Course Of Long-term Treatment Research Articles

Customizing subcutaneous immunoglobulin administration in primary antibody deficiency: patient-centric care perspectives.

This report delves into the challenges and potential solutions associated with flexible, customized subcutaneous immunoglobulin (SCIG) infusion regimens for patients with primary antibody deficiency disease (PAD). Advances in the treatment of inborn errors of immunity, particularly PAD, have converted fatal diseases into chronic, complex, long-term conditions that make adherence to treatment a critical issue. Conventional SCIG infusion regimens, while clinically effective, may not always align with the varied lifestyles, changing lifestyles and commitments of patients which can lead to missed doses, diminishing adherence thus posing potential health risks and compromising the overall effectiveness of treatment. For these reasons, it's important to develop flexible infusion regimens tailored to meet individual patient needs. Patient-centric strategies that promote shared decision-making and awareness of patient status not only promote medical efficacy but also enhance the overall patient experience. The authors of this report call attention for a need to shift toward more adaptable and individualized SCIG treatment plans for PAD patients whose needs may change over the long-term course of treatment.

CCR8/CCL1 and CXCR3/CXCL10 axis-mediated memory T-cell activation in patients with recalcitrant drug-induced hypersensitivity.

As a drug-induced hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS) is potentially fatal. Most patients with DRESS recover within a few weeks; however, some patients may suffer from a prolonged disease course and develop autoimmune sequelae. To investigate the immune mechanism and therapeutic targets of patients with recalcitrant DRESS with a prolonged disease course. Thirty-two patients with recalcitrant DRESS with a prolonged treatment course (≥ 8 weeks; 'prolonged DRESS'), 28 patients with DRESS with a short treatment course (< 2 weeks; 'short-duration DRESS') and 26 healthy donors (HDs) were enrolled. Bulk transcriptome results showed that the mRNA expression levels of CCR8 and CXCR3 were significantly increased in blood samples from patients in the acute stage of prolonged DRESS [Padj = 1.50 × 10-9 (CCR8) and Padj = 2.60 × 10-4 (CXCR3), patients with prolonged DRESS compared with the HD group]. Serum and skin lesion concentrations of CCL1 and CXCL10 (ligands of CCR8 and CXCR3, respectively) were significantly increased in patients with prolonged DRESS compared with patients with short-duration DRESS. The results from high-parameter flow cytometry and autoantibody screening also identified significant increases in CD8+ GNLY+ CXCR3+ effector memory T cells, CD8+ central memory T cells, CD4+ CCR8+ T helper 2 cells and IgG anti-HES-6 autoantibodies in patients with prolonged DRESS. Furthermore, in vitro blocking assays revealed that Janus kinase inhibitors (JAKi; mainly tofacitinib and upadacitinib) significantly decreased the release of CCL1 and CXCL10. Some patients with prolonged DRESS were successfully treated with JAKi. JAKi (tofacitinib and upadacitinib) were associated with decreased concentrations of CCL1 and CXCL10, suggesting that they may attenuate CCR8/CCL1 and CXCR3/CXCL10 axis-mediated memory T-cell activation, which contributes to disease pathogenesis in patients with recalcitrant DRESS and a long-term treatment course.

On the Way to Curing Advanced-Stage Mycosis Fungoides/Sézary Syndrome

Advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS) have poor prognosis with median survivals of less than 5 years. Although a variety of treatments are approved for MF/SS patients, durable complete remissions (CR) are rare. Advanced-stage MF or SS patients who achieved CR and maintained in CR or stage IA for more than 10 years were identified by a retrospective search of the principal investigator's database. Of 2266 patients diagnosed with MF or SS, 23 patients with advanced-stage MF/SS (6 IIB, 1 IIIB, 5 IVA1, 3 IVA2, 8 IVB) who achieved CR and maintained in CR or stage IA for ≥ 10 years were identified. As final/curative treatment, 11 patients underwent allogeneic stem cell transplantation (SCT). Most patients presented at young age, underwent SCT with reduced intensity conditioning regimen, had matched related donors, and controllable post-transplant graft versus host disease. Eleven patients were treated with TSEB as part of combined modality protocol in 2 patients and debulking therapy before allogeneic SCT in 9 patients. Five stage IIB patients achieved CR with radiotherapy. Four patients with blood involvement were treated with extracorporeal photopheresis (ECP) in combination with long-term antibiotics and immunomodulatory agents. Long-term antibiotics were given to 14 patients. TSEB followed by allogeneic SCT, radiotherapy, ECP plus long-term antibiotics and immunomodulatory agents were the most common curative/final treatments found in our patients. We are reporting the details of our long-term complete responders' treatment course in the hopes of obtaining more cure responses in the future.

