Duration Of Treatment Research Articles

Alpha-1 antagonist treatment for eyelid retraction in patients with thyroid eye disease-a prospective pilot study.

Sympathetic overstimulation of Müller's muscle is a suggested mechanism underlying upper eyelid retraction in thyroid eye disease (TED). We examined the effect of tamsulosin, an alpha-1 antagonist, on eyelid retraction in patients with TED. A single-centre prospective study. Patients with TED and associated eyelid retraction were treated with oral 0.4 mg/day tamsulosin for 3 months. Upper eyelid margins-to-reflex distance (MRD1), vertical palpebral fissure height (PFH), subjective improvement, signs and symptoms of dry eye, and lubricants use were assessed at baseline and at each subsequent visit. Eleven suitable patients (mean age 47.5 ± 9.68, 8 females) enrolled in the study. Three patients discontinued the drug due to mild adverse effects (dizziness, bradycardia, nausea, and gastrointestinal distress), which resolved immediately upon stopping treatment. The other eight patients tolerated the drug well and reported no side effects. Five patients experienced an objective improvement in eyelid position and subjective improvement in eye discomfort. The mean MRD1 decreased by -1.04 ± 0.81 mm (P = 0.015), and mean PFH decreased by -1.46 ± 1.33 mm (P = 0.039). Mean duration of tamsulosin treatment was 84.63 ± 71.9 days. Patients discontinued the drug due to no improvement in MRD1 (n = 3), referral for eyelid surgery with stable inactive TED (n = 2), treatment with intravenous methylprednisolone due to worsening active TED (n = 2), and patient choice after 5 months of treatment with spontaneous resolution of symptoms (n = 1). Tamsulosin is a safe potential treatment for eyelid retraction in TED and can be used as a temporary alternative therapeutic approach for patients unsuitable for surgery.

Overall survival after CDK4/6 inhibitor dose reduction in women with metastatic breast cancer

BackgroundBreast cancer is the most common cancer in women, and the first-line treatment for patients with hormone-receptor positive/HER2-negative metastatic breast cancer is CDK4/6 inhibitor plus endocrine therapy. Understanding the impact of CDK4/6 inhibitor dose reduction, which occurs in about half of the patients, is important.MethodsThis real-world cohort study is based on electronic health records from Capital Region of Denmark. All women with metastatic breast cancer initiating first-line treatment with CDK4/6 inhibitor between May 2017 and October 2022 were included.ResultsA total of 546 patients were eligible for inclusion in the 12-week landmark analysis and 192 (35%) experienced dose reduction. These patients were older, had worse ECOG PS, more received prior adjuvant endocrine treatment, and more received fulvestrant as the endocrine backbone. Dose reduction was associated with reduced overall survival (39.9 vs. 54.3 months) and shorter treatment duration (18.0 vs. 26.9 months). Adjusted hazard ratio for death was 1.38 (95% CI: 1.01–1.89).ConclusionsDose reduction of CDK4/6 inhibitors within the first 12 weeks of treatment was associated with significantly higher mortality and shorter treatment duration. These findings contrast with previous analyses showing no effect of dose reduction, likely due to considering immortal time bias in this study.

Functional properties of expanded austenite generated on AISI 316L by plasma nitrocarburizing using different active screen materials

Abstract This study investigates the functional properties of the expanded austenite layers generated on AISI 316L austenitic stainless steel resulting from active screen plasma nitrocarburizing using different active screen materials, i.e. steel or solid carbon. Treatments were conducted at 460 °C for 5 hours in a nitrogen-hydrogen feed gas, whereas for the treatments using a steel active screen, methane was added as carbon precursor. Additionally, the bias plasma conditions applied at the samples were varied between 0 kW and 1.25 kW. Samples were characterized by complementary microstructural and compositional investigations, surface roughness and hardness measurements, pin-on-disk tribological tests as well as potentiodynamic polarization tests in H2SO4 and NaCl electrolytes. The functional properties of the case are discussed based on the contents of nitrogen and carbon in the expanded austenite and on their effective diffusion depths. The results show that the usage of a carbon screen generally produces surfaces with uniform layer thickness, high hardness, improved wear resistance and a delayed tendency to pitting corrosion independent of the bias condition applied to the samples. When applying both screen materials at non-biased condition, the general corrosion resistance is slightly reduced under the conditions used, however, the layers generated using the carbon screen have a wear rate that is 3 times lower. It can be concluded that the carbon screen represents a robust treatment variant for austenitic stainless steels to produce sufficiently thick and wear-resistant surface layers in a short treatment duration, which still have the potential to maintain the corrosion resistance in different environments.

