Duration Of Treatment Research Articles

Efficacy and Safety of CDK4/6 Inhibitors: A Focus on HR+/HER2- Early Breast Cancer.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone-receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer, and are now also established agents in the treatment of high-risk and intermediate-risk HR+ early breast cancer. Several strategies regarding CDK4/6i combinations or continuation beyond progression have been successfully evaluated in the metastatic setting, and are considered a standard of care. Mechanism of action of and resistance mechanisms against CDK4/6i in addition to endocrine resistance represent an important research topic, important for the treatment of HR+ breast cancer. Clinically, CDK4/6i are efficient substances that are usually well tolerated. However, side effects differing between the substances have been reported, and might lead to treatment discontinuation, including in the early disease setting. In the adjuvant setting, the addition of palbociclib to standard endocrine treatment has not improved outcomes, whereas large randomized phase III trials have demonstrated significant disease-free survival benefit for the addition of ribociclib (NATALEE trial) and abemaciclib (monarchE trial). Patient selection, treatment duration, endocrine backbone therapy, and other study details differ between these pivotal trials. This review focuses on both the scientific background as well as all available clinical data of CDK4/6i, with particular emphasis on their use in early breast cancer.

Talimogene laherparepvec (T-VEC) as a treatment for melanoma: A systematic review.

Melanoma now presents an average risk of 1 in 50 in the Western world. Talimogene laherparepvec (T-VEC), an FDAapproved oncolytic virus derived from Herpes Simplex Virus type 1 (HSV-1), has proven effective in reducing morbidity and mortality from melanoma but causes adverse effects like chills, fever, exhaustion, and injection site discomfort. Research focuses on combining T-VEC with immune checkpoint inhibitors, such as pembrolizumab, to enhance its efficacy and broaden its application. A systematic search was conducted using PubMed, Scopus, Web of Science, Google Scholar, and ProMED, adhering to PRISMA guidelines. Results were tabulated and analyzed. This review included 15 studies comprising nine cohorts, four case reports, a case series, and a randomized control trial, involving 779 melanoma patients in stages IIIB to IV, 58% of whom were male with a mean age of 65 years. Treatment duration with T-VEC averaged 35.07 weeks, with dosages ranging from 10^6 to 10^8 PFU/ml. The intervention yielded a mean DRR of 41.87% and an ORR of 62.2%. The most common side effect was chills, affecting 21.69% of participants. Pyrexia was reported by 20.41% of participants, followed by influenzalike illness (14.89%). T-VEC effectively improves ORR and DRR in melanoma patients. However, further research is needed on combination therapy prospects and its adverse effects.

Prognostic impact of psychoeducation program completion on inpatients with schizophrenia: a pilot cohort study

BackgroundPsychoeducation programs can reduce the risk of recurrence and readmission in patients with schizophrenia. However, almost all previous studies of program efficacy have included only patients completing the program, which may not be possible in all cases. The objective of this pilot cohort study was to compare the prognoses of inpatients with schizophrenia who did or did not complete a well-established institutional psychoeducation program.MethodsThis study is a pilot cohort study, and the participants were 32 inpatients in the psychiatric acute care ward. Among these patients, 18 completed the institutional psychoeducation program by discharge, whereas 14 missed one or more sessions for various reasons. The primary outcome was the duration of outpatient treatment (DOT) during the 5-year follow-up period, and the secondary outcomes were comparisons of the risk of all-cause discontinuation for outpatient treatment and correlations between the program participation rates and DOT.ResultsDOT was significantly longer in the program completion group than in the noncompletion group (918.2 (174.3) days vs. 225.5 (35.7) days, p = 0.001), and multivariate Cox proportional hazards regression analysis revealed that program noncompliance was associated with a 4.450-fold (p = 0.002) greater risk of discontinuation of outpatient treatment according to multivariate analysis. A significant weak correlation was found for DOT and rates of sessions admitted to the programme (Pearson's r = 0.384, p = 0.030).ConclusionsCompletion of a psychoeducation program could enhanced the success of outpatient treatment. As psychoeducation and related factors may have a positive effect of the prognosis after discharge, inpatient psychoeducation programs should be flexible enough to provide opportunities for completion.

