Continuous Therapy Research Articles

Effect of continuous positive airway pressure therapy on blood levels of IL-6, IL-10, IL-18, IL-1β, IL-4, and IL-17 in obstructive sleep apnoea adults: A systematic review, meta-analysis and trial sequential analysis

Obstructive sleep apnoea (OSA) is a long-term disorder characterized by frequent blockages in the upper respiratory tract during sleep, often leading to abrupt awakenings, with or without a decrease in oxygen levels. The systematic review and meta-analysis aimed to assess the effect of continuous positive airway pressure therapy (CPAP) on blood interleukin (IL) levels of IL-6, IL-10, IL-18, IL-1β, IL-4, and IL-17 in OSA adults. The published databases from PubMed, Scopus, Web of Science, and Cochrane Library were searched from 2003 to 2024, without any restrictions. The Review Manager software 5.3 was employed to compute effect sizes, which were presented as the standardized mean difference (SMD) along with a 95% confidence interval (CI). In total, 320 records were identified through database searching; ultimately, 42 articles were included in the qualitative synthesis and then the meta-analysis. The CPAP therapy significantly reduces IL-6 levels, as indicated SMD=0.64 [95% CI: 0.35, 0.93] and P<0.0001. CPAP therapy significantly reduced IL-18 and IL-1β levels in adults with OSA, but there is no significant difference in IL-10, IL-4, or IL-17 levels. Age, blood sample, body mass index, ethnicity, and treatment duration for IL-6 and apnoea-hypopnea index with IL-10 levels were effective factors in the pooled results. Experimentally, there was an interaction between IL-18 and IL-1β. CPAP therapy has a positive impact on inflammatory markers in OSA adults; remarkably, it reduces IL-6 and IL-1β levels. Nevertheless, more evidence (such as the role of ethnicity) and understanding of interactions are needed.

Hybrid similarity based feature selection and Cascade deep maxout fuzzy network for Autism Spectrum Disorder detection using EEG signal

Autism Spectrum Disorder (ASD) is a neurological disorder that influences a person’s comprehension and way of behaving. It is a lifetime disability that cannot be completely treated using any therapy up to date. Nevertheless, in time identification and continuous therapies have a huge effect on autism patients. The existing models took a long time to confirm the diagnosis process and also, it is highly complex to differentiate autism from various developmental disorders. To facilitate early diagnosis by providing timely intervention, saving healthcare costs and reducing stress for the family in the long run, this research introduces an affordable and straightforward diagnostic model to detect ASD using EEG and deep learning models. Here, a hybrid deep learning model called Cascade deep maxout fuzzy network (Cascade DMFN) is proposed to identify ASD and it is achieved by the integration of Deep Maxout Network (DMN) and hybrid cascade neuro-fuzzy. Moreover, hybrid similarity measures like Canberra distance and Kumar-hassebrook is employed to conduct the feature selection technique. Also, the EEG dataset and BCIAUT_P300 dataset are used for analyzing the designed Cascade DMFN for detecting Autism Spectrum disorder. The designed Cascade DMFN has outperformed other classical models by yielding a high accuracy of 0.930, Negative Predictive Value (NPV) of 0.919, Positive Predictive Value (PPV) of 0.923, True Negative Rate (TNR) of 0.926, and True Positive Rate (TPR) of 0.934.

Photobiomodulation reduces spinal cord edema by decreasing the expression of AQP4 in the astrocytes of male spinal cord injury rats via the JAK2/STAT3 signaling pathway.

BackgroundSpinal cord swelling commonly occurs following SCI. Previous studies suggest that PBM may reduce inflammation and scar formation after SCI. However, whether PBM can alleviate post-spinal cord injury edema and its underlying mechanisms have not yet been reported. This study aims to investigate the effects of PBM on spinal cord swelling in rats following SCI and explore the underlying mechanisms. MethodsA rat model of SCI was established, and the rats received continuous PBM therapy for two weeks. Tissue hydration, motor function, AQP4 expression, and pathological changes in the spinal cord were evaluated at different time points. In vitro, astrocytes were subjected to PBM and treated with either cucurbitacin I or TGN020 following OGD. ResultsThe results indicate that PBM reduces tissue swelling in rats with SCI, improves motor function recovery, and inhibits the upregulation of AQP4 and GFAP associated with SCI. In vitro, PBM reduces abnormal activation of the JAK2/STAT3 signaling pathway in astrocytes, leading to decreased AQP4 synthesis and astrocyte activation. ConclusionsThese findings suggest that PBM reduces spinal cord swelling in rats after injury. This effect is associated with the inhibition of JAK2/STAT3 signaling pathway activation in astrocytes and the reduction in AQP4 expression.

