Citations

Abstract Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2024 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2024 were reviewed—including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, endocrine drugs, generics, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2024 were based on a combination of quantitative analyses and expert opinion. Results In 2023, overall pharmaceutical expenditures in the US grew 13.6% compared to 2022, for a total of $722.5 billion. Utilization (a 6.5% increase), new drugs (a 4.2% increase) and price (a 2.9% increase) drove this increase. Semaglutide was the top drug in 2023, followed by adalimumab and apixaban. Drug expenditures were $37.1 billion (a 1.1% decrease) and $135.7 billion (a 15.0% increase) in nonfederal hospitals and clinics, respectively. In clinics, increased utilization drove growth, with a small impact from price and new products. In nonfederal hospitals, a drop in utilization led the decrease in expenditures, with price and new drugs modestly contributing to growth in spending. Several new drugs that will influence spending are expected to be approved in 2024. Specialty, endocrine, and cancer drugs will continue to drive expenditures. Conclusion For 2024, we expect overall prescription drug spending to rise by 10.0% to 12.0%, whereas in clinics and hospitals we anticipate an 11.0% to 13.0% increase and a 0% to 2.0% increase, respectively, compared to 2023. These national estimates of future pharmaceutical expenditure growth may not be representative of any health system because of the myriad of local factors that influence actual spending.

Abstract Background In 2021, the state of Arizona experienced the largest focal outbreak of West Nile virus (WNV) in US history. Timely and accurate diagnostic testing remains a challenge for WNV due to transient viremia and limited immunoassay specificity. Recent studies have identified whole blood (WB) and urine as more sensitive specimen types for the detection of WNV RNA. Methods We evaluated ordering practices, test performance, and patient characteristics of probable and confirmed cases. In total, we identified 190 probable and proven cases, including 127 patients (66.8%) with neuroinvasive disease. Results Among all cases, only 29.5% had WNV polymerase chain reaction (PCR) testing ordered on WB, of which 80.3% resulted as positive, including 7 cases in which WNV serologic testing was negative and 5 cases for which serologic testing was not ordered. In comparison, only 23.7% of cases that had cerebrospinal fluid (CSF) PCR ordered had a positive result, including 3 cases that were negative by PCR on WB. In contrast, WNV PCR on WB detected 12 neuroinvasive cases that were CSF PCR negative. WNV PCR testing in urine was only ordered on 2 patients, both of whom were positive. Crossing cycle threshold (Ct) values were not significantly different between WB and CSF specimen types, nor was there a correlation between Ct value and days from symptom onset at the time of sample collection; all specimen types and time points had Ct values, with 98% above 30. WB was positive by WNV PCR in several patients for >7 days (range, 7–25 days) after symptom onset, as was the CSF PCR. Conclusions Taken together, these findings indicate that WNV PCR testing on WB may be the best initial test for timely diagnosis of WNV infection, irrespective of clinical manifestation; however, if negative in patients with suspected neuroinvasive disease, WNV PCR testing on CSF should be ordered.

AbstractBackgroundScleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function. Pathologically, it encompasses the persistent presence of inflammation, abnormal collagen buildup, and restructuring of blood vessels in various organs, resulting in a wide range of clinical symptoms. This review incorporates the most recent scientific literature on scleroderma, with a particular emphasis on its pathophysiology, clinical manifestations, diagnostic approaches, and treatment options.MethodologyA comprehensive investigation was carried out on numerous databases, such as PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar, to collect pertinent studies covering diverse facets of scleroderma research.ResultsScleroderma presents with a range of systemic manifestations, such as interstitial lung disease, gastrointestinal dysmotility, Raynaud's phenomenon, pulmonary arterial hypertension, renal complications, neurological symptoms, and cardiac abnormalities. Serological markers, such as antinuclear antibodies, anti‐centromere antibodies, and anti‐topoisomerase antibodies, are important for classifying diseases and predicting their outcomes.DiscussionThe precise identification of scleroderma is crucial for promptly and correctly implementing effective treatment plans. Treatment approaches aim to improve symptoms, reduce complications, and slow down the progression of the disease. An integrated approach that combines pharmacological agents, including immunosuppressants, endothelin receptor antagonists, and prostanoids, with nonpharmacological interventions such as physical and occupational therapy is essential for maximizing patient care.ConclusionThrough the clarification of existing gaps in knowledge and identification of emerging trends, our goal is to improve the accuracy of diagnosis, enhance the effectiveness of therapeutic interventions, and ultimately enhance the overall quality of life for individuals suffering from scleroderma. Ongoing cooperation and creative research are necessary to advance the field and achieve improved patient outcomes and new therapeutic discoveries.