Exploration of an adaptive proton therapy strategy using CBCT with the concept of digital twins

Objective.This study aims to develop a digital twin (DT) framework to achieve adaptive proton prostate stereotactic body radiation therapy (SBRT) with fast treatment plan selection and patient-specific clinical target volume (CTV) setup uncertainty. Prostate SBRT has emerged as a leading option for external beam radiotherapy due to its effectiveness and reduced treatment duration. However, interfractional anatomy variations can impact treatment outcomes. This study seeks to address these uncertainties using DT concept to improve treatment quality.Approach. A retrospective study on two-fraction prostate proton SBRT was conducted, involving a cohort of 10 randomly selected patient cases from an institutional database (n= 43). DT-based treatment plans were developed using patient-specific CTV setup uncertainty, determined through machine learning predictions. Plans were optimized using pre-treatment CT and corrected cone-beam CT (cCBCT). The cCBCT was corrected for CT numbers and artifacts, and plan evaluation was performed using cCBCT to account for actual patient anatomy. The ProKnow scoring system was adapted to determine the optimal treatment plans.Main Results.Average CTV D98 values for original clinical and DT-based plans across 10 patients were 99.0% and 98.8%, with hot spots measuring 106.0% and 105.1%. Regarding bladder, clinical plans yielded average bladder neck V100 values of 29.6% and bladder V20.8 Gy values of 12.0cc, whereas DT-based plans showed better sparing of bladder neck with values of 14.0% and 9.5cc. Clinical and DT-based plans resulted in comparable rectum dose statistics due to SpaceOAR. Compared to clinical plans, the proposed DT-based plans improved dosimetry quality, improving plan scores ranging from 2.0 to 15.5.Significance.Our study presented a pioneering approach that leverages DT technology to enhance adaptive proton SBRT, potentially revolutionizing prostate radiotherapy to offer personalized treatment solutions using fast adaptive treatment plan selections and patient-specific setup uncertainty. This research contributes to the ongoing efforts to achieve personalized prostate radiotherapy.

The Role of Acupuncture and Stem Cell Therapy in Enhancing Stroke Recovery

Stroke is an acute neurological disorder caused by disrupted blood flow to the brain, depriving cells of oxygen. From 1990 to 2019, it was the world’s second-leading cause of death and the third-leading cause of combined death and disability. Acupuncture plays a role in stem cell treatment by activating the body's natural recovery processes through physical stimulation, aiding the recovery and rehabilitation of stroke patients. Several studies have explored combining stem cell therapy with acupuncture, yielding promising results in improving patient outcomes. This review assesses the effectiveness of combining acupuncture with stem cell therapy for stroke recovery. Analysis of seven randomized controlled trials shows that both stem cell transplantation and acupuncture contribute to the rehabilitation of stroke patients. When applied together, this combined therapy improves the survival, retention, and functional differentiation of implanted stem cells, creating a synergistic effect that amplifies the benefits of each treatment and compensates for their individual limitations. Key acupuncture points for this combination therapy include GV20, GV14, LI11, ST36, and GV26, with treatment durations ranging from 10 to 22 days.

