A Case of 'Neptune's Fix Elixir': The Dangerous Consequences of Unregulated Use of Tianeptine in Over-the-Counter Products.

Tianeptine is an atypical tricyclic antidepressant approved for the treatment of major depressive disorder in some European, Asian, and Latin countries. Along with its serotonergic properties, tianeptine also acts as a full agonist at the mu-opioid receptor, creating sensations of euphoric highs and significant risks of addiction and withdrawal. For this reason, along with increased reports of adverse effects and fatalities, tianeptine has not been approved in the US. Despite this, tianeptine continues to be accessible through unregulated online stores and small retailers under street names such as Zaza, Tia, Tianna, 'gas-station dope', and a product not mentioned in the literature previously: Neptune's Fix Elixir. In this report, we discuss the case of a 34-year-old male who presented to the ED via EMS after being found unresponsive secondary to the ingestion of Neptune's Fix Elixir, whose main active ingredient is tianeptine.

Ayurvedic Herbal Medicines: A Literature Review of Their Applications in Female Reproductive Health.

Ayurveda, an ancient holistic and personalized healing system originating from the Indian subcontinent, has been gaining increasing attention as a complementary and alternative medical practice for treating various health conditions, including those related to women's reproductive well-being. This comprehensive literature review examines a wide array of experimental and clinical studies exploring the diverse facets of Ayurvedic interventions in addressing issues such as menstrual irregularities, polycystic ovary syndrome (PCOS), infertility, and menopausal symptoms. The paper specifically focuses on discussing the available data regarding the efficacy of Tulsi (Ocimum tenuiflorum), ashwagandha (Withania somnifera), ginger (Zingiber officinale), cardamom (Elettaria cardamomum), turmeric (Curcuma longa), and Shatavari (Asparagus racemosus), which have traditionally been used in Ayurvedic medicine for centuries. The synthesis of literature not only highlights the potential benefits of these Ayurvedic interventions, but also critically assesses the methodological rigor of existing studies, identifying research gaps, and proposing directions for future investigations. While acknowledging the need for further rigorous research and clinical trials, the review emphasizes the benefits of collaborative and integrative healthcare. This review aims to serve as a valuable resource for healthcare practitioners, researchers, and individuals seeking holistic and natural alternatives for female reproductive health management.

Development of the Emirates Multi-Criteria Decision Analysis Tool for Orphan Drugs.

Background The number of orphan drug approvals is currently increasing globally. This creates a significant burden on payers and healthcare systems. This study aimed to create a multi-criteria decision analysis (MCDA) tool for evaluating orphan drugs within the United Arab Emirates (UAE). The intended result of the tool is to provide evidence-based guidance to decision-makers in reimbursement and procurement decisions. Methods We conducted a literature search and local expert interviews to identify relevant preliminary criteria for the MCDA tool. Then we conducted a structured consensus-building session for healthcare experts and decision-makers in the UAE to develop the Emirati MCDA tool for orphan drugs. The experts voted for the criteria to be included in the tool and their ranking according to importance, as well as the weight of each criterion and its scoring function. To improve understanding and facilitate the voting process, experts were provided with a brief illustration of similar tools conducted in other countries before the voting sessions. Finally, the tool was developed in a Microsoft Excel sheet (Microsoft Corporation, Redmond, Washington, United States), and it was validated and tested based on real case studies, then it was fine-tuned accordingly based on the experts' discussions. The final tool was provided to the attendees to guide their decisions in the reimbursement and procurement of orphan drugs. Results The created tool provides a score for each analyzed orphan drug based on its value. Ten criteria were included in the final MCDA tool. These were cost-effectiveness (25.1% of the weight), magnitude of health gain (20.1%), availability of therapeutic alternative (14.3%), disease severity (11%), budget impact (7.9%), disease rarity (5.6%), strength of clinical evidence (5.6%), burden on households (4.5%), indication uniqueness (3.2%), and patients' age (2.6%). Conclusions Implementation of evidence-based healthcare necessitates assessing the fair value of each health technology. Addressing the high unmet medical needs and improving healthcare for patients with rare diseases are priorities within the UAE. The created Emirates MCDA tool for orphan drugs has the potential to help decision-makers implement value-based and evidence-based reimbursement decisions for orphan drugs.