Risk of poor nutritional status and nutrition-related complaints in individuals attending a primary care dietitian after a COVID-19 infection: A prospective cohort study.

To report the changes in nutritional status, nutrition-related complaints and risk of sarcopenia in individuals attending a primary care dietitian in the Netherlands after a COVID-19 infection. The study was registered on the clinicaltrials.gov registry (NCT04735744). Nutritional status and nutrition-related complaints were assessed with the Patient-Generated Subjective Global Assessment Short Form and body composition measurements when possible. Risk of sarcopenia was assessed with the Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls questionnaire. Dietitians reported on treatment goals, content and volume of dietetic treatment. Descriptive statistics were used to describe the study population and outcomes at baseline and end of treatment. For continuous variables, paired samples t-tests were used to compare scores at the start and the end of dietetic treatment. For dichotomous variables. McNemar tests and Wilcoxon signed-rank tests were used to determine differences between the start and end of treatment. A total of 222 participants were included [mean age 50 (SD 13), 58% female, 34% overweight, 40% obese]. Malnutrition risk decreased from 44% (medium risk) and 20% (high risk) to 29% and 12% by the end of treatment (p < 0.001). The risk of sarcopenia decreased from 31% to 22% (p < 0.001). There was an imbalance between fat-free mass and fat mass in about half of the participants. The most commonly reported nutrition-related complaints were fatigue, no appetite, the feeling of being full and changed or loss of taste. Median treatment duration was 21 weeks [interquartile range (IQR) 13-26] and 5 consultations (IQR 4-7). Most participants (46%) aimed to maintain weight, with others aiming to lose (14%) or gain (14%) weight. At the end of treatment, 57% had achieved the goals. Significant improvements in nutritional status and risk of sarcopenia were observed after dietetic treatment in primary care, and most participants achieved the treatment goals. Nevertheless, nutrition-related complaints and the risk of malnutrition or sarcopenia remained prevalent.

Comparative analysis of hypofractionated short-course versus standard radiation therapy in elderly patients with glioblastoma: analysis of nationwide database.

Hypofractionated short-course radiation therapy (SCRT) is an alternative treatment option for elderly or frail patients with newly diagnosed glioblastoma (GBM) post-surgery. This study compares survival outcomes and treatment costs between patients receiving SCRT and those undergoing standard long-course radiation therapy (LCRT). This retrospective study utilized health insurance claims and national cancer registry data from Korea to compare overall survival (OS) and treatment costs between patients receiving SCRT and LCRT across all ages and sub-group analysis within the subgroup of cases aged 65 and older from 2016 onwards, a period when intensity-modulated radiotherapy (IMRT) was widely adopted. A total of 1,598 patients were included. Median OS since the first day of radiation therapy was 10.4 months (95% CI [9.6; 12.8]) for SCRT (n = 197) versus 16.2 months (95% CI [15.5; 16.9]) for LCRT (n = 1401) respectively. Subgroup analysis using stabilized inverse probability of treatment weighting (S-IPTW) showed indicating non-inferiority in elderly patients in median OS for elderly patients (≥ 65) with 10.6 months (95% CI [8.9; 14.0]) for SCRT (n = 147) versus 13.2 months (95% CI [8.9; 14.0]) for LCRT (n = 541). The median treatment cost of SCRT is about 6,000 USD lower, 25% less than LCRT. Compliance with the standard TMZ regimen post-radiation improved OS across all age groups. Considering comparable OS and shorter treatment duration, SCRT offers a viable, cost-effective option for elderly GBM patients. Adhering to standard TMZ also contributes to OS improvement. Further research reflecting key prognostic factors is essential to refining the role of SCRT.