Efficacy and safety of olverembatinib as maintenance therapy after allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Experience using olverembatinib as maintenance therapy in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) after allogeneic hematopoietic cell transplantation (allo-HCT) is limited. We retrospectively collected data from 26 patients with Ph+ ALL who received only olverembatinib as maintenance therapy after allo-HCT. Olverembatinib was administered as prophylaxis in 18 patients (69.2%), and preemptively in 8 patients (30.8%). The median time of olverembatinib initiation after transplantation was 2.5 months (range, 1-7.3). The median starting dose of olverembatinib was 35mg qod (range, 15-40). The median duration of olverembatinib treatment was 12.5 months (range, 6-23). Olverembatinib maintenance treatment was discontinued in 8 patients (8/26,30%), seven stopped the drug for a long-lasting BCR-ABL1 negativity and 1 for recurrent fever associated with the drug. BCR-ABL1 turned positive in 3 patients in 2, 3 and 6 months after discontinuation. During olverembatinib treatment, three patients developed grade ≥ 3 hematologic side effects, which resolved with dose interruption or dose reduction. The median follow-up time after allo-HCT were 17.75 months (range 7-31). The hematologic relapse rate was 7.7% (2/26), with no event in the preemptive group. The 3-year probability of overall survival and relapse free survival after allo-HCT was 91.7% and 79.1%, respectively. Only one patient in prophylaxis group died of central central nervous system (CNS) relapse. Thus, our data suggest that olverembatinib is effective and safe as maintenance treatment in patients with Ph+ ALL who underwent allo-HSCT. The main adverse effect was hematologic toxicity, which was tolerated.

Long-term safety and efficacy of Oleogel-S10 (birch bark extract) in epidermolysis bullosa: 24-month results from the Phase III EASE Study.

Epidermolysis bullosa (EB) is a group of rare, severe, genetic disorders characterised by persistent skin fragility and open wounds. EB manifests as cutaneous and mucosal blistering, erosions and impaired wound healing. To determine the long-term efficacy, tolerability and safety of Oleogel-S10 (birch bark extract) in dystrophic (DEB) and junctional (JEB) EB in the 24-months open-label phase (OLP) of the EASE study. EASE was a double-blind, randomised, controlled, phase III study consisting of two phases: a 90-day double-blind phase (DBP), and a 24-month OLP. Patients from both former treatment groups in the DBP entered the single-arm OLP (n = 205). Patients received Oleogel-S10 on all EB partial thickness wounds. OLP endpoints included: incidence, severity/relatedness of adverse events (AEs), wound infection maximum severity, changes in body surface area percentage (BSAP) of wounds, EB Disease Activity and Scarring Index (EBDASI), pain, itch, disease severity and quality of life outcomes. The OLP data demonstrated Oleogel-S10 target wound treatment adherence was >99% and mean treatment duration was 584.7 days (±246.1 days). 71.7% of patients in the OLP were aged <18 years and 86.8% had DEB; recessive DEB predominated (78.0%). AEs were reported in 77.1% of patients and were typically mild-to-moderate. Severe and serious AEs were observed in 18.0% and 24.4% of patients, respectively. AEs resulted in the withdrawal of 7.8% of patients (n = 16), including three with treatment-related AEs. Nine deaths were reported: none attributable to treatment. Incidence of target wound infections was low (n = 7); five were mild-to-moderate and two severe. In patients treated with Oleogel-S10 throughout, mean (SD) BSAP changes from DBP baseline at 3, 12 and 24 months were -4.3% (8.1), P < 0.0001; -5.9% (8.6), P < 0.0001; -3.7% (9.0), P = 0.0026, respectively. Similarly, significant changes in EBDASI skin activity score from DBP baseline were observed: -3.9 (8.3), P < 0.0001; -5.1 (8.2), P < 0.0001; -3.0 (8.3), P = 0.0068, at 3, 12 and 24 months, respectively. These data support an encouraging long-term safety profile of Oleogel-S10, and a sustained reduction in wound burden over at least 24 months of Oleogel-S10 treatment.

Treatment of Venous Thromboembolism with Edoxaban over 18 Months: Results from ETNA-VTE Europe.

