Treatment Decisions Research Articles

Identification and validation of M2 macrophage-related gene signature as a novel prognostic model for head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous tumor. Commonly used tumor staging don’t sufficiently and accurately assess the prognosis of HNSCC patients, resulting in a lack of guidance for clinical treatment decisions. M2 macrophage infiltration has been shown to be strongly associated with the tumor prognosis. In this study, we used the Cancer Genome Atlas (TCGA) data to screen for genes co-expressed with M2 macrophages in HNSCC. We used univariate Cox regression to screen out the genes associated with HNSCC prognosis, and constructed a HNSCC prognosis model by Lasso regression analysis. The results confirmed that the model had good predictive value and accuracy for the prognosis of HNSCC patients by survival analysis, ROC curve and nomogram. We divided the HNSCC samples into high-risk and low-risk groups according to the risk score, and the results showed that patients in the high-risk group were more prone to genetic mutations and had a higher tumor mutational burden. In addition, there were significant differences between risk groups in terms of immune cell infiltration and drug sensitivity. The HNSCC prognostic model established in this study may provide guidance for clinical therapeutic decision-making and provide a theoretical foundation for the development of new immunotherapy methods.

Expert consensus on the optimal management of BRAFV600E-mutant metastatic colorectal cancer in the Asia-Pacific region.

The burden of colorectal cancer (CRC) is high in the Asia-Pacific region, and several countries in this region have among the highest and/or fastest growing rates of CRC in the world. A significant proportion of patients will present with or develop metastatic CRC (mCRC), and BRAFV600E-mutant mCRC represents a particularly aggressive phenotype that is less responsive to standard chemotherapies. In light of recent therapeutic advances, an Asia-Pacific expert consensus panel was convened to develop evidence-based recommendations for the diagnosis, treatment, and management of patients with BRAFV600E-mutant mCRC. The expert panel comprised nine medical oncologists from Australia, Hong Kong, Singapore, and Taiwan (the authors), who met to review current literature and develop eight consensus statements that describe the optimal management of BRAFV600E-mutant mCRC in the Asia-Pacific region. As agreed by the expert panel, the consensus statements recommend molecular testing at diagnosis to guide individualized treatment decisions, propose optimal treatment pathways according to microsatellite stability status, advocate for more frequent monitoring of BRAFV600E-mutant mCRC, and discuss local treatment strategies for oligometastatic disease. Together, these expert consensus statements are intended to optimize treatment and improve outcomes for patients with BRAFV600E-mutant mCRC in the Asia-Pacific region.

Eliciting medication preferences of patients with type 2 diabetes under different insurance coverages in China

ObjectiveTo understand the medication preference of type 2 diabetes mellitus (T2DM) patients with different insurance coverages, and to provide reference for improving the patient-centered clinical treatment decision.MethodsThis study used Discrete Choice Experiment (DCE) to elicit preferences of T2DM patients with different insurance coverages in China. A multistage stratified cluster-sampling procedure for data collection and a total of 1,409 valid respondent were conducted.ResultsSeven attributes have significant influence on the preference of T2DM patients with Urban Employee Basic Medical Insurance (UEBMI) and Urban and Rural Residents Basic Medical Insurance (URRBMI) (p < 0.05). T2DM patients with UEBMI pay the most attention to Gastrointestinal adverse events, while T2DM patients with URRBMI pay the most attention to the Treatment efficacy/reduction in HbA1c. Patients with different medical insurance have different willingness to pay for Cardiovascular benefits, Mode of administration and Weight change. When Gastrointestinal adverse events is changed from higher (40%) to none (0%), patients with UEBMI are willing to pay ¥523.49 more per month, while patients with URRBMI are only willing to pay ¥266.62; When the Treatment efficacy/reduction in HbA1c changes from poor (0.5%) to Highest (2.5%), patients with UEBMI are willing to pay ¥518.44 more per month, while patients with URRBMI are willing to pay ¥328.33 more per month. The Gastrointestinal adverse events and the Treatment efficacy/reduction in HbA1c are the primary factors for T2DM patients with UEBMI and URRBMI, followed by the Hypoglycemic risk.ConclusionPhysicians should consider patients’ medication preferences in clinical medication treatment of T2DM patients with different insurance coverages, make targeted treatment decisions, and improve patients’ medication compliance to achieve better treatment results.

