Evaluating the impact of COVID-19 on medication adherence and health care utilization among individuals with psychotic disorders who are prescribed long-acting injectables (LAIs) or clozapine: A population-based study in Manitoba, Canada.

BACKGROUND: Ongoing psychiatric follow-up and medication adherence improve outcomes for patients with psychotic disorders. Due to COVID-19, outpatient care may have been disrupted, impacting healthcare utilization. METHODS: A retrospective population-wide study was conducted for adults in Manitoba, Canada. Medication adherence and healthcare utilization were examined from 2019 to 2021. The presence of a diagnosed psychotic disorder was identified in the five years before the index date in each year. The LAI and clozapine cohorts consisted of those who received at least two prescriptions in each year 180 days before the March 20th index date. The change in adherence was measured using the average Medication Possession Ratio. Healthcare utilization rates were compared using Generalized Estimating Equation models. RESULTS: There were no significant differences between LAI and clozapine discontinuation rates before and during the pandemic. In the LAI cohort, general practitioner visits decreased significantly (-3.5 %, p = 0.039) across four quarters of 2021 versus 2019. All-cause hospitalizations decreased by 16.8 % in 2020 versus 2019 (p = 0.0055), while psychiatric hospitalizations decreased by 18.7 % across four quarters in 2020 (p = 0.0052) and 13.7 % in 2021 (p = 0.0425), versus 2019 in the LAI cohort. There was a significant transition to virtual care during the first wave of COVID-19 (71 % in clozapine, 51 % in LAI cohorts). Trends in total outpatient visits and non-psychiatric hospitalizations remained stable. CONCLUSION: COVID-19 had no substantial impact on LAI and clozapine discontinuation rates for patients previously adherent. Outpatient care remained stable, with a significant proportion of visits being done virtually at the outset of the pandemic.

The fusion of vegetation indices increases the accuracy of cotton leaf area prediction.

Introduction: Rapid and accurate estimation of leaf area index (LAI) is of great significance for the precision agriculture because LAI is an important parameter to evaluate crop canopy structure and growth status. Methods: In this study, 20 vegetation indices were constructed by using cotton canopy spectra. Then, cotton LAI estimation models were constructed based on multiple machine learning (ML) methods extreme learning machine (ELM), random forest (RF), back propagation (BP), multivariable linear regression (MLR), support vector machine (SVM)], and the optimal modeling strategy (RF) was selected. Finally, the vegetation indices with a high correlation with LAI were fused to construct the VI-fusion RF model, to explore the potential of multi-vegetation index fusion in the estimation of cotton LAI. Results: The RF model had the highest estimation accuracy among the LAI estimation models, and the estimation accuracy of models constructed by fusing multiple VIs was higher than that of models constructed based on single VIs. Among the multi-VI fusion models, the RF model constructed based on the fusion of seven vegetation indices (MNDSI, SRI, GRVI, REP, CIred-edge, MSR, and NVI) had the highest estimation accuracy, with coefficient of determination (R2), rootmean square error (RMSE), normalized rootmean square error (NRMSE), and mean absolute error (MAE) of 0.90, 0.50, 0.14, and 0.26, respectively. Discussion: Appropriate fusion of vegetation indices can include more spectral features in modeling and significantly improve the cotton LAI estimation accuracy. This study will provide a technical reference for improving the cotton LAI estimation accuracy, and the proposed method has great potential for crop growth monitoring applications.

Physiologically-Based Pharmacokinetic Modeling and In Vitro-In Vivo Correlation of TV-46000 (Risperidone LAI): Prediction from Dog to Human.