The benefits and risks of extending anticoagulant treatment beyond the first 3 to 6 months in patients with venous thromboembolism (VTE) in clinical practice are not well understood. ETNA-VTE Europe is a prospective, noninterventional, post-authorization study in unselected patients with VTE treated with edoxaban in eight European countries for up to 18 months. Recurrent VTE, major bleeding, and all-cause death were the primary study outcomes. The median age of the 2,644 patients was 65 years; 46.6% were female, and 22.8% had a history of VTE. The median treatment duration was 50.6 weeks (interquartile range: 23.4-77.7). VTE recurrence occurred in 100 patients (3.8% at an annual rate of 2.7%/year); 37 patients (1.4%) were on edoxaban at the time of the event, with a corresponding annualized rate of 1.6%/year. Major bleeding was experienced by 37 patients (1.4%) during edoxaban treatment, corresponding to an annualized rate of 1.5%/year. Overall, 95 patients died (3.6%; annualized rate 2.6%/year), with the majority for reasons other than VTE- and cardiovascular (CV)-related causes. Out of 15 deaths (1.9%; annualized rate 2.1%/year) that occurred during edoxaban treatment, 1 was related to VTE and 11 related to CV (annualized rate 0.0%/year and 0.5%/year). ETNA-VTE Europe provides evidence for the real-world effectiveness of edoxaban treatment (up to 18 months) based on a low rate of VTE recurrence, all-cause death, and major bleeding, and is aligned with the results of the randomized clinical trial reassuring the use of edoxaban in the treatment of VTE in routine clinical practice.

Clinical implementation of next-generation sequencing testing and genomically-matched therapy: a real-world data in a tertiary hospital

Next-generation sequencing (NGS) cancer profiling has gained traction in routine clinical practice in South Korea. Here, we evaluated the use of NGS testing and genomically-matched therapies for patients with advanced solid tumors in a real-world clinical practice. We analyzed results from NGS cancer panel tests (SNUBH pan-cancer version 2) ordered from June 2019 to June 2020. Genomically-matched treatment was determined based on the novel information obtained from NGS testing, while results from conventional molecular tests were excluded. A total of 990 patients were included in the analysis (median age: 62, Stage IV: 82.5%). Using the Association for Molecular Pathology genetic variant classification system, we found that 257 (26.0%) patients harbored tier I variants, and 859 (86.8%) patients carried tier II variants. Among the tier I cases, the most frequently altered genes we detected were KRAS (106 patients, 10.7%), followed by EGFR (27 patients, 2.7%) and BRAF (17 patients, 1.7%). Of patients with tier I variants, 13.7% received NGS-based therapy as follows: Thyroid cancer (2/7, 28.6%), skin cancer (2/8, 25.0%), gynecologic cancer (7/65, 10.8%), and lung cancer (12/112, 10.7%). Of 32 patients with measurable lesions who received NGS-based therapy, 12 (37.5%) achieved a partial response, and 11 (34.4%) achieved stable disease. The median treatment duration was 6.4 months (95% CI, 4.4–8.4), and the median OS was not reached. In conclusion, NGS tumor profiling was successfully implemented in real-world clinical practice. This enabled the use of molecular profiling-guided therapy which improved survival outcome of selected patients.

Impact of switching from bisphosphonates to denosumab, teriparatide, or romosozumab in patients with postmenopausal osteoporosis: a case-control study.

To investigate the impact of switching from bisphosphonates (BP) to denosumab (DMAb), teriparatide (TPTD), or romosozumab (ROMO) in postmenopausal osteoporosis. This retrospective, case-controlled, multicenter study included 389 patients who switched from BP to DMAb, TPTD, or ROMO due to treatment inefficacy. Propensity score matching was used to align patient backgrounds, resulting in 45 patients per group. Baseline characteristics included a mean age of 73.8years, prior BP treatment duration of 37.1months, and bone mineral density (BMD) T-scores of -2.8 in the lumbar spine (LS), -2.5 in the total hip (TH), and -2.7 in femoral neck (FN). BMD and bone turnover markers were assessed over 12months. Following the switch from BP, the ROMO group demonstrated a dual effect of decreased bone resorption and increased bone formation markers. The TPTD group exhibited the highest increases in both markers, while the DMAb group suppressed both. After 12months, the ROMO group demonstrated significantly greater BMD increases in the LS (11.4%) compared to the DMAb (6.3%; p < 0.001) and TPTD (5.9%; p < 0.001) groups. Additionally, the ROMO group showed greater increases in the TH (3.3%) than TPTD group (0.8%; p < 0.01). Only the ROMO group showed a significant BMD increase in the FN (2.0%; p < 0.01 from baseline). Significant BMD increases were observed in the LS for all groups, in the TH for the ROMO and DMAb groups, and in the FN for the ROMO group. ROMO showed the most substantial BMD improvements following BP therapy.