Plasmodium falciparum Alba6 exhibits DNase activity and participates in stress response.

Alba domain proteins, owing to their functional plasticity, play a significant role in organisms. Here, we report an intrinsic DNase activity of PfAlba6 from Plasmodium falciparum, an etiological agent responsible for human malignant malaria. We identified that tyrosine28 plays a critical role in the Mg2+ driven 5'-3' DNase activity of PfAlba6. PfAlba6 cleaves both dsDNA as well as ssDNA. We also characterized PfAlba6-DNA interaction and observed concentration-dependent oligomerization in the presence of DNA, which is evident from size exclusion chromatography and single molecule AFM-imaging. PfAlba6 mRNA expression level is up-regulated several folds following heat stress and treatment with artemisinin, indicating a possible role in stress response. PfAlba6 has no human orthologs and is expressed in all intra-erythrocytic stages; thus, this protein can potentially be a new anti-malarial drug target.

Real-world effectiveness of a single conventional disease-modifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study.

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). Conclusion: In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Microbiological Evaluation of Herbal Extracts against Candida albicans in Early Childhood Caries Patients: An In Vitro Study.

Purpose: The current literature proposes a probable role of Candida albicans (C. albicans) in its etiopathogenesis in early childhood caries (ECC). This study aimed to isolate C. albicans species in children with and without ECC and compare the antifungal efficacy of neem, miswak, cinnamon, clove, stevia, and ketoconazole. This study also aimed to assess and compare salivary pH in children with and without ECC. Materials and methods: A total of 60 children were included in the study, who were divided into two groups-group I (children with ECC) and group II (children without ECC). Plaque samples were collected and streaked on Sabouraud dextrose agar (SDA). C. albicans isolates were evaluated, and their susceptibility to herbal agents was tested and compared. Saliva samples were collected, and salivary pH was tested and compared. Results: The presence of C. albicans was significantly higher in group I (76.7%) as compared to group II (23.3%). The mean zone of inhibition for neem was 4.9 mm, whereas, for miswak, it was 4.5 mm; for cinnamon, 9.3 mm; for clove, 3.8 mm; for stevia, 10.9 mm; and for ketoconazole it was 21.09 mm. The mean salivary pH for group I was 6.7, and that for group II was 7.3. Conclusion: Candida albicans (C. albicans) carriage in children with ECC was significantly higher than in children without ECC. All herbal agents showed significant antifungal activity, with stevia showing the highest activity. The average salivary pH of children without ECC was slightly higher than that of children with ECC. How to cite this article: Siddaiah SB, Sinha S, BR A. Microbiological Evaluation of Herbal Extracts against Candida albicans in Early Childhood Caries Patients: An In Vitro Study. Int J Clin Pediatr Dent 2024;17(1):26-30.

Epidemiology of first- and second-line drugs-resistant pulmonary tuberculosis in Iran: Systematic review and meta-analysis.