Long-term Efficacy of Oral Valganciclovir in Presumed Cytomegalovirus Unilateral Hypertensive Anterior Uveitis

ABSTRACT Purpose To describe long-term efficacy and safety of oral valganciclovir in the treatment of presumed cytomegalovirus (CMV) unilateral hypertensive anterior uveitis. Methods Retrospective review of 40 patients (40 eyes). Results All patients presented with high intraocular pressure (mean 39.35 ± 7.58 mmHg), associated with signs of mild anterior uveitis. Oral valganciclovir resulted in control of the intraocular pressures and inflammation in 35 eyes. At the dose of ≥450 mg twice daily, no relapses were documented. The follow-up period ranged from 12 to 108 months (24.45 ± 14.56). At the final follow-up, the intraocular pressure was reduced to 14.92 ± 2.43 mmHg (<0.001). Drug-related complications in the form of leukopenia and azoospermia were reported in one patient. Conclusions Oral valganciclovir effectively and safely controls intraocular pressure and inflammation in presumed CMV anterior uveitis. A long-term treatment course seems necessary.

The two-directional prospective association between inflammatory bowel disease and neurodegenerative disorders: a systematic review and meta-analysis based on longitudinal studies.

Previous studies reported possible connections between inflammatory bowel disease (IBD) and several neurodegenerative disorders. However, the comprehensive relationships between IBD and various neurodegenerative disorders were not summarized. We executed a meta-analysis of longitudinal studies to provide an estimate of the strength of the two-directional prospective association between IBD and neurodegenerative disorders. We accomplished a thorough bibliographic search of PubMed, Web of Science, Embase, PsycINFO, and Cochrane Library databases until June 2023 to locate relevant longitudinal studies. The extracted data were then analyzed via meta-analysis using either a fixed or random effects model. The final analysis encompassed 27 studies. Individuals with IBD faced an increased risk of developing four neurodegenerative disorders than the general public, namely, Alzheimer's disease (hazard ratio[HR] = 1.35, 95% confidence interval [CI]: 1.03-1.77, P=0.031), dementia (HR =1.24, 95% CI: 1.13-1.36, P<0.001), multiple sclerosis (HR =2.07, 95% CI:1.42-3.02, P<0.001) and Parkinson's disease (HR =1.23, 95% CI:1.10-1.38, P<0.001). Two articles reported an increased incidence of amyotrophic lateral sclerosis or multiple system atrophy in IBD patients. Three studies investigated the prospective association between multiple sclerosis and IBD, revealing an elevated risk of the latter in patients with the former. (HR=1.87, 95% CI:1.66-2.10, P<0.001). These findings verified the two-directional relationship between the brain-gut axis, specifically demonstrating a heightened risk of various neurodegenerative diseases among IBD patients. It may be profitable to prepare screening strategies for IBD patients to find neurodegenerative diseases during the long-term course of treatment for IBD with a view to potential earlier diagnosis and treatment of neurodegenerative diseases, reducing public health and social burden. PROSPERO (CRD42023437553).

Bone-Anchored Maxillary Protraction for Adolescents with Cleft Palate and Class III Malocclusion: A Case Series.

