Treatment Policy Research Articles

Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1–4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1–2) or a high-grade group (WHO/ISUP grade 3–4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5–18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6–17.4) in the high-grade group and 28.0 months (21.1–34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0–10.0) for the high-grade group and 10.0 months (6.8–13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135–2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.

Associated factors to non-medical and medical use of psychoactive medication among Mexican adolescents and adults in a national household survey

BackgroundNon-medical use of psychoactive medication is a public health problem. Studies in other contexts indicate that individual sociodemographic characteristics are associated with non-medical use, but these associations have not been assessed in the Mexican context. ObjectivesTo estimate the prevalence non-medical and medical use of psychoactive medication among Mexican adolescents and adults’ medication users and to estimate the associations between sociodemographic characteristics and non-medical use of psychoactive medication, using data from a nationally representative sample. MethodsSecondary analysis of data collected from the National Survey of Drug, Alcohol, and Tobacco Consumption (ENCODAT) 2016 to 2017. The analytical sample included people aged 12 to 65 years. The sample was stratified into two age categories: adolescents (12-17 years) and adults (18-65 years). Sub-analyses were performed to describe prevalence of use and non-medical use of psychoactive medication at the state-level. Descriptive statistics and multinomial logistic regression models were used to estimate associations between sociodemographic characteristics and medical, non-medical, and non-use of psychoactive medication in adolescents and adults. ResultsAmong Mexican medication users in 2016, the national prevalence of non-medical use of psychoactive drugs was 19.6%; 22.2% among adolescents and 19.4% among adults. States adjacent to the US-Mexico border reported the highest levels of non-medical use of psychoactive medication. Illicit drug consumption was associated with non-medical use. Sociodemographic characteristics associated with non-medical use varied between adolescents and adults. ConclusionsThere is a high proportion of non-medical use of psychoactive drugs among Mexican medication users, especially among young people. Understanding factors associated with the misuse of psychoactive medications in Mexico can inform policy for prevention and treatment.

The impact of squamous cell transformation on the prognosis of patients treated with radical nephroureterectomy

Background Limited information is available for guiding the management of upper urinary tract (UUT) urothelial carcinoma with squamous differentiation (UC-SqD). We did not even know about the difference between pure urothelial carcinoma (UC) and UC-SqD in the UUT regardless of treatment policy and prognosis. Instead of direct comparisons against each other, we included the third UUT malignancy, squamous cell carcinoma (SCC). This three-way-race model allows us to more clearly demonstrate the impact of squamous cell transformation on patient outcomes in UUT malignancy.MethodsWe retrospectively analysed 327 patients with UC, UC-SqD, or SCC who underwent radical nephroureterectomy with bladder cuff excision (RNU) at Taichung Veterans General Hospital, Taichung, Taiwan, between January 2006 and December 2013. A Kaplan–Meier survival analysis was used to evaluate the relationship between patient outcomes and histology. Multivariate Cox proportional hazards modelling was also used to predict patient prognoses.ResultsThe five-year postoperative cancer-specific survival (CSS) rates were 83.6% (UC), 74.4% (UC-SqD), and 55.6% (SCC), and the 5-year recurrence-free survival (RFS) rates were 87.7% (UC), 61.5% (UC-SqD), and 51.9% (SCC). UC patients had significantly better 5-year RFS than UC-SqD and SCC patients (P = 0.001 and P < 0.0001, respectively). Patients with pure UC had significantly better 5-year CSS than SCC patients (P = 0.0045). SCC or UC-SqD did not independently predict disease-specific mortality (HR 0.999, p = 0.999; HR 0.775, p = 0.632, respectively) or disease recurrence compared to pure UC (HR 2.934, p = 0.239; HR 1.422, p = 0.525, respectively). Age, lymphovascular invasion (LVI), and lymph node (LN) status independently predicted CSS, while pathological tumour stage, LN status, and LVI predicted RFS.ConclusionsSCC and UC-SqD are not independent predictors of survival outcomes in patients with UUT tumours. However, they are associated with other worse prognostic factors. Hence, different treatments are needed for these two conditions, especially for SCC.