Patients with Diabetes Mellitus and Comorbid Mental Disorders - Is there a Psychotherapeutic Undertreatment? - Results of the DiMPS Study

Diabetes mellitus is associated with an increased likelihood of mental disorders, especially depression. Despite a frequently postulated underprovision, the actual need for psychotherapeutic treatment in this patient group has hardly been investigated. The aim of this study is to analyze the care situation of diabetes patients with mental comorbidities in Germany. 240 consecutively treated patients with type 1 or type 2 diabetes were examined cross-sectionally and longitudinally in a tertiary diabetological center. After a screening and diagnostic examination, 94 patients with comorbid mental disorders were included in the study. Patients then decided on the treatment of their mental disorder according to a standardized shared decision-making process. At the 6-month follow-up, 77 of the 94 patients (81.9%) provided information about the realization of their treatment decision and the obstacles they encountered. 39.2% of patients with diabetes had a mental disorder. Of these, 44.2% were already receiving psychotherapy or medication. After six months, 46.8% were able to implement their treatment decision. Only 7.1% did not receive any treatment despite their efforts. The 6-month follow-up showed a significant reduction in diabetes-related distress (PAID; p<0.05) and an increase in psychological well-being in all subgroups, regardless of treatment initiation (WHO-5; p<0.05). Contrary to the widespread notion of a lack of access to psychotherapy for people with diabetes and mental disorders in Germany, this assumption could not be confirmed in this study. Equating the frequency of mental disorders with the need for psychotherapeutic and/or psychopharmacological treatment without considering the specific treatment needs and preferences of patients may lead to an overestimation of the need for care.

Frameshift mutations in the mmpR5 gene can have a bedaquiline-susceptible phenotype by retaining a protein structure and function similar to wild-type Mycobacterium tuberculosis.

Bedaquiline (BDQ) is crucial for the treatment of rifampicin-resistant tuberculosis, yet resistance threatens its effectiveness, mainly linked to mutations in the mmpR5 (Rv0678) gene. While frameshift mutations are thought to produce non-functional proteins, we hypothesize that they can result in conserved proteins through late-stop codons or alternative reading frames and remain BDQ susceptible. We extracted 512 isolates harboring frameshift mutations in mmpR5 from the World Health Organization (WHO) catalog and 68 isolates with minimum inhibitory concentration (MIC) in mycobacterial growth indicator tube (MGIT) through a literature review. Using BioPython and AlphaFold2 we computed open (ORF) and alternative reading frames (ARFs) sequences and protein structures and assessed similarity to the wild type using an alignment and template modeling (TM)-score. Among the WHO 512 isolates, 24.8% were BDQ-sensitive. Out of 184 unique frameshift mutations with available nucleotide information, a late-stop codon in the ORF occurred for 32% of the mutations. Also, 40.7% resulted in a conserved sequence, through the ORF or one of the forward ARFs. In 68 isolates with available MGIT MIC data, the presence of late-stop codons in the ORF (OR 4.71, 95% CI 1.36-19.3) or a conserved reading frame (OR 10.4, 95% CI 2.07-102.9) were associated with BDQ sensitivity. Protein structures from the conserved sequences showed high similarity (TM > 0.8). We show that frameshift mutations may retain BDQ susceptibility through late-stop codons in the ORF or conserved ARFs. These findings could improve the prediction of the BDQ phenotype from genomic data and have important implications for treatment decisions. Research Foundation-Flanders, Academy of Medical Sciences, the Wellcome Trust, the Government Department of Business, Energy and Industrial Strategy, the British Heart Foundation and Diabetes UK, and the Global Challenges Research Fund.IMPORTANCETuberculosis (TB), caused by Mycobacterium tuberculosis, remains the deadliest infectious disease and is particularly challenging to treat when it becomes drug-resistant. Bedaquiline (BDQ) is a recently recommended core drug for treating drug-resistant TB. However, resistance to bedaquiline is already emerging, primarily due to mutations in the mmpR5 gene. Identifying which mutations cause resistance and which do not is a critical knowledge gap. In particular, little is known about the effect of frameshift mutations, typically thought to make TB bacteria resistant to bedaquiline by producing non-functional proteins. Yet, one-quarter of isolates with a frameshift mutation are still susceptible to bedaquiline. How the bacteria produce a functional protein despite the frameshift mutation is unknown. We analyzed over 500 frameshift mutations using computational methods to model their effects on protein structure and bedaquiline resistance. Our findings revealed that some frameshift mutations can still produce functional proteins, allowing bacteria to remain sensitive to bedaquiline. Specifically, bacteria can produce a functional protein despite frameshift mutations if the mutation occurs near the end of the protein or if an alternative reading frame is available. These insights improve our ability to interpret mutations associated with bedaquiline, the most important drug for drug-resistant TB, allowing more accurate and effective treatment decisions.