To describe the long-term treatment course of bone-anchored maxillary protraction (BAMP) and evaluate orthognathic surgical indications after BAMP Retrospective case series Craniofacial/Cleft Palate Program at the Orthopaedic Institute for Children in Los Angeles, CA Twelve male patients with cleft palate (CP), unilateral cleft lip and palate (UCLP), or bilateral cleft lip and palate (BCLP) and Class III malocclusion treated with BAMP (mean age: 11.4 ± 2.6 years) were included. BAMP treatment was performed by placement of bone-anchored maxillary and mandibular plates connected with intraoral Class III dental elastics or maxillary plates connected to a facemask. We retrospectively assessed BAMP treatment variables, including age at surgery, revision surgeries, and treatment duration. The primary goal was correction to class I occlusion. Twelve patients underwent BAMP treatment for an average of 4.4 ± 2.4 years. Two patients were corrected to class I occlusion at the time of this report. Le Fort I advancement was no longer required in two patients (16.7%), it was required for nine patients (75.0%) and was completed for one patient following BAMP treatment (8.3%). This preliminary report demonstrated that BAMP treatment may be associated with a minimal reduction in the requirement for Le Fort I advancement at skeletal maturity. Future studies with larger sample sizes are necessary to confirm this association.

Adherence to treatment and parents’ perspective about effectiveness of melatonin in children with autism spectrum disorder and sleep disturbances

ObjectiveMelatonin is considered an effective pharmacological treatment for the sleep disturbances that are reported in > 50% of children with autism spectrum disorder (ASD). However, real-life data about the long-term course and effectiveness of melatonin treatment in children with ASD is lacking.MethodsIn this retrospective cohort study, we assessed the adherence to melatonin treatment and parents’ perspective of its effect on sleep quality and daytime behavior in children with ASD via a parental phone survey of children in the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) database. Cox regression analysis was used to assess the effect of key demographic and clinical characteristics on treatment adherence.ResultsMelatonin was recommended for ~ 8% of children in the ANCAN database. These children were characterized by more severe symptoms of autism. The median adherence time for melatonin treatment exceeded 88 months, with the most common reason for discontinuation being a lack of effectiveness (14%). Mild side-effects were reported in 14% of children, and 86%, 54%, and 45% experienced improvements in sleep onset, sleep duration and night awakenings, respectively. Notably, melatonin also improved the daytime behaviors of > 28% of the children. Adherence to treatment was independently associated with improvements in night awakenings and educational functioning (aHR = 0.142, 95%CI = 0.036–0.565; and aHR = 0.195, 95%CI = 0.047–0.806, respectively).ConclusionsBased on parents’ report, melatonin is a safe and effective treatment that improves both sleep difficulties and daily behavior of children with ASD.

Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis.

The effects of dipeptidyl peptidase 4 (DPP-4) inhibitors over the course of long-term treatment remain unclear, and concerns have been raised regarding the role of DPP-4 inhibitors in carcinogenesis in the pancreas. Earlier studies of pancreatic adverse events have reported conflicting results. This study analyzed Korean National Health Insurance Service data from January 2009 to December 2012. Patients who had type 2 diabetes mellitus and took two or more oral glucose-lowering drugs (GLDs) were included. Patients prescribed DPP-4 inhibitors (n=51,482) or other GLDs (n=51,482) were matched at a 1:1 ratio using propensity score matching. The risk of pancreatic cancer was calculated using Kaplan-Meier curves and Cox proportional-hazards regression analysis. During a median follow-up period of 7.95 years, 1,051 new cases of pancreatic cancer were identified. The adjusted hazard ratio (HR) for DPP-4 inhibitor use was 0.99 (95% confidence interval [CI], 0.88 to 1.12) compared with the other GLD group. In an analysis limited to cases diagnosed with pancreatic cancer during hospitalization, the adjusted HR for the use of DPP-4 inhibitors was 1.00 (95% CI, 0.86 to 1.17) compared with patients who took other GLDs. Using the other GLD group as the reference group, no trend was observed for elevated pancreatic cancer risk with increased DPP-4 inhibitor exposure. In this population-based cohort study, DPP-4 inhibitor use over the course of relatively long-term follow-up showed no significant association with an elevated risk of pancreatic cancer.