Real-World Effectiveness and Safety of Carotegrast Methyl in Japanese Patients with Moderately Active Ulcerative Colitis

Introduction: Carotegrast methyl (CGM) is an oral, small-molecule α4-integrin antagonist, which became clinically available in Japan in May 2022. CGM is approved for remission induction treatment for moderately active ulcerative colitis (UC) with an inadequate response or intolerance to 5-aminosalicylates. Methods: We performed a single-center, retrospective, observational study of Japanese patients with moderately active UC to assess the real-world effectiveness and safety of CGM as remission induction treatment. Results: Of 14 patients, 71% (10/14) were women, and the median (range) age was 47 (20–68) years. Disease types were proctitis in 7% (1/14), left-sided colitis in 50% (7/14), and total colitis in 43% (6/14). With a median (range) treatment duration of 8 (2–26) weeks, the rate of endoscopic improvement (Mayo endoscopic subscore [MES] of 0 or 1) was 64% (9/14), and the rate of endoscopic remission (MES of 0) was 57% (8/14). After treatment with CGM, the median (range) MES decreased significantly from 3.0 (2–3) to 0.0 (0–3) (p = 0.008), the Mayo score decreased significantly from 7.0 (5–9) to 0.0 (0–9) (p = 0.006), and the clinical activity index decreased significantly from 6.0 (1–11) to 0.0 (0–9) (p = 0.015). Stool and diarrhea frequencies decreased significantly after initiating CGM, and the percentage of patients with bloody stool and abdominal pain tended to decrease. The cumulative relapse-free rate at week 26 among 9 patients who achieved endoscopic improvement with CGM was 77.8% (95% confidence interval, 36.5%–93.9%). No adverse drug reactions, including progressive multifocal leukoencephalopathy, were reported during the study period. Conclusion: This single-center, retrospective, observational study of 14 Japanese patients with UC showed that CGM was safe and effective as a remission induction treatment for moderately active UC with an inadequate response to 5-aminosalicylates in real-world settings.

Improvement of Salt Leaching Efficiency and Water Content of Soil through Irrigation with Electro-Magnetized Saline Water

While the advantageous effects of using magnetic and electromagnetic treatment (ET) of brackish and saline waters on soil salinity reduction in the root zone were largely reported, more studies are needed to answer questions about the soil salt leaching efficiency and the effect of the duration of the exposure to ET. For this aim, pot experiments were conducted using an Aqua-4DR physical water treatment device. The first experiment included two trials. The first trial considered five concentrations: C0:1.0; C1:4.5; C2:9; C3:13.5; and C4:18 dS m−1. The results revealed that the volume and the salt concentrations of the drained waters were significantly higher under irrigation with ET saline waters than those provided by untreated waters. The drained fraction of water varied from 20 to 26% under irrigation with untreated water and increased from 33 to 56% under irrigation with electro-magnetized water, indicating an improvement in the salt leaching. The second trial was carried out with different irrigation doses. The results showed that the higher the dose, the more obvious and significant the ET effect. The different treatment durations of water exposure revealed that the volume and salinity of drained water significantly increase as the ET duration increases. An increase in the ET duration also induces an increase in the soil water content of around 2.5%. Based on the experimental findings, we may conclude that the ET of saline water can reduce the adverse effect of salinity on the top soil, but these leached salts are carried away in depth and there is no concentration limit of water to the effect of the ET.

Adherence to Exercise in People with Lung or Head and Neck Cancer: Self-Reported Symptoms and Motivation During Cancer Treatment Need to Be Considered.

