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Gastroesophageal reflux disease (GERD) is a chronic disorder characterized by the reflux of gastric contents into the esophagus, leading to symptoms and potential long-term complications such as Barrett esophagus and esophageal adenocarcinoma. Currently, there are various medical, endoscopic, and surgical therapeutic strategies for GERD. However, proton pump inhibitors (PPIs), which effectively suppress acid secretion but require daily administration, remain the mainstay of treatment. Noncontinuous therapy for GERD includes on-demand and different variations of intermittent administration of antireflux medication. Attributes that make an antireflux medication a good candidate for noncontinuous therapy for GERD include potent acid suppression, rapid effect, durability of antisecretory effect, and flexibility of administration. Noncontinuous therapy for GERD is appealing to patients because it is convenient, reduces cost, and alleviates concerns about complications of long-term PPI use. Patients with nonerosive esophageal reflux disease or low-grade erosive esophagitis who have episodic heartburn are probably best suited for such treatment. Although PPIs have been shown to be efficacious as on-demand or intermittent therapy for GERD, their usefulness as on-demand treatment for episodic heartburn has been limited by their slow maximal effect on intragastric acid secretion. In contrast, potassium-competitive acid blockers (P-CABs) demonstrate the pharmacokinetic and pharmacodynamic characteristics that make this class of drugs a good candidate for noncontinuous treatment of GERD. Early studies using P-CABs for noncontinuous treatment of GERD have demonstrated promising results. Future studies are needed to further establish the value of P-CABs for such a therapeutic approach. This article reviews the current evidence on the use of PPIs and P-CABs in noncontinuous therapy for GERD. [ABSTRACT FROM AUTHOR]

Background: To investigate the changes of natural killer (NK) cell phenotype in the interferon alpha (IFN-α) treatment of chronic hepatitis B (CHB) and its relationship with clinical indicators. Methods: The CHB patients who did not receive any antiviral treatment were set as initial treatment group and used pegylated interferon alpha (PEG-IFN a). Peripheral blood samples were collected at baseline, 4 weeks, and 12-24 weeks. For IFNtreated patients who entered the plateau were set as plateau group, and PEG-IFN a was discontinued and resumed after an interval of 12-24 weeks. Besides, we also enrolled some patients who had received oral drug for more than 6 months as oral drug group without follow up. Peripheral blood was collected during the plateau period, which was set as baseline, and after 12-24 weeks of intermittent treatment, and after 12-24 weeks of additional treatment with PEG-IFN α. The aim of the collection was to detect hepatitis B virus (HBV) virology, serology and biochemical indicators, and the NK cell related phenotype was detected by flow cytometry. Results: In the plateau group, subgroup of CD69+CD56dim was higher with statistical significance when comparing with the initial treatment group and oral drug group [10.49 (5.27, 19.07) vs 5.03 (3.67, 8.58), Z = -3.11, P = 0.002; 10.49 (5.27, 19.07) vs 4.04 (1.90, 7.26), Z = -5.30, P < 0.001)]. CD57+CD56dim was significantly lower than that in initial treatment group and oral drug group respectively [68.42 ±10.37 vs 55.85±12.87, t = 5.84, P < 0.001; 76.38±9.49 vs 55.85±12.87, t = -9.65, P < 0.001]. The CD56brightCD16- subgroup in the plateau group was higher with statistical significance compared with initial treatment group and oral drug group respectively [11.64 (6.05, 19.61) vs 3.58 (1.94, 5.60), Z = -6.35, P < 0.001; 11.64 (6.05, 19.61) vs 2.37 (1.70, 4.30), Z = -7.74, P < 0.001)]. CD57+CD56dim in the plateau group had a significant higher percentage than that at baseline after IFN discontinuation for 12-24 weeks (55.85±12.87 vs 65.95±12.94, t = -2.78, P = 0.011). Conclusion: During the long-term treatment of IFN, the killer subgroup of NK cells is continuously depleted, leading to the differentiation of the regulatory subgroup into the killer subgroup. In the killing subgroup, although the number is continuously depleted, the activity of the subgroup is continuously increased. In the plateau phase, after stopping IFN for a period of time, the number of NK cell subsets would gradually recover, but was still lower than that in the initial treatment group. [ABSTRACT FROM AUTHOR]

Background: To investigate the changes of human leukocyte antigen DR (HLA DR) and CD38 coexpression subsets on T lymphocytes following interferon (IFN) therapy for those who have chronic hepatitis B (CHB). Methods: A prospective cohort of CHB patients participated in this study. CHB patients without IFN treatment (including naïve and nucleoside [nucleotide] analogs [NAs]-treated patients) were given pegylated interferon alfa (Peg-IFNα) treatment. Peripheral blood samples were taken at baseline, 4 weeks and 12-24 weeks of Peg-IFNα treatment. For the patients who entered the Peg-IFNα plateau phase due to the stagnation of the decrease in HBsAg, and Peg-IFNα was discontinued and Peg-IFNα therapy was resumed after an interval of 12-24 weeks. During the interval, they received first-line NAs treatment. Peripheral blood samples were collected at the baseline of the plateau phase, 12-24 weeks of intermittent treatment, and 12-24 weeks of Peg-IFNα retreatment. The peripheral blood samples were taken to determine virological, serological and biochemical indices of hepatitis B virus (HBV), and T lymphocyte related phenotypes were detected using flow cytometry. Results: In the process of long-term treatment of Peg-IFNα, the percentage of HLA-DR+CD38dim subsets increased significantly at first, then decreased gradually, while the percentage of HLA-DR+CD38hi subsets markedly increased. During long-term Peg-IFNα treatment, there was a considerable negative correlation between HBsAg and the HLA-DR+CD38hi subset percentage. The persistent high proportion of HLA-DR+CD38hi subsets was related to the occurrence of Peg-IFNα plateau phase. After Peg-IFNα intermittent treatment, the percentage of HLA-DR+CD38hi subsets decreased significantly. After Peg-IFNα retreatment, the level of HBsAg began to decrease again. At the same time, the percentage of HLA-DR+CD38hi subsets significantly increased, but it was still lower than that at the baseline level. Conclusions: The spectrum of HLA-DR and CD38 coexpression subsets on T lymphocytes changed during the long-term treatment of IFN. The establishment of the IFN plateau phase was linked to the persistence of a considerable proportion of HLA-DR+CD38hi subsets on T lymphocytes. IFN intermittent treatment could significantly reduce the proportion of HLA DR+CD38hi subsets, helping regain the antiviral efficacy of IFN during IFN retreatment. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is the most common inflammatory skin disease. However, recent reports concerning the simple clinical aspects of treatment with topical glucocorticosteroids (TCS) and calcineurin inhibitors (TCI) are lacking. The objective of this study is providing an update on these characteristics of AD management. A group of 150 adults suffering from AD treated with TCS during last year was asked to fill an anonymous questionnaire. The course of topical treatment was analyzed in the context of the severity of symptoms and the knowledge of the patients about therapy. During the last year, the majority of patients (66%) were treated with class IV TCS; however, in the last two weeks, class I TCS was used the most frequently (35%). Only 11% were familiar with the concept of intermittent therapy and 4% used the fingertip unit (FTU). In total, 77% of them used TCI. Most of the patients used the same class of TCS permanently. Unfortunately, patients are unaware of simple approaches (like intermittent therapy or FTU) that increase both the effectiveness and safety of the treatment. Practicians should be aware of these problems to identify and eliminate them, primarily through the education of patients. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are key in understanding tumor growth and tumor progression. A counterintuitive effect of CSCs is the so-called tumor growth paradox: the effect where a tumor with a higher death rate may grow larger than a tumor with a lower death rate. Here we extend the modeling of the tumor growth paradox by including spatial structure and considering cancer invasion. Using agent-based modeling and a corresponding partial differential equation model, we demonstrate and prove mathematically a tumor invasion paradox: a larger cell death rate can lead to a faster invasion speed. We test this result on a generic hypothetical cancer with typical growth rates and typical treatment sensitivities. We find that the tumor invasion paradox may play a role for continuous and intermittent treatments, while it does not seem to be essential in fractionated treatments. It should be noted that no attempt was made to fit the model to a specific cancer, thus, our results are generic and theoretical. [ABSTRACT FROM AUTHOR]