Skin Clearance, Treatment Response Off-therapy, and Safety of Tapinarof Cream 1% Once Daily: Results from ADORING 3, a 48-week Phase 3 Trial in Adults and Children Down to 2 Years of Age with Atopic Dermatitis

Introduction: In the ADORING 1 and 2 phase 3 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) demonstrated significant efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis (AD). We present efficacy, safety, and tolerability outcomes from ADORING 3. Methods: Eligible patients from ADORING 1, ADORING 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild, or moderate or severe AD, that did not meet eligibility criteria for ADORING 1 or 2, received tapinarof cream 1% QD for up to 48 weeks. Efficacy endpoints included achievement of complete disease clearance (Validated Investigator Global Assessment for Atopic Dermatitis™ [vIGA-AD™] score=0 [clear]), and clear or almost clear skin (vIGA-AD™=0 or 1). Safety and tolerability were assessed. Patients entering with vIGA-AD™≥1 were treated with tapinarof until complete clearance (vIGA-AD™=0 [clear]). Those entering with or achieving complete clearance discontinued tapinarof and were assessed for maintenance of clear or almost clear skin off-treatment (duration of treatment-free interval). Patients whose AD returned to mild (vIGA-AD™≥2) were re-treated until complete clearance was achieved. Results: 728 patients enrolled; 83.0% were pediatric (2–17 years). Overall, 51.9% (378/728) achieved complete disease clearance, and 81.6% achieved clear or almost clear skin at least once in the trial. Mean duration of first treatment-free interval was 79.8 consecutive days (standard deviation: 81.4 days). No tachyphylaxis on either continuous or intermittent therapy was observed for up to 48 weeks. Most frequent adverse events were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%). Follicular events and contact dermatitis were mostly mild or moderate and associated with low discontinuations (1.0% and 0.4%, respectively). Tapinarof was well tolerated locally, even when applied on sensitive skin. Conclusions: Tapinarof cream monotherapy demonstrated a high rate of complete disease clearance in patients down to age 2 years with AD. After discontinuing tapinarof, patients maintained clear or almost clear skin for 79.8 consecutive days. Tapinarof was well tolerated over 48 weeks.

Rituximab Administration to Treat Nephrotic Syndrome in Children: 2-Year Follow-Up

Background: Steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) significantly affect children’s quality of life. There are frequent relapses in SSNS and progression in SRNS. IPNA guidelines suggest that monoclonal antibodies like rituximab (RTX) are promising treatments. Objective: This study aims to evaluate the long-term efficacy and safety of rituximab administration in children with SSNS, encompassing FRNS and SDNS, and SRNS over a two-year follow-up period, facilitating individualized management. Methods: We conducted an open-label, multicenter, randomized, and patient-oriented study (RICHNESS), involving children aged 3–18 with SRNS (18) and SSNS (11) undergoing 2 years continuous RTX therapy. The primary outcome was complete/partial remission (CR/PR), as defined by IPNA/KDIGO guidelines, at 6, 12, 18, and 24 months on RTX; secondary outcomes included adverse events. Key endpoints included the estimated glomerular filtration rate (eGFR), the albumin-to-creatinine ratio (ACR), CD20 levels, IgG levels, and the incidence of infections. Kidney biopsies were performed in 94% of SRNS patients. RTX was administered every 6–9 months, depending on CD20 levels, IgG levels, and the presence of infections. The eGFR and ACR were assessed every 6 months. Results: Some 31 children were selected for RTX treatment. Overall, 2 experienced severe allergic reactions, leading to their exclusion from the final analysis of 29 children. In the SSNS group, all children achieved and maintained complete remission within 2 years. Remission rates in the SRNS group ranged from 39% (RR 0.78; 95% CI: 16.4–61.4%, NNT 9) at the 6th month to 72% (RR 1.44; 95% CI: 51.5–92.9%) over the 2-year follow-up period due to continuous RTX therapy. The median duration of RTX use was 26.1 months, with a median cumulative dose of 1820 mg/m2. Adverse reactions and complications were presented by mild infusion-related reactions in 3 children (10.3%), severe allergic reactions in 2 children (6.2%), hypogammaglobulinemia in 7 children (24%), infections in 3 children (10.3%), severe destructive pneumonia in 1 child, recurrent respiratory infections in 2 children, and neutropenia in 1 child (3.44%). Conclusions: RTX was tolerated well, and proved highly effective as a steroid-sparing agent, offering potential in terms of stopping relapses and minimizing steroid-related side effects. It also demonstrated efficacy in slowing progression in SRNS, indicating potential for use in ACR reduction and renal function restoration, but requires careful use given potential severe allergic reactions and infectious complications. Further studies should focus on long-term cost-effectiveness and deferred side effects.