Examining the neural mechanisms of rTMS: a naturalistic pilot study of acute and serial effects in pharmacoresistant depression.

Previous studies have demonstrated the effectiveness of therapeutic repetitive transcranial magnetic stimulation (rTMS) to treat pharmacoresistant depression. Nevertheless, these trials have primarily focused on the therapeutic and neurophysiological effects of rTMS following a long-term treatment course. Identifying brain-based biomarkers of early rTMS therapeutic response remains an important unanswered question. In this pilot study, we examined the effects of rTMS on individuals with pharmacoresistant depression using a graph-based method, called Functional Cortical Networks (FCN), and serial electroencephalography (EEG). We hypothesized that changes in brain activity would occur early in treatment course. A total of 15 patients with pharmacoresistant depression underwent five rTMS sessions (5Hz over the left dorsolateral prefrontal cortex, 120%MT, up to 4,000 pulses/session). Five participants received additional rTMS treatment, up to 40 sessions. Resting EEG activity was measured at baseline and following every five sessions, using 64-channel EEG, for 10 minutes with eyes closed. An FCN model was constructed using time-varying graphs and motif synchronization. The primary outcome was acute changes in weighted-node degree. Secondary outcomes included serial FFT-based power spectral analysis and changes in depressive symptoms measured by the 9-Item Patient Health Questionnaire (PHQ-9) and the 30-item Inventory of Depressive Symptoms-Self Report (IDS-SR). We found a significant acute effect over the left posterior area after five sessions, as evidenced by an increase in weighted-node degree of 37,824.59 (95% CI, 468.20 to 75,180.98) and a marginal enhancement in the left frontal region (t (14) = 2.0820, p = 0.056). One-way repeated measures ANOVA indicated a significant decrease in absolute beta power over the left prefrontal cortex (F (7, 28) = 2.37, p = 0.048) following ten rTMS sessions. Furthermore, a significant clinical improvement was observed following five rTMS sessions on both PHQ-9 (t (14) = 2.7093, p = 0.017) and IDS-SR (t (14) = 2.5278, p = 0.024) and progressed along the treatment course. Our findings suggest that FCN models and serial EEG may contribute to a deeper understanding of mechanisms underlying rTMS treatment. Additional research is required to investigate the acute and serial effects of rTMS in pharmacoresistant depression and assess whether early EEG changes could serve as predictors of therapeutic rTMS response.

Refusal of Subsequent Treatment in Patients With EGFR-mutant Non-small-cell Lung Cancer After Response to EGFR-TKIs.

During the course of effective and long-term treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), some elderly patients might decline further treatment after EGFR-TKI. We conducted a study to try and understand the reasons for this treatment decision. We analyzed the medical records of all patients diagnosed with non-small-cell lung cancer with EGFR mutations between 2016 and 2021. There were 108 patients who received EGFR-TKIs. Of these, 67 patients responded to TKI. These responding patients were divided into two groups according to whether they received subsequent TKI treatment. At their request, 24 patients (group A) did not receive further anticancer treatment following TKI. The other 43 patients (group B) received anticancer therapy following TKI. Progression-free survival in group A patients was significantly longer (median=18 months, range=1-67 months) than in group B patients. The reasons for not wanting subsequent treatment after TKI were older age, reduced general condition, deterioration of physical comorbid disease and dementia. Dementia was the most common reason for patients over 75 years of age. Some elderly patients with well-controlled disease might express their refusal of all subsequent anticancer therapy after TKIs. Medical staff should respond seriously to these requests.