To summarize the principal findings of all available studies that have evaluated the use of inhaled corticosteroids (ICS) on an intermittent or as-needed basis as an add-on therapy to short-acting β2-agonists (SABAs) or fast-acting β2-agonists (FABAs) in pediatric asthmatic patients. Studies could either include or omit the use of ICS during stable periods of the disease. Electronic databases MEDLINE, EMBASE, CINAHL, SCOPUS, and the Cochrane Database of Systematic Reviews from inception to February 2021. Relevant articles in the literature published by February 2021. Of 294 references identified, 14 studies were included. The use of ICS on an intermittent or as-needed basis (as an add-on therapy to SABAs) has been shown to be more effective than treatment with SABA alone and to be similarly or less effective compared to regular daily ICS administration. Furthermore, strategies involving increasing the dose of ICS only when needed (as an add-on therapy to formoterol, a FABA) and keeping it low during stable stages of the disease (i.e. single maintenance and reliever therapy, SMART) have been shown to be similarly or more effective than comparators. The use of ICS on an intermittent or as-needed basis as an add-on therapy to SABAs or FABAs, with or without ICS use during stable periods of the disease in pediatric asthmatic patients, encompasses several effective treatment strategies. [ABSTRACT FROM AUTHOR]

Drug resistance remains one of the major impediments to treating cancer. Although many patients respond well initially, resistance to therapy typically ensues. Several confounding factors appear to contribute to this challenge. Here, we first discuss some of the challenges associated with drug resistance. We then discuss how a 'Team Medicine' approach, involving an interdisciplinary team of basic scientists working together with clinicians, has uncovered new therapeutic strategies. These strategies, referred to as intermittent or 'adaptive' therapy, which are based on eco-evolutionary principles, have met with remarkable success in potentially precluding or delaying the emergence of drug resistance in several cancers. Incorporating such treatment strategies into clinical protocols could potentially enhance the precision of delivering personalized medicine to patients. Furthermore, reaching out to patients in the network of hospitals affiliated with leading academic centers could help them benefit from such innovative treatment options. Finally, lowering the dose of the drug and its frequency (because of intermittent rather than continuous therapy) can also have a significant impact on lowering the toxicity and undesirable side effects of the drugs while lowering the financial burden carried by the patient and insurance providers. [ABSTRACT FROM AUTHOR]

Background: To investigate the effect of intermittent interferon therapy mode on the disappearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients. Methods: This is a retrospective cohort study in CHB patients who were suspended from pegylated interferon a (PEG-IFNa) therapy due to a plateau in HBsAg decline during the initial treatment period, and resumed interferon therapy after an interval of 3-6 months. Patients received entecavir or tenofovir during the interval period. Hepatitis B virus (HBV) virological and serological indexes, clinical biochemical indexes, and blood routine tests were performed at the baseline and every 3 months during follow-up of initial interferon treatment. A functional cure was analyzed as a primary outcome. Results: A total of 304 patients treated with intermittent PEG-IFNa were included in the statistical analysis, including 215 men and 89 women, aged 37.97 ± 8.53 years, and 73 hepatitis B e antigen (HBeAg)-negative and 231 HBeAg positive patients. In total 59 patients (19.41%) achieved HBsAg disappearance through the initial, intermittent, and retreatment of PEG-IFNa treatment, of whom 43 patients (14.14%) achieved HBsAg seroconversion. Early HBsAg response to initial treatment was significantly associated with HBsAg response at 12 and 24 weeks of retreatment. After the intermission period, the incidence of HBsAg disappearance in patients with early HBsAg response in the retreatment period was 43.87%. The baseline HBsAg and 12-week HBsAg response in the retreatment period had higher predictive value than the initial treatment HBsAg response. Conclusion: The initial, intermittent, and retreatment mode of interferon can help to improve the HBsAg disappearance rate in CHB patients. [ABSTRACT FROM AUTHOR]

Background. The chronic and recurrent nature of seborrheic dermatitis, its wide prevalence and multifactorial etiopathogenesis require a comparison of the effectiveness of different treatment strategies. Aim. In a randomized controlled trial to evaluate the effectiveness of standard and intermittent therapy with topical corticosteroids and activated zinc pyrithione (Skin-cap cream) in reducing the severity of clinical manifestations, the duration of remission of the disease, and compliance with treatment. Methods. The effectiveness of external therapy in patients with seborrheic dermatitis of the face and scalp was studied. All the examined patients had at least two episodes of exacerbation per year. Doctor's prescription Mometasone furoate cream 0.1% 1 time/day externally for 14 days, activated zinc pyrithione (Skin-cap cream) 2 times/day externally for 14 days, further 1 time a day 2 times a week for 14 days. Results. There was a comparable clinical effectiveness of antiinflammatory therapy in the short term with more stable results of intermittent therapy with the use of (Skin-cap cream) in the long term. Conclusions. Usage of activated zinc pyrithione (Skin-cap cream) according to the intermittent scheme in the treatment of seborrheic dermatitis of the face with the transition to the scalp is associated with long-term results. Safety of medicine allows to use it pro re nata by patients, e.g., in case of increased stress levels, diet incompliance, with no risks of adverse events, specific to topical corticosteroids, those increases treatment compliance.