The ‘Euphoria’ effect: A popular HBO show, Gen Z, and drug policy beliefs

AbstractObjectiveCan a fictional show affect its audience's perspectives on the issue of drug use and addiction in society? This article aims to answer that question.MethodsWe use a survey with an embedded experiment to assess the relationship between the popular HBO show Euphoria and attitudes of Gen Z on the issue of drugs, including: feelings toward drug users and those caught up in drug addiction; beliefs regarding the causes of drug addiction; and, attitudes toward harm reduction, treatment, and punitive drug policies. Subjects were recruited from Amazon's Mechanical Turk.ResultsWe found that reevoking the show by showing photos of two of the main characters led to drug attitudes consistent with the messages about drugs found in Euphoria. We also found that self‐reported exposure to the show was associated with perspectives on drugs consistent with the content of the show for respondents who scored higher on individual transportability—results that conform closely to theoretical expectations. The fact that these results were found in a study 8 months after the final episode of Euphoria was aired hints at the durability of the show's effects.ConclusionsThe results add to the growing body of research on the political effects of entertainment media and provide additional validation of new and important measures of the propensity of individuals to be transported by narratives and eudaimonic motivation in entertainment media choice.

Glioma grading using an optimized T1-weighted dynamic contrast-enhanced magnetic resonance imaging paradigm

BackgroundGlioma grading is a critical procedure for selecting the most effective treatment policy. Biopsy result is the gold standard method for glioma grading, but inherent sampling errors in the biopsy procedure could lead to tumor misclassification.AimThis study evaluated grading performances of a more comprehensive collection of the physiological indices quantified using an optimized dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) paradigm for glioma grading.MethodsThirty-five patients with glioma underwent DCE-MR imaging to evaluate the grading performances of DCE-MRI-derived physiological indices. The statistical differences in the physiological indices between the different grades of gliomas were studied, and the grading performances of these parameters were evaluated using the leave-one-out cross-validation method.ResultsThere were significant statistical differences in DCE-MRI-derived physiological indices between the different grades of gliomas. The mean rCBVs for grade II (low-grade glioma, LGG), grade III, grade IV, and high-grade (HGG) gliomas were 2.03 ± 0.78, 3.61 ± 1.64, 7.14 ± 3.19, and 5.28 ± 3.02, respectively. The mean rCBFs of 1.94 ± 0.97, 2.67 ± 0.96, 4.57 ± 1.77, and 3.57 ± 1.68 were, respectively, quantified for grade II (LGG), grade III, grade IV, and high-grade gliomas. The leave-one-out cross-validation method indicates that the grades of glioma tumors could be determined based on a specific threshold for each physiological index; for example, the optimal cutoff values for rCBF, rCBV, Ktrans, Kep, and Vp indices to distinguish between HGGs and LGGs were 2.11, 2.80, 0.025 mL/g min, 0.29 min−1, and 0.065 mL/g, respectively.ConclusionsFrom the results, it could be concluded that glioma grades could be determined using DCE-MRI-derived physiological indices with an acceptable agreement with histopathological results.

The association of family doctor contract service and patient trust in doctor: evidence from twenty-five village clinics of three counties in rural China

BackgroundChina is implementing the family doctor (FD) system to reform the primary healthcare (PHC). The family doctor contract service (FDCS) policy plays a crucial role in this system implementation, aiming to transform the doctor-patient relationship and enhance PHC quality. This study aims to investigate the impact of FDCS on the doctor-patient relationship in PHCs using field research methodology.MethodThe field research methodology was employed to address the research questions. Quantitative methods were utilized for data collection and analysis. A structure questionnaire was used to collect data based on the research questions. Our investigation encompassed twenty-five village clinics across three counties in China. A total of 574 subjects helped us to finish this investigation in the study. The collected data was analyzed using statistical analysis including ordinary least squares (OLS) model and propensity scores matching model (PSM) to estimate the relationship.ResultThe findings from ordinary least squares (OLS) regression revealed that FDCS had a positive influence on patient trust in doctors within PHCs, with patients who participated the FDCS exhibiting higher levels of trust compared to those who did not participate. Propensity score matching (PSM) analysis further confirmed these results by accounting for selection bias.ConclusionsThe implementation of family doctor contract service has brought about significant transformation in the doctor-patient relationship within rural Chinese PHCs. In essence, it has revolutionized the service model of doctor in PHC, playing a pivotal role in improving primary health quality and enhance the service capability of doctors in PHC. This transformative process has been crucial for carrying out hierarchical diagnosis and treatment policy, which aims to adjust the medical service structure and optimizing the health service system. Therefore, it is imperative for government authorities and health administration departments to ensure continuous support for this essential service through appropriate formulation.