Study protocol for a consortium linking health medical records, biospecimens, and biosignals in Korean patients with acute kidney injury (LINKA cohort).

Acute kidney injury (AKI) may transition into acute kidney disease (AKD) or chronic kidney disease (CKD), leading to subacute and chronic deterioration, respectively. Despite extensive research on AKI, a significant gap exists in understanding the specific biomarkers and development of individualized treatments prior to progression to AKD and CKD. As a consortium linking health medical records, biospecimens, and biosignals, eight Korean tertiary hospitals participated in the establishment of a retrospective and prospective cohort, each comprising approximately 1,500 patients with AKI receiving continuous kidney replacement therapy (CKRT). Other information included AKI-related information, CKRT prescriptions, and patient outcomes. Follow-up timeframes were set at baseline, 1 week, 3 months, and 1 year after the initiation of CKRT. Human biospecimens will be collected from the prospective cohort. An artificial intelligence model was developed using the retrospective cohort to predict the prognosis of AKD and its subsequent sequelae and to formulate patient-individualized treatments, with validation planned in a prospective cohort. Follow-up studies are scheduled to identify biomarkers related to outcomes using biospecimens. Finally, based on the results and literature review, decision-making on the prevention and management of diseases, as well as the development of treatment guidelines, are being planned. This study will provide scientific evidence on clinical insights and appropriate management targets for AKI and AKD, which will form the basis for relevant treatment guidelines. Additionally, these findings may facilitate a more personalized approach to patient care, enabling clinicians to tailor treatments based on individual biomarker profiles and predictive models.

Compatibility of hypokalaemia caused by low-dose prednisolone plus abiraterone acetate therapy for metastatic castration-resistant prostate cancer.

This study aimed to investigate the relationship between low-dose prednisolone (PSL) and the incidence of hypokalaemia at abiraterone acetate (abiraterone) plus PSL combination therapy targeting Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). This retrospective observational study included 153 Japanese patients treated with abiraterone and PSL for mCRPC at Kariya Toyota General Hospital and Gifu General Medical Center between September 2014 and October 2022. The incidence of grade ≥ 2 hypokalaemia as well as serum potassium level variations and the continuous combination therapy duration were compared between the low-dose (5mg/day of PSL) and the standard-dose (10mg/day of PSL) groups. This study included 153 patient of which 95 were matched to establish the analysis population. The low-dose and the standard-dose groups consisted of 13 and 82 patients, respectively. No significant difference in the incidence of grade ≥ 2 hypokalaemia was observed between the two groups [15.4% (2/13 patients) in the low-dose group and 12.2% (10/82 patients) in the standard-dose group, P = 0.667]. The low-dose group exhibited a decrease in serum potassium levels from 4.63 on day - 7 - 0 to 4.16 mmol/L on day 84 ± 10 (n = 7, P = 0.066), and serum potassium levels from day - 7 - 0 to 84 ± 10 in the low-dose group appeared to be great in the standard-dose group (n = 37, P = 0.475). The Kaplan-Meier curves for continuity of abiraterone and PSL therapy were not significantly different between the low-dose group (n = 13) and standard-dose group (n = 82, P = 0.427). Combination therapy with abiraterone and 5mg/day of PSL in Japanese patients with mCRPC did not change the incidence of grade ≥ 2 hypokalaemia. However, although not significant, 5mg/day of PSL demonstrated a decreasing trend in serum potassium levels with a larger degree of change than that of 10mg/day of PSL. Therefore, the combination of abiraterone and 5mg/day PSL can be administered to Japanese patients with mCRPC. The patients must be monitored for hypokalaemia through measurement of serum potassium levels and observation of subjective symptoms such as muscle weakness, convulsion etc. In addition, the doctor or the pharmacist must explain these symptoms to the patient and instruct them to consult their medical staff immediately in the event of development of such symptoms.