Objectives: Symptoms and motivation may impact adherence to home-based exercise training programs (HETP) during cancer treatment (CT) for lung or head and neck cancer. This study aimed to identify self-reported symptoms and their frequency, as well as motivation towards an HETP during CT for primary lung or head and neck cancer. Associations between symptoms and motivation with HETP adherence were also investigated. Methods: Participants underwent CT combined with an HETP that included aerobic (walk-based) and resistance training (Theraband®). Weekly assessment was conducted using a questionnaire developed by the researchers, evaluating the presence of symptoms. A scale (0 to 10) was used to assess motivation towards the HETP. Adherence was defined as the ratio between HETP sessions completed vs. the number prescribed. Symptom frequency was recorded as the number of weeks a symptom was experienced. Linear regression was used to explore associations. Results: Twenty-four participants were included (61 ± 7 yr; 21 males; head and neck cancer n = 18; median treatment duration: 9 [7 to 11] weeks). The most commonly reported symptoms were fatigue (33%), malaise (24%) and dysphagia (23%). Average score for motivation to exercise was 6.4 ± 2.0. Adherence to the HETP was 47%. Malaise was associated with reduced adherence to HETP (p = 0.002), explaining 35% of the variance. Motivation was associated with increased adherence (p = 0.008), explaining 28% of the variance. Conclusions: Fatigue, malaise and dysphagia were among the most frequently reported symptoms during treatment. Malaise and self-motivation to exercise can significantly influence adherence to HETPs. Symptom and motivational support might be necessary when implementing HETPs during CT.

Non-tuberculous mycobacterial bone and joint infections - a case series from a tertiary referral centre in Australia.

Non-tuberculous mycobacteria (NTM) are rare causes of bone and joint infection (BJI) and there is limited evidence on which to base management decisions. This study describes 1 year of experience from a multi-disciplinary BJI team which collects data on all cases reviewed at a tertiary referral centre in Queensland, Australia. The database was interrogated for all cases in which NTM were recovered from operative samples. Individual chart review was performed to collect the details of each case. A total of seven cases were managed between 1st February 2021 and 28th February 2022, comprising one patient with chronic osteomyelitis, three with fracture-related infections, two with prosthetic joint infections, and one with infection of a synthetic ligament graft. In contrast to pulmonary NTM infections, most patients were clinically well and immunocompetent, and most infections were propagated by direct inoculation. Time to diagnosis was unknown in three patients, with 1, 2, 2, and 5 months for the remaining four. Rapid growing NTM were diagnosed on routine cultures and specific mycobacterial cultures were confirmatory. Management was characterized by multiple stage surgical procedures and prolonged antimicrobial regimens. Antimicrobial complications were common; however, all patients were infection free at their latest follow up. Despite the inherent limitations, these results suggest that routinely ordering mycobacterial culture is of low yield. There is potential for shorter-term oral antimicrobial treatments. Prospective research is required to optimize treatment regimens and durations.

Renal Function Is Associated with Changes in Bone Mineral Density in Postmenopausal Osteoporotic Women Treated with Denosumab: Data From a Retrospective Cohort Study.

Background/Objectives: Renal function influences bone metabolism, as kidney failure can increase the risk of fractures. Denosumab is an approved osteoporosis treatment, but its efficacy in relation to renal function has not yet been studied in real-life scenarios. This study aimed to investigate the denosumab-induced change in bone mineral density (BMD) according to kidney function. Methods: A retrospective analysis was conducted at the outpatient clinic in postmenopausal women receiving denosumab (60 mg subcutaneously administered every 6 months). The glomerular filtration rate (eGFR) was measured by the 2021 CKD-EPI equation and patients were stratified for eGFR categories. BMD was measured by dual-energy X-ray absorptiometry. Results: 128 women (mean age 70.3 ± 9.4 years) were recruited. The mean denosumab treatment duration was 3.9 ± 1.4 years and all the participants had improved BMD values. In stepwise multiple regression analysis-after controlling for age, BMI, and treatment duration-the eGFR value (ß = -0.11, SE 0.04, p = 0.01) was independently associated with the lumbar spine BMD change. The same association remained when the eGFR categories were considered (ß = 3.564, SE 1.29, p = 0.007). In addition, after controlling for BMI and the duration of denosumab treatment, age (ß = -0.7915, SE 0.37, p = 0.03) and eGFR (ß = -0.3257, SE 0.1567, p = 0.04) were found to be associated with femoral neck BMD change. The association remained when considering eGFR categories (ß = 8.7339, SE 4.29, p = 0.04). Conclusions: This retrospective study suggests that eGFR is associated with denosumab efficacy in postmenopausal women treated for osteoporosis.

