Long-term Treatment Compliance Research Articles

Tumor treating fields in glioblastoma: long-term treatment and high compliance as favorable prognostic factors.

Tumor treating fields (TTFields) have earned substantial attention in recent years as a novel therapeutic approach with the potential to improve the prognosis of glioblastoma (GBM) patients. However, the impact of TTFields remains a subject of ongoing debate. This study aimed to offer real-world evidence on TTFields therapy for GBM, and to investigate the clinical determinants affecting its efficacy. We have reported a retrospective analysis of 81 newly diagnosed Chinese GBM patients who received TTFields/Stupp treatment in the Second Affiliated Hospital of Zhejiang University. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier method. Cox regression models with time-dependent covariates were utilized to address non-proportional hazards and to assess the influence of clinical variables on PFS and OS. The median PFS and OS following TTFields/STUPP treatment was 12.6 months (95% CI 11.0-14.1) and 21.3 months (95% CI 10.0-32.6) respectively. Long-term TTFields treatment (>2 months) exhibits significant improvements in PFS and OS compared to the short-term treatment group (≤2 months). Time-dependent covariate COX analysis revealed that longer TTFields treatment was correlated with enhanced PFS and OS for up to 12 and 13 months, respectively. Higher compliance to TTFields (≥ 0.8) significantly reduced the death risk (HR=0.297, 95%CI 0.108-0.819). Complete surgical resection and MGMT promoter methylation were associated with significantly lower risk of progression (HR=0.337, 95% CI 0.176-0.643; HR=0.156, 95% CI 0.065-0.378) and death (HR=0.276, 95% CI 0.105-0.727; HR=0.249, 95% CI 0.087-0.710). The TTFields/Stupp treatment may prolong median OS and PFS in GBM patients, with long-term TTFields treatment, higher TTFields compliance, complete surgical resection, and MGMT promoter methylation significantly improving prognosis.

Fecal and serum metabolomic signatures and gut microbiota characteristics of allergic rhinitis mice model.

The etiology of allergic rhinitis (AR) is complicated. Traditional therapy of AR still has challenges, such as low long-term treatment compliance, unsatisfactory therapeutic outcomes, and a high financial burden. It is urgent to investigate the pathophysiology of allergic rhinitis from different perspectives and explore brand-new possible preventative or treatment initiatives. The aim is to apply a multi-group technique and correlation analysis to explore more about the pathogenesis of AR from the perspectives of gut microbiota, fecal metabolites, and serum metabolism. Thirty BALB/c mice were randomly divided into the AR and Con(control) groups. A standardized Ovalbumin (OVA)-induced AR mouse model was established by intraperitoneal OVA injection followed by nasal excitation. We detected the serum IL-4, IL-5, and IgE by enzyme-linked immunosorbent assay (ELISA), evaluated the histological characteristics of the nasal tissues by the hematoxylin and eosin (H&E) staining, and observed the nasal symptoms (rubs and sneezes) to evaluate the reliability of the AR mouse model. The colonic NF-κB protein was detected by Western Blot, and the colonic histological characteristics were observed by the H&E staining to evaluate inflammation of colon tissue. We analyzed the V3 and V4 regions of the 16S ribosomal DNA (rDNA) gene from the feces (colon contents) through 16S rDNA sequencing technology. Untargeted metabolomics was used to examine fecal and serum samples to find differential metabolites. Finally, through comparison and correlation analysis of differential gut microbiota, fecal metabolites, and serum metabolites, we further explore the overall impact of AR on gut microbiota, fecal metabolites, and host serum metabolism and its correlation. In the AR group, the IL-4, IL-5, IgE, eosinophil infiltration, and the times of rubs and sneezes were significantly higher than those in the Con group, indicating the successful establishment of the AR model. No differences in diversity were detected between the AR and Con groups. However, there were modifications in the microbiota's structure. At the phylum level, the proportion of Firmicutes and Proteobacteria in the AR group increased significantly, while the proportion of Bacteroides decreased significantly, and the ratio of Firmicutes/Bacteroides was higher. The key differential genera, such as Ruminococcus, were increased significantly in the AR group, while the other key differential genera, such as Lactobacillus, Bacteroides, and Prevotella, were significantly decreased in the Con group. Untargeted metabolomics analysis identified 28 upregulated and 4 downregulated differential metabolites in feces and 11 upregulated and 16 downregulated differential metabolites in serum under AR conditions. Interestingly, one of the significant difference metabolites, α-Linoleic acid (ALA), decreased consistently in feces and serum of AR. KEGG functional enrichment analysis and correlation analysis showed a close relationship between differential serum metabolites and fecal metabolites, and changes in fecal and serum metabolic patterns are associated with altered gut microbiota in AR. The NF-κB protein and inflammatory infiltration of the colon increased considerably in the AR group. Our study reveals that AR alters fecal and serum metabolomic signatures and gut microbiota characteristics, and there is a striking correlation between the three. The correlation analysis of the microbiome and metabolome provides a deeper understanding of AR's pathogenesis, which may provide a theoretical basis for AR's potential prevention and treatment strategies.