Clinicopathological characteristics and outcomes of patients with unexplained renal impairment: a single center study

Background: Chronic kidney disease (CKD) is a growing health problem. About 20% of CKD patients have undetermined causes. Data describing histopathological patterns of unexplained impaired kidney functions in Egypt are lacking. We aimed to identify the clinicopathological characteristics and short-term outcomes of adult cases with unexplained impaired kidney functions.Methods: We conducted a prospective study in Assiut University Hospital from August 2018 to May 2022. It included patients with unexplained elevated serum creatinine (serum creatinine > 115 µmol/L) who underwent renal biopsies. Descriptive statistics were used to summarize data on patient demographics, histopathological patterns, and outcomes after three months. Clinical trial registration number: NCT03586531.Results: Overall, 210 native renal biopsies were included in the analysis. Glomerular diseases were the most common pathological finding (n=88, 44.9 %), amyloidosis and FSGS were the most prevalent glomerular pathology (15.2%, 14.3%, respectively). Chronic kidney disease of unknown etiology (CKDu) was diagnosed in 8.1% of the cases; histology suggestive of genetic origin was found in 2.5%, and LECT amyloidosis was found in 3.8% of the cases. Poor outcomes were observed in 43.6% of the patients i.e., renal replacement therapy or death. Treatment strategies were changed based on the biopsy findings in 86 patients (40%).Conclusion: Amyloidosis and FSGS were the most common causes of unexplained renal impairment. CKDu is not uncommon in Egypt, and more preventive measures are needed. This study supports the irreplaceable role of renal biopsy in disease diagnosis, treatment decisions, and predicting prognosis even in advanced stages.

Genome sequencing in the management of myelodysplastic syndromes and related disorders.

Myeloid neoplasms originate from the clonal proliferation of hematopoietic stem cells, which is driven by the acquisition of somatic genetic mutations. Within these disorders, myelodysplastic syndromes (MDS) are specifically characterized by morphologic abnormalities (dysplasia) and impaired maturation of myeloid precursors (ineffective hematopoiesis), resulting in peripheral blood cytopenia. Several studies have advanced the field of MDS, with a few landmark papers leading to a paradigm shift, opening new avenues of research and enabling a molecular revolution. These seminal papers include the first description of the 5q- syndrome, the identification of somatic mutations of TET2 in myeloid neoplasms, the detection of common pathway mutations in the splicing machinery, and the discovery of clonal hematopoiesis. The somatic genomic landscape of MDS is now well-defined. Genes that are recurrently mutated include epigenetic regulators, as well as genes of RNA splicing machinery, transcription regulation, DNA repair control, cohesin complex, and signal transduction. Furthermore, several disorders with a germline genetic predisposition to MDS have been identified, collectively accounting for up to 15% of all MDS cases. Genomic profiling can significantly improve the diagnostic approach to MDS, allowing the identification of distinct nosologic entities such as SF3B1-mutant or TP53-mutant MDS. The Molecular International Prognostic Scoring System for MDS (IPSS-M) has already proven to be a valuable tool for individualized risk assessment and treatment decisions. In addition, the recently developed molecular taxonomy of MDS will likely facilitate the implementation of precision medicine approaches for these disorders. This will necessitate the establishment of specialized infrastructures within public health systems, involving close collaboration between healthcare institutions, academia, and the life sciences industry.

Neurosurgical patients' preferences and experiences of involvement during hospitalisation.