Options for optimizing noninvasive respiratory support in the development of hypoxemic acute respiratory failure

Introduction. Acute respiratory failure (ARF) remains one of the most relevant problems of modern medicine and intensive care, and respiratory support (RS) remains the indispensable method of temporary external respiratory function replacement. Despite of widespread use of non-invasive ventilation (NIV) in clinical practice, at present systematic scientific data about possibilities for optimizing the use of these methods of RS in patients with hypoxemic ARF development is absent. It can be assumed that the combination of mask NIV and high-flow oxygen therapy (HFOT) at the stage of ARF development can improve results of treatment in this group of patients.The objective was to improve the results of treatment in patients with hypoxemic ARF through the combined use of mask NIV and HFOT.Materials and methods. The prospective cohort study included 77 patients aged 46.8 ± 11.8 years. Patients were randomized into three groups: in group A, RS was performed by using NIV and traditional low-flow oxygen therapy, in group B – by using HFOT, in group C – by sequential combination of NIV sessions and HFOT. The groups compared gas exchange rates, RS duration, intubation rate and nosocomial pneumonia (NP) incidence, length of treatment in the intensive care unit (ICU) and hospitalizations, overall mortality, and prognostic factors for tracheal intubation were also studied.Results. The combination of mask NIV and HFOT was found to be more clinically effective compared to their separate use. Combination of mask NIV and HFOT had the best effect on gas exchange rates in the long term period, reduced RS duration, intubation rate and pneumonia incidence, ICU treatment duration. Risk factors for tracheal intubation were revealed: RS duration more than 4.5 days, intra-abdominal pressure (IAP) more than 18 cm of water.Conclusions. The combination of mask NIV and HFOT increases the therapeutic potential of each of these RS methods and improves the results of treatment in patients with hypoxemic ARF development.

Enzalutamide versus abiraterone acetate in the development of new-onset or worsening type 2 diabetes mellitus in patients with metastatic castration-resistant prostate cancer: EVADE study

PurposeTo determine new-onset or worsening T2DM risk in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone acetate (AA) vs. enzalutamide (ENZA) in England.MethodsRecords of patients on AA and/or ENZA (2015−2021) were analysed retrospectively from UK- or England-wide databases and data sets. The primary endpoint was new-onset or worsening T2DM, analysed using a Cox model.ResultsOf 1382 patients, 84 (6.1%) met the primary endpoint; 42 of 826 patients (5.1%) received ENZA and 42 of 556 patients (7.6%) received AA. Among patients without baseline T2DM (n = 1049), 50 developed new-onset T2DM: 24 (3.9%) on ENZA and 26 (5.9%) on AA. Among patients with baseline T2DM (n = 333), 34 (10.2%) had worsening T2DM: 18 (8.3%) on ENZA and 16 (13.8%) on AA. Patients on ENZA had longer median follow-up (445 vs. 408 days) and treatment duration (164 vs. 139 days) than those on AA, who were also more likely to have new-onset or worsening T2DM than those on ENZA (HR: 1.8; 95% CI: 1.4–2.7; P = 0.0101). The number needed to harm for an additional patient to experience new-onset or worsening T2DM when receiving AA instead of ENZA was 40 overall, 50 in patients without baseline T2DM, and 18 in patients with baseline T2DM.ConclusionPatients with mCRPC receiving AA were more likely to experience new-onset or worsening T2DM than those on ENZA, despite having a shorter treatment duration. Further research is required to substantiate these findings in earlier disease settings with longer treatment duration.

Конструкционные плиты из гидродинамически активированной коры сосны (Pinus sylvestris) без связующих веществ