Drug resistance among Mycobacterium tuberculosis (MTB) strains is a growing concern in developing countries. We conducted a comprehensive search for relevant studies in Iran on PubMed, Scopus, and Embase until June 12, 2020. Our study focused on determining the prevalence of antibiotic resistance in MTB isolates, with subgroup analyses based on year, location, and drug susceptibility testing (DST) methods. Statistical analyses were performed using STATA software. Our meta-analysis included a total of 47 articles. Among new TB cases, we found the following prevalence rates: Any-resistance to first-line drugs: 31 % (95 % CI, 24-38), mono-drug resistance: 15 % (95 % CI, 10-22), and multidrug resistance to first-line drugs: 6 % (95 % CI, 4-8). There was a significant variation in the rate of MDR among new TB cases based on the year of publication, location, and DST methods (P < 0.0001). We observed substantial variability in multidrug-resistant TB rates among new cases across the studies. Stratified analyses revealed that publication years and DST methods significantly affected resistance rates. Studies from southern and central Iran reported higher any-drug resistance rates, suggesting regional differences. Among retreatment cases, the prevalence rates were as follows: Any resistance: 68 % (95 % CI 58-78), mono-resistance: 19 % (95 % CI 7-34), multidrug resistance: 28 % (95 % CI 15-43). Our study revealed that the prevalence of drug-resistant TB (DR-TB) among TB cases in Iran is higher than the global average. Particularly, MDR-TB among retreatment TB cases is a significant public health issue.

Isolated Bilateral Upper Limb Amelia - A Rare Case Report.

Introduction: Congenital upper limb amelia is one of the extremely rare conditions. It is defined as a complete absence of upper limbs. It may present as isolated or with other associated anomalies. Case Report: We present a case of a 2-year-old male child with congenital complete absence of bilateral upper limb. This male child was born after four female children. With the advancement in modern-era prenatal diagnostic facilities and a better understanding of fetal-maternal drug pharmacology, such cases are rare entity. Conclusion: Amelia is a very rare and challenging situation for clinicians. Regular prenatal checkup and knowledge of maternal and fetal drug interactions during pregnancy are key factors for prevention.

Targeted therapy of kidney disease with nanoparticle drug delivery materials.

With the development of nanomedicine, nanomaterials have been widely used, offering specific drug delivery to target sites, minimal side effects, and significant therapeutic effects. The kidneys have filtration and reabsorption functions, with various potential target cell types and a complex structural environment, making the strategies for kidney function protection and recovery after injury complex. This also lays the foundation for the application of nanomedicine in kidney diseases. Currently, evidence in preclinical and clinical settings supports the feasibility of targeted therapy for kidney diseases using drug delivery based on nanomaterials. The prerequisite for nanomedicine in treating kidney diseases is the use of carriers with good biocompatibility, including nanoparticles, hydrogels, liposomes, micelles, dendrimer polymers, adenoviruses, lysozymes, and elastin-like polypeptides. These carriers have precise renal uptake, longer half-life, and targeted organ distribution, protecting and improving the efficacy of the drugs they carry. Additionally, attention should also be paid to the toxicity and solubility of the carriers. While the carriers mentioned above have been used in preclinical studies for targeted therapy of kidney diseases both in vivo and in vitro, extensive clinical trials are still needed to ensure the short-term and long-term effects of nano drugs in the human body. This review will discuss the advantages and limitations of nanoscale drug carrier materials in treating kidney diseases, provide a more comprehensive catalog of nanocarrier materials, and offer prospects for their drug-loading efficacy and clinical applications.

How new nanotechnologies are changing the opioid analysis scenery? A comparison with classical analytical methods.

Opioids such as heroin, fentanyl, raw opium, and morphine have become a serious threat to the world population in the recent past, due to their increasing use and abuse. The detection of these drugs in biological samples is usually carried out by spectroscopic and/or chromatographic techniques, but the need for quick, sensitive, selective, and low-cost new analytical tools has pushed the development of new methods based on selective nanosensors, able to meet these requirements. Modern sensors, which utilize "next-generation" technologies like nanotechnology, have revolutionized drug detection methods, due to easiness of use, their low cost, and their high sensitivity and reliability, allowing the detection of opioids at trace levels in raw, pharmaceutical, and biological samples (e.g. blood, urine, saliva, and other biological fluids). The peculiar characteristics of these sensors not only have allowed on-site analyses (in the field, at the crime scene, etc.) but also they are nowadays replacing the gold standard analytical methods in the laboratory, even if a proper method validation is still required. This paper reviews advances in the field of nanotechnology and nanosensors for the detection of commonly abused opioids both prescribed (i.e. codeine and morphine) and illegal narcotics (i.e. heroin and fentanyl analogues).