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Interferon (IFN) and nucleoside (nucleotide) analogs (NAs) are two effective antiviral drugs for chronic hepatitis B (CHB). More and more evidence shows that the combination of the two drugs can better inhibit viral replication and even achieve clinical cure. IFN intermittent therapy is also considered to be an important measure to resolve IFN fatigue when hepatitis B surface antigen (HBsAg) decline appears stagnated during IFN-based antiviral therapy. A 36-year-old male NA-experienced patient with hepatitis B e antigen (HBeAg)-positive CHB was admitted to our hospital. After a poor response to tenofovir disoproxil fumarate (TDF) monotherapy for 1 year, the patient was treated with pegylated interferon alfa-2a combination therapy and finally achieved HBsAg clearance. During the treatment and follow-up, HBsAg, HBeAg, hepatitis B virus (HBV) DNA, and serum alanine aminotransferase, etc. were monitored every 3 months. Between weeks 58 and 71 of combination therapy, IFN was discontinued because of a slow decline in HBsAg, and TDF alone was used for maintenance therapy. Complete virological response, HBeAg and HBsAg seroconversion were observed at weeks 44, 96, and 122, respectively. After 24 weeks of consolidation therapy, HBsAg, HBeAg, and HBV DNA were consistently negative, and hepatitis B surface antibody was 729.30 mIU/mL at week 146 of the combination therapy, then we stopped drugs. Following up after 28 weeks of cessation therapy, the patient still remained clinically cured. [ABSTRACT FROM AUTHOR]

Osteoporosis is a bone disease identified by disordering of bone formation and resorption cells. It increases the risk of bone fragility and fracture. Autocrine and paracrine signalling of osteoclasts and osteoblasts plays an important role in the regulation of bone remodelling. Calcitonin is an approved pharmacologic agent for the treatment of osteoporosis. A novel mathematical model comprising the interaction among osteoclasts and osteoblasts cells with intermittent administration of calcitonin has been presented to study the dynamics of osteoporotic bone. The stability of model and sensitivity of parameters are also discussed. The population of osteoclastic and osteoblastic cells has been predicted via numerical simulation. The results of Monte Carlo sensitivity analysis are shown via tornado diagram. It is concluded that intermittent administration of calcitonin is an effective therapy for the treatment of osteoporosis. • We focus on the impact of calcitonin and its intermittent input. • We discuss the stability of the model with the help of Lyapunov stability theory. • We also discuss the sensitivity analysis of our proposed model by using the Monte Carlo method. • Clinical trials and their conclusions are revisited for Analysis. • A novel mathematical model is synchronised with Sensitivity-Analysis. • Dose rates for intermittent therapy, relative to time are presented. [ABSTRACT FROM AUTHOR]

Introduction: Considering the differences in overall survival (OS) and progression-free survival (PFS), treatment options for metastatic colorectal cancer (mCRC) are still inconclusive. We carried out a meta-analysis of maintenance and intermittent strategies for the treatment of mCRC aiming at providing an accurate estimation of different treatments in increasing the chance and duration of survival.Methods: PubMed, Embase and CNKI were systematically searched. The pooled hazard ratio (HR) and 95% confidence interval (CI) were counted. We used STATA 12.0 and RevMan 5.2 for statistical analyses.Results: A total of six publications with a population of 1975 mCRC patients were included in our meta-analysis. Analysis of OS revealed a statistically significant benefit associated with maintenance therapy (HR: 0.86, 95% CI 0.75-0.98, P = 0.02). Comparing maintenance therapy with an intermittent strategy, the first progression-free survival (PFS1) showed no significant difference (HR, 0.77; 95% CI 0.48-1.24, P = 0.29), but maintenance therapy improved the second progression-free survival (PFS2) significantly (HR, 0.66; 95% CI 0.54-0.81, P < 0.001). Sensitivity analysis was carried out to assess the stability of results. No publication bias was detected during analysis.Conclusion: Compared with the maintenance strategy, first-line chemotherapy that was completely stopped until disease progression did not benefit mCRC patients in terms of OS and PFS2. Therefore, a maintenance strategy is a good option for individualized mCRC patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate non‐inferiority of intermittent docetaxel compared to continuous docetaxel in patients with metastatic castration‐resistant prostate cancer (mCRPC). Patient and Methods: The investigator initiated randomised phase III study included 187 chemotherapy‐naïve patients with mCRPC who were allocated to two treatment arms: intermittent docetaxel and continuous docetaxel. Docetaxel was applied in both arms as weekly (35 mg/m2) or 3‐weekly (75 mg/m2). The primary endpoint was 1‐year survival, which was tested for non‐inferiority (margin δ = 0.125). The secondary endpoints were: overall survival (OS), progression‐free survival (PFS), median time to treatment failure (TTF), and toxicity. Results: Of 156 eligible patients, 78 were allocated to each arm. The intermittent treatment met the non‐inferiority criteria for 1‐year survival (two‐sided 95% confidence interval, −0.12, 18, P = 0.022), but not for OS, according to the result of a post hoc analysis. The differences between the study arms in PFS and TTF were not significant. The median (range) treatment holiday in the intermittent arm was 110 (13–486) days, or 38% of the overall treatment duration. Safety profiles of both study arms were comparable. The main limitation of this study was that the planned number of patients could not be recruited. Conclusion: Intermittent docetaxel chemotherapy was non‐inferior to continuous therapy for 1‐year survival; non‐inferiority in regard to OS was not reached. [ABSTRACT FROM AUTHOR]

Background. Intermittent regimens offer operational advantages in tuberculosis treatment, but their efficacy has been questioned. We updated a systematic review and metaanalysis to examine the efficacy of different intermittent dosing schedules in firstline pulmonary tuberculosis therapy. Methods. An updated search included randomized control trials (RCTs) that reported on first-line pulmonary tuberculosis therapy between June 2008 and March 2016. We pooled proportions of failure, relapse, and acquired drug resistance (ADR) for 4 dosing schedules: daily throughout, thrice weekly throughout, daily (intensive phase) then thrice weekly (continuation phase), and daily (intensive phase) then twice weekly (continuation phase). Metaregression was performed using a negative binomial regression model. Results. After screening 5874 citations, 7 RCTs with 10 arms were added for a total of 56 RCTs with 110 arms. The pooled proportion of relapse was significantly higher in arms with thrice weekly therapy throughout (6.8; 95% confidence interval [CI], 3.8-9.9) and twice weekly therapy in the continuation phase (7.3; 95% CI, 3.5-11.1) when compared with daily therapy (2.5; 95% CI, 1.8-3.2; P < .01). Metaregression revealed higher rates of relapse (2.2; 95% CI, 1.2-4.0), failure (3.7; 95% CI, 1.1-12.6), and ADR (10.0; 95% CI, 2.1-46.7) in arms with thrice weekly throughout and higher rates of failure (3.0; 95% CI, 1.0-8.8) with twice weekly in the continuation phase when compared with daily therapy. Conclusion. Thrice weekly dosing throughout therapy, and twice weekly dosing in the continuation phase appear to have worse microbiological treatment outcomes when compared with daily therapy. [ABSTRACT FROM AUTHOR]