Effects of Longitudinal Changes in Neuroticism and Stress on Cognitive Decline

ObjectiveThe relationships among depression, personality factors, stress, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Independently, the presence of neuroticism and the number of stressful life events are each associated with worsening cognitive decline in depressed older adults. Yet little is known about combined effects of changes in neuroticism and changes in stress on cognitive decline among older depressed adults. DesignLongitudinal observational study. SettingAcademic Health Center. ParticipantsThe authors examined 62 participants in the Neurobiology of Late-life depression (NBOLD) study to test the hypothesis that, compared with older depressed subjects who experience improved neuroticism and lower psychosocial stressors over time, those with worsening neuroticism and greater psychosocial stressors will demonstrate more cognitive decline. MeasurementsThe authors measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Ǻsberg Depression Rating Scale. At annual assessments, subjects reported the number of psychosocial stressors in the prior year and completed a neuropsychological evaluation. Participants completed a detailed neuropsychological battery at baseline and annually over 3 years. The battery included a test of delayed story memory (Logical Memory-2 or LMII). The outcome 3-year change in cognitive scores was regressed against 3-year change scores of neuroticism and number of psychosocial stressors, plus their interaction, while adjusting for sex, age, race, education, baseline cognitive score, and 3-year change in MADRS score as covariates. ResultsIn multivariable linear regression analysis with the above covariates, the interaction effect of 3-year change in Total Neuroticism score and 3-year change in Total Stressors on change in LMII performance was statistically significant (B = −0.080[95%CL: −0.145 to −0.015], T = −2.48, df = 52, p = 0.017). Further exploration of this finding showed that 1) when total stressors increased by 2 or more over 3 years, LMII change was inversely associated with neuroticism change; and 2) when neuroticism improved less, LMII change score was inversely associated with total stressor change. There were no other significant interactions between stress and neuroticism on cognition. ConclusionOur findings document the importance of tracking change in neuroticism and monitoring psychosocial stress over the long-term course of treatment in geriatric depression. Both factors exert important combined effects on memory over time. Future studies in larger samples are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.

Long-Term Management of Advanced Basal Cell Carcinoma: Current Challenges and Future Perspectives.

Simple SummaryLocal therapies are no longer an option for locally advanced basal cell carcinoma. Abnormal activation of the hedgehog signaling pathway leads to uncontrolled tumor growth. Hedgehog pathway inhibitors are an effective treatment option for this kind of tumor. However, treatment-related toxicity under long-term treatment may lead to limitations in quality of life, and thus to therapy interruption or even discontinuation. This review summarizes pertinent treatment adjustments and novel therapeutic strategies for effective treatment of locally advanced basal cell carcinoma.The first-line therapy for locally advanced basal cell carcinoma (laBCC) is Hedgehog pathway inhibitors (HHIs), as they achieve good efficacy and duration of response. However, toxicity in the course of long-term treatment may lead to a decrease in the quality of life, and consequently to interruption or even discontinuation of therapy. As HHI therapy is a balancing act between effectiveness, adverse events, quality of life, and adherence, numerous successful treatment strategies have evolved, such as dose reduction and dose interruptions with on-off treatment schedules or interruptions with re-challenge after progression. As a small percentage of patients show primary or acquired resistance to HHIs, the inhibition of programmed cell death protein 1 (PD-1) has been approved as a second-line therapy, which may also be accompanied by immune-related toxicities and non-response. Thus, optimization of current treatment schedules, novel agents, and combination strategies are urgently needed for laBCC. Here, we narratively model the treatment sequence for patients with laBCC and summarize the current state of approved treatment regimens and therapeutic strategies to optimize the long-term management of laBCC.

ID:16318 Complication of Spinal Cord Stimulator Fractured Lead Extraction After 8 Years of Implantation: Retained Lead

Lead fracture is a well-known complication of spinal cord stimulation (SCS). Although hardware and implantation techniques for SCS are continuously developing, equipment failures, such as percutaneous lead fracture, over the course of long-term treatment are still encountered in a relatively high proportion of the cases.