North Carolina Medicaid System Perspectives on Substance Use Disorder Treatment Policy Changes During the COVID-19 Pandemic.

This study aimed to describe perspectives from stakeholders involved in the Medicaid system in North Carolina regarding substance use disorder (SUD) treatment policy changes during the coronavirus disease 2019 pandemic. We conducted semistructured interviews in early 2022 with state agency representatives, Medicaid managed care organizations, and Medicaid providers (n = 22) as well as 3 focus groups of Medicaid beneficiaries with SUD (n = 14). Interviews and focus groups focused on 4 topics: policies, meeting needs during COVID, demand for SUD services, and staffing. Overall, policy changes, such as telehealth and take-home methadone, were considered beneficial, with participants displaying substantial support for both policies. Shifting demand for services, staffing shortages, and technology barriers presented significant challenges. Innovative benefits and services were used to adapt to these challenges, including the provision of digital devices and data plans to improve access to telehealth. Perspectives from Medicaid stakeholders, including state organizations to beneficiaries, support the continuation of SUD policy changes that occurred. Staffing shortages remain a substantial barrier. Based on the participants' positive responses to the SUD policy changes made during the coronavirus disease 2019 pandemic, such as take-home methadone and telehealth initiation of buprenorphine, these changes should be continued. Additional steps are needed to ensure payment parity for telehealth services.

Cultural engagement and prevalence of pain in socially isolated older people: a longitudinal modified treatment policy approach

It remains uncertain whether cultural engagement positively influences the reduction of pain risk, particularly depending on the social isolation status. The aim of this study was to examine the impact of cultural engagement on the reduction of pain prevalence over a 6-year follow-up period among older people, particularly those experiencing different dimensions of social isolation. This study was a prospective longitudinal study. We analysed the English Longitudinal Study of Ageing cohort, consisting of 6468 community-dwelling adults aged ≥50 years old who provided data in waves 6 (2012-2013), 7 (2014-2015), 8 (2016-2017), and 9 (2018-2019). Self-reported cultural engagement (going to museums, art galleries, exhibitions, the theatre, concerts, or the opera) measured in waves 6-8 was used as the exposure variable. Meanwhile self-reported moderate-to-severe pain in wave 9 was used as the outcome variable. Social isolation was considered in waves 6-8, and the possibility of effect modification was captured by assessing each component of the social isolation index: not married or cohabiting with a partner, fewer than monthly contact with children/other immediate family/friends, and not engaging in any organisations, religious groups, or committees. The estimated pain prevalence was 29.2% (95% confidence interval, 28.1-30.3; reference) after adjusting for time-variant, time-invariant, and loss to follow-up factors. Cultural engagement led to a reduction in pain prevalence to 24.1% for all individuals, representing a decrease of 5.1% (95% confidence interval, 0.6-9.6; P-value, 0.03). In older people who were not married or cohabiting, cultural engagement resulted in a decrease in pain prevalence to 25.8%, a reduction of 3.4% (95% confidence interval, 0.4-6.4; P-value, 0.01). For those with less frequent contact with close family members, the pain prevalence decreased to 25.3%, a reduction of 3.9% (95% confidence interval, 0.2-7.6; P-value, 0.03). Meanwhile, other dimensions of social isolation did not show a significant reduction in pain prevalence. Cultural engagement may help to reduce the risk of pain in socially isolated older adults. Those who were single or living alone and had less frequent contact with immediate family were particularly vulnerable. While cultural engagement might help certain socially isolated older people feel better, its effectiveness varies, highlighting the need for targeted interventions. The Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number (22K17648, Ikeda).