Impulse control and correlation to dopamine agonist serum concentrations in people with Parkinson's disease

BackgroundImpaired impulse control is often seen in Parkinson’s disease (PD) patients using dopamine agonists.MethodsWe performed a therapeutic drug monitoring study of 100 PD patients using ropinirole or pramipexole extended release. Three blood samples were collected on the same day. Serum concentrations were measured, and 24 h area under the curve (AUC) calculated. The validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) was used for assessing impulse control.ResultsTotal ropinirole drug exposure showed weak, but significant correlation to the QUIP-RS score. No correlation between pramipexole serum concentrations and QUIP-RS was found. In ropinirole patients, both agonist dose and total dopaminergic treatment were correlated with QUIP-RS. Duration of ropinirole treatment correlated with impaired impulse control, and duration of dopaminergic treatment of any type correlated with QUIP-RS scores in both ropinirole and pramipexole patients.ConclusionsOur main finding is that impaired impulse control is correlated to both total drug exposure (AUC) and dopamine agonist dose for ropinirole, but not for pramipexole. These observations indicate that different strategies may be useful for treating PD patients with impaired impulse control: ropinirole dose reduction could be beneficial, whereas pramipexole treatment may have to be stopped.

Is There a Role for Daratumumab Retreatment in Patients with Relapsed/Refractory Multiple Myeloma?

Multiple myeloma (MM) is a hematologic disease characterized by the clonal expansion of malignant plasma cells that accumulate in the bone marrow, leading to osteolytic bone disease, hypercalcemia, anemia, and renal dysfunction. Daratumumab was the first monoclonal anti-CD38 antibody approved for the treatment of MM, initially in relapse/refractory settings and, more recently, for newly diagnosed patients. Increased first-line usage of daratumumab will also substantially change treatment approaches for patients with relapsed/refractory disease. Due to the cost and availability of bispecific T cell redirecting antibodies (BsAbs) and chimeric antigen receptor T cell therapy (CAR-T) in real-life settings in many countries, retreatment with daratumumab in subsequent lines of therapy might be a reasonable choice. Data regarding efficacy and optimal combinations of daratumumab retreatment are lacking, and here we provide a short literature review of available data. We identified only a small number of articles based on retrospective analysis of medical records in real-life settings. A strong consistency in results regarding response rates and treatment duration was noticed among mainly heavily pre-treated MM patients, with approximately half of patients achieving at least partial remission (PR) after retreatment with daratumumab-based protocol. The duration of treatment and time to the next treatment for retreatment episodes were considerable and consistent with clinical expectations for later lines of therapy. The analysis of data in this literature review indicates that daratumumab retreatment may provide meaningful clinical benefit to some patients with relapsed/refractory MM despite having prior exposure. However, further research is needed to identify clinical and biological parameters that may predict favorable responses to daratumumab retreatment.

The Safety and Efficacy of Dietary Epigallocatechin Gallate Supplementation for the Management of Obesity and Non-Alcoholic Fatty Liver Disease: Recent Updates

Epigallocatechin gallate (EGCG) is the predominant bioactive catechin in green tea, and it has been ascribed a range of beneficial health effects. Current increases in obesity and non-alcoholic fatty liver disease (NAFLD) rates represent a persistent and burdensome threat to global public health. While many clinical studies have demonstrated that EGCG is associated with positive effects on various health parameters, including metabolic biomarkers, waist circumference, and body weight when consumed by individuals affected by obesity and NAFLD, there are also some reports suggesting that it may entail some degree of hepatotoxicity. The present review provides a comprehensive summary of the extant clinical findings pertaining to the safety and effectiveness of EGCG in managing obesity and NAFLD, with a particular focus on how treatment duration and dose level affect the bioactivity of this compound.