Oral Transport, Penetration, and Aspiration in PD: Insights from a RCT on STN + SNr Stimulation.

Dysphagia is frequent and detrimental in advanced Parkinson's disease (PD) and does not respond to standard treatments. Experimental models suggested that pathological overactivity of the substantia nigra pars reticulata (SNr) may hinder oral contributions to swallowing. Here, we hypothesized that the combined stimulation of subthalamic nucleus (STN) and SNr improves measures of dysphagia after eight weeks of active treatment. We enrolled 20 PD patients with dysphagia and deep brain stimulation (DBS). Patients were assessed in 'medication on' and 'STN' stimulation at baseline (V1) and then were randomized 1:1 to 'STN' or 'STN + SNr' stimulation. In addition, patients of both groups received swallowing therapy as a standard of care. The primary endpoint was the change in Penetration-Aspiration Scale (PAS) at eight-week follow-up (V2) with respect to the baseline (V1) under the hypothesis, that 'STN + SNr' was superior to 'STN'. We obtained further secondary endpoints on oral preparation, transport, pharyngeal phase, penetration, and aspiration. PAS change from V1 to V2 was not significantly different between groups (p = 0.221). When considering all patients for secondary analyses, we found that the entire study cohort showed better PAS scores at V2 compared to V1 irrespective from DBS treatment allocation (p = 0.0156). Both STN and STN + SNr treatments were safe. 'STN + SNr' stimulation was not superior compared to standard 'STN' stimulation both on PAS and the secondary endpoints. We found that the entire study cohort improved dysphagia after eight weeks, which presumably mirrors the effect of continued swallowing therapy and the increased patient attention on swallowing.

Effect of Interrupting Prolonged Sitting with Frequent Activity Breaks on Postprandial Glycemia and Insulin Sensitivity in Adults with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy: A Randomized Crossover Pilot Trial.

Objective: This study examined acute effects of interrupting prolonged sitting with short activity breaks on postprandial glucose/insulin responses and estimations of insulin sensitivity in adults with type 1 diabetes (T1D). Method: In a randomized crossover trial, eight adults (age = 46 ± 14 years [mean ± SD], body mass index [BMI] = 27.2 ± 3.8 kg/m2) receiving continuous subcutaneous insulin infusion (CSII) therapy completed two 6-h conditions as follows: uninterrupted sitting (SIT) and sitting interrupted with 3-min bouts of simple resistance activities (SRAs) every 30 min. Basal and bolus insulin were standardized across conditions except in cases of hypoglycemia. Postprandial responses were assessed using incremental area-under-the-curve (iAUC) and total AUC (tAUC) from half-hourly venous sampling. Meal-based insulin sensitivity determined from glucose sensor and insulin pump (SiSP) was assessed from flash continuous glucose monitor and insulin pump data. Outcomes were analyzed using mixed models adjusted for sex, BMI, treatment order, and preprandial values. Results: Glucose iAUC did not differ by condition (SIT: 19.8 ± 3.0 [estimated marginal means ± standard error] vs. SRA: 14.4 ± 3.0 mmol.6 h.L-1; P = 0.086). Despite CSII being standardized between conditions, insulin iAUC was higher in SRA compared to SIT (137.1 ± 22.7 vs. 170.9 ± 22.7 mU.6 h.L-1; P < 0.001). This resulted in a lower glucose response relative to the change in plasma insulin in SRA (tAUCglu/tAUCins: 0.32 ± 0.02 vs. 0.40 ± 0.02 mmol.mU-1; P = 0.03). SiSP was also higher at dinner following the SRA condition, with no between-condition differences at breakfast or lunch. Conclusion: Regularly interrupting prolonged sitting in T1D may increase plasma insulin and improve insulin sensitivity when meals and CSII are standardized. Future studies should explore underlying mechanistic determinants and the applicability of findings to those on multiple daily injections. Trial Registration: Australian and New Zealand Clinical Trial Registry Identifier-ACTRN12618000126213 (www.anzctr.org.au).