Effectiveness of methotrexate and leflunomide as corticoid-sparing drugs in patients with polymyalgia rheumatica.

Objectives: The need for glucocorticoid-sparing drugs (GCSD) remains an important issue and is an unmet need in the treatment of polymyalgia rheumatica (PMR). We therefore aimed to assess the effectiveness and safety of methotrexate (MTX) and of leflunomide (LEF) in daily clinical practice in PMR patients from Argentina. Methods: A multicentre and observational study (medical records review) of PMR patients seen between 2007 and 2023, who had at least three months of follow-up after starting a GCSD, either MTX or LEF, was performed. Results are expressed as medians and interquartile ranges [25th-75th (IQR)] for continuous variables and percentages for categorical ones. The two treatment groups were compared using χ2 test for categorical variables, Mann-Whitney U test for continuous variables and the log-rank test for time-to-event data. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. In all cases, a p-value <0.05 was considered statistically significant. Results: One-hundred and eighty-six patients (79% female) with a median age of 72 years (IQR, 65-77 years) were included. One-hundred and forty-three patients (77%) were prescribed MTX (15, IQR 10-15) and 43 (23%) LEF (20 mg, fixed dose). Flare-ups (relapses and recurrences) occurred in 13 patients (7%) and were comparable between both groups. Persistent GCSD intake was observed in 145 patients (78%). Glucocorticoid (GC) withdrawal was achieved in 67 of these 145 patients (46%) and this occurred more frequently in the LEF group (P = 0.001). Furthermore, time until prednisone discontinuation was shorter in the LEF-treated patients (4.7 months, IQR 3-20 on LEF versus 31.8 months, IQR 10-82 on MTX, P = 0.000). Remission was found more frequently in the LEF group (P = 0.003). In the multivariate analysis, the probability of remission was higher with LEF therapy (P = 0.010) and this finding persisted in the subgroup analysis who were followed up < 40 months (OR 3.12, 95% CI = 1.30-7.47, P = 0.011). Conclusions: This study demonstrated the clinical effectiveness of LEF and even its superiority in achieving remission when compared with MTX as GCSD in PMR patients. Further research is needed to support these findings.

The Potential of FOXP3 in Predicting Survival and Treatment Response in Breast Cancer.

Background: Breast cancer (BC) continues to pose a substantial challenge to global health, necessitating an enhanced understanding of its fundamental mechanisms. Among its various pathological classifications, breast invasive carcinoma (BRCA) is the most prevalent. The role of the transcription factor forkhead box P3 (FOXP3), associated with regulatory T cells, in BRCA's diagnosis and prognosis remains insufficiently explored, despite its recognized importance. Methods: We examined the mRNA expression profile of FOXP3 in BRCA patients, assessing its correlation with disease detection, patient survival, immune checkpoint alterations, and response to anticancer drugs. Results: Our analysis revealed significantly elevated FOXP3 mRNA levels in BRCA patients, with a 95.7% accuracy for BRCA detection based on the area under the curve. High FOXP3 mRNA levels were positively correlated with overall survival and showed significant associations with CTLA4, CD274, PDCD1, TMB, and immune cell infiltration status. Furthermore, FOXP3 mRNA expression was linked to the efficacy of anticancer drugs and the tumor inflammation signature. Discussion: These findings suggest that FOXP3 serves as a promising biomarker for BRCA, offering valuable insights into its diagnosis and prognosis. The correlation between FOXP3 expression and immune checkpoint alterations, along with its predictive value for treatment response, underscores its potential in guiding therapeutic strategies. Conclusion: FOXP3 stands out as an influential factor in BRCA, highlighting its diagnostic accuracy and prognostic value. Its association with immune responses and treatment efficacy opens new avenues for research and clinical applications, positioning FOXP3 as a vital target for further investigation in BRCA management.