The interest in the development and therapeutic application of long-acting injectable products for chronic or long-term treatments has experienced exponential growth in recent decades. TV-46000 (Uzedy, Teva) is a long-acting subcutaneous (sc) injectable formulation of risperidone, approved for the treatment of schizophrenia in adults. Following sc injection, the copolymers together with risperidone precipitate to form a sc depot under the skin to deliver therapeutic levels of risperidone over a prolonged period of either 1 month or 2 months, depending upon the dose. This work presents the strategy and the results of the physiologically-based pharmacokinetic (PBPK) modeling and establishing of in vitro-in vivo correlation (IVIVC) for the prediction of TV-46000 pharmacokinetic profile in humans, using in vitro release, intravenous (iv), and sc single-dose pharmacokinetic data in beagle dogs. The resulting simulated TV-46000 PK profile in humans showed that the shape of the predicted risperidone and its active metabolite 9-OH-risperidone PK profiles was different from the observed one, thus suggesting that the TV-46000 release profile was species-dependent and cannot be directly extrapolated from dog to human. In conclusion, while level A IVIVC cannot be claimed, this work combining PBPK and IVIVC modeling represents an interesting alternative approach for complex injectable formulations where classical methods are not applicable.

[Long-acting injection therapies: New opportunities and challenges]. / Lang wirksame Injektionstherapien: Chance und Herausforderung.

Since the development of an effective antiretroviral therapy (ART) in 1996, substantial progress has been made in terms of efficacy, safety and ease of use. While at the beginning of the ART era the foremost goal necessarily was patient survival, over time it has become increasingly possible to shift the focus towards aspects of patient's quality of life. The latest developments are the long-acting injection therapies (LAI), foregoing for the first time the necessity to take pills. The only available injection therapy so far comprises 2 intramuscular injections every 2 months, with 3 ml of Cabotegravir 600 mg and 3 ml of Rilpivirine 900 mg being injected, respectively. Through this, patient's needs that were hitherto precluded from consideration could be addressed. These needs are inextricably linked to the stigmata people living with HIV (PLWH) are still confronted with on a daily basis. LAI have the potential to relieve PLWH of some of the heavy psychological burdens associated with the continued stigmatization. However, as a new therapy, new challenges need to be considered the use of LAI.

Recommendations from Black and Latinx sexual minority males to include pharmacists to increase greater accessibility and OnlyFans stars to promote uptake of injectable PrEP.

BACKGROUND: Pre-exposure Prophylaxis (PrEP) medication is the keystone of preventative measures to curtail the spread of HIV. However, oral PrEP, the pill intended to prevent HIV, has been slow to proliferate among men who have sex with men (MSM). This is of major concern as MSM account for the largest number of new HIV diagnoses in the U.S. More recently, the newest generation of PrEP in the form of a long-acting injectable (LAI) is to be administered every two months as an intramuscular injection and many MSM indicate preferring LAI-PrEP to the oral form of PrEP. However, uptake of PrEP, in all forms, remains low. Research is sparse that focuses on LAI-PrEP uptake among Black/African American and Latinx men who have sex with men (BLMSM). OBJECTIVE: To address this concern, this study explored the willingness to uptake LAI-PrEP, and recommendations for increasing awareness and encouraging uptake of LAI-PrEP among BLMSM. METHODS: Qualitative data were collected between February 2022 to December 2022 through focus groups via Zoom with BLMSM (N=30; Black=14, Latinx=16) aged 18 to 29 (Mean = 23, SD = 3) in Los Angeles County. RESULTS: Findings revealed that while 90% of BLMSM were aware of PrEP in oral form, only 10% were aware of LAI-PrEP. Findings from the qualitative analysis suggested to consider self-administration of LAI-PrEP, allow local community pharmacists to assess and administer it, and promote uptake of LAI-PrEP using high-profile male content creators and stars on OnlyFans social media platform. CONCLUSION: Increasing PrEP uptake, in all forms available, such as promoting awareness through popular social media stars, and engaging community pharmacists in feasible ways, is critical for addressing the disproportionate impact of HIV among the BLMSM community.

Association between the irrigation-agitation techniques and Periapical Healing of large periapical lesions: a Randomized Controlled Trial.