Albumin and platelet loss during the application of CytoSorb® in critically ill patients: a post-hoc analysis of the Cyto-SOLVE trial.

Adsorption devices like CytoSorb® (CS) are increasingly used in critically ill patients. However, potential adverse effects have not been sufficiently investigated. The aim of this post-hoc analysis of the monocentric prospective Cyto-SOLVE study was to examine albumin concentration and platelet count during the application of CS in intensive care unit (ICU) patients with different indications for CS therapy. 29 Adult ICU patients receiving continuous kidney replacement therapy and CS application for 12 hours were included. Albumin concentration and platelet count were measured before, during, and after application. Changes in albumin concentration and platelet count were investigated. Since 10/29 patients were substituted with platelets during CS therapy and 20/29 received albumin, subgroup analysis was performed in patients receiving no platelet concentrate and <20g albumin substitution during CS application. The dependent sample t-test was used to detect significant (p<0.05) changes over time and multivariate models were investigated. We observed a significant reduction in platelets (p=0.005, mean 14 G/l, 95% confidence interval (CI) 4 - 23G/l) during CS therapy with an even more pronounced drop in those 19 patients without platelet substitution (p=0.001, mean 22G/l, 95% CI 10 - 34). No significant change was detected in the albumin concentration of all patients. However, a significant albumin decrease was observed in those 17 patients with less than 20g albumin substitution during CS therapy (p=0.007, mean 0.17g/dL, 95% CI 0.05 - 0.29). No other potential covariates for the decrease could be identified in a multivariate model. Since a drop in albumin and platelets occurred during the use of CS, an increased substitution might be necessary. Knowledge of potential side effects is of great importance to prevent harm during the use of extracorporeal procedures. This knowledge should be considered for a reliable risk-benefit assessment in the future.

Analysis of treatment-free remission outcomes in patients with chronic myeloid leukemia who received sequential nilotinib therapy after achieving deep molecular response to imatinib

Objective: To analyze the treatment-free remission (TFR) outcomes in patients with chronic myeloid leukemia (CML) treated sequentially with nilotinib (NIL) after achieving deep molecular response (DMR) to imatinib (IM). Methods: Retrospectively enrolled 103 CML patients from 6 hematological centers in Henan Province who chose sequential NIL therapy or continued IM therapy after achieving DMR to first-line IM from June 2, 2013 to August 30, 2022. Among them, 42 cases were treated with sequential NIL and 61 cases continued IM therapy. The 42 patients in the sequential NIL group were further divided into 3 subgroups based on the duration of DMR at switching to sequential NIL therapy: Group 1 (17 cases): DMR duration<12 months at switching to sequential NIL therapy; Group 2 (8 cases): DMR duration≥12 months to<24 months at switching to sequential NIL therapy; Group 3 (17 cases): DMR duration≥24 months at switching to sequential NIL therapy. Follow-up ended on January 9, 2024, with a median follow-up of 40 (16, 91) months for the sequential NIL group and 49 (21, 123) months for the continuous IM group. Survival curves were plotted using the Kaplan-Meier method and the log-rank test was performed to compare the TFR rates between groups. Results: There were 19 males and 23 females with a median age [M (Q1, Q3)] of 43 (31, 50) years in the sequential NIL group. There were 32 males and 29 females with a median age of 41 (31, 50) years in the continuous IM group. Kaplan-Meier survival curve analysis showed that the TFR rate was higher in the sequential NIL group than in the continuous IM group (88.1% vs 63.9%, P=0.005). The results of subgroup analysis showed that the TFR rates in Group 1, Group 2 and Group 3 were 94.1%, 87.5% and 82.4%, respectively, with no statistically significant differences (all P>0.05).The TFR rate in Group 1 was higher than in the continued IM group (P=0.017), and there were no statistically significant differences in Group 2 and Group 3 compared with the continuous IM group(all P>0.05). Conclusion: Sequential NIL therapy after achieving DMR with IM therapy can improve the TFR rate in CML patients, especially in those with DMR duration<12 months before switching to sequential NIL therapy.

Safety of and chorioretinal circulation during repeated low-level red-light therapy for myopic children.