Individualizing treatment choices for patients with type 2 diabetes according to patient preference

Many patients with Type 2 diabetes will require additional glucose lowering treatment to achieve optimal glucose control. Ensuring treatment adherence is therefore crucial in order to reduce the long-term risks of complications. A study recently published in Nature Medicine, known as the TriMaster study is the first study to evaluate the effectiveness of allowing people with type 2 diabetes to choose their own second/third line medication to manage hyperglycaemia. This approach was thought to balance the potential efficacy with potential side effects profiles of the selected drugs. The study led by academics from the University of Exeter was a randomized double-blind, three-way cross over trial where patients received three different second- or third-line once-daily type 2 diabetes glucose-lowering drugs (pioglitazone 30 mg, sitagliptin 100 mg and canagliflozin 100 mg). As part of a prespecified secondary endpoint, patients' drug preference were examined after they had tried all three drugs. In total, 448 participants were treated with all three drugs which overall showed similar glucose lowering outcomes. In terms of preference, 115 patients (25%) preferred pioglitazone, 158 patients (35%) sitagliptin and 175 patients (38%) canagliflozin. The drug preferred by individual patients was associated with a lower HbA1c (mean: 4.6; 95% CI: 3.9, 5.3) mmol mol−1 lower versus nonpreferred) and was associated with fewer side effects (mean: 0.50; 95% CI: 0.35, 0.64) fewer side effects versus nonpreferred). This study showed that allocating therapy based on patients individually preferred drugs, rather than allocating all patients the overall most preferred drug (canagliflozin), would result in more patients achieving the lowest HbA1c for them (70% versus 30%) and the fewest side effects (67% versus 50%). Given the comparable glucose lowering ability of different drugs, allowing patients to try suitable medications before they choose long-term therapy according to their treatment preference could be a practical alternative to individualised treatment strategy for type 2 diabetes that would facilitate long-term treatment compliance.

The effect of the COVID-19 pandemic on long-term treatment compliance and disease control in children with persistent asthma.

No long-term data exists on asthma treatment compliances (ATC), exacerbations (AE), and control (AC) during the COVID-19 pandemic in children. This study aimed to evaluate ATC, AE, AC and the related factors among children with persistent asthma (PA) within the first year of the pandemic Methods. Children aged 6-18 years with PA who were under regular inhaled corticosteroid treatment for at least a year prior to the first COVID-19 case in Türkiye were included. Data on AE and AC were collected from medical files. Factors affecting ATC and AC as well as COVID-19 history were assessed by means of a questionnaire. The study included 247 cases. COVID-19 was detected in 14.5% of them. In the first year of the pandemic, ATC decreased to 56.7% and the most common reason was the absence of asthma symptoms. There was a significant improvement in AC (p < 0.001). The number of upper respiratory tract infections (URTI) and AE were significantly decreased during the first year of the pandemic (p < 0.001). COVID-19 infection, smoking in the household, school attendance, a family member working outside the home, house dust mite sensitization or allergic rhinitis had no significant effect on AC (p > 0.05). Regression analysis determined that children who did not have any URTI had 2.4 times better AC compared to those who had (p= 0.02; %95 CI: 1.1-5.4). Although ATC decreased significantly in the long-term in the first year of the pandemic, significant improvement was observed in AE and AC compared to the previous year, which was related only to not having URTI.

ABCL-052 MINDway: A Phase Ib/II Dose Optimization Study to Assess Safety and Pharmacokinetics of Tafasitamab + Lenalidomide in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