Abstract Background/Aims Features of centralised pain, encompassing widespread pain and non-pain features such as multisensory hypersensitivity, fatigue, and sleep disturbance are common in RA. We hypothesise that centralised pain in early RA affects response to standard first-line treatment. Methods Prospective cohort study of adults with a clinical diagnosis of RA recruited from the early inflammatory arthritis clinic, Oxford University Hospitals, who completed an online assessment within two weeks of starting a DMARD. Centralised pain was assessed using three measures: the 2016 Fibromyalgia Survey Criteria (0-31), Central Sensitisation Inventory (CSI, 0-100), and PainDetect (0-38). The primary outcome, bodily pain, was assessed using the Short Form-36 Bodily Pain Scale (BPS), where lower scores indicate worse pain severity. During follow-up, participants completed three sets of follow-up questionnaires at 3-, 6- and 12-months. Linear mixed effects models were used to account for repeated measurements and patient variability. Three models were fitted, for an association between baseline values of each centralised pain measure with BPS over time. An interaction between centralised pain scores with time was fitted to assess for effect of the exposure on change over time. Age, sex, and symptom duration at baseline were included as confounding variables. Ethical approval was granted by South Central Oxford B Research Ethics Committee. Results Of 149 participants, 117 (79%) completed follow-up: median (IQR) age 59.8 (24.6) years; 36% male; 30% with symptoms >1 year at baseline. There were no significant baseline differences among those lost to follow-up, apart from a longer symptom duration (53% vs 30% symptom duration >1 year; P = 0.033). At baseline, median (IQR) Fibromyalgia Survey Criteria, CSI, and PainDetect scores were 12 (6), 36 (17), and 14 (9) respectively. The median (IQR) BPS at baseline was 32.5 (22.5). Measures of centralised pain were moderately-to-strongly correlated with each other, and with BPS. Individuals with symptoms for >1 year had higher scores on the PainDetect (P = 0.0015), but not the CSI (P = 0.0545) or Fibromyalgia Survey Criteria (P = 0.672). After adjusting for age, sex, and symptom duration, there was a significant association between centralised pain at baseline and BPS over follow-up, e.g.; for every unit increase in the fibromyalgia survey criteria at baseline, the BPS decreased by 2.40 (95%CI -3.29, -1.49; P < 0.001) points over follow-up. Similar relationships were seen with the CSI and PainDetect scores. Conclusion Centralised pain measures in early RA patients can be indicative of the severity of bodily pain experienced during the subsequent 12 months after starting a DMARD treatment. Recognising and assessing centralised pain in early RA patients may enable us to tailor more effective and individualised treatment regimens. Further studies, especially those utilising neuroimaging and QST, are essential to elucidate the neural mechanisms underlying the impact of centralised pain on treatment outcomes in RA. Disclosure E. Kelleher: None. A.J. Wall: None. M.T. Sanchez-Santos: None. V. Wanigasekera: None. A. Irani (nee Soni): None.

Purpose of review Pediatric obesity is a growing concern globally. Patients with a history of overweight/obesity often experience stigmatization, especially in the healthcare setting, and are at increased risk of developing psychological comorbidities including eating disorders. This review appraises the most recent studies evaluating eating disorder risk in youth undergoing treatment for obesity, identifies gaps in the literature, and offers practical guidelines to pediatric providers regarding the management of this population. Recent findings Recent studies suggest that structured weight management programs may decrease the risk of and/or improve symptoms of certain eating disorders such as binge eating disorder and bulimia nervosa. There is a paucity of research on some components of obesity management such as obesity pharmacotherapeutics and eating disorder risk. Summary Children and adolescents with obesity are a psychologically vulnerable population with increased risk for the development of eating disorders. Further study is needed to evaluate general risk in the setting of specialized and primary care obesity interventions and develop appropriate screening and mitigation tools. Some evidence-based strategies can aid pediatric providers in both weight management and eating disorder prevention and risk assessment.