To evaluate the safety of repeated low-level red-light (RLRL) therapy in children, and the dynamic evolution of choroidal and retinal blood flow. This is a single-centre, randomised, single-blind, parallel-group clinical trial. Seventy myopic children were randomly assigned to either the intervention group [receiving RLRL therapy plus single-vision spectacle (SVS)] or the control group (wearing SVS). Participants underwent comprehensive ophthalmic examinations following their first irradiation, 9 months continuous RLRL therapy and stop of treatment. Quantitative analyses of choroidal and retinal microcirculation were analysed via optical coherence tomography angiography. Over 9 months of treatment, while the RLRL treatment demonstrated significantly less increases in refractive error and axial length compared with the SVS treatment (ps < 0.05), no abnormalities in fundus structure or visual function (mfERG, VEP and microperimetry) were detected (ps > 0.05). A single red-light exposure did not exert a significant influence on choroidal thickness (ps > 0.05). Upon continuous treatment, the RLRL group achieved peak values in these circulations at 9 months (ps < 0.05). Following cessation of exposure, all circulations exhibited a declining trend, reaching similar levels in both groups (ps > 0.05). As the frequency of red-light exposures intensified, there was a consistent surge in these circulations (ps < 0.05). Nine months of continuous RLRL exposure does not cause toxic side effects on retinal or optic nerve functions, and there is a time-dependent cumulative response in choroidal and retinal circulation.

CARDIOMYOPATHIES IN CHILDHOOD: CLINICAL COURSE, DIAGNOSIS AND CARE TACTICS

The article examines aspects of the clinical course, diagnostics and treatment of various forms of cardiomyopathy (dilated, hypertrophic, restrictive) in children. Due to the relevance of the problem, the obtained data on the features of the clinical course, diagnostics and tactics of patient management are of interest to cardiologists, general practitioners and pediatricians of family clinics. A total of 37 children aged 0-17 years were examined. Among those examined, the frequency of various forms of cardiomyopathy was: dilated - 62.1%, hypertrophic - 32.4%, restrictive - 5.4%. Anamnestic data, severity of the course, features of ECG, echocardiography, radiography for each form of cardiomyopathy were studied. Latent, mild, but more often moderate and severe course of the disease was noted. Patients with DCM and HCM often have various rhythm and conduction disorders. Outpatient observation and timely (continuous) therapy of CHF are indicated for children with cardiomyopathies. In severe cases of HCM with obstructive forms of HCM, the issue of surgical treatment is considered.

Telemedicine for long-term continuous positive airway pressure therapy: A six-month follow-up study in Japan using propensity score matching

BackgroundDuring the coronavirus disease (COVID-19) pandemic, Japan's health insurance system allowed continuous positive airway pressure (CPAP) telephone consultations to extend clinic visit intervals. This study aimed to determine whether 6-month CPAP adherence in the telemedicine (TM) group was inferior to that in the standard care group. MethodsPatients receiving long-term CPAP therapy for at least 6 months for obstructive sleep apnea (OSA) from two clinics in Japan were recruited between May and July 2020. The TM group consisted of patients who had not visited the clinic in person for 6 months, with physicians providing telephone consultations every 1–2 months. The standard care group included patients who visited the clinic monthly for physician consultation. In both groups, physicians reviewed CPAP usage data via telemonitoring. Patients were classified into three groups according to change in adherence: ≤ −5%, > −5 to <5%, and ≥5%. The primary outcome was the number of patients with worsened CPAP adherence (≤−5%). ResultsOf the 479 patients in the TM group and 146 in the standard care group, 120 were matched using propensity score 1:1 nearest neighbor matching and selected from both groups. Adherence worsened in 41 (34.2%) and 32 (26.7 %) patients in the TM and standard care groups, respectively. The TM group was not inferior to the standard care group in terms of the proportion of patients with worsened CPAP adherence (χ2 = 1.81, df = 1, P = 0.178). ConclusionsThis study found no significant difference in the 6-month CPAP adherence between the TM and standard care groups.