The chemo-free immunotherapy tafasitamab + lenalidomide has been granted FDA accelerated approval and EU conditional marketing authorization for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) treatment in autologous stem cell transplant-ineligible adults. Treatment schedule optimization aims to reduce the frequency of hospital visits and decrease treatment burden and healthcare utilization. MINDway (NCT05222555) will investigate if tafasitamab administration at levels higher than the approved 12 mg/kg dose at a reduced dosing frequency maintains the benefit-risk relationship of tafasitamab + lenalidomide for patients with R/R DLBCL. To assess an optimized tafasitamab treatment schedule in patients with R/R DLBCL. Open-label, multicenter, Phase Ib/II study. Currently enrolling; the planned sample size is 51 patients. Eligible patients are aged 18-80 years with histologically confirmed R/R DLBCL and 1-3 prior systemic regimens, including CD20-targeted therapy. Patients previously treated with CD19-targeted therapy or immunomodulatory imide drugs, such as lenalidomide, are excluded. The modified dosing regimen will be investigated in a stepwise design: two sequential dose-finding cohorts (planned n=6 each) followed by an expansion cohort (planned n=39). Lenalidomide 25 mg will be administered in all cohorts on Days 1-21 of each 28-day cycle for up to 12 cycles. After Cycle 12, patients will continue tafasitamab monotherapy at the assigned dosing regimen until progression. After reviewing safety and pharmacokinetic data from Cohorts 1 and 2, patients will be enrolled in an expansion cohort to receive tafasitamab + lenalidomide (tafasitamab dose: 24 or 30 mg/kg) for further evaluation. No intra-patient dose escalation from 24 to 30 mg/kg is permitted. The primary endpoints are the incidence and severity of treatment-emergent adverse events. Key secondary endpoints are tafasitamab serum concentration after 3 and 12 cycles, best objective response rate, duration of response, and progression-free survival. Not yet available. MINDway will evaluate an optimized tafasitamab dosing regimen to reduce the frequency of hospital/clinic visits for tafasitamab-treated patients with R/R DLBCL. Reducing the frequency of visits by half is expected to reduce patient burden and support long-term treatment compliance. Fewer visits may result in less exposure to hospital infections in this already susceptible population. MorphoSys AG.

A Quasi-Randomized Controlled Trial of an Integrated Healthcare Model for Patients with Coronary Heart Disease.

An increasing number of coronary heart disease (CHD) patients with an aging population are demanding available and effective out-of-hospital continuous healthcare services. However, great efforts still need to be made to promote out-of-hospital healthcare services for better CHD secondary prevention. This study aims to evaluate the effectiveness of a hospital-community-family (HCF)-based integrated healthcare model on treatment outcomes, treatment compliance, and quality of life (QoL) in CHD patients. A quasi-randomized controlled trial was conducted at the Department of Cardiology, a tertiary A-level hospital, Wuhan, China from January 2018 to January 2020 in accordance with the Consolidated Standards of Reporting Trials guidelines. CHD patients were enrolled from the hospital and quasi-randomly assigned to either HCF-based integrated healthcare model services or conventional healthcare services. The treatment outcomes and QoL were observed at the 12-month follow-up. Treatment compliance was observed at the 1-month and 12-month follow-ups. A total of 364 CHD patients were quasi-randomly assigned to either integrated healthcare model services (n = 190) or conventional healthcare services (n = 174). Treatment outcomes including relapse and readmission rate (22.6% vs 41.9%; relative risk [RR] = 0.54; 95% confidence interval [CI], 0.40-0.74; p = 0.0031), the occurrence of major cardiovascular events (19.5% vs 45.4%; RR = 0.43; 95% CI, 0.30-0.59; p = 0.0023), complication rate (19.5% vs 35.0%; RR = 0.56; 95% CI, 0.39-0.79; p = 0.0042), and the control rate of CHD risk factors (p 0.05, average p = 0.009) at the 12-month follow-up in the intervention group were better than those of the control group. There was no significant difference in treatment compliance at the 1-month follow-up between groups (p 0.05, average p = 0.872). Treatment compliance at the 12-month follow-up in the intervention group, including correct medication, reasonable diet, adherence to exercise, emotional control, self-monitoring, and regular re-examination, was higher than that of the control group (p 0.05, average p = 0.007). No difference was found in the compliance with smoking cessation and alcohol restriction at the 12-month follow-up between groups (p = 0.043). QoL at the 12-month follow-up in the intervention group was better than that of the control group (86.31 9.39 vs 73.02 10.70, p = 0.0048). The integrated healthcare model effectively improves treatment outcomes, long-term treatment compliance, and QoL of patients, and could be implemented as a feasible strategy for CHD secondary prevention.

