respective national EMLs were 2/6 (33%), 15/19 (79%) and 4/5 (80%) in Kenya, Tanzania and Uganda. All tuberculosis medicines included in Kenya's and Uganda's STGs were registered compared with only 12/19 (63%) tuberculosis medicines in Tanzania's STG. Conclusions: Alignment between treatment guidelines, EMLs and drug registers is crucial for effective national pharmaceutical policy. Research is needed to understand the inclusion of medicines on STGs and DSGs which fall outside WHO treatment guidelines; the non-alignment of some STGs and DSGs, and STGs and DSGs including medicines which are not on country EML and drug register.

GC-CDSS: Personalized gastric cancer treatment recommendations system based on knowledge graph.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in the world, posing a serious threat to human health. Currently, gastric cancer treatment strategies emphasize a multidisciplinary team (MDT) consultation approach. However, there are numerous treatment guidelines and insights from clinical trials. The application of AI-based Clinical Decision Support System (CDSS) in tumor diagnosis and screening is increasing rapidly. OBJECTIVE: The purpose of this study is to (1) summarize the treatment decision process for GC according to the treatment guidelines in China, and then create a knowledge graph (KG) for GC, (2) based on aforementioned KG, built a CDSS and conducted an initial feasibility evaluation for the current system. METHODS: Firstly, we summarized the decision-making process for treatment of GC. Then, we extracted relevant decision nodes and relationships and utilized Neo4j to create the KG. After obtaining the initial node features for building the graph embedding model, graph embedding algorithm, such as Node2Vec and GraphSAGE, were used to construct the GC-CDSS. At last, a retrospective cohort study was used to compare the consistency between GC-CDSS and MDT in treatment decision making. RESULTS: In current study, we introduce a GC-CDSS, which is constructed based on Chinese GC treatment guidelines knowledge graph (KG). In the KG, we define four types of nodes and four types of relationships, and it comprise a total of 207 nodes and 300 relationships. Regarding GC-CDSS, the system is capable of providing dynamic and personalized diagnostic and treatment recommendations based on the patient's condition. Furthermore, a retrospective cohort study is conducted to compare GC-CDSS recommendations with those of the MDT group, the overall consistency rate of treatment recommendations between the auxiliary decision system and MDT team is 92.96%. CONCLUSIONS: We construct a GC treatment support system, GC-CDSS, based on KG. The GC-CDSS may help oncologists make treatment decisions more efficient and promote standardization in primary healthcare settings.

Off-label prescribing of psychotropics in a psychiatric patient population in Australia.

BACKGROUND: This study aimed to investigate the practice of off-label prescribing in both in- and outpatient psychiatry practice. METHODS: One-hundred inpatient and 100 outpatient medical records from adult patients of an Australian psychiatry service from 2020 to 2021 were examined to determine the prevalence of off-label prescribing as defined by Therapeutic Goods Administration (TGA) indications, adherence to Royal Australian and New Zealand College of Psychiatrists (RANZCP) treatment guidelines, frequency of off-label prescription, and the quality of documentation and informed consent process. RESULTS: Most prescribing events in both in- and outpatient settings were either on-label or off-label but consistent with RANZCP guidelines. Patients with a schizoaffective disorder diagnosis or displaying aggression were most likely to receive off-label prescriptions. There was no significant difference between in- and outpatient groups in the quality of documentation or consent process. CONCLUSIONS: In general, off-label prescribing across groups was common, but many decisions were then in line with RANZCP recommendations. That there is a discrepancy between clinical and regulatory bodies has implications for how off-label status is decided.

A Re-audit of the Management of Diabetic Ketoacidosis (DKA): The Importance of the Seven-Day Working Inpatient Diabetes Specialist Nurse Service.

Background Diabetic ketoacidosis (DKA) is a life-threatening metabolic emergency due to insulin deficiency in patients with diabetes mellitus. The United Kingdom national survey and local audits of the management of DKA have revealed several areas of suboptimal care, and room for improvement, necessitating the need for intensified education, updating local guidelines, and increased recruitment of seven-day working inpatient diabetes specialist nurses. Therefore, this project aimed to re-audit our adherence to the DKA treatment guidelines. Methodology A retrospective re-audit examining patient admissions with DKA between October 2022 and September 2023. A list of 18 standards/criteria, adopted from the Joint British Diabetes Society (JBDS) DKA treatment guidelines was used for this re-audit. Results were compared with that of the previous audit. Results We had 126 patients admitted with DKA between October 2022 and September 2023. There were 62 males and 64 females with an average (range) age of 46.5 (19-92) years. Eighty percent had type 1 diabetes, and common precipitating factors for admission included infection and poor adherence to insulin treatment. The median (IQR) length of hospital stay was 2.1 (1.0-5.1) days. Compared to the previous audit, improvements occurred in 11 of 18 standards/criteria. This included timely commencement of intravenous fluids and fixed-rate insulin, commencing glucose infusion to prevent hypoglycemia, potassium replacement, continuation of long-acting insulin during treatment, timely conversion to variable-rate insulin infusion, and conversion to the usual subcutaneous insulin regimen. Additionally, 124 patients (98.4%) were reviewed at least once by the inpatient diabetes specialist nurses (DSN) during their admission. Complications of treatment, namely, iatrogenic hypoglycemia and transient hypokalemia occurred in 13 (10.3%) and 40 (31.7%) patient admissions, respectively. Conclusions This re-audit demonstrated improved adherence to the guidelines during several steps in the management of DKA. It also demonstrated room for improvement regarding other aspects of care. The importance of continued education, accurate documentation, and the presence of seven-day working inpatient DSN cover cannot be overemphasized.

Antifungal Selection for the Treatment of Onychomycosis: Patient Considerations and Outcomes.

Onychomycosis, a common fungal nail infection, affects >20% of adults over age 60 and >50% of people over age 70. Onychomycosis may cause pain, psychosocial problems, and secondary infections, therefore meriting treatment. This review describes the range of treatment modalities, including FDA-approved systemic drugs and topical therapies. Additionally, new and emerging oral and topical therapies are discussed. We emphasize the importance of tailoring onychomycosis therapy to individual patient characteristics, comorbidities, preferences, extent of nail involvement, and fungal species, such that physicians may optimize treatment outcomes, patient satisfaction, and safety.