High effectiveness of isotretinoin treatment for severe types of acne resistant to antibiotics has been widely recognized. However, the recommended doses in conventional therapy, according to consensus of the Polish Dermatological Society, may cause serious adverse effects. Thus, research into less stressful, alternative treatment regimens with the use of low doses of isotretinoin has been carried out. The aim of the paper was to review the selected papers where authors present the results of their studies on different regimens with the use of isotretinoin in low doses in patients with acne, evaluate their efficacy, patient satisfaction, frequency of adverse effects, recurrences and also treatment costs. [ABSTRACT FROM AUTHOR]

Taiwan has never implemented supervised intermittent chemotherapy for pulmonary tuberculosis, and its application and results are unknown. The purpose of this study was to evaluate the efficacy and feasibility of a 62-dose, four-drug, 6-month, twice-weekly regimen administered by directly observed therapy for the treatment of pulmonary tuberculosis. Methods: From January 2004 through December 2006, a total of 116 patients with suspected or confirmed pulmonary tuberculosis were enrolled. Thirty-two of these patients were excluded from the analysis because of drug resistance, negative culture, self withdrawal and drug reactions. Isoniazid, rifampin, pyrazinamide, and ethambutol were administered daily for 2 weeks, followed by twice weekly at a higher dose for 6 weeks. Thereafter, isoniazid, ethambutol and rifampin were administered twice weekly for 18 weeks. Treatment was directly observed by nurses or outreach workers. Results: Of the 84 evaluable patients, 75 [89.3%, 95% confidence interval (CI): 80.6s–95.0%] patients were considered as successfully treated, three (3.6%, 95% CI: 0.7–10.1%) transferred out, five (6.0%, 95% CI: 2.0–13.3%) were unsuccessful and one (1.2%, 95% CI: 0.03–6.5%) died. Five patients were treatment failure (6.0%, 95% CI: 2.0–13.3%). Three patients had recurrences of pulmonary tuberculosis, and the recurrences were 4, 6 and 15 months after the completion of therapy. Sixpatients (5.2%) had severe adverse drug reactions and had their regimen modified. Conclusion: Prior to this study, intermittent therapy has not been attempted in Taiwan. This four-drug mostly twice-weeldy pulmonary tuberculosis treatment regimen is efficacious and relatively nontoxic, with a higher treatment success rate and a lower death rate. It considerably simplifies treatment and facilitates the execution of directly observed therapy. The reasons for the relatively high failure rate require further studies.

The time the earth takes to rotate its axis (the day) has dictated how often pharmaceutical compounds are dosed. The scientific link between the 2 events is materia medica arcana. As an example, in the treatment of invasive candidiasis, antifungal therapy with intravenous micafungin is dosed daily. A literature review revealed population pharmacokinetic analyses, in vivo pharmacokinetics/pharmacodynamics studies, and maximum-tolerated-dose studies of micafungin that examined optimal micafungin dosing strategies. The half-life of micafungin in patient blood was 14 hours in several studies, but was even longer in different organs, so that the concentration will persist above minimum inhibitory concentrations of Candida species for several days. Studies in mice and rabbits with persistent neutropenia and disseminated candidiasis, otherwise fatal, demonstrated that a single large dose of micafungin could clear disseminated candidiasis, even though the micafungin half-life in such animals is shorter than in humans. Human pharmacokinetics/pharmacodynamics studies confirmed this link between micafungin efficacy and the ratio of the area under the concentration-time curve, and the optimal exposures initially identified in neutropenic animals. Maximum tolerated dose studies have demonstrated safety of 900 mg administered daily for several weeks, whereas case reports demonstrate efficacy and safety of single 1400-mg doses. Thus, a single dose of micafungin, or 2 such doses within a few days of each other, is not only logical, but might even lead to faster clearance of Candida. [ABSTRACT FROM AUTHOR]

Background: To investigate the changes of natural killer (NK) cell phenotype in the interferon alpha (IFN-α) treatment of chronic hepatitis B (CHB) and its relationship with clinical indicators., Methods: The CHB patients who did not receive any antiviral treatment were set as initial treatment group and used pegylated interferon alpha (PEG-IFN α). Peripheral blood samples were collected at baseline, 4 weeks, and 12-24 weeks. For IFN-treated patients who entered the plateau were set as plateau group, and PEG-IFN α was discontinued and resumed after an interval of 12-24 weeks. Besides, we also enrolled some patients who had received oral drug for more than 6 months as oral drug group without follow up. Peripheral blood was collected during the plateau period, which was set as baseline, and after 12-24 weeks of intermittent treatment, and after 12-24 weeks of additional treatment with PEG-IFN α. The aim of the collection was to detect hepatitis B virus (HBV) virology, serology and biochemical indicators, and the NK cell related phenotype was detected by flow cytometry., Results: In the plateau group, subgroup of CD69 + CD56 dim was higher with statistical significance when comparing with the initial treatment group and oral drug group [10.49 (5.27, 19.07) vs 5.03 (3.67, 8.58), Z = -3.11, P = 0.002; 10.49 (5.27, 19.07) vs 4.04 (1.90, 7.26), Z = -5.30, P < 0.001)]. CD57 + CD56 dim was significantly lower than that in initial treatment group and oral drug group respectively [68.42±10.37 vs 55.85±12.87, t = 5.84, P < 0.001; 76.38±9.49 vs 55.85±12.87, t = -9.65, P < 0.001]. The CD56 bright CD16 - subgroup in the plateau group was higher with statistical significance compared with initial treatment group and oral drug group respectively [11.64 (6.05, 19.61) vs 3.58 (1.94, 5.60), Z = -6.35, P < 0.001; 11.64 (6.05, 19.61) vs 2.37 (1.70, 4.30), Z = -7.74, P < 0.001)]. CD57 + CD56 dim in the plateau group had a significant higher percentage than that at baseline after IFN discontinuation for 12-24 weeks (55.85±12.87 vs 65.95±12.94, t = -2.78, P = 0.011)., Conclusion: During the long-term treatment of IFN, the killer subgroup of NK cells is continuously depleted, leading to the differentiation of the regulatory subgroup into the killer subgroup. In the killing subgroup, although the number is continuously depleted, the activity of the subgroup is continuously increased. In the plateau phase, after stopping IFN for a period of time, the number of NK cell subsets would gradually recover, but was still lower than that in the initial treatment group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer WW declared a shared parent affiliation with the authors XB, SWa, WC, LY, TJ, WD, SWu, RL, YG, GS, MC, HH, MX, XC, LH, YL, LZ, YX, ML to the handling editor at the time of review., (Copyright © 2023 Bi, Xie, Wu, Cao, Lin, Yang, Jiang, Deng, Wang, Liu, Gao, Shen, Chang, Hao, Xu, Chen, Hu, Lu, Zhang, Xie and Li.)