CLEC4G, a glycan-binding receptor, has previously been demonstrated to inhibit Aβ generation, yet its brain localization and functions in Alzheimer’s disease (AD) are not clear. We explored the localization, function, and regulatory network of CLEC4G via experiments and analysis of RNA-seq databases. CLEC4G transcripts and proteins were identified in brain tissues, with the highest expression observed in neurons. Notably, AD was associated with reduced levels of CLEC4G transcripts. Bioinformatic analyses revealed interactions between CLEC4G and relevant genes such as BACE1, NPC1, PILRA, TYROBP, MGAT1, and MGAT3, all displaying a negative correlation trend. We further identified the upstream transcriptional regulators NR2F6 and XRCC4 for CLEC4G and confirmed a decrease in CLEC4G expression in APP/PS1 transgenic mice. This study highlights the role of CLEC4G in protecting against AD progression and the significance of CLEC4G for AD research and management.

This report aims to shed light on the intricate challenges encountered during the diagnosis and treatment of an uncommon variant of prostate cancer—mixed adenosquamous cell carcinoma of the prostate. Prostate cancers of this nature pose distinctive diagnostic and therapeutic dilemmas due to their rarity and complex histological composition. We present a case of a 63-year-old man with metastatic prostate cancer, featuring adenocarcinoma with squamous cell differentiation, who underwent a multimodal treatment approach. The patient responded to first-line carboplatin, docetaxel, and androgen deprivation therapy, followed by androgen receptor pathway inhibitor (ARPI) maintenance. However, disease progression led to radiation therapy and a subsequent switch to Lutetium (177Lu) vipivotide tetraxetan after chemotherapy challenges. Comprehensive genetic profiling revealed shared mutations in the prostate and liver lesions, emphasizing the role of targeted therapies. Prostate-specific membrane antigen (PSMA)-targeted therapy resulted in a notable PSA decline. This case highlights the evolving treatment landscape for rare prostate cancers, integrating genetic insights for tailored interventions. In conclusion, squamous cell carcinoma (SCC) of the prostate is rare, emphasizing the imperative for enhanced comprehension in diagnosis and management. Our case suggests the potential efficacy of ARPI and PSMA-targeted therapies. Our findings advocate for a more nuanced approach to the management of this rare prostate cancer variant, leveraging genomic insights for personalized treatment strategies. This exploration serves as a foundation for further research and clinical considerations in addressing the challenges posed by mixed adenosquamous cell carcinoma of the prostate.

Abstract Background and study aims Transoral outlet reduction (TORe) has long been employed in treating weight regain after Roux-en-Y gastric bypass. However, its impact on gut hormones and their relationship with weight loss remains unknown. Patients and methods This was a substudy of a previous randomized clinical trial. Adults with significant weight regain and dilated gastrojejunostomy underwent TORe with argon plasma coagulation (APC) alone or APC plus endoscopic suturing (APC-suture). Serum levels of ghrelin, GLP-1, and PYY were assessed at fasting, 30, 60, 90, and 120 minutes after a standardized liquid meal. Results were compared according to allocation group, clinical success, and history of cholecystectomy. Results Thirty-six patients (19 APC vs. 17 APC-suture) were enrolled. There were no significant baseline differences between groups. In all analyses, the typical postprandial decrease in ghrelin levels was delayed by 30 minutes, but no other changes were noted. GLP-1 levels significantly decreased at 12 months in both allocation groups. Similar findings were noted after dividing groups according to the history of cholecystectomy and clinical success. The APC cohort presented an increase in PYY levels at 90 minutes, while the APC-suture group did not. Naïve patients had significantly lower PYY levels at baseline (P = 0.01) compared with cholecystectomized individuals. This latter group experienced a significant increase in area under the curve (AUC) for PYY levels, while naïve patients did not, leading to a higher AUC at 12 months (P = 0.0001). Conclusions TORe interferes with the dynamics of gut hormones. APC triggers a more pronounced enteroendocrine response than APC-suture, especially in cholecystectomized patients.