The ion channel basis of pharmacological effects of amiodarone on myocardial electrophysiological properties, a comprehensive review.

Amiodarone is a benzofuran-based class III antiarrhythmic agent frequently used for the treatment of atrial and ventricular arrhythmias. The primary target of class III antiarrhythmic drugs is the cardiac human ether-a-go-go-related gene (hERG) encoded channel, KCNH2, commonly known as HERG, that conducts the rapidly activating delayed rectifier potassium current (IKr). Like other class III antiarrhythmic drugs, amiodarone exerts its physiologic effects mainly through IKr blockade, delaying the repolarization phase of the action potential and extending the effective refractory period. However, while many class III antiarrhythmics, including sotalol and dofetilide, can cause long QT syndrome (LQTS) that can progress to torsade de pointes, amiodarone displays less risk of inducing this fatal arrhythmia. This review article discusses the arrhythmogenesis in LQTS from the aspects of the development of early afterdepolarizations (EADs) associated with Ca2+ current, transmural dispersion of repolarization (TDR), as well as reverse use dependence associated with class III antiarrhythmic drugs to highlight electropharmacological effects of amiodarone on the myocardium.

Clinical Progress of Targeted Therapy for Breast Cancer: A Comprehensive Review.

The discovery of effective breast cancer therapy is both urgent and daunting, beset by a myriad of challenges that range from the disease's inherent heterogeneity to its complex molecular underpinnings. Drug resistance, the intricacies of the tumor microenvironment, and patient-specific variables further complicate this landscape. The stakes are even higher when dealing with subtypes like triple-negative breast cancer, which eludes targeted hormonal therapies due to its lack of estrogen, progesterone, and HER2 receptors. Strategies to overcome such challenges include combinations of drugs and identifying new drug targets. Developing new drugs based on such targets could be a better solution than relying on costly immunotherapy or combinational therapies. In this review, we have endeavored to comprehensively examine the proven therapeutic drug targets associated with breast cancer and elucidate their respective molecular mechanisms and current clinical status. This study aims to facilitate researchers in conducting a comparative analysis of different targets to select single and multi- targeted drug discovery approaches for breast cancer.

Assessing provider knowledge of the federal 340B Drug Pricing Program in a federally qualified health center.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The 340B Drug Pricing Program is important to healthcare organizations that serve vulnerable communities. However, it is unknown whether healthcare providers in these organizations understand the 340B program and how it supports enhanced patient services. This study aims to characterize the knowledge, attitudes, and beliefs of healthcare providers toward the 340B program in a multisite federally qualified health center (FQHC). METHODS: This was a cross-sectional survey. A 27-item survey designed to assess prescriber knowledge and perspectives toward the 340B program was developed and administered. Closed-ended items were summarized using descriptive statistics, and open-ended items were analyzed with qualitative methods. RESULTS: A total of 198 healthcare providers with prescribing authority received the survey; of those, 65 (32.8%) participated. The majority of respondents (66.2%) were female; 41.5% were 35 years of age or younger, and 49.2% were physicians. The majority of respondents agreed that patients benefited from access to the organization's 340B pharmacies (95%) and that 340B pricing is important to consider when prescribing medications (78.3%). However, knowledge of the 340B program was limited, with only half of respondents (54%) able to correctly answer at least 4 of 7 knowledge-focused items. Reponses to a patient case suggested that some providers may be unfamiliar with which drugs are available at reduced prices. CONCLUSION: The findings suggest that providers believe the 340B program benefits patients and the organization but often lack a complete understanding of the program. Future research should focus on prescriber education as a strategy to help organizations optimize their 340B programs and facilitate patient access to medications.

Development of an LC-MS/MS method for the determination of five psychoactive drugs in postmortem urine by optimization of enzymatic hydrolysis of glucuronide conjugates.