Background: To investigate the changes of human leukocyte antigen DR (HLA-DR) and CD38 coexpression subsets on T lymphocytes following interferon (IFN) therapy for those who have chronic hepatitis B (CHB)., Methods: A prospective cohort of CHB patients participated in this study. CHB patients without IFN treatment (including naïve and nucleoside [nucleotide] analogs [NAs]-treated patients) were given pegylated interferon alfa (Peg-IFNα) treatment. Peripheral blood samples were taken at baseline, 4 weeks and 12-24 weeks of Peg-IFNα treatment. For the patients who entered the Peg-IFNα plateau phase due to the stagnation of the decrease in HBsAg, and Peg-IFNα was discontinued and Peg-IFNα therapy was resumed after an interval of 12-24 weeks. During the interval, they received first-line NAs treatment. Peripheral blood samples were collected at the baseline of the plateau phase, 12-24 weeks of intermittent treatment, and 12-24 weeks of Peg-IFNα retreatment. The peripheral blood samples were taken to determine virological, serological and biochemical indices of hepatitis B virus (HBV), and T lymphocyte related phenotypes were detected using flow cytometry., Results: In the process of long-term treatment of Peg-IFNα, the percentage of HLA-DR + CD38 dim subsets increased significantly at first, then decreased gradually, while the percentage of HLA-DR + CD38 hi subsets markedly increased. During long-term Peg-IFNα treatment, there was a considerable negative correlation between HBsAg and the HLA-DR + CD38 hi subset percentage. The persistent high proportion of HLA-DR + CD38 hi subsets was related to the occurrence of Peg-IFNα plateau phase. After Peg-IFNα intermittent treatment, the percentage of HLA-DR + CD38 hi subsets decreased significantly. After Peg-IFNα retreatment, the level of HBsAg began to decrease again. At the same time, the percentage of HLA-DR + CD38 hi subsets significantly increased, but it was still lower than that at the baseline level., Conclusions: The spectrum of HLA-DR and CD38 coexpression subsets on T lymphocytes changed during the long-term treatment of IFN. The establishment of the IFN plateau phase was linked to the persistence of a considerable proportion of HLA-DR + CD38 hi subsets on T lymphocytes. IFN intermittent treatment could significantly reduce the proportion of HLA-DR + CD38 hi subsets, helping regain the antiviral efficacy of IFN during IFN retreatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Shen, Xie, Bi, Lu, Yang, Jiang, Deng, Wang, Zhang, Lu, Gao, Hao, Wu, Liu, Chang, Xu, Hu, Chen, Huang, Li and Xie.)

This paper studies the dynamics of the hepatitis B virus (HBV) model and the therapy regimens of HBV disease. First, we propose a new mathematical model of HBV with drug resistance, and then analyze its qualitative and dynamical properties. Combining the clinical data and theoretical analysis, we demonstrate that our model is biologically plausible and also computationally viable. Second, we demonstrate that the intermittent antiviral therapy regimen is one of the possible strategies to treat this kind of complex disease. There are two main advantages of this regimen, i.e. it not only may delay the development of drug resistance, but also may reduce the duration of on-treatment time compared with the long-term continuous medication. Moreover, such an intermittent antiviral therapy can reduce the adverse side effects. Our theoretical model and computational results provide qualitative insight into the progression of HBV, and also a possible new therapy for HBV disease. [ABSTRACT FROM AUTHOR]

This study was conducted with the aim to investigate the feasibility of intermittent treatment with docetaxel chemotherapy for castration-resistant prostate cancer (CRPC). A total of 51 men with CRPC received docetaxel at 75 mg/m2 every 3 weeks combined with oral dexamethasone 1.0-2.0 mg/day between 2008 and 2013. The prostate-specific antigen (PSA) level was monitored every 3 weeks. Chemotherapy was suspended when the serum PSA level decreased to <4 ng/ml, with a reduction rate of >50% from the baseline. Treatment was resumed when serum PSA increased to >2 ng/ml, with an increase rate of >50% from the nadir. Of the 51 cases, 27 (52.9%) qualified for intermittent treatment; 17 patients received two courses of docetaxel chemotherapy and 10 received three courses. The median off-treatment interval was 266 days for the first drug holiday, 129.5 days for the second and 146.5 days for the third. The multivariate analysis indicated low baseline PSA (

Risk factors for acquired rifampicin resistance (ARR) among tuberculosis patients on thrice-weekly antituberculosis therapy were baseline isoniazid resistance and HIV. Among HIV-infected patients, higher mycobacterial burden and lower CD4 count, but not highly active antiretroviral therapy, were significantly associated with ARR.Background. Risk factors for acquired rifampicin resistance (ARR) in human immunodeficiency virus (HIV)/tuberculosis coinfection, in the highly active antiretroviral therapy (HAART) era, needs evaluation. We studied the impact of HIV and HAART on ARR among patients taking thrice-weekly antituberculosis therapy.Methods. This cross-protocol analysis included patients with newly diagnosed, rifampicin-susceptible pulmonary tuberculosis, with and without HIV, enrolled in clinical trials (who took >80% of medication) at the National Institute for Research in Tuberculosis between 1999 and 2013. All patients received rifampicin and isoniazid for 6 months reinforced with pyrazinamide and ethambutol in the first 2 months, given thrice-weekly throughout the study along with HAART in one of the groups. Outcomes were categorized and multivariate logistic regression analysis performed to identify risk factors for ARR.Results. The per-protocol results included patients with tuberculosis: 246 HIV-uninfected patients (HIV–TB+), 212 HIV patients not on HAART (non-HAART), and 116 HIV-infected patients on HAART. Median CD4 counts of the latter 2 groups were 150 and 93 cells/µL, respectively, and the median viral loads were 147 000 and 266 000 copies/mL, respectively. Compared with HIV–TB+, the relative risks (RRs) for an unfavorable response in the coinfected, non-HAART and HAART groups were 2.1 (95% confidence interval [CI], 1.7–14.8; P<.0001) and 2.1 (95% CI, .9–5.2; P=.3), whereas for ARR, the RRs were 21.1 (95% CI, 2.6–184; P<.001) and 8.2 (95% CI, .6–104; P=.07), respectively.Conclusions. HIV-infected patients with tuberculosis treated with a thrice-weekly antituberculosis regimen are at a higher risk of ARR, compared with HIV-uninfected patients, in the presence of baseline isoniazid resistance. HAART reduces but does not eliminate the risk of ARR. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study was to compare intermittent (IAD) and continuous (CAD) androgen deprivation therapy (ADT) between locally advanced (M0) and metastatic (M1) prostate cancer, and the effect of ADT on the quality of life. Material and methods. In total, 852 men with advanced prostate cancer were enrolled to receive goserelin acetate for 24 weeks. Of these, 554 patients whose prostate-specific antigen (PSA) decreased to less than 10 ng/ml or by at least 50% (<20 ng/ml at baseline) were randomized to IAD or CAD. In the IAD arm, ADT was resumed for at least 24 weeks whenever PSA increased to greater than 20 ng/ml or above baseline. Results. Median follow-up time was 65 months. Median times from randomization to progression, death, prostate cancer death and treatment failure in M0 and M1 patients were 46.8 and 21.4, 57.6 and 40.3, 59.5 and 40.7, and 41.9 and 20.0 months, respectively ( p < 0.001). No significant differences emerged between IAD and CAD. ADT showed a beneficial effect on pain, activity limitation and social functioning in M1 patients, and a deleterious effect on physical capacity in M0 patients and on sexual functioning in both groups. IAD offered extra benefit for activity limitation, social functioning and recovery of sexual functioning. Conclusions. IAD is as efficient as CAD in treatment of locally advanced and metastatic prostate cancer. ADT improves quality of life in M1 patients, with IAD offering extra benefit. [ABSTRACT FROM AUTHOR]