Efficacy of drugs against clonorchiasis and opisthorchiasis: a systematic review and network meta-analysis

Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are the three most important human liver fluke species in the Opisthorchiidae family, infecting approximately 25 million people worldwide. Drug treatment is needed to control morbidity and is also useful in lowering transmission. Several drugs used in various regimens are available to treat these infections, but their comparative efficacy is uncertain. We aimed to compare the efficacy in terms of cure rate and egg reduction rate of currently registered drugs against human liver fluke infection. We conducted a systematic review using readily available electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, KoreaMed, China National Knowledge Infrastructure, and Wanfang Data) without language restrictions from inception until June 29, 2021. Clinical trials with pairwise comparison of drugs (praziquantel, albendazole, mebendazole, tribendimidine, or combinations of these drugs) against C sinensis, O viverrini, and O felineus were eligible, including trials comparing these drugs or their combinations with placebo. We compared efficacy in terms of cure rate by network meta-analysis. We conducted mixed binomial regression analyses for each species to derive predicted median cure rates for each drug regimen. The models included treatment and infection intensity as fixed factors, year of publication as covariate, and random effects of the different studies assumed to be normally distributed. We also assessed the quality of the included studies. This study was registered with PROSPERO (CRD42018109232). Overall, 26 trials from 25 studies were included, of which 18 involved C sinensis, seven studied O viverrini, and one focused on O felineus. These trials included a total of 3340 participants. The two long-term treatment courses against C sinensis infection using 400 mg of albendazole (400 mg twice a day for 5 days and 400 mg twice a day for 7 days) resulted in cure rates of 100%, while two other multiple-dose regimens of albendazole resulted in high predicted cure rates: 300 mg twice a day for 5 days (93·9% [95% CI 49·6-99·6]) and 400 mg twice a day for 3 days (91·0% [50·9-99·0]). The WHO-recommended praziquantel regimen (25 mg/kg three times a day for 2 days) also showed a high predicted cure rate (98·5% [85·4-99·9]) in C sinensis infection, and predicted cure rates were above 90% for several other multiple-dose praziquantel regimens, including 20 mg/kg three times a day for 3 days (97·6% [74·7-99·8]), 14 mg/kg three times a day for 5 days (93·9% [44·8-99·7]), and 20 mg/kg twice a day for 3 days (91·0% [50·9-99·0]). In O viverrini infection, the regimen of 50 mg/kg and 25 mg/kg of praziquantel given in a single day showed the highest predicted cure rate (93·8% [85·7-97·5]), while a single dose of 50 mg/kg praziquantel also resulted in a high predicted cure rate (92·1% [64·9-98·6]). The single dose of 400 mg tribendimidine showed a high predicted cure rate of 89·8% (77·5-95·8). A low quality of evidence was demonstrated in most studies, especially those published before 2000. Selection bias due to poor random sequence generation and allocation concealment was high, and performance and detection biases were frequently unreported. Praziquantel shows high efficacy against clonorchiasis and opisthorchiasis. Tribendimidine might serve as a treatment alternative and warrants further investigation. Although albendazole is efficacious when long treatment schedules (5 days or 7 days) are applied, limited size of studies and high risk of bias affect the interpretation of results. More high-quality studies are needed to promote the establishment of treatment guidelines for human liver fluke infection. Fourth Round of Three-Year Public Health Action Plan (2015-2017; Shanghai, China) and Swiss National Science Foundation.

Long-term Effect of Denosumab on Bone Microarchitecture as Assessed by Tissue Thickness-Adjusted Trabecular Bone Score (TBS) in Postmenopausal Women with Osteoporosis: Results from the Freedom and Open-Label Extension (OLE)