PURPOSE: Toxicological analyses of biological samples play important roles in forensic and clinical investigations. Ingested drugs are excreted in urine as conjugates with endogenous substances such as glucuronic acid; hydrolyzing these conjugates improves the determination of target drugs by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, we sought to improve the enzymatic hydrolysis of glucuronide conjugates of five psychoactive drugs (11-nor-9-carboxy-Δ9-tetrahydrocannabinol, oxazepam, lorazepam, temazepam, and amitriptyline). METHODS: The efficiency of enzymatic hydrolysis of glucuronide conjugates in urine was optimized by varying temperature, enzyme volume, and reaction time. The hydrolysis was performed directly on extraction columns. This analysis method using LC-MS/MS was applied to forensic autopsy samples after thorough validation. RESULTS: We found that the recombinant ß-glucuronidase B-One® quantitatively hydrolyzed these conjugates within 3 min at room temperature directly on extraction columns. This on-column method saved time and eliminated the loss of valuable samples during transfer to the extraction column. LC-MS/MS-based calibration curves processed with this method showed good linearity, with r2 values exceeding 0.998. The intra- and inter-day accuracies and precisions of the method were 93.0-109.7% and 0.8-8.8%, respectively. The recovery efficiencies were in the range of 56.1-104.5%. Matrix effects were between 78.9 and 126.9%. CONCLUSIONS: We have established an LC-MS/MS method for five psychoactive drugs in urine after enzymatic hydrolysis of glucuronide conjugates directly on extraction columns. The method was successfully applied to forensic autopsy samples. The established method will have broad applications, including forensic and clinical toxicological investigations.

An update review of post-transplant diabetes mellitus: Concept, risk factors, clinical implications and management.

OBJECTIVE: Kidney transplantation is the gold standard therapeutic alternative for patients with end-stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post-transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies. METHODS: Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies. RESULTS: PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post-transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large-scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose-lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients. DISCUSSION: The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients.

Patterns of initial and first-intensifying antidiabetic drug utilization among patients with type 2 diabetes mellitus in Scotland, 2010-2020: A retrospective population-based cohort study.

AIM: To evaluate the utilization and prescribing patterns of antidiabetic drugs (ADDs) for patients with type 2 diabetes mellitus (T2DM) at treatment initiation and first intensification. METHODS: A retrospective cohort study was performed using linked routinely collected data of patients with T2DM who received ADDs between January 2010 and December 2020 in Scotland. The prescribing patterns were quantified using frequency/percentages, absolute/relative change, and trend tests. RESULTS: Overall, 145 909 new ADD users were identified, with approximately 91% (N = 132 382) of patients receiving a single ADD at first treatment initiation. Metformin was the most often prescribed monotherapy (N = 118 737, 89.69%). A total of 50 731 patients (39.40%) who were started on metformin (N = 46 730/118 737, 39.36%) or sulphonylurea (SU; N = 4001/10 029, 39.89%) monotherapy had their treatment intensified with one or more additional ADD. Most initial-metformin (45 963/46 730; 98.36%) and initial-SU users (3894/4001; 97.33%) who added further drugs were intensified with single ADDs. SUs (22 197/45 963; 48.29%) were the most common first-intensifying monotherapy after initial metformin use, but these were replaced by sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2019 (SGLT2 inhibitors: 2039/6065, 33.62% vs. SUs: 1924/6065, 31.72%). Metformin was the most frequently added monotherapy to initial SU use (2924/3894, 75.09%). Although the majority of patients received a single ADD, the use of combination therapy significantly increased over time. Nevertheless, there was a significant increasing trend towards prescribing the newer ADD classes (SGLT2 inhibitors, dipeptidyl peptidase-4 inhibitors) as monotherapy or in combination compared with the older ones (SUs, insulin, thiazolidinediones) at both drug initiation and first intensification. CONCLUSIONS: An overall increasing trend in prescribing the newer ADD classes compared to older ADDs was observed. However, metformin remained the most commonly prescribed first-line ADD, while SGLT2 inhibitors replaced SUs as the most common add-on therapy to initial metformin use in 2019.