OBJECTIVES: The aim of this study was to evaluate the effects of manual dynamic activation (MDA), passive ultrasonic irrigation (PUI), and laser-activated irrigation (shock wave-enhanced emission photoacoustic streaming (SWEEPS)) on the periapical healing of large periapical lesions following nonsurgical root canal treatment. MATERIALS AND METHODS: A total of fifty-six systemically healthy patients with a mandibular single-rooted tooth with periapical lesions of endodontic origin and a periapical index score of 3 or higher were included in the study. Before the treatment procedures, lesion volumes were determined volumetrically using cone-beam computed tomography (CBCT). Patients were randomized into treatment (MDA, PUI, SWEEPS) and control groups (n = 14). Root canal treatment and irrigation procedures were performed by a calibrated postgraduate operator and completed at one visit. For routine follow-up, clinical and radiographic evaluations were performed by a blinded evaluator using periapical (PA) radiographs according to Molven's criteria at 3, 6, and 9 months. At 12 months, lesion volumes were quantified volumetrically using CBCT (ITK-SNAP). The data were statistically analyzed with the Wilcoxon test. The significance level was set at p < 0.05. RESULTS: In all groups, the mean lesion volume after treatment was significantly smaller than the mean volume before treatment (p = 0.001). Among the 56 teeth, 11 teeth were 'totally healed', and 39 teeth were 'reduced' on PA radiographs. No 'enlargement' was detected in any group. On CBCT, the lesion volume decreased in the following order: LAI-SWEEPS (86.9%) > PUI (85.4%) > MDA (80.4%) > control (74.5%), with no statistically significant difference (p > 0.05). CONCLUSIONS: Despite the limitations of the present study, although a greater percentage of healing was observed in the LAI-SWEEPS and PUI groups, irrigation procedures had no statistically significant effect on the healing of periapical lesions with a single root canal at the 12-month follow-up. On the other hand, the outcome may change in multirooted teeth with curved and complex root canal systems. CLINICAL RELEVANCE: In the short term and in single-canal teeth, advanced irrigation agitation methods such as laser and ultrasonic did not make a difference in healing other than manual irrigation agitation.

Rural ambulatory care pharmacists providing in-clinic and home visit services improve adherence to long-acting injectable antipsychotics.

Patients with schizophrenia often experience symptoms such as poor insight and disorganized thought, which limit their ability to seek and receive care consistently. In rural settings, systemic factors, including limited resources and transportation, further contribute to difficulties in health care access. Long-acting injectable antipsychotics (LAIs) can improve medication adherence and reduce hospitalizations from relapse. Opportunities exist for pharmacists to provide individualized care and improved health care access. The pilot service took place in ambulatory care clinics and home care settings. Pharmacists performed weekly reviews of patients with active orders for LAIs, coordinated care with nonadherent patients, and offered follow-up appointments in the Patient Centered Medical Home (PCMH). For patients unable to be reached, outreach pharmacists provided psychiatric assessment and LAI medication administration at home visits. There were 10 patients with LAI prescriptions in the past year selected for review. The period reviewed was 90 days before and after start of service. Pharmacist interventions resulted in 4 patients reestablished with care who were previously lost to follow-up. The percentage of days covered by LAI fills increased from an average 26% to 67% of days covered (P = .06). Total emergency room visits related to mental health episodes decreased from 11 to 2 visits (P = .03). Four patients who did not have metabolic lab monitoring in more than 1 year received lab monitoring as indicated. PCMH pharmacy services, including home visits by outreach pharmacists, may improve access and bridge care gaps for patients on LAIs by providing community-based services in addition to traditional clinic-based care.

Long-acting intramuscular injections of ELQ-331, an antimalarial agent.

The overarching premise of this investigation is that injectable, long-acting antimalarial medication would encourage adherence to a dosage regimen for populations at risk of contracting the disease. To advance support for this goal, we have developed oil-based formulations of ELQ-331 (a prodrug of ELQ-300) that perform as long-acting, injectable chemoprophylactics with drug loading as high as 160 mg/ml of ELQ-331. In a pharmacokinetic study performed with rats, a single intramuscular injection of 12.14 mg/kg maintained higher plasma levels than the previously established minimum fully protective plasma concentration (33.25 ng/ml) of ELQ-300 for more than 4 weeks. The formulations were well tolerated by the rats and the tested dose produced no adverse reactions. We believe that by extending the length of time between subsequent injections, these injectable oil-based solutions of ELQ-331 can offer a more accessible, low-cost option for long-acting disease prevention and reduced transmission in malaria-endemic regions and may also be of use to travelers.