There has been an increased focus on patient involvement in health care worldwide, with studies showing that involving patients in their treatment and care is associated with positive outcomes. However, there is a dearth of knowledge about inpatient preferences and experiences of involvement in neurosurgery in Scandinavian countries. This study aimed to identify inpatients' preferences regarding their involvement in their treatment and the extent to which they experienced being involved in their treatment and care during admission. A questionnaire survey was administered in a neurosurgical department. Patients' preferences and experiences regarding their involvement in their treatment and care were assessed using a validated questionnaire. One hundred patients were enrolled in the study. Eighty-two percent of them preferred sharing responsibility for their treatment with their doctor, 16% preferred leaving their treatment decisions entirely up to the doctor; and two percent preferred making the final decision about their treatment independently. The average participation score for information, communication, and participation was 4.08, suggesting that the patients experienced a high level of involvement in their care and treatment. Thirty patients reported preferences for changes during admission, while 25 suggested ideas for improvement. The patients mostly preferred shared decision-making about their treatment during hospitalization and generally reported high involvement in their treatment and care. The results showed a desire for improved information sharing and dialog among healthcare professionals, patients, and relatives.

Shared decision-making for patients with vaccine-related concerns of blood transfusion: A single institution experience.

Some patients express concerns regarding receipt of allogeneic blood transfusions from donors potentially vaccinated against SARS-CoV-2 (COVID-19). However, limited information exists about patients' expression of these concerns or how to address them during the blood transfusion consent process. In this study, we describe our experience of working collaboratively with patients with vaccine-related transfusion concerns prior to elective surgery, summarizing treatment decisions and clinical outcomes. This observational descriptive study includes patients seen in our Bloodless Medicine and Surgery clinic between June 2022 and June 2024 for vaccine-related transfusion concerns prior to elective surgery. A shared decision-making framework was employed to foster conversation, share information, provide reassurance, reconcile conflict, and match preferences with available care options. Patient characteristics, treatment decisions, and surgical outcomes were reviewed and summarized. Thirty-five patients were included, with median (1st, 3rd quartile) age of 61 (53, 69) years. Cardiac surgery was the most common type of surgery (29%). Twelve patients (34%) were anemic preoperatively, and all received preoperative treatment. After discussion with a Bloodless Medicine specialist, 24 (68.6%) decided to consent to the use of all blood products, 5 (14.3%) accepted only red blood cells, and 6 (17.1%) declined all blood products. Among 28 patients undergoing surgery, only 4 (14%) received allogeneic transfusion perioperatively. Many patients concerned about the vaccination status of blood donors may ultimately consent to allogeneic blood products after shared decision-making with a Bloodless Medicine specialist, highlighting the importance of patient empowerment and collaborative care.

HBV biomarkers and their role in guiding treatment decisions.

Over 300 million individuals worldwide are chronically infected with Hepatitis B Virus and at risk for progressive liver disease. Due to the lack of a therapy that reliably achieves viral elimination and the variability of liver disease progression, treatment decisions are guided by the degree of liver disease and viral biomarkers as the viral life-cycle is well characterised and largely conserved between individuals. In contrast, the immunological landscape is much more heterogenous and diverse and the measurement of its components is less well standardized. Due to the lack of a universal and easily measurable set of biomarkers, clinical practice guidelines remain controversial, aiming for a balance between simplifying treatment decisions by reducing biomarker requirements and using all available biomarkers to avoid overtreatment of patients with low risk for disease progression. While approved therapies such as nucleos(t)ide analogues improve patient outcomes, the inability to achieve complete cure highlights the need for novel therapies. Since no treatment candidate has demonstrated universal efficacy, biomarkers will remain important for treatment stratification. Here, we summarize the current knowledge on virological and immunological biomarkers with a specific focus on how they might be beneficial in guiding treatment decisions in chronic Hepatitis B.

Diversity of Campylobacter spp. circulating in a rhesus macaque (Macaca mulatta) breeding colony using culture and molecular methods.