PB2112: MINDWAY: A PHASE IB/II DOSE OPTIMIZATION STUDY TO ASSESS SAFETY AND PHARMACOKINETICS OF TAFASITAMAB + LENALIDOMIDE IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA

Background: Tafasitamab is an Fc-enhanced, humanized, anti-CD19 monoclonal antibody which, in combination with the immunomodulatory drug lenalidomide, has been granted accelerated FDA approval and EU conditional marketing authorization based on results from L-MIND (NCT02399085) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in adult patients ineligible for autologous stem cell transplant. Treatment schedule optimization aims to reduce the frequency of hospital visits and decrease treatment burden and healthcare utilization while maintaining clinical benefits. Aims: MINDway (NCT05222555) will investigate if administration of tafasitamab at levels higher than the approved 12 mg/kg dose at a reduced dosing frequency can maintain the benefit-risk relationship of tafasitamab + lenalidomide treatment for patients with R/R DLBCL. Methods: MINDway is an open-label, multicenter, Phase Ib/II study in patients aged 18‒80 years with histologically confirmed DLBCL and R/R status after at least one, but no more than three, prior systemic regimens, including CD20-targeted therapy. Patients previously treated with CD19-targeted therapy or with immunomodulatory imide drugs such as lenalidomide are excluded. The modified tafasitamab dosing regimen will be investigated in a stepwise design with two sequential dose-finding cohorts (planned n=6 each) followed by an expansion cohort (planned n=39; Figure). Lenalidomide 25 mg will be administered in all cohorts on Day (D) 1‒21 of each 28-D cycle for up to 12 cycles. After Cycle 12, patients will continue tafasitamab monotherapy at the assigned dosing regimen until progression. Following a review of the safety and pharmacokinetic data from Cohorts 1 and 2, patients will be enrolled in an expansion cohort to receive tafasitamab + lenalidomide at the tafasitamab dose of 24 mg/kg or 30 mg/kg for further evaluation. No intra-patient dose escalation from 24 mg/kg to 30 mg/kg is permitted. The primary endpoint is the incidence and severity of treatment-emergent adverse events; key secondary endpoints include tafasitamab serum concentrations after 3 and 12 treatment cycles and best objective response rate, duration of response, and progression-free survival by investigator assessment. All endpoints will be analyzed using descriptive statistics; no formal statistical tests will be performed. MINDway is currently enrolling, with a planned sample size of 51 patients. Results: Results for this study are not yet available: outcome data as described above will be presented in due course. Image:Summary/Conclusion: MINDway will optimize the tafasitamab dosing regimen to reduce the frequency of hospital/clinic visits for tafasitamab treated R/R DLBCL patients. Reducing the overall frequency of clinic visits by half is expected to reduce the patient burden and support long-term treatment compliance. Furthermore, given the severity of the disease, reduced hospital visits may result in less exposure to hospital infections in this already susceptible population.

Urinary system complications and long-term treatment compliance in chronic traumatic spinal cord injury patients with neurogenic lower urinary tract dysfunction.

Objectives The aim of this study was to evaluate upper and lower urinary tract complications and the compliance of long-term treatment in patients with spinal cord injury (SCI) by urodynamic examination. Patients and methods Between January 1997 and May 2007, a total of 89 patients with SCI (79 males, 19 females; mean age: 39.8±12.2 years; range, 19 to 72 years) who were admitted to physical medicine and rehabilitation clinic were retrospectively analyzed. Demographic, neurological, and urodynamic data of the patients with the diagnosis of neurogenic lower urinary tract dysfunction (NLUTD) in their initial urodynamic examination and without regular follow-up were recorded. Results The mean time to the first urodynamic examination was 8.6±5.4 months. Sixty-seven patients who had neurogenic detrusor overactivity (NDO) in their first urodynamic tests were recommended anticholinergics. Clean intermittent catheterization (CIC) was recommended after initial urodynamic examination in all patients. Thirty-nine patients of 67 who had NDO were taking medications, while 28 were not. In the patients who continued anticholinergic treatment, bladder capacity was found to statistically significantly increase, compared to the initial measurement values and detrusor pressures significantly decreased (p<0.001). The compliance rate with CIC and anticholinergic treatment was 79.8% and 58.2%, respectively. Sixteen of the patients had calculus in the urinary system. Forty-two patients had infections more than once a year and used antibiotics. Conclusion Neurogenic bladder should be evaluated at the beginning of SCI and, then, followed on a regular basis. Urodynamic tests should be performed immediately after spinal shock and can be repeated, as indicated.

