Intermittent Treatment Regimen Research Articles

Impact of Everolimus Initiation and Corticosteroid Weaning During Acute Phase After Heart Transplantation on Clinical Outcome: Data from the Korean Organ Transplant Registry (KOTRY).

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

Stakeholders’ perspective on the daily regimen of tuberculosis treatment- A qualitative approach

IntroductionIn the context of changing over from an intermittent treatment regimen to a daily regimen, it becomes crucial to understand the impact of a daily regimen on the treatment process and outcome. It enables health professionals to strengthen strategies, to enhance the quality of treatment as well as the quality of life of TB patients. The perspective of each stakeholder involved in the process is important in assessing the impact of the daily regimen. ObjectivesTo understand patients' and providers' perspectives on the daily regimen of Tuberculosis treatment. MethodologyA qualitative study was conducted between March 2020 to June 2020, including in-depth interviews with TB patients on treatment and DOT providers, and Key Informant Interview(KII) with TB Health Visitors(TBHV) and family members of TB patients. A thematic-network analysis approach was utilized to get the results. ResultsTwo sub-themes emerged: (i) Acceptance of the daily regimen of treatment; (ii) operational difficulties of the daily regimen. No injections in the regimen, fewer side effects of drugs as dose depends on weight band, family members can be treatment supporter, awareness about disease and treatment, the drugs are as same as private drugs available, adherence has improved, monthly DBT were found to some of the enablers in the study. The Barriers found in the study were traveling daily to get drugs, loss of daily wages, accompanying patients daily, tracing private patients, pyridoxine is not given free in this regimen, increased workload for treatment providers, etc. ConclusionThe study points out that acceptance of the patient to the daily regimen is better as they have lesser side effects. The operational difficulties in the implementation of the daily regimen can be addressed by providing family members as treatment supporters.

English

BACKGROUND Sputum smear conversion is the negative conversion of the sputum smear at the end of the second month of treatment regimen under the National Tuberculosis Elimination Program (NTEP). When the acid-fast bacillus (AFB) smear comes negative at the end of an intensive phase, the treatment regimen can shift to the continuation phase that indicates bacillary load is a minimum. Although some authors consider the conversion of cultures when the AFB smear is negative, two potent drugs in the continuation phase are sufficient to kill the remaining bacilli. The drug that can kill bacteria in the first 2 days of treatment is called early bactericidal activity (EBA). This can be assessed by the percentage of negative conversion of cultures at the end of the intensive phase of the treatment regimen. EBA is very essential because it reduces the transmission in the community and chances of patient death. When the purpose is to kill as many bacilli as possible in the first few days and weeks of treatment, it is very important to include bactericidal drugs in the treatment regimen so that it reduces the chances of patient death and infectiousness and the negative conversion of the cultures after 2-month treatment regimen is an indication of the bactericidal capacity of the drug. The purpose of this study was to compare sputum smear conversion in daily versus intermittent treatment regimens in diagnosed cases of new sputum smear-positive pulmonary tuberculosis patients. METHODS This retrospective observational study was carried out in the Department of Respiratory medicine and nodal drug resistance tuberculosis centre (DR-TB) at the Government medical college and hospital, Akola. In this study, a total of 120 new patients were taken. 60 patients were given daily and intermittent regimens respectively under NTEP. RESULTS Out of 120 patients, 56 (93.33 %) patients in intermittent and 53 (88.33 %) patients in daily regimen were sputum smear-negative at the end of 2nd month (intensive phase) and at the end of 6th month (continuation phase). 1 patient (1.6 %) remained sputum smear-positive after the intensive phase. That patient was given 1 month of extension of anti-tuberculosis treatment (AKT) in the intensive phase and the patient became sputum negative after 1 month of extension. CONCLUSIONS It was concluded in this study, daily regimens and intermittent regimens were equally effective in negative conversion of the sputum smear at the end of the intensive phase and the end of the continuation phase. Negative conversion of the sputum smear is quite important because the bacillary load will be so low at the end of 2nd month that reduces the chances of patient death and transmission in the community. KEY WORDS Pulmonary Tuberculosis (PTB), Drug-Resistant TB (DR-TB), National Tuberculosis Programme (NTP), Revised National TB Control Program (RNTCP), Intensive Phase (IP), continuation Phase (CP), National Tuberculosis Elimination Program (NTEP).