Combination of Two Long-Acting Antipsychotics in Schizophrenia Spectrum Disorders: A Systematic Review.

BACKGROUND: Up to 34% of patients with schizophrenia are resistant to several treatment trials. Lack of continuous and adequate treatment is associated with relapse, rehospitalization, a lower effect of antipsychotic therapy, and higher risk of side effects. Long-acting injectables antipsychotics (LAI APs) enhance compliance and improve clinical outcomes and quality of life in patients with schizophrenia, and thus it may be advisable to administer two LAI APs at the same time in cases of treatment-resistant schizophrenia. The purpose of this review is to summarize the available literature regarding the combined use of two LAI APs in patients with schizophrenia or other psychotic spectrum disorders. METHODS: An extensive literature search for relevant articles regarding any combination of two long-acting injectable antipsychotics has been performed from inception up to 9 February 2024, on PubMed, Scopus and APA PsycInfo, according to the PRISMA statement. Only studies reporting combination of two LAI APs and its clinical outcome in patients with schizophrenia and related disorders were selected. RESULTS: After the selection process, nine case reports, four case series and two observational retrospective studies were included in the final analysis. All patients treated with dual LAI APs reported a good response, and no new or unexpected adverse effects due to the combination of two LAIs were reported. Different drug combinations were used, and the most frequent association resulted in aripiprazole monohydrate + paliperidone palmitate once monthly (32 times). CONCLUSIONS: Our review highlights that the treatment regimen with two concurrent LAI APs is already widely used in clinical practice and is recognized as providing a promising, effective, and relatively safe therapeutic strategy for treating the schizophrenia spectrum disorders.

CMIP6 ESMs overestimate greening and the photosynthesis trends in Dryland East Asia.

The Dryland East Asia (DEA) is one of the largest inland arid regions, and vegetation is very sensitive to climate change. The complex environment in DEA with defects of modeling construction make it difficult to simulate and predict changes in vegetation structure and productivity. Here, we use the emergent constraint (EC) method to constrain the future interannual leaf area index (LAI) and gross primary productivity (GPP) trends in DEA, under four scenarios of the latest Sixth Coupled Model Intercomparison Project (CMIP6) model ensemble. LAI and GPP increase in all scenarios in the near term (2015-2050), with continued growth in SSP370 and SSP585 and stasis in SSP126 and SSP245 in the far term (2051-2100). However, after building effective EC relationships, the constrained increasing trends of LAI (GPP) are reduced by 43.5 %-53.9 % (30.5 %-50.0 %) compared with the uncertainties of the original ensemble, which are reduced by 10.0 %-45.7 % (4.6 %-34.3 %). We also extend the EC in moving windows and grid cells, further strengthening the robustness of the constraints, especially by illustrating spatial sources of these emergent relationships. Overestimations of LAI and GPP trends suggest that current CMIP6 models may be insufficient to capture the complex relationships between climate change and vegetation dynamics in DEA; however, these models can be adjusted based on established emergent relationships.

Acceptability of Long-Acting Injectable Antiretroviral Therapy Among People with HIV Receiving Care at Three Ryan White Funded Clinics in the United States.

Understanding the acceptability of long-acting injectable antiretroviral therapy (LAI-ART) among people with HIV (PWH), especially priority populations, is essential for effective implementation. We conducted semi-structured interviews with patients in three Ryan White-funded HIV clinics in San Francisco, Chicago, and Atlanta. We employed maximal variation sampling across age, gender, race, ethnicity, and time living with HIV and oversampled for individuals with suboptimal clinical engagement. An 8-step hybrid deductive and inductive thematic analysis approach guided data analysis. Between August 2020 and July 2021, we conducted 72 interviews. Median age was 46 years; 28% were ciswomen, 7% transwomen, 44% Black/African-American and 35% Latinx, 43% endorsed a psychiatric diagnosis, 35% were experiencing homelessness/unstable housing, and 10% had recent substance use. Approximately 24% were sub-optimally engaged in care. We observed a spectrum of LAI-ART acceptability, ranging from enthusiasm to hesitancy to rejection. We also characterized four emergent orientations towards LAI-ART: innovator, pragmatist, deliberator, and skeptic. Overall, the majority of participants expressed favorable initial reactions towards LAI-ART. Most approached LAI-ART pragmatically, but acceptability was not static, often increasing over the course of the interview. Participants considered their HIV providers as essential for affirming personal relevance. HIV stigma, privacy concerns, and medical mistrust had varied impacts, sometimes facilitating and other times hindering personal relevance. These findings held across priority populations, specifically young adults, cis/trans women, racial/ethnic minorities, and individuals with suboptimal clinical engagement. Further research is needed to explore the transition from hypothetical acceptance to uptake and to confirm the actual benefits and drawbacks of this treatment.