A model of cancer growth based on the Gompertz stochastic process with jumps is proposed to analyze the effect of a therapeutic program that provides intermittent suppression of cancer cells. In this context, a jump represents an application of the therapy that shifts the cancer mass to a return state and it produces an increase in the growth rate of the cancer cells. For the resulting process, consisting in a combination of different Gompertz processes characterized by different growth parameters, the first passage time problem is considered. A strategy to select the inter-jump intervals is given so that the first passage time of the process through a constant boundary is as large as possible and the cancer size remains under this control threshold during the treatment. A computational analysis is performed for different choices of involved parameters. Finally, an estimation of parameters based on the maximum likelihood method is provided and some simulations are performed to illustrate the validity of the proposed procedure. [ABSTRACT FROM AUTHOR]

Use of intermittent androgen-deprivation therapy ( IADT) in patients with prostate cancer has been evaluated in several studies, in an attempt to delay the development of castration resistance and reduce side-effects associated with ADT. However it is still not clear whether survival is adversely affected in patients treated with IADT. In this review, we explore the available data in an attempt to identify the most suitable candidate patients for IADT, and discuss factors that may inform appropriate patient stratification. ADT is first-line treatment for advanced/metastatic prostate cancer and is also recommended for use with definitive radiotherapy for high-risk localised prostate cancer. The changes in hormone levels induced by ADT can lead to short- and long-term side-effects which, although treatable in most cases, can significantly reduce the tolerability of ADT treatment. IADT has been investigated in several phase II and phase III studies in patients with locally advanced or metastatic prostate cancer, in an attempt to delay time to tumour progression and reduce the side-effect burden of ADT. In selected patient groups IADT is no less effective than continuous ADT, ameliorating the impact of ADT-related side-effects, and, to a degree, their impact on patient health-related quality of life ( HRQL). Further comparative study is required, particularly in relation to HRQL and long-term complications associated with ADT. [ABSTRACT FROM AUTHOR]

Abstract: Context: Intermittent androgen deprivation (IAD) in prostate cancer (PCa) patients has been proposed to delay development of castration resistance and to reduce the side effects and costs of androgen deprivation therapy (ADT). Objective: This review analyzes (1) the oncologic and quality of life (QoL) results from randomized phase 3 trials comparing IAD and continuous ADT and (2) the prognostic parameters for IAD. Evidence acquisition: We searched the Medline and Cochrane Library databases (primary fields: prostate neoplasm and intermittent androgen deprivation; secondary fields: randomized trials, survival, quality of life, predictors) without language restriction. Evidence synthesis: We found seven extensively described phase 3 trials randomizing 4675 patients to IAD versus continuous ADT. Other randomized trials investigating IAD have been performed, but available data are limited and have been published only in preliminary fashion. In all seven trials, patients spent most of their time on, rather than off, ADT. The induction periods ranged from 3 mo to 8 mo; in all but one trial, the PSA level designated for ADT discontinuation was <4 ng/ml. Mean follow-up ranged from 40–108 mo. Collectively, these trials support the concept that, mainly in metastatic cases, IAD can produce oncologic results similar to continuous ADT. In terms of overall survival, the hazard ratios for IAD and continuous ADT were very similar (range: 0.98–1.08). The QoL benefit of IAD appears to be modest at best. With IAD, QoL is likely influenced by the duration of the off-treatment periods and by the rate of testosterone recovery. Conclusions: The evidence indicates that IAD is not inferior to continuous ADT. Data are insufficient to determine whether IAD is able to prevent the long-term complications of ADT. More comparative analysis focused on QoL is warranted. [Copyright &y& Elsevier]

Abstract: Background: Intermittent dosing may reduce the adverse events (AEs) of androgen-deprivation therapy (ADT). Objective: To compare intermittent androgen deprivation (IAD) and continuous androgen deprivation (CAD) with regard to health-related quality of life (QoL). Design, setting, and participants: A total of 852 men with advanced prostate cancer (PCa) were enrolled to receive goserelin acetate 3.6mg every 28 d for 24 wk. A total of 554 patients whose prostate-specific antigen (PSA) decreased to <10 ng/ml or by ≥50% (<20 ng/ml at baseline) were randomised to IAD or CAD. Intervention: In the IAD arm, ADT was resumed for at least 24 wk whenever PSA increased >20 ng/ml or above baseline. Outcome measurements and statistical analysis: QoL was monitored with a validated Cleary 30-item questionnaire and analysed by the Mann-Whitney U test, 0.5 standard deviation rule, and repeated measures analysis of variance. AEs and adverse drug reactions (ADRs) were analysed by the chi-square test. Results and limitations: Median follow-up was 65 mo. Significant differences in QoL emerged in activity limitation, physical capacity, and sexual functioning, favouring IAD. No significant differences emerged in the prevalence of AEs: 87 patients in the IAD arm (31.8%) and 95 in the CAD arm (33.9%) had cardiovascular (CV) AEs (p =0.59), with 25 (9.1%) and 29 (10.4%) withdrawn (p =0.62), and 21 (7.7%) and 24 (8.6%) dying because of a CV event (p =0.70), respectively; bone fractures occurred in 19 (6.9%) and 15 (5.4%) patients (p =0.44), respectively. Hot flushes or night sweats were the most common ADRs (47.1% vs 50.4%; p =0.44). Erectile dysfunction (15.7% vs 7.9%; p =0.042) and depressed mood (2.2 vs 0%; p =0.032) were more common in the IAD arm. Conclusions: IAD showed benefits in the treatment of advanced PCa with respect to QoL. The prevalence of AEs was not significantly lower with IAD. Trial registration: ClinicalTrials.gov, NCT00293670. [Copyright &y& Elsevier]