Bark is a large-tonnage waste in a number of wood processing technologies requiring efficient use. One of the promising areas of bark use is the production of boards without synthetic binders. Research has been conducted on the production of structural boards from Pinus sylvestris bark without a binder. The method is based on preliminary hydrodynamic activation of bark. The initial bark undergoes primary crushing in a hammer mill. After that, it is mixed with water at a concentration of 6 %. Then the resulting mass is activated in a rotary pulsation disperser, a carpet is formed from it, cold pressing is carried out, and then hot pressing. As a criterion for assessing the degree of mass activation, water-retaining capacity is adopted. The dependencies have been determined between the duration of treatment and water-retaining capacity, as well as the strength of the boards and water-retaining capacity. The latter made it possible to obtain the optimal value of the water-retaining capacity equal to 290 %. A multifactorial experiment has been conducted to develop the optimal hot pressing mode. As a result, the optimal mode for pressing the boards has been determined: temperature – 190 °C; specific process duration – 2.8 min/mm; pressing pressure – 4.4 MPa. The properties of the boards produced in this mode are: density – 980 kg/m 3 ; bending strength – 24 MPa; swelling during soaking for 24 hours – 5 %; water absorption – 9 %. After soaking and subsequent drying to a moisture content of 5 %, the boards retain 75 % of their before soaking. In this case, the geometric dimensions return to the original ones. The resulting boards can be used as a sheet finishing and structural material, in house-building (as a base for floor and roofing materials), in furniture production, especially in severe temperature and humidity conditions. The conducted research shows the possibility of producing board materials with high performance properties from pine bark without binders.

Double-Layer Traction Method for Treating Severe Upper Auricular Adhesion Malformation in Infants: A Prospective Randomized Controlled Study.

Severe upper auricular adhesion malformation poses a significant challenge for complete correction through ear molding. This prospective randomized controlled study aimed to assess the efficacy of a new method in addressing severe upper auricular adhesions. In this non-blinded randomized controlled study, we enrolled 72 infants with severe upper auricular adhesion malformation who underwent treatment with the EarWell system. They were randomly assigned to either the double-layer traction (DLT) group or the control group. We compared the effectiveness of treatment, treatment duration, and potential complications between the two groups. All 72 infants completed the treatment and follow-up, with 38 (52.8%) in the DLT group and 34 (47.2%) in the control group. The DLT group exhibited significantly shorter treatment times and a lower incidence of pressure sores than the control group. The DLT method, along with unilateral malformation, independently predicted positive long-term outcomes. The DLT method demonstrated superior effectiveness, shorter treatment duration, and lower complication rates than traditional methods when treating severe upper auricular adhesion malformation in infants. The DLT method is safe and effective and merits broader adoption in clinical practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Apoptosis, Mitochondrial Autophagy, Fission, and Fusion Maintain Mitochondrial Homeostasis in Mouse Liver Under Tail Suspension Conditions

Microgravity can induce alterations in liver morphology, structure, and function, with mitochondria playing an important role in these changes. Tail suspension (TS) is a well-established model for simulating the effects of microgravity on muscles and bones, but its impact on liver function remains unclear. In the current study, we explored the regulatory mechanisms of apoptosis, autophagy, fission, and fusion in maintaining liver mitochondrial homeostasis in mice subjected to TS for 2 or 4 weeks (TS2 and TS4). The results showed the following: (1) No significant differences were observed in nuclear ultrastructure or DNA fragmentation between the control and TS-treated groups. (2) No significant differences were detected in the mitochondrial area ratio among the three groups. (3) Cysteine aspartic acid-specific protease 3 (Caspase3) activity and the Bcl-2-associated X protein (bax)/B-cell lymphoma-2 (bcl2) ratio were not higher in the TS2 and TS4 groups compared to the control group. (4) dynamin-related protein 1 (DRP1) protein expression was increased, while mitochondrial fission factor (MFF) protein levels were decreased in the TS2 and TS4 groups compared to the control, suggesting stable mitochondrial fission. (5) No significant differences were observed in the optic atrophy 1 (OPA1), mitofusin 1 and 2 (MFN1 and MFN2) protein expression levels across the three groups. (6) Mitochondrial autophagy vesicles were present in the TS2 and TS4 groups, with a significant increase in Parkin phosphorylation corresponding to the duration of the TS treatment. (7) ATP synthase and citrate synthase activities were significantly elevated in the TS2 group compared to the control group but were significantly reduced in the TS4 group compared to the TS2 group. In summary, the coordinated regulation of apoptosis, mitochondrial fission and fusion, and particularly mitochondrial autophagy preserved mitochondrial morphology and contributed to the restoration of the activities of these two key mitochondrial enzymes, thereby maintaining liver mitochondrial homeostasis in mice under TS conditions.