RESUMEN: La aceptabilidad de la terapia antirretroviral inyectable de acción prolongada (LAI-ART, por su sigla en inglés) entre personas con VIH es esencial para una implementación efectiva. Durante el periodo de agosto de 2020 a julio de 2021, realizamos 72 entrevistas semiestructuradas con personas con VIH en clínicas públicas ubicadas en San Francisco, Chicago y Atlanta. Un análisis temático, tanto deductivo como inductivo, guio nuestra investigación. Observamos un espectro de aceptabilidad de LAI-ART que va desde el entusiasmo hasta la indecisión y el rechazo. También caracterizamos cuatro orientaciones actitudinales emergentes hacia LAI-ART: innovadora, pragmática, deliberativa y escéptica. Los participantes también señalaron la importancia de sus proveedores de VIH para validar su relevancia personal. El estigma asociado al VIH, preocupaciones sobre la privacidad y desconfianza en el sistema médico tuvieron diversos impactos, a veces facilitando y otras veces obstaculizando la relevancia personal. Entre las poblaciones prioritarias del estudio, los resultados fueron consistentes.

A case report of LAI two injection start in a 16-year-old adolescent with severe manic episode and comorbid cannabinoid use disorder.

There is a lack of randomized clinical trials and few studies regarding long-acting injectable antipsychotics (LAIs) in adolescents. Non-adherence, aggressiveness, comorbid substance use disorder and lack of insight may represent the main reasons for starting LAIs. Hereby we describe a 16-year-old male adolescent subject with bipolar type I disorder and comorbid cannabinoid use disorder, successfully treated with two-injection start regimen of LAI aripiprazole. Two-injection start regime of aripiprazole could represent an effective and safe therapeutic option for adolescents with early onset bipolar disorder.

Long-acting second-generation injectable antipsychotics for the maintenance treatment of bipolar disorder: a narrative review.

INTRODUCTION: Non-adherence to medication significantly affects bipolar disorder outcomes. Long-Acting Injectable antipsychotics show promise by ensuring adherence and averting relapses. AREAS COVERED: This narrative review sought to evaluate the efficacy of second-generation injectable antipsychotics in bipolar disorder through searches in Embase, MEDLINE, and PsycInfo for randomized controlled trials and mirror-image studies.Risperidone and aripiprazole Long-Acting Injectables demonstrated effectiveness in preventing mood recurrences compared to placebos in adults with bipolar disorder. They showed superiority in preventing mania/hypomania relapses over placebos but did not appear to significantly outperform active oral controls. Notably, active controls seem to be more effective in preventing depression relapses than Long-Acting Injectables. Mirror-Image studies point toward the reduction of hospitalization rates following LAI initiation. EXPERT OPINION: The available evidence points thus toward the efficacy of LAIs, especially in managing manic episodes and reducing hospitalizations, The current evidence does not however immediately support prioritizing LAIs over oral medications in bipolar disorder treatment. More high-quality studies, especially comparing LAIs directly with active controls, are crucial to gain a comprehensive understanding of their efficacy. These findings highlight the need for further research to guide clinicians in optimizing treatment strategies for bipolar disorder.

Continuous Microfluidic Antisolvent Crystallization as a Bottom-Up Solution for the Development of Long-Acting Injectable Formulations.