Background: To investigate the effect of intermittent interferon therapy mode on the disappearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients., Methods: This is a retrospective cohort study in CHB patients who were suspended from pegylated interferon α (PEG-IFNα) therapy due to a plateau in HBsAg decline during the initial treatment period, and resumed interferon therapy after an interval of 3-6 months. Patients received entecavir or tenofovir during the interval period. Hepatitis B virus (HBV) virological and serological indexes, clinical biochemical indexes, and blood routine tests were performed at the baseline and every 3 months during follow-up of initial interferon treatment. A functional cure was analyzed as a primary outcome., Results: A total of 304 patients treated with intermittent PEG-IFNα were included in the statistical analysis, including 215 men and 89 women, aged 37.97 ± 8.53 years, and 73 hepatitis B e antigen (HBeAg)-negative and 231 HBeAg positive patients. In total 59 patients (19.41%) achieved HBsAg disappearance through the initial, intermittent, and retreatment of PEG-IFNα treatment, of whom 43 patients (14.14%) achieved HBsAg seroconversion. Early HBsAg response to initial treatment was significantly associated with HBsAg response at 12 and 24 weeks of retreatment. After the intermission period, the incidence of HBsAg disappearance in patients with early HBsAg response in the retreatment period was 43.87%. The baseline HBsAg and 12-week HBsAg response in the retreatment period had higher predictive value than the initial treatment HBsAg response., Conclusion: The initial, intermittent, and retreatment mode of interferon can help to improve the HBsAg disappearance rate in CHB patients., Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04028856]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer, BF, declared a shared parent affiliation with several authors, ZZ, YnL, ML, and YX, to the handling editor at the time of review., (Copyright © 2022 Li, Xie, Bi, Sun, Zeng, Deng, Jiang, Lin, Yang, Lu, Zhang, Yi and Xie.)

Study Type - Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Intermittent androgen deprivation therapy (ADT) involves cycling ADT, allowing hormonal recovery during off-treatment periods. This could lead to a better quality of life during off-treatment periods and could delay progression to castration resistance. Safety and feasibility of intermittent ADT have been shown but tolerability and health-related quality of life improvement have been suggested but questioned by others. Results from randomized trials, including relapsing or mixed populations, have suggested intermittent ADT to be as effective as continuous ADT. In this study of only metastatic patients, no statistical difference in either overall survival or progression-free survival was shown between intermittent and continuous ADT and suggests that intermittent might be as safe as continuous castration. It could be an option in highly responding and well-informed metastatic patients even if no clear benefit in health-related quality of life was shown. This intermittent modality could be of interest in metastatic patients with significant treatment-induced side-effects. OBJECTIVE To compare intermittent androgen deprivation therapy (ADT) and continuous ADT after 6 months of induction of ADT in patients with metastatic prostate cancer (PCa)., PATIENTS AND METHODS This is an open-label randomized multi-centre study conducted in 58 centres in Europe., Patients with metastatic PCa and prostate-specific antigen (PSA) level >20 ng/mL at selection were randomized after 6 months of induction of ADT (leuprorelin and flutamide) if PSA level had decreased below 4 ng/mL., Patients received either continuous or intermittent ADT. All patients were treated until signs of disease progression under treatment or until study end with a monthly central PSA determination and follow-up visits were performed every 3 months., The primary endpoint was overall survival. Secondary endpoints included progression-free survival, health-related quality of life (QLQ C30 questionnaire) and safety criteria., RESULTS Of 383 selected patients, 173 had a PSA level below 4 ng/mL after 6 months of induction of ADT and were randomized. Median overall survival (52 vs 42 months, P= 0.75) and median progression-free survival (15.1 vs 20.7 months, P= 0.74) were not significantly different between continuous and intermittent ADT., Although some differences in quality of life were observed, most of the functional and symptom scales showed no significant difference between the two groups., Significantly fewer treatment-emergent adverse events occurred in the intermittent group ( P= 0.042), with the incidence of headache and hot flushes also lower., CONCLUSIONS This first randomized trial comparing continuous with intermittent ADT in metastatic PCa suggests that intermittent ADT might be as safe as continuous ADT., It could be an option in highly responding and well-informed patients even if no clear benefit in health-related quality of life was shown. [ABSTRACT FROM AUTHOR]

Background/purpose: Taiwan has never implemented supervised intermittent chemotherapy for pulmonary tuberculosis, and its application and results are unknown. The purpose of this study was to evaluate the efficacy and feasibility of a 62-dose, four-drug, 6-month, twice-weekly regimen administered by directly observed therapy for the treatment of pulmonary tuberculosis.Methods: From January 2004 through December 2006, a total of 116 patients with suspected or confirmed pulmonary tuberculosis were enrolled. Thirty-two of these patients were excluded from the analysis because of drug resistance, negative culture, self withdrawal and drug reactions. Isoniazid, rifampin, pyrazinamide, and ethambutol were administered daily for 2 weeks, followed by twice weekly at a higher dose for 6 weeks. Thereafter, isoniazid, ethambutol and rifampin were administered twice weekly for 18 weeks. Treatment was directly observed by nurses or outreach workers.Results: Of the 84 evaluable patients, 75 [89.3%, 95% confidence interval (CI): 80.6s-95.0%] patients were considered as successfully treated, three (3.6%, 95% CI: 0.7-10.1%) transferred out, five (6.0%, 95% CI: 2.0-13.3%) were unsuccessful and one (1.2%, 95% CI: 0.03-6.5%) died. Five patients were treatment failure (6.0%, 95% CI: 2.0-13.3%). Three patients had recurrences of pulmonary tuberculosis, and the recurrences were 4, 6 and 15 months after the completion of therapy. Sixpatients (5.2%) had severe adverse drug reactions and had their regimen modified.Conclusion: Prior to this study, intermittent therapy has not been attempted in Taiwan. This four-drug mostly twice-weeldy pulmonary tuberculosis treatment regimen is efficacious and relatively nontoxic, with a higher treatment success rate and a lower death rate. It considerably simplifies treatment and facilitates the execution of directly observed therapy. The reasons for the relatively high failure rate require further studies. [ABSTRACT FROM AUTHOR]