External comparators and estimands

The estimand framework as defined by the ICH E9(R1) addendum aims to clearly define “the treatment effect reflecting the clinical question posed by the trial objective”. It intends to achieve this goal of a clear definition by specifying the 5 estimand attributes: treatment conditions, population, endpoints, handling of intercurrent events (IEs), and population-level summary. However, hybrid clinical/observational research like External Comparators (ECs) leads to new reflections on existing attributes and to considerations for additional ones. Specifically, treatment conditions and exposure may be more difficult to handle in the EC, and especially Standard of Care (SoC) treatment needs detailed attention. The external population typically cannot be based on the classical Intention-to-treat population and constitutes also an approximation only. Endpoints may not be comparable across cohorts, and IEs may be more different than in an RCT setting, such that the hypothetical treatment policy according to the ICH E9(R1) addendum may become of greater interest especially for long-term endpoints. Finally, the necessary assumptions for some population-level summaries (e.g., the proportional hazards assumption) can become more fragile when joining data from different sources due to induced heterogeneity. Finally, it is shown that the baseline definition and the marginal estimator are candidates for additional estimand attributes in case the estimand framework is revised to account for observational study needs.

Don't rash it! The clinical significance of positive Varicella zoster virus PCR in cerebrospinal fluid of patients with neurological symptoms

BackgroundVaricella zoster virus (VZV) is among the leading pathogens causing meningitis and encephalitis. While VZV-PCR-positive CSF is considered a gold-standard for diagnosis, it is not-uncommon to detect VZV-DNA in CSF of patients with other acute or chronic illness. Our goal was to determine the clinical relevance of VZV-PCR-positive CSF when investigating patients with neurological symptoms. MethodsIn this retrospective cohort from the largest hospital in Israel, we collected demographic, clinical and laboratory data of patients with VZV-PCR-positive CSF, analyzing the significance of various parameters. ResultsDuring a 5-years study, 125 patient-unique VZV-PCR-positive CSFs were recorded, in which only 9 alternative diagnoses were noted. The commonest symptoms were headache (N = 104, 83 %) and rash (N = 96, 76 %). PCR-cycle-threshold (Ct), a surrogate of viral burden, did not significantly vary across the clinical manifestations; however, patients with rash and Ct<35 were prone to develop stroke in the following year (N = 6, 7 %). Empiric nucleoside-analogue treatment was not associated with a better outcome compared to treatment administered upon a positive-PCR result. DiscussionOur findings suggest that in patients with neurological symptoms, detection of VZV-DNA in CSF renders VZV the probable culprit. Nevertheless, a systematic evaluation of treatment and follow-up algorithms of patients with suspected or proved VZV meningitis and encephalitis is needed. The benefits of a prompt treatment should be weighed against the potential complications of nucleoside-analogue. Conversely, the propensity for stroke in patients with higher viral-burden, necessitates further studies assessing VZV causal role, directing additional workup, treatment and monitoring policy.

Unsupervised Learning in NBA Injury Recovery: Advanced Data Mining to Decode Recovery Durations and Economic Impacts

This study utilized advanced data mining and machine learning to examine player injuries in the National Basketball Association (NBA) from 2000–01 to 2022–23. By analyzing a dataset of 2296 players, including sociodemographics, injury records, and financial data, this research investigated the relationships between injury types and player recovery durations, and their socioeconomic impacts. Our methodology involved data collection, engineering, and mining; the application of techniques such as Density-Based Spatial Clustering of Applications with Noise (DBSCAN), isolation forest, and the Z score for anomaly detection; and the application of the Apriori algorithm for association rule mining. Anomaly detection revealed 189 anomalies (1.04% of cases), highlighting unusual recovery durations and factors influencing recovery beyond physical healing. Association rule mining indicated shorter recovery times for lower extremity injuries and a 95% confidence level for quick returns from “Rest” injuries, affirming the NBA’s treatment and rest policies. Additionally, economic factors were observed, with players in lower salary brackets experiencing shorter recoveries, pointing to a financial influence on recovery decisions. This study offers critical insights into sports injuries and recovery, providing valuable information for sports professionals and league administrators. This study will impact player health management and team tactics, laying the groundwork for future research on long-term injury effects and technology integration in player health monitoring.

Dental decision-making for persons with dementia: A systematic narrative review.