A bottom-up approach was investigated to produce long-acting injectable (LAI) suspension-based formulations to overcome specific limitations of top-down manufacturing methods by tailoring drug characteristics while making the methods more sustainable and cost-efficient. A Secoya microfluidic crystallization technology-based continuous liquid antisolvent crystallization (SCT-CLASC) process was optimized and afterward compared to an earlier developed microchannel reactor-based continuous liquid antisolvent crystallization (MCR-CLASC) setup, using itraconazole (ITZ) as the model drug. After operating parameter optimization and downstream processing (i.e., concentrating the suspensions), stable microsuspensions were generated with a final solid loading of 300 mg ITZ/g suspension. The optimized post-precipitation feed suspension consisted of 40 mg ITZ/g suspension with a drug-to-excipient ratio of 53:1. Compared to the MCR-CLASC setup, where the post-precipitation feed suspensions contained 10 mg ITZ/g suspension and had a drug-to-excipient ratio of 2:1, a higher drug concentration and lower excipient use were successfully achieved to produce LAI microsuspensions using the SCT-CLASC setup. To ensure stability during drug crystallization and storage, the suspensions' quality was monitored for particle size distribution (PSD), solid-state form, and particle morphology. The PSD of the ITZ crystals in suspension was maintained within the target range of 1-10 µm, while the crystals displayed an elongated plate-shaped morphology and the solid state was confirmed to be form I, which is the most thermodynamically stable form of ITZ. In conclusion, this work lays the foundation for the SCT-CLASC process as an energy-efficient, robust, and reproducible bottom-up approach for the manufacture of LAI microsuspensions using ITZ at an industrial scale.

Patient Education and Decision Support for Long-Acting Injectable HIV Antiretroviral Therapy: Protocol for Tool Development and Pilot Testing with Ryan White HIV/AIDS Program Medical Case Management Programs in New York.

BACKGROUND: Long-acting injectable (LAI) HIV antiretroviral therapy (ART) presents a major opportunity to facilitate and sustain HIV viral suppression, thus improving health and survival among people living with HIV and reducing the risk of onward transmission. However, realizing the public health potential of LAI ART requires reaching patients who face barriers to daily oral ART adherence and thus can clinically benefit from alternative treatment modalities. Ryan White HIV/AIDS Program Part A medical case management (MCM) programs provide an array of services to address barriers to HIV care and treatment among economically and socially marginalized people living with HIV. These programs have demonstrated effectiveness in improving engagement along the continuum of care, but findings of limited program impact on durable viral suppression highlight the need to further innovate and hone strategies to support long-term ART adherence. OBJECTIVE: This study aims to adapt and expand Ryan White MCM service strategies to integrate LAI ART regimen options, with the larger goal of improving health outcomes in the populations that could most benefit from alternatives to daily oral ART regimens. METHODS: In 3 phases of work involving patient and provider participants, this study uses role-specific focus groups to elicit perceptions of LAI versus daily oral ART; discrete choice experiment (DCE) surveys to quantify preferences for different ART delivery options and related supports; and a nonrandomized trial to assess the implementation and utility of newly developed tools at 6 partnering Ryan White HIV/AIDS Program Part A MCM programs based in urban, suburban, and semirural areas of New York. Findings from the focus groups and DCEs, as well as feedback from advisory board meetings, informed the design and selection of the tools: a patient-facing, 2-page fact sheet, including frequently asked questions and a side-by-side comparison of LAI with daily oral ART; a patient-facing informational video available on YouTube (Google Inc); and a patient-provider decision aid. Implementation outcomes, measured through provider interviews, surveys, and service reporting, will guide further specification of strategies to integrate LAI ART options into MCM program workflows. RESULTS: The study was funded in late April 2021 and received approval from the institutional review board in May 2021 under protocol 20-096. Focus groups were conducted in late 2021 (n=21), DCEs ran from June 2022 to January 2023 (n=378), and tools for piloting were developed by May 2023. The trial (May 2023 through January 2024) has enrolled >200 patients. CONCLUSIONS: This study is designed to provide evidence regarding the acceptability, feasibility, appropriateness, and utility of a package of patient-oriented tools for comparing and deciding between LAI ART and daily oral ART options. Study strengths include formative work to guide tool development, a mixed methods approach, and the testing of tools in real-world safety-net service settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT05833542; https://clinicaltrials.gov/study/NCT05833542. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56892.