Anticonvulsant Activity of Helianthus tuberosus Against Maximal Electroshock Induced Convulsions in Rats

Epilepsy is an episodic brain dysfunction featured by recurring erratic spontaneous seizures followed by cognitive, social, neurobiological, and psychological consequences. Conventional anti-epileptic drugs are associated with several untoward effects, and hence long-term treatment compliance is a major problem in the management of epilepsy. Herbal drugs have shown promising efficacy as potent anticonvulsants in the past few years. In light of this, the anticonvulsant effect of alcoholic extract of leaves of Helianthus tuberosus (AHT) against maximal electroshock (MES) induced convulsions was investigated. In the present investigation, an indigenous plant, H. tuberosus was studied for its protective effect against maximal electroshock (MES) induced convulsions in Wistar albino rats. The rats were pre-treated with different doses (100, 200, 400 mg/kg) of alcoholic extract of leaves of H. tuberosus for 14 days, and then, they were subjected to maximal electroshock seizures (40 mA for 0.2 seconds) treatment. Alcoholic extract of leaves of H. tuberosus at the dose of 400 mg/kg significantly reduced the duration of hind limb extension and the protection of rats against maximal electroshock-induced seizures. The reference standards phenytoin (20 mg/kg) provided complete protection. Thus, the present study revealed an anticonvulsant effect of H. tuberosus against maximal electroshock-induced convulsions in rats.

Pediatric Wilson's Disease: Phenotypic, Genetic Characterization and Outcome of 182 Children in France.

To describe a cohort of Wilson disease (WD) pediatric cases, and to point out the diagnostic particularities of this age group and the long-term outcome. Clinical data of 182 pediatric patients included in the French WD national registry from 01/03/1995 to 01/06/2019 were gathered. Diagnosis of WD was made at a mean age of 10.7 ± 4.2 years (range 1-18 years). At diagnosis, 154 patients (84.6%) had hepatic manifestations, 19 (10.4%) had neurological manifestations, and 9 patients (4.9%) were asymptomatic. The p.His1069Gln mutation was the most frequently encountered (14% of patients).Neurological patients were diagnosed at least 1 year after they presented their first symptoms. At diagnosis, the median urinary copper excretion (UCE) was 4.2 μmol/24 hours (0.2-253). The first-line treatment was d-penicillamine (DP) for 131 (72%) patients, zinc salts for 24 (13%) patients, and Trientine for 17 (9%) patients. Liver transplantation was performed in 39 (21.4%) patients, for hepatic indications in 33 of 39 patients or for neurological deterioration in 6 of 39 patients, mean Unified Wilson's Disease Rating Scale of the latter went from 90 ± 23.1 before liver transplantation (LT) to 26.8 ± 14.1 (P < 0.01) after a mean follow-up of 4.3 ± 2.5 years. Overall survival rate at 20 years of follow-up was 98%, patient and transplant-free combined survival was 84% at 20 years. Diagnosis of WD can be challenging in children, particularly at the early stages of liver disease and in case of neurological presentation; hence the support of clinical scores and genetic testing is essential. Diagnosis at early stages and proper treatment ensure excellent outcomes, subject to good long-term treatment compliance. LT is a valid option for end-stage liver disease not responding to treatment and can be discussed for selected cases of neurological deterioration.

Treatment Burden and Quality of Life of Patients with Neovascular Age-Related Macular Degeneration (nAMD) and Their Caregivers—A Review

The growing incidence of neovascular age-related macular degeneration (nAMD) in India and its debilitating consequences, such as physical, psychological, and emotional stress, are a cause of significant concern. Failing eyesight due to nAMD hinders the ability of patients to perform daily tasks, leading to dependency on others – often resulting in anxiety and depression. Although treatment options such as anti-vascular endothelial growth factors (anti-VEGFs) are readily available, long-term treatment compliance is often compromised. Thus, it is important for health care providers to be aware of the burden associated with nAMD for both patients and caregivers. India, with its large urban and rural population base, faces varied challenges in health care accessibility and affordability. Further, there is a paucity of India-specific studies to ascertain patient and caregiver burden related to nAMD. A deeper understanding of disease awareness and treatment expectations from an Indian perspective may further help clinicians to provide optimum management to patients. The current review provides insights into the quality of life (QoL) and treatment-related burden for patients with nAMD and their caregivers. Further, it emphasizes the need of PAN-India studies to ascertain the patient and caregiver burden related to nAMD, which may assist in devising treatment algorithms and pricing policies suited to the Indian population and enable patients to receive quality eye care.