Alzheimer's Disease and (Phyto) Estrogen Treatment: Modification of Effects by Age, Type of Treatment, and Duration of Use.

There is a continued debate on whether menopausal hormone therapy (MHT) protects women against Alzheimer's disease (AD). It is also unclear whether phytoestrogen could be an alternative treatment for AD. To investigate whether mixed study findings may be due to differences in age at initiation of MHT and duration of prescription of different types of MHT using meta-analyses. After a systematic literature search, meta-analyses were carried out using Cochrane Revman 5.4.1.software including data from large nationwide studies of registered medically diagnosed AD and prescribed MHT. These analyses were stratified for duration and type of treatment, by age at start of prescription of therapy. Insufficient quality data were available for phytoestrogen treatment and AD meta-analyses. A total of 912,157 women were included from five registries, of whom 278,495 had developed AD during follow-up. Meta-analyses suggested a small increased AD risk after 5-10 years prescription of combination MHT regardless of age, and over 10 years only in women younger than 60 years of age. No association was seen for estrogen alone for women younger than 60 years of age, but AD risk did increase for women over 60 years of age for up to 5 years of MHT prescriptions. Combination MHT should probably be prescribed for less than 5 years after menopause to reduce risk for AD, while estrogen alone should not be prescribed to women over 60. For phytoestrogen, small treatment trials suggested some benefit of tempeh (fermented soy), which should be investigated further.

Clemastine Induces Oligodendrocyte Progenitor Pool Exhaustion and Senescence in the Context of Chronic Demyelination in a Rabbit Model.

Clemastine has emerged as a promising therapy for the restoration of neurologic function in patients with multiple sclerosis (MS). However, clemastine and other agents with prodifferentiative effects on oligodendrocyte progenitor cells (OPCs) in rodent models have underperformed in clinical trials. We hypothesized that the preclinical studies showed more robust effects because of the abundance of OPCs in rodent models. To better examine the therapeutic potential of clemastine, we examined its effect on demyelinated white matter lesions in rabbits, which exhibit progenitor densities and limited remyelination more closely matching those found in tissues from patients with MS. We used lysolecithin to induce demyelination in white matter of New Zealand rabbits and then administered oral clemastine (10mg/kg/day) for various periods before assessing the OPC and oligodendrocyte (OL) populations in these lesions. Daily administration of clemastine for the full study period (56 days) increased oligodendrogenesis in white matter lesions. However, shorter durations of treatment failed to increase overall OL density despite enhancing OPC-to-OL differentiation. This effect was due to exhaustion of the OPC pool, as the differentiating progenitors were not replaced because of reduced OPC proliferation. Notably, delayed administration of clemastine led to an accumulation of activated OPCs expressing markers of senescence. Although capable of driving OL differentiation, clemastine treatment in rabbits hampered progenitor pool replenishment, induced senescence, and promoted conversion of microglia/macrophages to a proinflammatory phenotype. Whether these effects would also occur in humans or with other prodifferentiative therapies should be studied further, but our data suggest the need to carefully consider progenitor dynamics in the treatment of MS. ANN NEUROL 2024.

Association Between Variables and Transitions Among No Opioid Use, Opioid Use, and Subsequent Dropout Among Participants on Methadone Treatment: A Retrospective Study Utilizing a Multistate Model.

Although previous studies have reported the variables that influence opioid use or dropout among participants receiving methadone treatment, limited attention has been given to the variables related to transitions among no opioid use, opioid use, and dropout. This retrospective study utilized data collected from June 2010 to June 2022 at 11 methadone treatment clinics in Guangdong Province, China. Two transient states (no opioid use and opioid use) and 1 absorbing state (dropout) were defined based on monthly urine morphine test results and daily methadone intake records. We used a multistate model to explore the variables associated with transitions among no opioid use, opioid use, and dropout among participants. Among 3136 participants, with an average treatment duration of 497 days, 1646 (52.49%) underwent at least 1 period of opioid use, resulting in 3283 transitions from no opioid use to opioid use. The transitions between no opioid use and opioid use were significantly associated with variables such as age, gender, employment status, marital status, living situation, travel time to the clinic, human immunodeficiency virus and hepatitis C virus infection statuses, average methadone dosage, and attendance rates. The variables influencing participants' dropout varied depending on their opioid use behaviors. Additionally, the probability of a specified opioid use state remaining unchanged or transitioning to a different state at a defined time point would change over time. The opioid use behaviors of participants are dynamic. Methadone providers should offer targeted interventions based on participants' opioid use behaviors to effectively decrease rates of opioid use and improve retention.