Gastrointestinal disease is one of the most common reasons for hospitalization in non-human primate colonies and accounts for over one-third of non-research related euthanasia. In rhesus macaques, this manifests as both acute diarrhea and chronic enterocolitis (CE), a syndrome of chronic diarrhea resulting in poor weight gain or weight loss which is minimally responsive to treatment. Campylobacter spp. are major causes of acute enterocolitis in rhesus macaques and may predispose individuals to the development of CE, similar to post-infectious irritable bowel syndrome in humans. Despite these concerns, there are few studies characterizing Campylobacter in rhesus macaque colonies, in particular utilizing whole genome sequencing and assessing findings with respect to the health status of the host. Our findings provide insight into Campylobacter strains circulating in rhesus macaque colonies, which can improve clinical monitoring, assist in treatment decisions, and provide new avenues of investigation into campylobacteriosis as a catalyst for CE.

Attitudes and awareness in autonomous decision on medical treatment or inclusion in clinical trials amongst Slovenian adolescents: an online survey

BackgroundIn Europe and elsewhere in the world, activities are taking place to improve the awareness of children and adolescents (hereinafter: adolescents) regarding their rights and obligations in autonomous decision-making about their own medical treatment and participation in clinical research.MethodsThe cross-sectional survey of adolescents was carried out using an anonymous online questionnaire. We obtained consent from the Commission of the Republic of Slovenia for Medical Ethics. Participating young people were invited through the network of primary and secondary schools, the Society of Dystrophy of Slovenia and through the dissemination of electronic messages. The online questionnaire was open from April 25 to May 6, 2023. Young people aged 13 to 20 joined the survey. The association between several factors and awareness of the minimum age limit was tested by univariate logistic regression. All statistical testing was performed at a significance level of 0.05.ResultsThe responses of 458 respondents were analysed, of which 281 were male. Only 8.3% of participating adolescents knew the age limit set by law for autonomous decision-making about medical treatment at 15 years old. Most answered that a medical institution should inform them about their rights (62.4%). Only 5.02% responded that they do not need their parents’ consent when making decisions; 2.6% of respondents answered that they autonomously decided to undergo treatment without their parents’ knowledge. The majority obtained information about treatment from a doctor (more than 70%); 42.8% were in favour of new forms of treatment, especially chronic patients (more than 70%); 44.8% had already heard about clinical research, most of them through the media (55.4%); 70% of the respondents answered correctly about making an autonomous decision about participation in research at the age of 18. About three-quarters (75.6%) of respondents who had heard of clinical research believe that an individual should be paid for participating.ConclusionsOur research showed insufficient awareness of the age limit of adolescents regarding medical treatment decisions and clinical research. The prevailing view is that health professionals should inform young people more about their rights. Most adolescents believe they should be paid to participate in clinical research.

Rare Head and Neck Cancers and Pathological Diagnosis Challenges: A Comprehensive Literature Review

Head and neck cancers (HNCs) arise from anatomically adjacent sites and subsites, with varying etiological factors, diagnostic strategies, prognoses, and treatment approaches. While conventional squamous cell carcinoma (SCC) is the most common histology in the head and neck district, HNCs encompass a variety of rare histopathological entities, categorized into epithelial tumors such as salivary gland cancers, sinonasal tumors, neuroendocrine tumors, malignant odontogenic tumors, and SCC variants versus non-epithelial tumors including soft tissue sarcomas, mucosal melanomas, and hematological malignancies. Rare HNCs (R-HNCs) represent a diagnostic and clinical challenge, requiring histopathological expertise, the availability of peculiar molecular analysis, and the personalization of local and systemic treatments, all guided by a multidisciplinary tumor board. Here, we provide a comprehensive literature review on R-HNCs, emphasizing key histopathological and molecular characteristics that are crucial for guiding treatment decisions. An insight about the latest developments in systemic treatments is also reported.

Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement.