Ефективне лікування й профілактика часто рецидивуючої інфекції сечовивідних шляхів препаратом золотарника звичайного (Solidago virgaurea) Цисто-аурин®

Нами проведено дослідження клінічної та лабораторної ефективності, а також оцінка впливу на якість життя інтермітуючої терапії препаратом золотарника звичайного Цисто-аурин у 96 хворих на часто рецидивуючу інфекцію сечовивідних шляхів (ІСШ). Після отримання інформованої згоди хворі були розділені на три статистично однорідні групи. Протягом лікування пацієнтки всіх груп використовували стратегію поведінкової терапії та посткоїтальної профілактики. Пацієнтки групи А додатково отримували Цисто-аурин по 1 табл. 4 рази на день курсами по 15 днів кожного місяця протягом 6 місяців, групи В — той же препарат по 2 табл. 2 рази на день такими ж курсами, пацієнтки групи С (порівняння) спеціальної терапії не отримували. Упродовж дослідження отримані об’єктивні дані, що свідчать про вірогідне зниження числа рецидивів ІСШ на 92,3 і 73,3 % протягом 6 місяців лікування, залежно від кратності прийому препарату. Аналіз впливу досліджуваного препарату на лабораторні прояви часто рецидивуючої інфекції сечової системи показав позитивний ефект інтермітуючого режиму терапії щодо піурії, редукцію прозапальної активності та статистично вірогідне зменшення проявів запалення в сечовій системі. Ефективність редукції лейкоцитурії у хворих, які приймали препарат, становила 73,4 і 44,6 %, тобто лейкоцитурія була в 3,7 і 1,8 раза нижче вихідних значень. У той же час серед хворих групи С статистично значущої динаміки виявлено не було. Дискретна і кількісна оцінка впливу досліджуваного препарату на бактеріурію показала клінічно значущий і статистично вірогідний бактеріо­статичний ефект Цисто-аурину як в процесі лікування препаратом (на 41,0 і 27,6 % відповідно), так і в проспективному 6-місячному періоді спостереження після його прийому (на 30,3 і 18,0 % відповідно), що є важливим підтвердженням впливу препарату на персистенцію мікробів у сечовій системі. Структуризація антибактеріального ефекту щодо клінічно значущих уропатогенів підтвердила редукцію штамів E.сoli на 61,1 і 31,9 %, Klebsiella pneumoniae — на 33,1 і 17,1 %, P.mirabilis — на 19,1 і 12, 9 %, P.aeruginosa — на 21,1 і 14,1 %, Candida spp. — на 19,4 і 14,5 % відповідно. Оцінка впливу досліджуваного препарату на симптоматику рекурентного хронічного циститу (шкала UTISA) показала вірогідне зниження ключових клінічних симптомокомплексів рецидивної ІСШ: полакіурії (на 48,3 % в обох групах), імперативних позивів (59,8 і 30,1 %), болю й печіння (42,6 і 30,2 %), неповного випорожнення сечового міхура (53,8 і 30,9 %), а також інтегрального показника клінічних проявів патології (24,7 і 39,2 % відповідно). Динаміка показників якості життя, що пов’язана із здоров’ям (шкала SF-36), на тлі прийому препарату продемонструвала статистично значущу індукцію ключових доменів якості життя хворих на часто рецидивуючу ІСШ: психічного здоров’я (33,4 % проти 32,5 %) і кумулятивного показника загальної якості життя (19,6 % проти 14,6 % відповідно).