Integrated care van delivery of evidence-based services for people who inject drugs: A cluster-randomized trial.

BACKGROUND AND AIMS: People who inject drugs (PWID) are at risk for adverse outcomes across multiple dimensions. While evidence-based interventions are available, services are often fragmented and difficult to access. We measured the effectiveness of an integrated care van (ICV) that offered services for PWID. DESIGN, SETTING AND PARTICIPANTS: This was a cluster-randomized trial, which took place in Baltimore, MD, USA. Prior to randomization, we used a research van to recruit PWID cohorts from 12 Baltimore neighborhoods (sites), currently served by the city's mobile needle exchange program. INTERVENTION AND COMPARATOR: We randomized sites to receive weekly visits from the ICV (n = 6) or to usual services (n = 6) for 14 months. The ICV offered case management; buprenorphine/naloxone; screening for HIV, hepatitis C virus and sexually transmitted infections; HIV pre-exposure prophylaxis; and wound care. MEASUREMENTS: The primary outcome was a composite harm mitigation score that captured access to evidence-based services, risk behaviors and adverse health events (range = 0-15, with higher numbers indicating worse status). We evaluated effectiveness by comparing changes in the composite score at 7 months versus baseline in the two study arms. FINDINGS: We enrolled 720 cohort participants across the study sites (60 per site) between June 2018 and August 2019: 38.3% women, 72.6% black and 85.1% urine drug test positive for fentanyl. Over a median of 10.4 months, the ICV provided services to 734 unique clients (who may or may not have been cohort participants) across the six intervention sites, including HIV/hepatitis C virus testing in 577 (78.6%) and buprenorphine/naloxone initiation in 540 (74%). However, only 52 (7.2%) of cohort participants received services on the ICV. The average composite score decreased at 7 months relative to baseline, with no significant difference in the change between ICV and usual services (difference in differences: -0.31; 95% confidence interval: -0.70, 0.08; P = 0.13). CONCLUSIONS: This cluster-randomized trial in Baltimore, MD, USA, found no evidence that weekly neighborhood visits from a mobile health van providing injection-drug-focused services improved access to services and outcomes among people who injected drugs in the neighborhood, relative to usual services. The van successfully served large numbers of clients but unexpectedly low use of the van by cohort participants limited the ability to detect meaningful differences.

Tongue edema as an adverse drug reaction to low-dose olanzapine in a cancer patient receiving palliative care.

OBJECTIVES: Olanzapine is an atypical neuroleptic indicated for treatment of various psychiatric disorders, but it has also several indications in palliative care (PC) patients: opioids misuse, nausea not related to chemotherapy, anorexia-cachexia syndrome, and sleep and mood disorders. Peripheral and facial edema are a rare side effect of the treatment with olanzapine. I report a case of an advanced cancer patient cared receiving PC who developed moderate tongue edema on day 1 of a low dose of olanzapine. METHODS: A patient with advance and metastatic colon cancer presented moderate tongue edema on day 1 of a low dose (2.5 mg) of olanzapine for the treatment of his nausea, anorexia-cachexia syndrome, and mood disorder (mainly anxiety). RESULTS: The patient discontinued the drug with resolution of the edema. The day after he called our outpatients' service, a prompt physical examination, together with blood tests, excluded other differential diagnosis. SIGNIFICANCE OF RESULTS: To the best of our knowledge, this is the second case reporting head and neck localized edema due to olanzapine treatment in a patient with advanced cancer receiving PC. Considering the increasing use of olanzapine as off-label treatment in these patients (often for cluster symptoms), our report could help clinicians in daily practice and researchers on put a deeper focus on indications for olanzapine in PC.