Treatment patterns and clinical profile in progressive pulmonary fibrosis: a Japanese cross-sectional survey

BackgroundThere is a paucity of real-world data on patients with interstitial lung diseases (ILDs) that are progressive, other than idiopathic pulmonary fibrosis (IPF), including treatment patterns and attitudes toward treatment. This study aimed to investigate the diagnosis, clinical characteristics, treatment paradigm and current decision-making practices of IPF and progressive pulmonary fibrosis (PPF) in a Japanese real-world setting.MethodsData were drawn from the Adelphi Real World PPF-ILD Disease Specific Programme™, a cross-sectional survey with retrospective data collection of pulmonologists and rheumatologists in Japan from April to October 2022. Physicians provided data for up to 12 consecutive patients with a physician-confirmed diagnosis of progressive ILD; patients were also invited to complete patient self-completion forms. Analyses were descriptive.ResultsA total of 63 physicians (43 pulmonologists and 20 rheumatologists) provided data on 312 patients with PPF and 70 patients with IPF. Patients had a mean (standard deviation [SD]) age at survey date of 68.0 (11.6) years, 43.5% were female, 50.3% were former smokers and 18.1% were employed full time. For breathlessness, 26.5% of patients had Grade 2 physician-reported breathlessness; this was 16.7% when reported by patients themselves. A total of 81.4% of patients were currently receiving treatment for ILD. Mean (SD) duration of current treatment was 1.5 (1.4) years. Slowing disease progression was the primary reason influencing physicians’ choice of current ILD treatment (48.5%). A total of 16.0% had never been treated (most frequent physician-reported reason: disease was manageable without treatment, 55.7%) and 2.6% had treatment discontinued (most frequent reason: patient request, 70.0%). Physicians reported 82.3% of patients as fully compliant with their treatment regimen. As reported by patients themselves (n = 53), 49.1% never and 37.7% rarely missed a dose.ConclusionThis analysis of real-world data from Japan provides insights into the clinical profile of patients with IPF and PPF in Japan, and highlights differences between physicians and patients in perception of symptom severity and attitudes to treatment.

Ocrelizumab dose selection for treatment of pediatric relapsing–remitting multiple sclerosis: results of the OPERETTA I study

BackgroundThe presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).MethodsPatients with POMS aged 10–17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period. Primary endpoints: pharmacokinetics, pharmacodynamics (CD19+ B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.ResultsA total of 23 patients (cohort 1: n = 6, age 10–12 years, BW 27.0–39.0 kg; cohort 2: n = 17, age 11–17 years, BW 42.1–108.4 kg) were enrolled. Median treatment duration was 120 (range, 24–193) weeks at the primary analysis cutoff (October 5, 2023). Overall, the pharmacokinetic data were within the range observed at 600 mg in adult patients with MS; however, the exposure at 300 mg in patients < 40 kg was lower than with 600 mg in patients ≥ 40 kg. Shifting the cutoff to 35 kg would provide better exposure to patients with 35–40 kg body weight. Sustained, near-complete B-cell depletion was observed. The safety profile was consistent with that in adults. EDSS scores remained stable; no clinical relapses were observed.ConclusionA dosing regimen of 300 mg ocrelizumab for patients < 35 kg, and 600 mg for patients ≥ 35 kg (every 24 weeks), was selected for the phase 3 OPERETTA II trial (NCT05123703).Trial registrationClinicalTrials.gov: NCT04075266.

Dexmedetomidine improves clinical outcomes in sepsis-induced myocardial injury: a retrospective cohort study