Omparative Study Between Pulsed and Continuous Itraconazole for the Treatment of Onychomycosis

Objective: To compare efficacy of pulsed versus continuous daily oral Itraconazole in the treatment of onychomycosis. Study Design: Randomized Control Trial (ClinicalTrials.gov: NCT05567484). Place and Duration of Study: Department of Dermatology, Combined Military Hospital, Abbottabad, Pakistan, from May to Dec 2021. Methodology: We enrolled 60 patients whose toenails showed signs of onychomycosis (crumbling nail plates, thicker nail beds, and yellowing). They were randomly divided into Group-A and Group-B, with 30 patients each. Group -A (Pulse Therapy) took two capsules of oral Itraconazole 100 mg twice weekly for one week every month for three months while Group-B (Continuous Therapy) received continuous oral 100 mg of Itraconazole once daily for 12 weeks continuously. Patients were subjected to an Onychomycosis Severity Index-based clinical evaluation. Results: In Group-A (Pulse Therapy), 25(83.3%) patients showed mycological cure whereas in Group-B (Continuous Therapy), 23(76.7%) patients showed mycological cure but difference in the efficacy of both drugs was not statistically significant (p-value=0.519). Conclusion: Pulsed therapy with Itraconazole and continuous Itraconazole therapy have comparable efficacies in treating dermatophyte toenail onychomycosis.

Clinical characteristics and outcomes of cerebral venous sinus thrombosis in patients with antiphospholipid syndrome.

Cerebral venous sinus thrombosis (CVST) is a rare but serious manifestation of venous thrombosis in patients with antiphospholipid syndrome (APS). This study investigated the risk factors, clinical characteristics and prognosis of CVST in APS patients. This retrospective cohort study included all thrombotic APS (tAPS) patients from Peking Union Medical College Hospital (PUMCH) from April 2005 to August 2023. Demographic characteristics, laboratory data and thrombotic risk factors were compared between tAPS-CVST group and tAPS-non-CVST group. Kaplan-Meier survival analysis was utilized to compare the recanalization rate and the recurrence rate. A total of 453 APS patients were enrolled, and 40 (8.8%) APS patients were with CVST. The median age of the APS-CVST patients was 27 (21.25, 32.75) years, and 72.5% were females. In 50% of these patients, CVST was the initial symptom of APS, with headache being the most prevalent clinical symptom (95%). Involvement of more than two venous sinuses were observed in 79.5% of patients, with the transverse sinus (79.5%) and sigmoid sinus (74.4%) being the most commonly affected sites. Oral contraceptives, intracranial infections and malignancy were identified as risk factors of APS-CVST. There were no statistically significant differences in baseline characteristics or the distribution of antiphospholipid antibodies profiles between the two groups. After a median follow-up of 24 (12, 52) months, 21 patients (52.5%) experienced recanalization, and 13 patients (32.5%) had a thrombotic recurrence. Survival analysis indicated that adequate anticoagulant therapy significantly contributed to recanalization (HR 6.27, 95% CI 2.616-15.02, P = 0.003), while continuous anticoagulant therapy was highly effective in reducing the recurrence of thrombotic events (HR 0.14, 95% CI 0.0447-0.4328, P = 0.0007). CVST should be considered in APS patients who experience sudden onset headaches, particularly those with thrombotic risk factors, such as the use of oral contraceptives, intracranial infections and malignancy. Continuous and adequate anticoagulant therapy is pivotal and beneficial for achieving recanalization and prevention of recurrence. Key Points • The prevalence of CVST in patients with APS may be underestimated. • APS-CVST is associated with special risk factors, including pregnancy, intracranial infection, oral contraceptives and tumors. • Long-term and adequate anticoagulation therapy can increase the vascular recanalization rate and reduce thrombosis recurrence.

Cardiovascular effects of obstructive sleep apnoea and effects of continuous positive airway pressure therapy: evidence from different study models

INTRODUCTIONCardiovascular consequences of obstructive sleep apnoea (OSA) and the effects of continuous positive airway pressure (CPAP) therapy on blood pressure, endothelial dysfunction, and MACE (major adverse cardiovascular events) have been studied over decades using different study designs. However, clinical findings from different study models on cardiovascular outcomes are sometimes contradictory.METHODSA literature search was conducted in PubMed for randomised controlled trials, meta-analyses, population-based epidemiological studies and OSA cohort studies up to September 2023 investigating the cardiovascular effect of OSA and CPAP in adults with OSA on the following cardiovascular endpoints: blood pressure, arterial hypertension, endothelial function, and MACE (myocardial infarction, stroke, transient ischemic attack, cardiovascular death). The level of evidence for these outcomes was discussed on the basis of different study models.RESULTS AND CONCLUSIONSThere is high-level evidence of a causal relationship between OSA and arterial hypertension and endothelial dysfunction, as well as on higher MACE incidence among subgroups of patients with untreated OSA. The cardiovascular effects of OSA depend on the severity of OSA, symptoms, phenotype, and comorbidities. The blood pressure-lowering effect of CPAP is mainly observed in uncontrolled and treatment-resistant hypertension. The MACE risk reduction in OSA depends on good long-term CPAP adherence. Younger, sleepy patients with more severe OSA, higher hypoxaemic burden and without overt cardiovascular end-organ disease may particularly benefit from CPAP treatment in terms of cardiovascular risk reduction. Randomised controlled trials of CPAP or other effective OSA treatments in primary cardiovascular prevention and in patients at highest risk are lacking.