Effects of Cox interaction model of client health behavior-based nursing intervention on health outcomes among patients receiving liver transplantation

Objective To explore the effects of Cox interaction model of client health behavior (Cox-IMCHB) -based nursing intervention on health outcomes and quality of life (QOL) among patients receiving liver transplantation. Methods From October 2014 to August 2016, this study selected 65 patients met the inclusion and exclusion criteria in the First Bethune Hospital of Jilin University as subjects. Patients were divided into control group (n=32) and observation group (n=33) according to surgery order. Control group carried out the routine nursing for patients receiving liver transplantation, while observation group implemented the comprehensive nursing based on the Cox-IMCHB theory. Treatment compliance, follow-up rate and nursing service satisfaction of patients between two groups were observed one month and six months after surgery. Results One month after surgery, there was no statistical difference in the compliance of patients between two groups (P>0.05) . Six months after surgery, the total score of treatment compliance, scores of self-monitoring compliance, living habits compliance and follow-up compliance in observation group were 42.00 (40.00, 43.00) , 2.00 (2.00, 3.00) , 17.00 (16.00, 18.00) and 7.00 (7.00, 8.00) higher than those in control group with statistical differences (P 0.05) . Six months after surgery, the patient satisfaction and rate of follow-up in observation group were higher than those in control group with statistical differences (P<0.05) . Conclusions Cox-IMCHB-based nursing intervention for patients receiving liver transplantation can improve patients' long-term treatment compliance and patient satisfaction with utilization of medical service resource as well as nursing care so as to promote favorable outcomes. Key words: Liver transplantation; Quality of life; Health outcome; Cox interaction model of client health behavior; Compliance; Satisfaction; Follow-up

The Effect of Hajj Pilgrimage on Treatment Compliance in Individuals with Chronic Diseases.

This study was performed in order to determine the effect of Hajj pilgrimage on treatment compliance in individuals with chronic diseases. A total of 168 individuals were included in the prospective and descriptive study. Data were collected in three interviews using a patient identification form and the Religiousness Inclination Scale. When the medicine compliances of the individuals before and after Hajj pilgrimage were compared, a statistically meaningful difference between their regular uses of medicine statuses was found (p = 0.011). However, no difference was detected in the 3-month follow-up (p = 0.094). Additionally, it was found that in individuals with internally driven religiousness inclinations there was no relationship between their statuses regarding having changes in their disease-related complaints after Hajj pilgrimage and their status regarding coping with disease. Hajj pilgrimage was found to negatively affect treatment compliance in the short term in individuals with chronic diseases, while there were no changes in long-term treatment compliance.

Chronic dosing with mirtazapine does not produce sedation in rats.

Objective:Sedation/somnolence are major side effects of pharmacotherapies for depression, and negatively affect long-term treatment compliance in depressed patients. Use of mirtazapine (MIR), an atypical antidepressant approved for the treatment of moderate to severe depression with comorbid anxiety disorders, is associated with significant sedation/somnolence, especially in short-term therapy. Nonetheless, studies with human subjects suggest that MIR-induced sedation is transient, especially when high and repeated doses are used. The purpose of this study was to explore the effects of acute and chronic administration of different doses of MIR on sedation in the rat.Methods:Assessment of sedation was carried out behaviorally using the rotarod, spontaneous locomotor activity, and fixed-bar tests.Results:A 15-mg/kg dose of MIR induced sedative effects for up to 60 minutes, whereas 30 mg/kg or more produced sedation within minutes and only in the first few days of administration.Conclusion:These results suggest that 30 mg/kg is a safe, well-tolerated dose of MIR which generates only temporary sedative effects.

Registry on the management of postmenopausal and corticosteroid-induced osteoporosis in Egypt

ObjectivesOsteoporosis is a systemic disease which is characterized by low bone mineral density and abnormal bone architecture, which subsequently leads to bone fractions. The most common types of osteoporosis are postmenopausal osteoporosis and corticosteroid-induced osteoporosis. Long-term treatment and high compliance are required in treatment of osteoporosis to successfully achieve the beneficial goal of reducing future fractures and enhancing quality of life. Hence, the primary objective of this disease registry study was to describe the therapeutic management trends for postmenopausal and corticosteroids-induced osteoporosis and to improve our understanding of the choice of medication prescribed by the physicians, whereas the secondary objectives were to characterize the factors influencing patient compliance and to collect inefficacy data and fracture data in compliant and noncompliant patients over long term (over 6 months of treatment).Patients and methodsThis study was a local, multicenter, observational disease registry. The study comprised a single baseline visit and four follow-up phone calls over 6 months of duration. A total of 571 patients were enrolled who fulfilled the inclusion and the exclusion criteria of the study.ResultsThe most commonly prescribed osteoporosis treatment class was bisphosphonates in 523 (91.6%) patients, followed by calcium in 458 (80.18%) patients, vitamin D3 or vitamin D in 288 (50.4%) patients, and calcitonin in 35 (6.1%) patients. The assessment of patient compliance showed that 409 (71.6%) patients were fully compliant throughout the 6-month follow-up period, whereas 162 (28.4%) patients were noncompliant. The most frequent causes of noncompliance were gastritis, missing doses, poor improvement, and patient on several medications. Patients who were compliant to their medications showed lower fracture rates than those who were noncompliant.ConclusionBisphosphonates and calcium were the most frequently prescribed medications. Lower numbers of fractures were noticed in compliant patients than in noncompliant patients.