For children with tuberculosis (TB), how do intermittent and daily treatment regimens compare?

For children with tuberculosis (TB), how do intermittent and daily treatment regimens compare?

A comparative assessment of daily dosage regimen versus intermittent treatment regimen of tuberculosis at the RNTCP centres in Chitradurga district

The treatment of pulmonary tuberculosis is quite challenging. The national tuberculosis programs are shifting the trend to adopt daily regimen than the intermittent regimen. Hence, this study was undertaken to study the effectiveness and adverse drug reactions of the daily and intermittent regimens.A retrospective study was conducted in the department of Chest and TB in Basaveshwara Medical College and Hospital, Chitradurga and District Tuberculosis Centre, Chitradurga, India. About 55 patients on daily regimen and 50 patients on intermittent regimen constituted the study sample. The details regarding the age, sex, initiation and termination of the treatment, outcome and adverse drug reactions were collected using a predesigned proforma.Majority of the patients in daily regimen were 56 – 65 years and intermittent regimen was aged between 26 – 35 years. More number of the cases in both the regimen were males. Vomiting was the main adverse drug reaction in patients on daily regimen and Abdominal pain in intermittent regimen. About 54.5% of the patients on daily regimen and 62% on intermittent regimen were cured. The death and defaulter rate was higher in patients on intermittent regimen.Even though the cure rate is good in intermittent regimen, the adverse reactions are quite high in this study.

A proof-of-concept study in HCV-infected Huh7.5 cells for shortening the duration of DAA-based triple treatment regimens

With the development of more effective direct-acting antivirals (DAAs), dual- or triple-therapy regimens represent the major strategy used to cure chronic hepatitis C virus (HCV) infection. Thus, shorter treatment duration regimens with low burden, few adverse effects and good patient adherence are urgently needed. This study theoretically demonstrates a proof-of-concept approach for shortening therapy duration by examining HCV-infected Huh7.5 cells after treatment with a high or low fixed dose of three DAAs (simeprevir + daclatasvir + sofosbuvir) for 6–15 days. The results demonstrated that HCV-infected Huh7.5 cells achieved an ultrarapid virologic response with undetectable HCV RNA and protein and were cured after treatment with the triple-therapy regimen for 15 days. When the treatment duration was shortened, virologic relapse might occur after treatment with a low fixed dose of the three DAAs for 9 days and did occur after treatment with a low fixed dose for 6 days, although HCV was below detectable levels at the end of treatment. However, virologic relapse could be avoided with treatment of a high fixed dose of the three DAAs for 9 or 6 days. Although a virologic breakthrough occurred after an intermittent treatment regimen at the low fixed dose, the high fixed dose cured HCV-positive Huh7.5 cells with intermittent treatment. In conclusion, HCV is persistently present below detectable levels in HCV-infected Huh7.5 cells for a long time after treatment, and a shortened therapy duration is associated with an increased risk of virologic relapse, but virologic relapse or breakthrough might be avoided by treatment with a combination of more highly effective DAAs.

Establishment and Characterization of 5-Fluorouracil-Resistant Human Colorectal Cancer Stem-Like Cells: Tumor Dynamics under Selection Pressure.

5-Fluorouracil (5-FU) remains the gold standard of first-line treatment for colorectal cancer (CRC). Although it may initially debulk the tumor mass, relapses frequently occur, indicating the existence of cancer cells that are therapy-resistant and are capable of refueling tumor growth. To identify mechanisms of drug resistance, CRC stem-like cells were subjected to long-term 5-FU selection using either intermittent treatment regimen with the IC50 drug dose or continuous treatment regimen with escalating drug doses. Parental cancer cells were cultivated in parallel. Real-time PCR arrays and bioinformatic tools were used to investigate gene expression changes. We found the first method selected for cancer cells with more aggressive features. We therefore transplanted these cancer cells or parental cells in mice, and again, found that not only did the 5-FU-selected cancer cells generate more aggressive tumors with respect to their parental counterpart, but they also showed a different gene expression pattern as compared to what we had observed in vitro, with ID1 the top upregulated gene. We propose ID1 as a stemness marker pervasively expressed in secondary lesions emerging after completion of chemotherapy.