TBS is an indirect measure of bone microarchitecture assessed on lumbar spine (LS) DXA scans and provides information beyond bone mineral density (BMD). TBS algorithm has been updated to account for regional soft tissue noise in DXA images. This retrospective analysis applied updated built-in tissue thickness-adjusted TBS algorithm to investigate the long-term effect of denosumab on bone microarchitecture in FREEDOM and OLE. This analysis included 279 postmenopausal women with LS or total hip BMD T-score <−2.5 and ≥−4.0 who completed the FREEDOM DXA sub study and continued in the OLE study: 150 women received denosumab 60 mg subcutaneously every 6 months for 3 years and same-dose open-label denosumab for 7 years (long-term denosumab group); 129 women received placebo for 3 years and open-label denosumab for 7 years (crossover denosumab group). BMD and TBS were assessed on LS DXA scans, blinded from treatment allocation, at FREEDOM: baseline, Month 1, and Years 1, 2, and 3; and at OLE: baseline, Years 1, 2, 3, 5, and 7. Baseline characteristics were similar between groups. Long-term denosumab led to significant and progressive increases in TBS over 10 years of treatment (Figure). A similar trend was observed in the crossover group during 7 years of denosumab therapy. In the long-term denosumab group, % of patients with normal microarchitecture (TBS >1.074) increased from 26.1% at baseline to 53.2% up to Year 10, and % of patients with degraded (TBS ≤1.027) or partially degraded (1.027< TBS≤1.074) microarchitecture decreased from 48.6% to 29.1% and from 25.4% to 17.7%, respectively (P < 0.0001; TBS thresholds equivalent to 1.230 and 1.310 for the classical TBS algorithm corrected for body mass index). A similar improvement in bone microarchitecture was observed in the crossover group from OLE baseline up to OLE Year 7 (P < 0.0001). Over the course of long-term denosumab treatment, TBS changes were largely unrelated to LS BMD changes: r2 was 0.05 from baseline to Year 10 in the long-term group and 0.28 from OLE baseline to OLE Year 7 in the crossover group. Up to 10 years of denosumab treatment significantly and progressively improved TBS assessment of bone microarchitecture independently of BMD in postmenopausal women with osteoporosis.

Continuous positive airway pressure treatment in sleep apnea: patient compliance and impact on the right heart

Obstructive sleep apnea syndrome (OSAS) is considered to be an important predisposing factor for cardiovascular diseases. The main objective of this study was to investigate the impact of CPAP treatment on cardiac structure and function and to assess patient compliance over a long-term course of CPAP treatment. A total of 50 patients diagnosed with moderate-to-severe OSAS based on overnight study, without relevant concomitant diseases were enrolled. Patient compliance, along with echocardiographic and CPAP parameters, was assessed. The average time to follow-up was 38 ± 4.2 months. An increase in tricuspid annular plane systolic excursion (TAPSE) (22.1 ± 4.3–25.5 ± 4.6 mm, p = 0.005) and peak early systolic tricuspid annular velocity (S’) (14 ± 3.2–17.2 ± 5.2 cm/s, p = 0.005) after CPAP treatment was noted. In patients without CPAP, no significant change in right ventricular (RV) contractility was found. There were no significant differences regarding right atrial (RA) and RV diameters, as well as tricuspid regurgitant peak gradient (TRPG) in both groups; however, a predisposition to increased RA size along with RV and tricuspid annulus diameters was revealed. The mean duration of nightly CPAP use was 3 ± 2.3 h/night in all-day analysis and 4.7 ± 2.1 h/night on days with device usage. The non-adherence rate was 57%. The use of effective CPAP therapy may lead to increased RV systolic function in patients with OSAS in long-term observation. However, long-term patient compliance is generally poor. Regardless of CPAP therapy, a gradual increase in heart size is observed.

Special Aspects of the Surface Scale Growth during Oxidation of V–Cr–Ta–Zr Alloy in Air

The results of a study of features of the surface scale growth on the V–Cr–Ta–Zr vanadium alloy specimens during short-term oxidation in air are presented. It is shown that in the initial oxidation stages, irrespective of the specimen microstructure, the surface scale growth rate can be an order of magnitude higher than that in the course of long-term treatment. It is found out that the scale is characterized by open porosity formed as a result of sticking of the V2O5 plate-like flakes together. It is suggested that a decrease in the oxidation rate is a consequence of an increase in the surface scale thickness, resulting in a slower supply of oxygen to the specimen surface on which the processes of scale nucleation and growth, as well as diffusion saturation of the subsurface vanadium-alloy layer with oxygen are observed.

Laser therapy in cutaneous and genital warts: A review article.