Dental decision-making represents the establishment of a common understanding between the dental professional and the recipient of the intervention, which determines oral healthcare and dental treatment policies. Dental decision-making for persons with dementia can be challenging, and there have been no systematic reviews on this topic. Therefore, this systematic narrative review aimed to identify the current state of dental decision-making in persons with dementia. Literature search was performed using PubMed, Web of Science, Cochrane Library, CINAHL, and Google Scholar databases. Through the process of research selection, 7 articles with a high risk of bias were included in this study. This review clarified that there is limited information on the dental decision-making processes for persons with dementia. In conclusion, although this may be difficult due to different medical and socioeconomic conditions, the dilemma between the need to establish evidence for dental decision-making and medical ethics that prioritize a patient-centered position should be discussed globally in the future.

Understanding the LGBTQ+ Divide: A review on the impact of geographic location and political climate on LGBTQ+ patient care in the United States.

Background: In the United States, laws and policies are proposed and passed daily that either protect or restrict transgender patients’ access to care. The objective of this study is to review the existing body of literature on the effect of state-level policy on transgender patients’ overall health. Methods: Primary literature was identified through PubMed and the National Institutes of Health. Search terms included keywords related to the following concepts: LGBTQ terms, differentiating terms, regional terms, and health outcome terms. Inclusion criteria: Quantifiable studies conducted on the American LGBTQ and Transgender population from January 2015 to April 2023. Exclusion criteria: Studies not conducted in English, on the American population, and not relevant to the research question. Results were individually discussed and then synthesized using a narrative approach. Results: A total of 6 studies were identified for review. The difference in rates of suicidality, suicide attempt, depression, and anxiety between Democratic and Republican states was statistically significant (p Conclusion: Republican-run states, on average, had policies in place restricting access and treatment for transgender patients which is correlated with worse health outcomes. Advocacy is greatly needed to help protect this at-risk population and further research is needed to better understand how state-level barriers impact transgender patients across the US.

Biotransformation of diclofenac by isolated super-degrader Pseudomonas sp. DCα4: Postulated pathways, and attenuated ecotoxicological effects

Significant concentrations of emerging xenobiotics, like diclofenac (DCF), possessing severe irreversible eco-toxicological threats, has been detected in aquatic systems worldwide, raising the concerns. This present investigation is intended to explore an efficient solution to support the existing wastewater treatment policies to handle DCF contamination by bacteria-mediated biotransformation. DCF-tolerant bacterial strains were isolated from pharmaceutical wastewater and selected based on their non-virulence nature and degradation ability. Among those, Pseudomonas sp. DCα4 was found to be the most dominant DCF degrader exhibiting 99.82% removal of DCF confirmed by HPLC after optimization of temperature at 30.02 °C, pH at 6.9, inoculum of 4.94%, and time 68.02 h. The degradation kinetics exhibited the process of DCF degradation followed a first-order kinetics with k of 0.108/h and specific degradation rate of 0.013/h. Moreover, the enzyme activity study indicated predominant hydrolase activity in the DCF treatment broth of DCα4, implying hydrolysis as the main force behind DCF biotransformation. HRMS analysis confirmed the presence of 2-hydroxyphenylacetic acid, 1,3-dichloro,2-amino, 5-hydroxybenzene, and benzylacetic acid as major intermediates of DCF biodegradation indicating non-specific hydrolysis of DCF. Whole genome analysis of most related strains which were confirmed by near full 16S rRNA gene sequence homology study, predicted involvement of different N–C bond hydrolase producing genes like puud, atzF, astB, nit1, and nylB. The ecotoxicological study using Aliivibrio fischeri exhibited 47.51% bioluminescence inhibition by DCF-containing broth which was comparable to the same caused by 1 mg/mL of K2Cr2O7 whereas remediated broth exhibited only 0.51% inhibition implying reduction of the ecotoxic load caused by DCF contamination. Cost analysis revealed that possible integration of the process with existing ones would increase per litre expense by $0.45. These results indicated that the described process of DCF biodegradation using the super-degrader DCα4 would be an advancement of existing pharmaceutical wastewater treatment processes for DCF bioremediation.

Application of hypothetical strategies in acute pain.