770. Multi-Drug-Resistant Tuberculosis Cases in Arkansas in 2017: A Tale of Two Threats

BackgroundMulti-drug-resistant tuberculosis (MDR-TB) is a threat to TB elimination strategies worldwide. From 1998 to 2016, six cases of MDR-TB were reported in Arkansas. In 2017 alone, three cases were detected. We sought to describe the characteristics of these cases to inform our MDR-TB prevention strategy in AR.MethodsThe surveillance database identified three MDR-TB cases in 2017. A detailed review was done to define the demographics, clinical presentation, and laboratory reports relating to drug susceptibility testing (DST), including molecular detection of drug resistance (MDDR). A search was done in the Genotyping database for genotype patterns of the patient isolates.ResultsAll three cases were born outside the United States and developed active disease after arrival in AR. Case 1, age 52, was born in the Marshall Islands, arrived in 2016, and had a history of Type 2 diabetes. He developed MDR-TB in February 2017. Case 2, age 42, was born in Mexico, arrived over 20 years ago, and was HIV positive. He developed TB in July 2016 with a pan-sensitive organism and completed an intermittent treatment regimen. A second TB episode with matching genotype but different drug sensitivities occurred in April 2017, less than 4 months after treatment completion, and was considered treatment failure. Case 3, age 56, was born in the Philippines, arrived in 1990, and was reportedly treated for latent TB infection in 1993 with 6 months of isoniazid. She visited the Philippines April–May 2017 and developed MDR-TB in October 2017. Her isolate was in cluster with a case in Oklahoma who came from Mexico in 2006 and was admitted in an AR hospital with a pan-sensitive organism. There are no epidemiological links between the two cases; only one isolate in each case. Because both isolates were identified in AR State TB laboratory, a complex contamination has been considered with no definite resolution at this time.ConclusionMDR-TB, due to both primary and secondary drug resistance, remains a threat in AR. Cooperation and communication between all levels of healthcare are crucial to avoid delayed diagnosis of MDR-TB. Timely DST via technologies like GeneXpert and MDDR service at CDC is critical. Consultation from Centers of Excellence is vital in the treatment of MDR-TB complicated by diabetes and HIV. Whole-genome sequencing could provide clarity in the cluster with discordant DST patterns.Disclosures All authors: No reported disclosures.

Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats

Clinical evidence suggests superior antidepressant response over time with a repeated, intermittent ketamine treatment regimen as compared to a single infusion. However, the club drug ketamine is commonly abused. Therefore, the abuse potential of repeated ketamine injections at low doses needs to be investigated. In this study, we investigated the abuse potential of repeated exposure to either 0, 2.5, or 5 mg/kg ketamine administered once weekly for seven weeks. Locomotor activity and conditioned place preference (CPP) were assayed to evaluate behavioral sensitization to the locomotor activating effects of ketamine and its rewarding properties, respectively. Our results show that while neither males nor females developed CPP, males treated with 5 mg/kg and females treated with either 2.5 or 5 mg/kg ketamine behaviorally sensitized. Furthermore, dendritic spine density was increased in the NAc of both males and females administered 5 mg/kg ketamine, an effect specific to the NAc shell (NAcSh) in males but to both the NAc core (NAcC) and NAcSh in females. Additionally, males administered 5 mg/kg ketamine displayed increased protein expression of ΔfosB, calcium calmodulin kinase II alpha (CaMKIIα), and brain-derived neurotrophic factor (BDNF), an effect not observed in females administered either dose of ketamine. However, males and females administered 5 mg/kg ketamine displayed increased protein expression of AMPA receptors (GluA1). Taken together, low-dose ketamine, when administered intermittently, induces behavioral sensitization at a lower dose in females than males, accompanied by an increase in spine density in the NAc and protein expression changes in pathways commonly implicated in addiction.