The use and misuse of opioids are a growing global problem. Although the effects of these drugs on the human endocrine system have been studied for decades, attention on their related clinical consequences, particularly on the hypothalamic-pituitary system and bone health, has intensified over recent years. This Statement appraises research data related to the impact of opioids on the gonadal and adrenal function. Whereas hypogonadism is well recognized as a side effect of opioids, the significance of their inhibitory actions on the hypothalamic-pituitary-adrenal system and the occurrence of clinically relevant adrenal insufficiency is not fully elucidated. The often-inconsistent results of studies investigating how opioids affect the secretion of GH, prolactin, arginine vasopressin, and oxytocin are assessed. The accumulating evidence of opioid actions on bone metabolism and their negative sequelae on bone mineral density and risk of fracture are also reviewed. In each section, available data on diagnostic and management approaches for opioid endocrine sequelae are described. This Statement highlights a plethora of gaps in research associated with the effects and clinical consequences of opioids on the endocrine system. It is anticipated that addressing these gaps will improve the care of people using or misusing opioids worldwide. The Statement is not intended to serve as a guideline or dictate treatment decisions.

Consensus on drivers of maintenance treatment choice and patterns of care in advanced ovarian cancer

ObjectivesMaintenance therapies, including poly (ADP-ribose) polymerase (PARP) inhibitors and/or bevacizumab, have substantially improved the prognosis of patients with advanced ovarian cancer. Owing to the variability in treatment strategies across Europe,...

Treatment sequencing in gastroenteropancreatic neuroendocrine tumors

SummaryThe oncological treatment of neuroendocrine tumors (NET) has improved significantly in the last few years. Several informative clinical studies on NET have been conducted recently and updated NET guidelines have been published by the European Neuroendocrine Tumor Society (ENETS) in 2023 and 2024. With the growing number of positive phase III trials in NET, the main difficulty today is selecting the most appropriate treatment for a patient at the right time. The purpose of this short review is to delineate the main concepts and important changes in the therapy sequences for gastroenteropancreatic NET (gepNET) outlined in current European guidelines. In clinical practice, more individualized treatment decisions are often required that go beyond these general recommendations.

Optimizing lung cancer surgery in the elderly: sublobar resection versus lobectomy for early-stage non-small cell lung cancer patients aged 80 and above

The optimal surgical approach for elderly patients with early-stage non-small cell lung cancer (NSCLC) remains a topic of debate. A retrospective analysis was conducted on patients who underwent pulmonary resection for early-stage NSCLC at our single institution between January 2018 and December 2022. Propensity score matching was used to balance baseline characteristics between the sublobar resection and lobectomy groups. Perioperative outcomes, pulmonary function recovery, postoperative quality of life, and survival were compared between the two groups. A total of 151 patients were included, with 42 undergoing sublobar resection and 109 undergoing lobectomy. After propensity score matching, baseline characteristics were well-balanced between the two groups. Sublobar resection was associated with shorter operative time (125.83 ± 33.56 min vs. 161.14 ± 61.54 min, p = 0.048), less intraoperative blood loss [65 (30, 75) ml vs. 120 (70, 170) ml, p < 0.001], shorter drainage duration [3 (2, 5) days vs. 5 (3, 6) days, p < 0.001], shorter hospital stay [6 (4, 8) days vs. 10 (7, 13) days, p < 0.001], and fewer postoperative complications (11.9% vs. 47.6%, p < 0.001), compared to lobectomy. Moreover, sublobar resection led to better pulmonary function recovery and higher postoperative quality of life scores, with no significant difference in overall and disease-free survival between the groups. Sublobar resection in patients aged 80 and above with early-stage NSCLC offered comparable oncological outcomes to lobectomy while preserving more lung function and providing better postoperative recovery and long-term quality of life. These findings have important implications for treatment decision-making in elderly NSCLC patients.

Guiding treatment decisions in renal cell carcinoma: the role of biomarkers and clinical factors.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for metastatic renal cell carcinoma (mRCC), significantly improving overall survival and achieving durable responses. This review is timely due to the increasing number of ICI-based regimens now considered standard care for RCC. There is an urgent need to identify reliable biomarkers that can predict therapeutic responses and resistance, a key challenge in current research. While tumor-specific factors such as pathological characteristics, genomic mutations, and transcriptional profiles have been extensively studied, no definitive predictive biomarker has yet emerged. Additionally, advanced technologies are being explored to address tumor heterogeneity. Recent research has focused on novel areas such as the microbiome, radiomics, and spatial transcriptomics, which show promise as potential biomarkers. The translation of these emerging biomarker findings into clinical practice is essential to improving personalized treatment strategies for RCC. Until reliable biomarkers are clinically available, clinical factors may play a pivotal role in guiding individualized treatment decisions to optimize patient outcomes.