Assessing tea plantations biophysical and biochemical characteristics in Northeast India using satellite data.

Despite advancements in using multi-temporal satellite data to assess long-term changes in Northeast India's tea plantations, a research gap exists in understanding the intricate interplay between biophysical and biochemical characteristics. Further exploration is crucial for precise, sustainable monitoring and management. In this study, satellite-derived vegetation indices and near-proximal sensor data were deployed to deduce various physico-chemical characteristics and to evaluate the health conditions of tea plantations in northeast India. The districts, such as Sonitpur, Jorhat, Sibsagar, Dibrugarh, and Tinsukia in Assam were selected, which are the major contributors to the tea industry in India. The Sentinel-2A (2022) data was processed in the Google Earth Engine (GEE) cloud platform and utilized for analyzing tea plantations biochemical and biophysical properties. Leaf chlorophyll (Cab) and nitrogen contents are determined using the Normalized Area Over Reflectance Curve (NAOC) index and flavanol contents, respectively. Biophysical and biochemical parameters of the tea assessed during the spring season (March-April) 2022 revealed that tea plantations located in Tinsukia and Dibrugarh were much healthier than the other districts in Assam which are evident from satellite-derived Enhanced Vegetation Index (EVI), Modified Soil Adjusted Vegetation Index (MSAVI), Leaf Area Index (LAI), and Fraction of Absorbed Photosynthetically Active Radiation (fPAR), including the Cab and nitrogen contents. The Cab of healthy tea plants varied from 25 to 35 µg/cm2. Pearson correlation among satellite-derived Cab and nitrogen with field measurements showed R2 of 0.61-0.62 (p-value < 0.001). This study offered vital information about land alternations and tea health conditions, which can be crucial for conservation, monitoring, and management practices.

The role of partial area under the curve and maximum concentrations in assessing the bioequivalence of long-acting injectable formulation of exenatide_A sensitivity analysis.

To ensure therapeutic equivalence between the long-acting injectable (LAI) products, additional PK metrics other than Cmax and AUC were considered necessary. However, regarding the selection of additional PK metrics for bioequivalence (BE) assessment of exenatide LAI, a discrepancy existed between EMA's and USFDA's product-specific guidance. The EMA recommends that both the maximum plasma concentration in the initial-release phase (Cmax,1) and the extended-release phase (Cmax,2) should be determined. Nevertheless, the USFDA recommends the use of the partial area under the curve (i.e., the area under the curve from week 4 to the last sampling point; pAUC4w-t). The focus of this study was to compare the sensitivity of different PK metrics, including Cmax,1, Cmax,2, pAUC4w-t, early and late pAUC metrics truncated at different time points (three, four, five, six and seven weeks), to formulation-related parameters and pharmacodynamic (PD) markers of glycemic control. A sensitivity analysis was conducted using the published PK/PD model of exenatide LAI. The results indicated that Cmax,1 and Cmax,2 exhibited comparable sensitivities. AUC4w-t was sensitive to changes in detecting the differences in formulation-related parameters and PD markers of glycemic control, but did not provide superior sensitivity performance compared to Cmax,1 and Cmax,2. Among all tested PK metrics, AUC7w-t was found to be the most sensitive. The optimal cut-off time point for the pAUC should be set at the time of maximum plasma concentration in the extended-release phase (approximately 6-7 weeks). These results may provide useful insights into the selection of appropriate PK metrics for BE determination of exenatide LAI.

Neural basis of writing in prodromal to mild dementia with lewy bodies.