Increased cortical porosity is associated with daily, not weekly, administration of equivalent doses of teriparatide

IntroductionThe pharmacokinetic profile of parathyroid hormone (PTH) determines its effects on bone resorption and formation. When administered intermittently, anabolic effects are favored in comparison with the continuous treatment. Among the intermittent treatment regimens, lower frequency of administration may have a lower effect on bone remodeling. We therefore hypothesized that weekly administration of teriparatide will produce less increase in intracortical remodeling and porosity than reported using daily treatment. MethodsWe treated 17 female New Zealand white rabbits aged 6months for 1month with teriparatide [human PTH(1-34)] as follows. (i) Vehicle-treated Control (n=4); (ii) 20μg/kg daily (n=3); (iii) 40μg/kg daily (n=3); (iv) 140μg/kg weekly (n=3); (v) 280μg/kg weekly (n=4). Proximal femurs were imaged ex vivo using micro-CT (Scanco Viva CT-40) at 15μmvoxel size. Areas, pore size, and porosity were analyzed on the total, compact cortex (CC), and transitional zones in a 10mm length region of interest (ROI) starting at the midshaft using StrAx1.0. ResultsCompared to controls, the 20μg/kg daily was associated with 3.0% higher porosity in the transitional zone (p=0.09) while the 40μg/kg daily was associated with a higher porosity in the cortex (8.7%; p=0.04) and in the transitional zone (5.7%; p=0.007). The daily regimens were also associated with a greater proportion of porosity due to pores >15μm2; particularly in the transitional zone where 20 and 40μg/kg daily increased porosity 2 fold (p=0.06) and 5 fold (p=0.04) relative controls respectively. The 140 and 280μg/kg weekly were not associated with an increase in porosity. There was no difference in total, compact or transitional zone cross sectional areas between the groups. ConclusionEffects of intermittent teriparatide depend on the dose and frequency of administration. Daily dosing, particularly the higher dose, but not weekly dosing, increased cortical porosity. Work is needed to investigate the effects of the regimens on bone formation.

1152P - Evaluation of the pharmacokinetic (PK) profile of vismodegib (VISMO) in patients (pts) with multiple basal cell carcinomas (BCCs) across two intermittent treatment regimens in the MIKIE study

1152P - Evaluation of the pharmacokinetic (PK) profile of vismodegib (VISMO) in patients (pts) with multiple basal cell carcinomas (BCCs) across two intermittent treatment regimens in the MIKIE study

Continuous alternating inhaled antibiotics for chronic pseudomonal infection in cystic fibrosis

BackgroundInhaled antibiotics are standard of care for treating chronic pseudomonal respiratory infections in cystic fibrosis patients, initially approved for intermittent administration. However, use of continuous inhaled antibiotic regimens of differing combinations is growing. MethodsThis double-blind trial compared continuous alternating therapy (CAT) to an intermittent treatment regimen. Subjects were treated with 3cycles of 28-days inhaled aztreonam (AZLI) or placebo 3-times daily alternating with 28-days open-label tobramycin inhalation solution (TIS). Results90 subjects were randomized over 18months. Study enrollment was limited, in part because of evolving practices by clinicians of adopting a CAT regimen in clinical practice; consequently the study was underpowered. AZLI/TIS treatment reduced exacerbation rates by 25.7% (p=0.25; primary endpoint) and rates of respiratory hospitalizations by 35.8% compared with placebo/TIS (p=0.14). AZLI/TIS CAT therapy was well tolerated. ConclusionsThis trial illustrates challenges with studying treatment regimens in a constantly evolving CF care environment. Nonetheless, the results of this trial indicate that AZLI/TIS CAT is well tolerated and may provide additional clinical benefit in CF patients compared with intermittent use of TIS alone.Clinicaltrials.gov: NCT01641822.

Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice.

Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen-2mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans.

Reconsidering the benefit of intermittent versus continuous treatment in the maintenance treatment setting of metastatic colorectal cancer.

Colorectal cancer is one of the most frequent solid tumors in the western world, with low survival rates in patients with metastatic disease. Doublet chemotherapy regimens such as FOLFOX or FOLFIRI are the mainstay of standard first-line chemotherapy in the metastatic setting. The conventional treatment as a first-line approach is continuous application until progression or intolerable toxicities. However, only one third of patients are treated until progression mainly due to the side effects of chemotherapy. Notably, oxaliplatin-containing regimens such as FOLFOX/CapOx or FOLFOXIRI are associated with oxaliplatin-induced neuropathy, which is the main reason for treatment discontinuation or treatment de-escalation. On this basis, recent studies have investigated the clinical benefits of bevacizumab-based intermittent and continuous treatment regimens in the metastatic colorectal setting, together with various strategies to optimize maintenance therapy including regimens with targeted therapies, such as cetuximab, ziv-aflibercept and regorafenib. Recent studies have also investigated when maintenance therapy should be initiated as well individualizing treatment based on patient, tumor and treatment characteristics, as well as molecular biomarkers. This article reviews the current evidence for the clinical benefit of intermittent versus continuous treatment in the maintenance treatment setting of metastatic colorectal cancer, and also evaluates the effect of RAS and BRAF mutational status on maintenance strategies.

English

Egypt is considered one of the high-burden countries in WHO’s Eastern Mediterranean region. This study determined the sociodemographic, microbial and phylogentic characteristics for Mycobacterium tuberculosis cases diagnosed in El-Minia governorate in upper Egypt. Fifty clinical samples were collected (male-to-female sex ratio 1.5 and 50% within the 21- to 40-years old) with complete history of patients; samples were cultured and identified by biochemical tests. DNA was extracted and tested for plc gene. Seven isolates were subjected to sequencing analysis of the amplified plc fragment and a phylogentic tree for these strains was formed. Out of 50 samples, 24 samples were culture positive, all grown isolates were identified as M. tuberculosis according to physical characters, rate of growth, biochemical tests. Direct polymerase chain reaction (PCR) method based on the amplification of 350 bp region of plc gene was used for the detection of M. tuberculosis, to differentiate it from Mycobacterium bovis in clinical samples. It was found that all isolates were positive for plc gene. Direct sequencing of 350 bp region of plc gene revealed many substitution mutations along the entire sequenced fragment. The main cause for such condition may rely on inadequate treatment regimen. The phylogenetic tree of the seven sequenced isolates were classified into three distinct nodes. We concluded that all cases were positive for M. tuberculosis and most of them were from rural area. There was different substitution mutations in the plc gene which may be due to the intermittent treatment regimens that made the tested strains under stress resulting in mutation. Key words: Mycobacterium tuberculosis, plc gene, phylogentic tree, mutation.

Efficacy and cost of etanercept in long-term psoriasis: Rational use in clinical practice

Introduction: The advent of the biological therapies has led health expenditure in dermatology units. This study aims to evaluate, in our regular clinical practice, the patterns of use of etanercept and its influence on efficacy and safety outcomes, as well as the real costs associated with continuous and intermittent treatment regimens. Methods: Observational, retrospective, non-interventionist, and multicenter study to analyze the experience of the treatment with etanercept in the management of moderate-to-severe plaque psoriasis, given according to the daily clinical practice of the Dermatology Departments of the Complejo Hospitalario de Jaén and the Hospital Universitario Virgen del Rocío (Seville). Results: 83.3% (n = 45) of the 54 patients included in our study received the continuous regimen of Etanercept, whereas 16.7% (n = 9) were given the intermittent regimen. 94.4% (n = 51) of the patients studied began the Etanercept treatment at a dose of 50 mg/week. The mean patient/year cost of the study population is €11 298.80 (95%CI €10 551.40–€12 046.20). Breaking down the first and the second year of treatment by regimen, in the continuous regimen the mean cost would be €12 294.15 and €12 327.05 in the first and the second year, respectively, and €10 302.07 and €4986.51 in the intermittent regimen. Discussion: Etanercept is a biologic that had demonstrated its versatility over the years and permits the individualization of treatment in our patients, thus having a direct impact on drug-related costs. This is well demonstrated in our series, where 94.4% of our patients begin with the dose of 50 mg/d. Our study yields relatively higher figures in patients on continuous therapy, with 77.1% of them maintaining PASI75 at week 24. Conclusions: We present our experience in regular clinical practice with etanercept, showing it to be an effective, safe, and versatile drug that permits patient-tailored treatment, delivering a frankly satisfactory control of our psoriasis patients.