Effects of HIV protease, nucleoside/non-nucleoside reverse transcriptase inhibitors on Bax, Bcl-2 and apoptosis in two cervical cell lines

Protease inhibitors (PIs) and reverse transcriptase drugs are important components of highly active antiretroviral therapy (HAART) for treating human acquired immunodeficiency syndrome (AIDS). Long-term clinical therapeutic efficacy and treatment compliance of these agents have been limited by undesirable adverse effects and their oncogenicity has been queried. This study investigated the effects of selected antiretroviral agents on the expression of key apoptotic regulatory genes; Bax and Bcl-2 in two cervical cell lines HCS-2 and NCE16IIA by real-time qPCR gene expression and immunocytochemistry. The anti-apoptotic effects of the PI-LPV/r were investigated by cell death detection ELISA and acridine orange staining. All the antiretroviral drugs and combinations tested had no effects on Bax and Bcl-2 gene expression and protein localisation in both cell lines. The protease inhibitors–LPV/r exhibited significant (P<0.05) inhibition of camptothecin-induced apoptosis in the cervical cancer HCS-2 cell line but not in the normal immortalised NCE16IIA cell line. This anti-apoptotic property of HIV protease inhibitors, although shown so far not to involve protein and RNA synthesis might promote the development of cancer.

Erectile Dysfunction Diagnosis and Treatment as a Means to Improve Medication Adherence and Optimize Comorbidity Management

Optimal pharmacologic management of diseases comorbid with erectile dysfunction (ED), such as cardiovascular disease, depression, diabetes, dyslipidemia, hypertension, and benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), is dependent upon long-term treatment compliance and may be complicated by poor adherence to medication use. ED may contribute to poor adherence to medication use because poor quality erectile function may be an unwanted adverse effect of antihypertensives, antidepressants, and 5-α reductase inhibitors for treatment of BPH/LUTS. Diminished erectile spontaneity, rigidity, and/or sustaining capability also negatively affects mood, self-esteem, and confidence, which compromise motivation to be compliant with medications that treat diseases comorbid with ED. Literature review was performed to explore the role of ED diagnosis and effective treatment in enhancing overall management of selected ED comorbidities, highlighting the role of medication adherence. Several PubMed searches were performed. Diagnosis and successful treatment of concomitant ED may promote improved adherence and management of comorbid diseases. Concomitant ED management may improve treatment outcome, decrease healthcare costs, and possibly prevent or even improve deterioration in medical conditions comorbid with ED. Because ED is a silent marker and predictor of comorbidities, especially cardiovascular disease, earlier diagnosis of ED may provide an opportunity to prevent future cardiovascular events. In men presenting with complaints of ED, screening for, monitoring, and appropriately treating diseases that are comorbid with ED is essential. Screening for and appropriately treating ED is important for enhanced life quality and improved motivation in men with existing ED comorbidities or risk factors. Appropriate management of ED and its risk factors may have beneficial effects on diseases that are comorbid with ED, and vice versa, most likely via shared pathophysiological pathways. Clinicians may need to consider men's health overall, of which sexual health is a central component, in order to provide optimal disease management.

Efficacité clinique et obtention d’une rémission complète dans la dépression : intérêt de l’escitalopram