Traditional treatment modalities for wart require long-term treatment course and usually have high recurrence rates and unwanted side effects. In this review article, we evaluated different types of laser therapy in the treatment of warts. Published articles since 2000 up to July 2020 about laser therapy in genital and non-genital warts were searched and assessed. Fifty articles were selected for the final review, including 22 pulsed dye laser (PDL), 10 neodymium-yttrium-aluminum-garnet (Nd: YAG), 3 erbium-doped yttrium-aluminum-garnet (Er: YAG), 14 carbon dioxide (CO2 ) laser and one systematic review. Complete response rates were different in terms of laser type used (0%-100%, 9.1%-100%, 83.3%-100%, and 59.15%-100% for PDL, Nd: YAG, Er: YAG, and CO2 laser, respectively). There was no significant difference between conventional treatment modalities and laser therapy regarding efficacy and recurrence rate. Combination of lasers with keratolytic agents, immunomodulators and photodynamic therapy can be helpful especially in immunosuppressed patients, refractory, and recurrent lesions. PDL has the lowest occurrence of adverse effects relative to other types of lasers.

The association between anti-inflammatory effects of long-term lithium treatment and illness course in Bipolar Disorder.

Introduction: Altered levels of acute-phase proteins are often described in different conditions in BD. Nevertheless, data on the association between lithium treatment and inflammatory markers in the long-term course of BD are still missing. The aim of the study was to examine the long-term course of BD concerning long-term lithium treatment, chronic inflammatory processes and symptom progression. Furthermore, the association between duration of lithium treatment and levels of hsCRP was explored. Methods: 267 individuals (males= 139, females= 128) with BD were included. Duration of lithium treatment as well as symptom progression, defined as the increase in severity of symptoms, number of episodes a year and duration of episodes within a period of 1.5 years in the past and hsCRP were evaluated. Results: Male individuals with symptom progression over time had significantly lower duration of lithium treatment compared to individuals without symptoms progression (U= 47.4, p=.037). There were significantly higher levels of hsCRP in male individuals with symptom progression compared to males without symptom progression (U= 47.5, p=.027). Further, there was a significant negative correlation between the duration of lithium treatment and hsCRP levels in the whole sample (r= -.276, p<.05). Conclusion: Our results show that an altered inflammatory state may be associated with a more severe illness course in BD. Further, a longer duration of lithium treatment may be associated with lower symptom progression. The shown association between hsCRP-levels and lithium treatment duration suggests a potential anti-inflammatory effect of lithium as a mediator of its significant positive outcome effect in BD.

Evaluation of Nasal Patency Among Patients With Unilateral Cleft Lip and Palate: Cleft Versus Non-Cleft Side.

To evaluate the nasal patency using acoustic rhinometry (AR) in patients with unilateral cleft lip and palate (UCLP) and to ascertain the rhinological importance of the same. Eccovision Acoustic Rhinometer system was used for assessment of nasal cross-sectional area (CSA) and volume in 15 patients with UCLP. The CSA1, CSA2, and CSA3, which represent the CSA at the nasal valve area and anterior end of the inferior turbinate, the anterior half of the inferior turbinate and the anterior end of the middle turbinate, and the region of middle portion of middle turbinate, respectively, were compared on the cleft and non-cleft side. The mean ± SD of CSA1, CSA2, and CSA3 as well as the overall nasal CSA were significantly higher on non-cleft side compared to cleft side (P value < .001). The mean ± SD of nasal volume was also significantly higher in non-cleft side compared to cleft side (P value < .001). The nasal patency among patients with UCLP demonstrates a range of impairments that can be objectively measured using acoustic rhinometry. The orthodontic, orthopedic, or orthosurgical management of maxillary deficiency in these patients can affect the nasal area and volume and can have an impact on breathing, speech, and sleep. The pretreatment assessment may be useful to identify patients who are at potential risk of deterioration of nasal patency and airway post-intervention. Taking into consideration the multiple diagnostic procedures in the course of long-term multidisciplinary treatment of patients with cleft lip and palate, a noninvasive investigation technique such as AR may be the preferred mode of investigation to ascertain nasal patency.