Since the publication of ICH E9 (R1), "Addendum to statistical principles for clinical trials: on choosing appropriate estimands and defining sensitivity analyses in clinical trials," there has been a lot of debate about the hypothetical strategy for handling intercurrent events. Arguments against the hypothetical strategy are twofold: (1) the clinical question has limited clinical/regulatory interest; (2) the estimation may need strong statistical assumptions. In this article, we provide an example of a hypothetical strategy handling use of rescue medications in the acute pain setting. We argue that the treatment effect of a drug that is attributable to the treatment alone is the clinical question of interest and is important to regulators. The hypothetical strategy is important when developing non-opioid treatment as it estimates the treatment effect due to treatment during the pre-specified evaluation period whereas the treatment policy strategy does not. Two widely acceptable and non-controversial clinical inputs are required to construct a reasonable estimator. More importantly, this estimator does not rely on additional strong statistical assumptions and is considered reasonable for regulatory decision making. In this article, we point out examples where estimators for a hypothetical strategy can be constructed without any strong additional statistical assumptions besides acceptable clinical inputs. We also showcase a new way to obtain estimation based on disease specific clinical knowledge instead of strong statistical assumptions. In the example presented, we clearly demonstrate the advantages of the hypothetical strategy compared to alternative strategies including the treatment policy strategy and a composite variable strategy.

Confucianism and employee treatment: Evidence from China

AbstractThis study examines the effect of Confucianism, an influential cultural belief and ethical philosophy in East Asia, on employee treatment policies within Chinese listed companies from 2010 to 2020. Our key finding is that Confucianism is positively associated with employee‐friendly practices. We further identify three plausible economic channels through which Confucianism shapes employee‐friendly treatment: valuing human‐centric ethics, mitigating managerial myopia, and alleviating agency conflicts. Cross‐sectionally, the documented impact is more prominent for firms operating with weaker union power and those with executives lacking overseas experience. Additionally, employee‐friendly firms exhibit higher employee efficiency, innovation output, and firm value, indicating that investing in employee benefits ultimately translates into better financial performance. Collectively, we shed light on the unique role of cultural norms in fostering employee treatment policies and their consequential effects on organizational value.

The Impact of Glucagon-like Peptide 1 Receptor Agonists on Obstructive Sleep Apnoea: A Scoping Review.

Obstructive sleep apnoea (OSA) and associated hypopnoea syndromes are chronic conditions of sleep-disordered breathing with significant sequelae if poorly managed, including hypertension, cardiovascular disease, metabolic syndrome and increased mortality. Glucagon-like peptide 1 receptor agonists (GLP-1RA) have recently garnered significant interest as a potential therapeutic, attributed to their durable effects in weight loss and glycaemic control in metabolic syndromes, such as obesity and type 2 diabetes mellitus. This has led to significant investment into companies that produce these medications and divestment from traditional gold standard methods of OSA management such as continuous positive airway pressure machines. Despite these sentiments, the impacts of these medications on OSA outcomes are poorly characterised, with no high-quality evidence at this stage to support this hypothesis. This scoping review therefore aims to address the research question of whether GLP-1RAs lead to a direct improvement in OSA and associated hypopnoea syndromes. A scoping review was performed following a computer-assisted search of Medline, Embase and Cochrane Central databases. Papers that evaluated the use of GLP-1RA medications related to sleep-disordered breathing, OSA or other sleep-related apnoeic or hypopnoeic syndromes were included. Literature search and evaluation identified 9 articles that were eligible for inclusion. Of these, 1 was a study protocol, 1 was a case report, 1 was an abstract of a randomised controlled trial (RCT), 1 was a non-randomised clinical trial and the remaining 5 were randomised clinical trials of variable rigour. All studies evaluated the outcomes of GLP-1RAs in patients with diagnosed OSA or symptoms suggestive of this condition. This scoping review identified early evidence to suggest that GLP-1RAs may improve OSA as defined by reduction in apnoea-hypopnoea index (AHI). This evidence is however conflicting due to contradicting results demonstrated from other studies. Overall, these medications were tolerated well, with minor gastrointestinal side-effects reported in some cases. Of all included studies, the quality of evidence was low, with short lengths of follow-up to identify durable effects of these medications on OSA outcomes and identify adverse events. More rigorous, RCTs with sufficient length of follow-up are required before consideration of formalising these medications into OSA treatment guidelines, frameworks and policies are warranted.