OBJECTIVES: We have previously demonstrated difficulties in written production in dementia with Lewy bodies (DLB) patients. We now aim to determine the neural correlates of writing production in DLB, combining clinical data and structural MRI measures. METHOD: Sixteen prodromal to mild DLB patients were selected to participate in the study. The GREMOTS test was used to assess writing production. Using three-dimensional T1 brain MRI images, correlations between the GREMOTS test and grey matter (GM) volume were performed using voxel-based morphometry (VBM; SPM12, XjView and Matlab R2021b softwares). RESULTS: VBM analysis (p < 0.001, uncorrected) revealed a positive and significant correlation between both left anterior insula and left supramarginal gyrus GM volumes and DLB patients' ability to write logatoms using the phonological route. The handwriting deficit was negatively and significantly correlated to the supplementary motor area. The parkinsonism-like characteristics of agraphia were negatively and significantly correlated with both right anterior and right posterior cerebellum GM volumes. Our study also revealed a negative and significant correlation between grammatical spelling impairments and an area of the orbitofrontal gyrus, and a negative and significant correlation between supramarginal gyrus and general slowness in dictation tasks. CONCLUSION: Writing disorders in early DLB patients appears to be GM decreases in several brain regions, such as the left anterior insula, the left supramaginal gyrus, as well as two areas of the right cerebellum.

Injectable long-acting ivacaftor-loaded poly (lactide-co-glycolide) microparticle formulations for the treatment of cystic fibrosis: In vitro characterization and in vivo pharmacokinetics in mice.

Optimizing a sustained-release drug delivery system for the treatment of cystic fibrosis (CF) is crucial for decreasing the dosing frequency and improving patients' compliance with the treatment regimen. In the current work, we developed an injectable poly(D,L-lactide-co-glycolide) (PLGA) microparticle formulation loaded with ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that increases the open probability of the CFTR anion channel, using a single emulsion solvent evaporation technique. We aimed to study the effect of different parameters on the characteristics of the prepared formulations to select an optimized microparticle formulation to be used in an in vivo pharmacokinetic study in mice. First, a suite of ivacaftor-loaded microparticles were prepared using different formulation parameters in order to study the effect of varying these parameters on microparticle size, morphology, drug loading, encapsulation efficiency, and in vitro release profiles. Prepared microparticles were spherical with diameters ranging from 1.91-6.93 µm, percent drug loading (% DL) of 3.91-10.3%, percent encapsulation efficiencies (% EE) of 26.6-100%, and an overall slow cumulative release profile. We selected the formulation that demonstrated optimal combined % DL and % EE values (8.25 and 90.7%, respectively) for further studies. These microparticles had an average particle size of 6.83 µm and a slow tri-phasic in vitro release profile (up to 6 weeks). In vivo pharmacokinetic studies in mice showed that the subcutaneously injected microparticles resulted in steady plasma levels of ivacaftor over a period of 28 days, and a 6-fold increase in AUC 0 - t (71.6 µg/mL*h) compared to the intravenously injected soluble ivacaftor (12.3 µg/mL*h). Our results suggest that this novel ivacaftor-loaded microparticle formulation could potentially eliminate the need for the frequent daily administration of ivacaftor to people with CF thus improving their compliance and ensuring successful treatment outcomes.

Assessment of Forest Ecosystem Variations in the Lancang-Mekong Region by Remote Sensing from 2010 to 2020.

Five countries in the Lancang-Mekong region, including Myanmar, Laos, Thailand, Cambodia, and Vietnam, are facing the threat of deforestation, despite having a high level of forest coverage. Quantitatively assessing the forest ecosystem status and its variations based on remote sensing products for vegetation parameters is a crucial prerequisite for the ongoing phase of our future project. In this study, we analyzed forest health in the year 2020 using four vegetation indicators: forest coverage index (FCI), leaf area index (LAI), fraction of green vegetation cover (FVC), and gross primary productivity (GPP). Additionally, we introduced an ecosystem quality index (EQI) to assess the quality of forest health. To understand the long-term trends in the vegetation indicators and EQI, we also performed a linear regression analysis from 2010 to 2020. The results revealed that Laos ranked as the top-performing country for forest ecosystem status in the Lancang-Mekong region in 2020. However, the long-term trend analysis results showed that Cambodia experienced the most significant decline across all indicators, while Vietnam and Thailand demonstrated varying degrees of improvement. This study provides a quality assessment of forest health and its variations in the Lancang-Mekong region, which is crucial for implementing effective conservation strategies.