Potential Risks Associated With Long-term Use of Proton Pump Inhibitors and the Maintenance Treatment Modality for Patients With Mild Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) significantly affects the health-related quality of life and healthcare costs. The prevalence of this disease is increasing in Asia, leading to a rapid increase in the demand of proton pump inhibitors (PPIs). Despite effective symptom management during initial treatment, relapse rates after PPI cessation remain high in patients with GERD, warranting longterm maintenance therapy. Concerns regarding potential side effects related to the long-term use of PPIs are escalating with increased usage. Studies have reported diverse side effects of PPIs, such as increased fracture risk, cardiovascular concerns, enteric infections, neurological diseases, and potential associations with gastric cancer. However, definitive causal relationships remain unclear. This review comprehensively summarizes the latest knowledge on the potential risks associated with long-term use of PPIs. Continuous or noncontinuous therapy can be used as a maintenance treatment modality for GERD. For patients with mild GERD, including those with nonerosive and mildly erosive reflux disease, on-demand therapy following a sufficient period of continuous maintenance therapy is recommended as a long-term maintenance treatment option.

Endocrine disorders in Kearns-Sayre syndrome with different severity of symptoms: two case reports and a literature review.

Kearns-Sayre Syndrome (KSS) is a variant of mitochondrial disorder caused by a Mitochondrial Deoxyribonucleic Acid (mtDNA) deletion. Clinical manifestations of KSS can include different organ and system involvement. Different organ malfunctions, more often cardiac dysfunction, can lead to death. No effective treatment of this condition exists to date. Here, we report two patients with KSS. Female patient with a large-scale deletion of 7,020 base pairs (bp) suffered from hypogonadism, diabetes mellitus with fluctuating glucose levels, and had poor general health. A male patient with a common 4,977 bp deletion did not have diabetes mellitus but had impaired glucose tolerance. He also had a higher level of general health than our female patient. Both patients had reduced Bone Mineral Density (BMD). In female patients, calcium and vitamin D supplementation combined with metabolic therapy and nutritional drink supplements helped increase BMD (up to 32% in L1-L4). Comparing these two patients suggests that the larger the mtDNA deletion is, the more severe the course of the disease is. Not only does the size of the mtDNA deletion probably determine the severity of the disease, but also such factors as mtDNA heteroplasmy level, presence of mtDNA duplications, and pleioplasmy. Moreover, continuous nonconsecutive metabolic therapy and nutritional supplements are helpful in the prevention of deterioration of symptoms and general health.

Dysphasia: metastatic prostate cancer to the leptomeninges: a case report

BackgroundLeptomeningeal metastasis occurs in 5% of patients with prostate cancer and indicates a very poor prognosis.Case presentationA 60-year-old Caucasian male patient diagnosed with metastatic castration-resistant prostate cancer with sclerotic bone metastases and soft tissue metastases underwent multiple courses of chemotherapy and hormone therapy. The diagnosis of prostate cancer is based on elevated prostate-specific antigen levels and tissue biopsy. He subsequently presented with expressive aphasia. Nonspecific, diffuse irregular dural/pachymeningeal thickening enhancement was noted on magnetic resonance imaging. Upon evaluation by neurology, electroencephalogram was negative for an epileptiform correlate. The workup included a lumbar puncture to rule out infectious etiology. The patient’s neurological status stabilized, and he was discharged home with a plan for continued therapy with abiraterone and prednisone. Due to advanced malignancy, the patient enrolled in hospice and died 3 weeks after hospital discharge.ConclusionsCentral nervous system metastasis occurs very rarely in prostate cancer. With the increase in life expectancy and advances in oncologic therapy for prostate cancer, physicians should be aware of and consider central nervous system metastasis in men aged 50 years and above.