BackgroundThe efficacy of dexmedetomidine (DEX) in treating sepsis-induced myocardial injury (SIMI) remains unclear. In this study, we explored the relationship between DEX use and clinical outcomes of patients with SIMI, focusing on the dosage and treatment duration.MethodsIn this retrospective cohort analysis, we identified patients with SIMI from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and categorized them into the DEX and non-DEX groups based on intensive care unit treatment. The baseline bias was reduced through propensity score matching (PSM). The primary outcome was 28-day mortality, whereas the secondary outcomes were in-hospital mortality and mortality rates at 7 days, 90 days, and 1 year. The association between DEX use and in-hospital mortality was assessed using Kaplan–Meier analysis and Cox proportional hazards models.ResultsAfter PSM, 373 patients in the DEX group were matched with 579 patients in the non-DEX group to achieve a balanced distribution of the covariates. The Cox regression model demonstrated a significant reduction in the 28-day mortality associated with DEX use, yielding a hazard ratio (HR) of 0.61 (95% confidence interval [CI]: 0.47–0.78, P &amp;lt; 0.001). In-hospital mortality also significantly decreased (HR = 0.43, 95% CI: 0.33–0.57, P &amp;lt; 0.001). Lower mortality rates were observed at 7 days, 90 days, and 1 year. DEX doses &amp;gt;0.4 μg/kg/h, particularly in the range of 0.400–0.612 μg/kg/h, total doses &amp;gt;3.113 mg during hospitalization, and treatment durations exceeding 72 h were associated with improved mortality risk at all intervals. Regarding DEX efficacy at 28 days, our subgroup analyses indicated a significant interaction between the Sequential Organ Failure Assessment score and invasive mechanical ventilation.ConclusionDEX administration was associated with improved in-hospital mortality and reduced mortality rates at 7 days, 28 days, 90 days, and 1 year in patients with SIMI. These findings require validation in future studies.

Meta-Analysis of Placebo-Treated Patients: Dropout Rates From Treatment in MASH Randomised Controlled Trials.

Dropout is common and affects the statistical power and randomization balance of randomised controlled trials (RCTs). To estimate the dropout rate in RCTs of metabolic dysfunction-associated steatohepatitis (MASH) and to examine factors associated with dropout in placebo-treated participants. PubMed and Cochrane databases were searched for phase 2-4 MASH RCTs with placebo arms through November 24, 2024. Dropout was defined as the attrition of patients included in the intention-to-treat analysis but did not complete treatment. RCTs were qualitatively reviewed to assess the expected and observed dropouts. Generalised linear mixed model was used to estimate pooled dropout rates. Sixty RCTs with 3230 placebo-treated participants with MASH were analysed. Thirty-three RCTs reported the dropout rate used to estimate the effect size. Of these, 60.6%, 36.4%, and 3.0% had an expected dropout rate that was higher, lower, and similar, respectively, than the observed dropout rate in the placebo arm. Overall, the dropout rate was 11.06% (95% confidence interval [CI] 9.07 to 13.42), with a higher rate in phase 3-4 trials than in phase 2 trials. The corresponding rates due to adverse events, loss to follow-up and patient choice were 2.41% (95% CI 1.67 to 3.48), 1.79% (95% CI 1.06 to 2.99) and 4.06% (95% CI 2.97 to 5.53), respectively. Meta-regression determined that the dropout rate increased with longer treatment duration. Placebo dropout in MASH RCTs is significant, mainly due to patient choice. Factors such as trial phase and treatment duration should be considered when calculating sample size in future clinical trials.

Dental Education in the Interior of a Brazilian State: Profile of Patients and Procedures Performed in a Teaching Clinic

Objective: This study aimed to identify the profile of adult patients treated at the Integrated Clinic of the UFVJM Dentistry course in Diamantina-MG between 2010 and 2019. Methods: A retrospective analysis was conducted using patient records from individuals who had completed treatment and were discharged. Only fully completed and legible records were included, while those that were incomplete, illegible, or related to ongoing treatments were excluded. Data collected encompassed gender, age, place of origin, race, comorbidities (such as diabetes and hypertension), treatment duration, start and end year of treatment, smoking habits, alcohol consumption, and the types of procedures performed, categorized into various treatment groups. Results: Out of 469 records analyzed, 414 met the inclusion criteria. The majority of patients were female (63.5%), predominantly of mixed race (46.3%), with an average age of 34.1 years, and most resided in Diamantina (84.7%). The highest number of treatment initiations occurred in 2018 (41.6%), which also had the most discharges (38.4%). The average treatment duration was 66.3 days. Radiography was the most frequently performed procedure (22.3%), while endodontic treatment was the least common (2%). A positive correlation was identified between age and the creation of removable prostheses. Conclusion: The predominant profile of patients treated at the clinic consists of young, mixed-race women, primarily residents of Diamantina, who tend not to smoke but frequently consume alcohol. These findings provide insights into the demographic and treatment needs of the population served by the clinic, informing potential improvements in patient care and educational approaches in the dentistry program.