The potential promise and pitfalls of point-of-care viral load monitoring to expedite HIV treatment decision-making in rural Uganda: a qualitative study

BackgroundHIV treatment programs in Africa have implemented centralized testing for routine viral load monitoring (VLM), which may result in specimen processing delays inhibiting timely return of viral load results. Decentralized, point-of-care (PoC) VLM is a promising tool for expediting HIV clinical decision-making but remains unavailable in most African settings. We qualitatively explored the perceived feasibility and appropriateness of PoC VLM to address gaps along the viral load monitoring continuum in rural Uganda.MethodsBetween May and September 2022, we conducted 15 in-depth interviews with HIV clinicians (facility in-charges, clinical officers, nurses, counselors) and six focus group discussions with 47 peer health workers from three south-central Ugandan districts. Topics explored centralized VLM implementation and opportunities/challenges to optimizing routine VLM implementation with PoC testing platforms. We explored perspectives on PoC VLM suitability and feasibility using iterative thematic analysis. Applying the Framework Method, we then mapped salient constraints and enablers of PoC VLM to constructs from the Consolidated Framework for Implementation Research.ResultsClinicians and peers alike emphasized centralized viral load monitoring’s resource-intensiveness and susceptibility to procedural/infrastructural bottlenecks (e.g., supply stockouts, testing backlogs, community tracing of clients with delayed VLM results), inhibiting timely clinical decision-making. Participants reacted enthusiastically to the prospect of PoC VLM, anticipating accelerated turnarounds in specimen processing, shorter and/or fewer client encounters with treatment services, and streamlined efficiencies in HIV care provision (including expedited VLM-driven clinical decision-making). Anticipated constraints to PoC VLM implementation included human resource requirements for processing large quantities of specimens (especially when machinery require repair), procurement and maintenance costs, training needs in the existing health workforce for operating point-of-care technology, and insufficient space in lower-tier health facilities to accommodate installation of new laboratory equipment.ConclusionsAnticipated implementation challenges, primarily clustering around resource requirements, did not diminish enthusiasm for PoC VLM monitoring among rural Ugandan clinicians and peer health workers, who perceived PoC platforms as potential solutions to existing inefficiencies within the centralized VLM ecosystem. Prioritizing PoC VLM rollout in facilities with available resources for optimal implementation (e.g., adequate physical and fiscal infrastructure, capacity to manage high specimen volumes) could help overcome anticipated barriers to decentralizing viral load monitoring.

Early use of long-acting injectable antipsychotics in bipolar disorder type I: An expert consensus.

Long-acting injectable antipsychotics (LAIs) are not routinely offered to patients living with bipolar disorder type I (BP-I), despite widespread evidence that supports their benefits over oral antipsychotics, particularly in early disease. A round-table meeting of psychiatrists convened to discuss barriers and opportunities and provide consensus recommendations around the early use of LAIs for BP-I. LAIs are rarely prescribed to treat BP-I unless a patient has severe symptoms, sub-optimal adherence to oral antipsychotics, or has experienced multiple relapses. Beyond country-specific accessibility issues (e.g., healthcare infrastructure and availability/approval status), primary barriers to the effective use of LAIs were identified as attitudinal and knowledge/experience-based. Direct discussions between healthcare providers and patients about treatment preferences may not occur due to a preconceived notion that patients prefer oral antipsychotics. Moreover, as LAIs have historically been limited to the treatment of schizophrenia and the most severe cases of BP-I, healthcare providers might be unaware of the benefits LAIs provide in the overall management of BP-I. Improved treatment adherence associated with LAIs compared to oral antipsychotics may support improved outcomes for patients (e.g., reduced relapse and hospitalization). Involvement of all stakeholders (healthcare providers, patients, and their supporters) participating in the patient journey is critical in early and shared decision-making processes. Clinical and database studies could potentially bridge knowledge gaps to facilitate acceptance of LAIs. This review discusses the benefits of LAIs in the management of BP-I and identifies barriers to use, while providing expert consensus recommendations for potential solutions to support informed treatment decision-making.