Such a prevalent disease as Major Depressive Disorder (MDD), associated with prominent impairment in physical and social functioning, implies as well an increased morbidity and mortality. Long-term treatments are required due to the frequent occurrence of relapses. Patient compliance is a core factor in both acute and continuation treatment, closely related to tolerability issues. We have partially reviewed the literature published on PubMed since 2004 which assess the relative antidepressant efficacy of escitalopram and comparator antidepressants in adult patients who met DSM-IV criteria for major depressive disorder (MDD). Clinically important differences exist between commonly prescribed antidepressants. These analyses are in favor of a superior efficacy and tolerability of long-term escitalopram treatment (10 to 20mg/day) compared with active controls, including selective serotonin re-uptake inhibitors (SSRIs) (paroxetine, citalopram, bupropion, fluoxetine, fluvoxamine, sertraline), serotonin/noradrenaline reuptake inhibitors (SNRIs) (venlafaxine, milnacipran and duloxetine) and noradrenergic and specific serotonergic antidepressants (NaSSAs) (mirtazapine). Cipriani et al. (2009) have performed a network meta-analysis of 12 new generation antidepressants. They have shown that clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favor of escitalopram and sertraline in acute treatment, defined as 8-week treatment. Kasper et al. (2009) conducted a post-hoc pooled analysis of data from two 6-month randomized controlled trials that revealed superior efficacy and tolerability of escitalopram when compared with paroxetine. The pooled analysis of four randomized, double-blind, active comparator, 6-month trials in MDD, by Wade et al. (2009), showed that short-term outcomes may predict long-term treatment compliance and outcomes. A higher probability of achieving remission was associated with responding after 8 weeks and with completing 6 months of treatment. Furthermore, Week 24 complete remission (MADRS≤5) was significantly (P<0,01) higher for escitalopram (51.7%) than for the pooled comparators (45.6%). And after 6 months, fewer patients discontinued treatment with escitalopram (15.9%) than with the pooled comparators (23.9%) (P<0.001). This fragmentary review of the literature shows that it is necessary to adopt a stringent definition of remission in depression, especially in clinical trials; a MADRS total score less or equal to 10 to define remission, a MADRS total score less or equal to 5 to define complete remission, and moreover no MADRS single item greater than 1 to define symptom-free remission. In all these meta-analyses, the superiority of escitalopram compared with other antidepressants was confirmed for both acute and long-term treatment of MDD, especially in harshly depressed patients.

Evaluation of HIV protease and nucleoside reverse transcriptase inhibitors on proliferation, necrosis, apoptosis in intestinal epithelial cells and electrolyte and water transport and epithelial barrier function in mice

BackgroundProtease inhibitors (PI's) and reverse transcriptase drugs are important components of highly active antiretroviral therapy (HAART) for treating human acquired immunodeficiency syndrome (AIDS). Long-term clinical therapeutic efficacy and treatment compliance of these agents have been limited by undesirable side-effects, such as diarrhea. This study aims to investigate the effects of selected antiretroviral agents on intestinal histopathology and function in vivo and on cell proliferation and death in vitro.MethodsSelected antiretroviral drugs were given orally over 7 days, to Swiss mice, as follows: 100 mg/kg of nelfinavir (NFV), indinavir (IDV), didanosine (DDI) or 50 mg/kg of zidovudine (AZT). Intestinal permeability measured by lactulose and mannitol assays; net water and electrolyte transport, in perfused intestinal segments; and small intestinal morphology and cell apoptosis were assessed in treated and control mice. In vitro cell proliferation was evaluated using the WST-1 reagent and apoptosis and necrosis by flow cytometry analysis.ResultsNFV, IDV, AZT and DDI caused significant reductions in duodenal and in jejunal villus length (p < 0.05). IDV and AZT increased crypt depth in the duodenum and AZT increased crypt depth in the jejunum. NFV, AZT and DDI significantly decreased ileal crypt depth. All selected antiretroviral drugs significantly increased net water secretion and electrolyte secretion, except for DDI, which did not alter water or chloride secretion. Additionally, only NFV significantly increased mannitol and lactulose absorption. NFV and IDV caused a significant reduction in cell proliferation in vitro at both 24 h and 48 h. DDI and AZT did not alter cell proliferation. There was a significant increase in apoptosis rates in IEC-6 cells after 24 h with 70 ug/mL of NFV (control: 4.7% vs NFV: 22%) while IDV, AZT and DDI did not show any significant changes in apoptosis compared to the control group. In jejunal sections, IDV and NFV significantly increased the number of TUNEL positive cells.ConclusionThe PI's, NFV and IDV, increased cell apoptosis in vivo, water and electrolyte secretion and intestinal permeability and decreased villus length and cell proliferation. NFV was the only drug tested that increased cell apoptosis in vitro. The nucleoside reverse transcriptase inhibitors, AZT and DDI, did not affect cell apoptosis or proliferation. These findings may partly explain the intestinal side-effects associated with PI's.

Benefits of statin therapy and compliance in high risk cardiovascular patients.

Cardiovascular disease (CVD) remains the top cause of global mortality. There is considerable evidence that supports the mortality and morbidity benefit of statin therapy in coronary heart disease (CHD) and stroke, both in primary and secondary prevention settings. Data also exist pointing to the advantage of statin treatment in other high-risk CVD conditions, such as diabetes, CKD, CHF, and PVD. National and international clinical guidelines in the management of these CVD conditions all advocate for the utilization of statin therapy in appropriate patients. However, overall compliance to statin therapy remains suboptimal. Patient-, physician-, and economic-related factors all play a role. These factors need to be considered in devising approaches to enhance adherence to guideline-based therapies. To fully reap the benefits of statin therapy, interventions which improve long-term treatment compliance in real-world settings should be encouraged.