Transcutaneous vagus nerve stimulation for Parkinson’s disease: a systematic review and meta-analysis

BackgroundTranscutaneous vagus nerve stimulation (tVNS) has emerged as a novel noninvasive adjunct therapy for advanced Parkinson’s disease (PD), yet no quantitative analysis had been conducted to assess its therapeutic effect.ObjectivesThis review aimed to investigate the efficacy of tVNS on motor function, other potential clinical targets and its safety in various treatment conditions.MethodsWe searched six databases for randomized controlled trials (RCTs) that involved treating PD patients with tVNS. Primary outcome was motor functions, including severity of motor signs, functional mobility and balance, and gait parameters. Secondary outcomes were cognition, emotion, sleep related impairments, patient reported non-motor outcomes, and any adverse events. All outcomes were classified and analyzed according to the treatment duration and medication condition of an included study. Risk of bias was evaluated by referencing Cochrane risk of bias tool 1.0. Data was analyzed by Revman 5.4.Results6 RCTs with 176 PD patient were included. Several motor functions and non-motor functions measured during on-medication condition (severity of motor signs −0.48 [95% CI −0.93, −0.04], gait −0.48 [95% CI −0.85, −0.1], patients reported non-motor outcomes −0.4 [95% CI −0.78, −0.03]), improved significantly. However, verbal fluency, sleep-related impairment, and fatigue were negatively impacted by tVNS during on-medication condition. No distinct adverse events were reported.ConclusiontVNS is a relatively safe adjunct treatment for PD. It has small to moderate therapeutic effects on motor functions and may negatively impact on a few other outcomes. Quality level of the evidence is low and further research is warranted.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024503322 (PROSPERO).

Trifluridine/Tipiracil (FTD/TPI) in Metastatic Colorectal Cancer in Hong Kong: A Territory-Wide Cohort Study.

Randomized phaseIII trials showed that using trifluridine/tipiracil (FTD/TPI) in patients with pre-treated metastatic colorectal cancer (mCRC) conferred survival benefit versus placebo. Here, we investigated the effectiveness and safety of FTD/TPI and sought to identify prognostic factors among the mCRC population in Hong Kong. A non-interventional, retrospective, multicenter cohort study enrolled patients with mCRC who received FTD/TPI in seven public hospitals in Hong Kong between 2016 and 2020. Overall survival (OS) was the primary endpoint; treatment duration and occurrence of neutropenia were secondary endpoints. We also performed a post hoc analysis to identify factors influencing OS and treatment duration. Overall, 456 patients were included (median age, 64.0years; 57.5% men). Approximately half (225/456; 49.3%) had RAS wild-type tumors; the median treatment duration was 12.4weeks (95% confidence interval [CI] 11.1-13.1). Median OS was 7.59months (95%CI 7.00-8.21). Overall, 289 (63.4%) patients developed neutropenia of any grade and 159 (34.9%) developed grade ≥ 3 neutropenia. Neutropenia at 1month occurred in 193 (43.1%) patients. The use of granulocyte colony-stimulating factor for neutropenia was reported for 42 (9.2%) patients. The development of neutropenia, absolute neutrophil count decrease of ≥ 2 grades in 1month, absence of liver metastasis, and RAS wild-type status were associated with significantly longer OS and, except for RAS wild-type status (not analyzed), longer treatment duration (p < 0.05 for all comparisons). Our data show that treatment with FTD/TPI offers survival benefits in patients with refractory mCRC in Hong Kong consistent with randomized controlled trials and other real-world studies. Furthermore, the prognosis in patients receiving FTD/TPI appears to be significantly better in those who develop neutropenia, with RAS wild-type status, or those without liver metastases, despite a higher rate of dose reduction in the real-world setting.