Quality of Life of Breast Cancer Women under Treatment at a Tertiary Care Center of Western Maharashtra

Background: ‘Breast cancer’ the most common cancer amongst females in India. Having good Quality of life (QoL) among the patients undergoing treatment is one of the vital and significant factors for ensuring holistic approach to treatment and well-being of cancer patients. The present study was conducted to assess the QoL and its determinants among breast cancer patients undergoing treatment at a tertiary care institute in western Maharashtra. Material and Methodology: 300 histopathologically confirmed breast cancer patients undergoing treatment at a tertiary care centre were divided into three groups to include 100 patients in each group. Group 1 (patients with duration of treatment 1 to 2 years) Group 2 (patients with duration of treatment 2 to 5 years) and Group 3 (more than 5 years). Validated tool Function Assessment of Cancer Therapy Breast specific (FACT-B) questionnaire was used to collect information on QoL and analysed using appropriate statistical tests. Results: Mean age of patients was 53.2 + 10.08 years, 136 (45.33%) were from age group 51 to 65 years. Majority of the patients 106 (35.33%) were educated till secondary schooling and 172 (57.33 %) were belonging to the middle-upper class. Lump in breast was most common presenting symptom in 235 (78.33%) cases followed by nipple retraction. 275 (91.67 %) cases had infiltrating ductal Carcinoma and 144 (48%) patents were in Stage II cancer. Over all mean FACT-B score for QoL was 104.02 + 18.65 out of 141. Mean FACT-B score for Group 1, Group 2 and Group 3 was 88.18 +17.20, 105.89 + 11.78 and 118.28 + 12.45 respectively with (p&lt; 0.05), suggests significant improvement in QoL with increase in time elapsed since treatment. Conclusion: Socio-demographic factors, type of surgery and duration of treatment had significant effect on QoL among breast cancer patients. Apropos physicians, paramedic staff and domestic care givers need to be sensitised on importance of QoL for collective and deliberate efforts to achieve holistic care. QoL can be made integral part of breast cancer treatment and management policy or programme.

Factors prolonging antibiotic duration and impact of early surgery in thoracolumbar pyogenic spondylitis treated with minimally invasive posterior fixation.

A standard 6-12-week course of antibiotics is recommended for pyogenic spondylitis. Recent evidence supports early minimally invasive posterior fixation surgery; however, its effect on antibiotic treatment duration is unclear. This study aims to identify factors associated with prolonged antibiotic treatment in thoracolumbar pyogenic spondylitis patients resistant to conservative treatment and assess whether early surgery can reduce treatment duration. We retrospectively reviewed 74 patients with thoracolumbar pyogenic spondylitis undergoing minimally invasive posterior fixation at nine facilities. Patients were grouped based on antibiotic duration (≥ 6 or < 6 weeks) and timing of surgery (≤ 3 weeks or > 3 weeks of starting antibiotics). Univariable and multivariable logistic regression analyses were used to identify factors associated with prolonged antibiotic treatment and study the outcomes of patients undergoing early surgery. Forty-nine patients (66%) required prolonged antibiotic treatment. The presence of an iliopsoas abscess (p = 0.0006) and elevated C-reactive protein (CRP) levels (≥ 10mg/dL, p = 0.015) were independently associated with prolonged antibiotic treatment. Early surgery significantly reduced total antibiotic duration (5.3 weeks vs. 9.9 weeks, p < 0.0001) without increasing the incidence of postoperative infection recurrences and unplanned additional surgeries. Despite factors associated with prolonged antibiotic treatment, early surgery consistently shortened the treatment duration compared to late surgery. Early surgery (within three weeks) with minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis is associated with reduced antibiotic duration and overall treatment duration regardless of the presence of prolonging factors like iliopsoas abscess and elevated CRP levels.