Evaluating Policies of Expanding Versus Restricting First-Line Treatment Choices: A Cost-Effectiveness Analysis Framework

ObjectivesHealthcare payers often implement coverage policies that restrict the utilization of costly new first-line treatments. Cost-effectiveness analysis can be conducted to inform these decisions by comparing the new treatment with an existing one. However, this approach may overlook important factors such as treatment effect heterogeneity and endogenous treatment selection, policy implementation costs, and diverse patient preferences across multiple treatment options. We aimed to develop a cost-effectiveness analysis framework that considers these real-world factors, facilitating the evaluation of alternative policies related to expanding or restricting first-line treatment choices. MethodsWe introduced a metric of incremental cost-effectiveness ratio (ICER) that compares an expanded choice set (CS) including the new first-line treatment with a restricted CS excluding the new treatment. ICER(CS) accounts for treatment selection influenced by heterogeneous treatment effects and policy implementation costs. We examined a basic scenario with 2 standard first-line treatment choices and a more realistic scenario involving diverse preferences toward multiple choices. To illustrate the framework, we conducted a retrospective evaluation of including versus excluding abiraterone acetate plus prednisone (AAP) (androgen deprivation therapy [ADT] + AAP) as a first-line treatment for metastatic hormone-sensitive prostate cancer. ResultsThe traditional ICERs for ADT + AAP versus ADT alone and ADT+ docetaxel were $104 269 and $206 324/quality-adjusted life-year, respectively. The ICER(CS) for comparing an expanded CS with ADT + AAP with a restricted CS without ADT + AAP was $123 179/quality-adjusted life-year. ConclusionsThe proposed framework provides decision makers with policy-relevant tools, enabling them to assess the cost-effectiveness of alternative policies of expanding versus restricting patients’ and physicians’ first-line treatment choices.

Public water quality in surface and groundwater collection systems in Brazil

Water is a vital natural resource for the existence of life, maintenance of ecosystems and the development of society. Many cities and communities rely on surface catchment systems, which involve collecting water from rivers, lakes and dams. Others, in turn, use underground collection systems, obtaining water from aquifers and artesian wells. Each of these methods presents specific challenges regarding water quality, as surface water is more exposed to organic and inorganic pollutants, while groundwater may contain minerals and dissolved substances that affect its potability. In general, the quality of water that reaches homes and commercial establishments is determined by the analysis of microbiological indicators, free residual chlorine, turbidity, total coliforms and fluoride. This narrative review seeks to clarify the nuances of water capture systems, their particularities and the factors that affect water quality in Brazil, highlighting the importance of constant monitoring, adequate treatment and effective water management policies in guaranteeing access to fresh water high quality for everyone.

Contrasting income-based inequalities in incidence and mortality of breast cancer in Korea, 2006-2015.

Breast cancer incidence and mortality rates in Korea are increasing. This study analyzed income-based inequalities in the incidence and mortality of women breast cancer from 2006 to 2015, using national data that covered all Korean women. We used the National Health Information Database from 2006 to 2015. For women aged 20 and older, the age-standardized incidence and mortality rates of breast cancer per 100,000 by income quintile per year were calculated using the direct method. The rate ratio and rate difference (RD) of the age-standardized incidence and mortality rates of breast cancer per 100,000 between the top and bottom income quintiles were calculated as relative and absolute measures for inequalities. When comparing 2006 and 2015, both the incidence and mortality rates of breast cancer increased. The lowest income quintile experienced higher mortality rates despite having lower incidence rates. In 2015, the income-based RD in incidence and mortality rates between the highest and lowest income quintiles (Q1-Q5) was -19.9 (95% confidence interval [CI], -24.3 to -15.5) and 4.4 (95% CI, 2.9 to 5.8), respectively. Throughout this period, there was no statistically significant trend in income-based disparities in breast cancer incidence and mortality. The age-specific contributions to the absolute magnitude of inequality (RD) in incidence and mortality were more pronounced among middle-aged women than among older women. This study found that breast cancer in Korea exhibited pro-rich inequalities in mortality despite pro-poor inequalities in incidence. More equitable policies for screening and treatment of breast cancer are needed.