Immune-mediated thrombocytopaenia secondary to pulmonary tuberculosis: Diagnostic and therapeutic dilemma.

A myriad of haematological manifestations are reported with tuberculosis (TB) such as anaemia, leucocytosis and pancytopenia. Thrombocytopenia occurring in association with TB can be immune mediated, often induced by anti-tubercular drugs. Immune-mediated thrombocytopenia due to TB itself is extremely rare. Isolated thrombocytopenia has been reported in 23–43% of patients with disseminated TB.[1] Newly diagnosed immune thrombocytopenia in TB is rare; only 27 cases have been reported so far.[2] When a patient with TB presents with haemoptysis to the Intensive Care Unit (ICU), one should rule out coexisting thrombocytopenia. Untreated thrombocytopenia may result in dreaded complications such as retro-orbital, retro-peritoneal and intracranial haemorrhage.

Treatment adherence to different etanercept regimens, continuous vs. intermittent, in patients affected by plaque-type psoriasis.

Treatment adherence to anti-tumor necrosis factor alpha (anti-TNF-α) agents is marker of treatment success, but overall efficacy of anti-TNF-α therapy decreases over time leading to a progressive loss of adherence. The present observational study was conducted in order to estimate the long-term adherence to etanercept in patients affected by plaque-type psoriasis, evaluating differences among intermittent and continuous treatment regimen. Our findings reflect routine clinical practice in three academic referral centers and show high treatment adherence with etanercept in psoriatic patients. Treatment survival was consistently high in the short/medium term. The univariate analysis showed longer treatment duration in patients undergoing intermittent treatment regimen (mean 1,706 days) compared with continuous regimen (mean 1,249 days). Results showed that a flexible pulsed treatment with etanercept can be optimal in terms of clinical success and adherence.

Effect of intermittent and daily regimens of minodronic Acid on bone metabolism in an ovariectomized rat model of osteoporosis.

The goal of the study was to compare the effects of minodronic acid on bone mineral density (BMD) and bone turnover in a rat ovariectomized (OVX) osteoporosis model, using two intermittent treatment regimens (weekly and 4 continuous days every 4weeks) and a daily regimen. Female F344 rats (age 14weeks) underwent ovariectomy or a sham operation. Minodronic acid was orally administered at 0.042, 0.21, and 1.05mg/kg in the intermittent regimens, and at 0.03 and 0.15mg/kg in the daily regimen for 12weeks from the day after surgery. Minodronic acid dose-dependently ameliorated the decreases in areal BMD of the lumbar vertebrae and femur, and volumetric BMD of total and trabecular bone in the distal femur. Minodronic acid also suppressed the increase in urinary deoxypyridinoline levels and reduced serum osteocalcin levels. In bone histomorphometry, all three minodronic acid regimens suppressed OVX-induced increases in bone turnover at the tissue level and ameliorated all structural indices, except that an effect on trabecular thickness only occurred with daily treatment. In conclusion, minodronic acid administered weekly or for 4 continuous days every 4weeks suppressed increased bone resorption and BMD to a similar extent to that of a similar total dose given daily in a rat OVX model.