Objectives: Many asthmatics take therapy intermittently because of their scarce compliance. It is not known if this is effective in controlling and slowing down the lung function decline in asthma. Our aim was to compare the effect of a regular treatment and an intermittent one on some clinical aspects and on the forced expiratory volume 1 (FEV1) decline in 165 persistent asthmatics with FEV1 >70% (60 men; age 40.87±14.05; FEV1 95.03±13.1%), in a retrospective way over 4 years. Patients and Methods: Eighty-four patients took inhaled corticosteroids (ICSs) plus long-acting bronchodilator agents (LABAs) regularly (Regular) and 81 patients took ICSs plus LABAs intermittently for short periods when symptoms appeared (Intermittent). Results: Less patients (p<0.05) took oral corticosteroids, short-acting bronchodilators as needed in Regular compared to Intermittent. More patients increased the therapy (step-up) in Intermittent (p<0.01) More patients reported a subjective improvement while fewer reported a worsening in Regular (p<0.05). After 4 years, the variation in maximal mid expiratory flow (FEF25-75) was lower in Regular (-159.40±472.79 ml/sec; CI 95% -261.99, 56.82) than in Intermittent (-324.44±569.97 ml/sec; CI 95% -450.48, -198.41); whereas the FEV1 decline was similar between Regular (-276.97±199.37 ml; CI 95% -316.24, -229.71) and Intermittent (-317.65± 194.05 ml; CI 95% -360.56, -274.74). In males and females, in smokers and non-smokers no differences were found in the FEV1 decline. Conclusions: In conclusion, the Regular use of ICSs plus LABAs is better than the irregular use of them in controlling asthma over a long period of time. Whereas, after 4 years the Regular treatment may not decrease the FEV1 decline more effectively than the Intermittent therapy. [ABSTRACT FROM AUTHOR]

Background: Stopping and restarting etanercept is well tolerated in adult psoriasis, but little is known about intermittent use in pediatric psoriasis. Objective: We sought to assess safety and efficacy of etanercept administered intermittently in children with psoriasis. Methods: At study entry, patients were 4 to 17 years old with moderate to severe stable plaque psoriasis (Psoriasis Area and Severity Index [PASI] score ≥ 12). After an initial 12-week, double-blind period and a 24-week, open-label period, eligible patients (ie, achieved 75% improvement in PASI response from baseline [PASI 75]) were re-randomized to a 12-week, double-blind withdrawal-retreatment period: patients received placebo (withdrawal) or etanercept as long as they maintained PASI 75; otherwise, they were retreated with open-label etanercept (retreatment). Results: The 138 patients who entered the withdrawal-retreatment period were re-randomized equally between placebo and etanercept. In the group treated with blinded or open-label etanercept, 52 of 65 (80%; observed data) patients maintained or regained PASI 75 at the end of the 12-week period. In all, 45 of 64 (70%) patients on blinded etanercept maintained PASI 75 at every study visit during the 12-week period, compared with 35 of 65 (54%) patients who did so on blinded placebo. No patient had a serious adverse event, serious infection, or withdrew from study because of an adverse event. Limitations: Small study and short observation period are limitations. Conclusion: During the final 12-week withdrawal-retreatment period of this 48-week study, intermittent etanercept therapy appeared safe, with no patients experiencing a serious adverse event or serious infection, and effective, with 80% of patients on etanercept maintaining or regaining PASI 75 at the end of the 12-week period. [ABSTRACT FROM AUTHOR]

Abstract: Context: Androgen-deprivation therapy (ADT) is the mainstay of treatment for metastatic prostate cancer and is also recommended in association with external-beam radiation therapy (EBRT) for patients with high-risk disease. Objective: Our aim was to make recommendations regarding optimal timing of ADT, target serum testosterone levels, intermittent ADT delivery, and quality of life (QoL) during ADT. Evidence acquisition: This review contains recommendations from a European expert panel held in May 2009. Evidence synthesis: There is ongoing debate over whether ADT should be initiated at diagnosis or delayed until biochemical or symptomatic progression. Immediate ADT is recommended for metastatic disease to defer symptom development and reduce serious complications. In node-positive disease or high-risk nonmetastatic disease unfit for curative therapy, immediate ADT is also an option. Furthermore, there is a clear benefit of adjuvant ADT in association with EBRT in patients with high-risk disease. Some retrospective evidence also supports adjuvant ADT use following radical prostatectomy for high-risk localised disease. In cases of biochemical relapse after definitive local therapy, early ADT may benefit patients with poor prognostic factors. For patients on ADT, the traditional <50ng/dl target for serum testosterone levels should be considered outdated. It is now clear that a <20ng/dl threshold better reflects the outcome of bilateral orchidectomy, which is considered the standard of reference in ADT. Recent data demonstrate a clinical benefit of testosterone reduction to more stringent targets than the historical <50ng/dl threshold. In addition, emerging evidence suggests that intermittent scheduling of ADT can reduce adverse events and improve QoL without compromising survival, but further data are needed to guide its clinical use. Finally, adverse events of ADT may affect QoL and must be discussed with patients. Conclusions: Based on current evidence, the panel made several recommendations for the clinical implementation of ADT. [Copyright &y& Elsevier]

We conducted this study to assess the efficacy of intermittent short course therapy in all forms of pediatric tuberculosis using a coordinated approach with Revised National Tuberculosis Control Programme (RNTCP). Sixty-five children were treated using RNTCP protocols with some modifications, such as dose adjustments or prolongation of treatment in selected children. Overall response rate was 95% (pulmonary 94% and extra pulmonary 97%). There was one case with possible relapse. With dynamic inputs from both the treating pediatrician and personnel from Directly Observed Treatment -- Short-course (DOTS) centers, we could successfully implement RNTCP protocols in childhood tuberculosis. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of intermittent with daily chemotherapy (both containing rifampicin) in childhood tuberculosis (age ≤16yrs) in achieving cure/ significant improvement. Design: Systematic Review and Meta-analysis. Methods: MEDLINE and the Cochrane Library were searched for randomized trials of antitubercular regimens containing rifampicin, in children 16 yrs or less with tuberculosis. Two reviewers independently assessed trial eligibility and quality. Data from full articles of selected studies were independently extracted by two authors and analyzed. The odds ratio was obtained for the pooled data in two groups (intermittent and daily therapy). Outcome variables: Cure/significant improvement, relapse rate and adverse events. Results: Four randomized controlled trials comparing twice weekly and daily therapy including 466 children (pulmonary 439; extrapulmonary 27) met the inclusion criteria. Baseline data were comparable. On quality assessment, 3 studies scored 2 and one study scored 3 out of 5 points. Per protocol analysis showed that children receiving intermittent regimen were less likely to be cured than those receiving daily therapy (OR 0.27; 95% CI: 0.14, 0.51). The results of intention to treat analysis suggest similar trend towards lower cure rates with twice weekly regimen (OR 0.66; 95% CI: 0.23-1.84). Conclusion: Twice weekly intermittent short course therapy is less likely to cure tuberculosis in children as compared to daily therapy. There is a need for better quality randomized controlled trials for assessing efficacy of alternate schedule for intermittent therapy for childhood tuberculosis. [ABSTRACT FROM AUTHOR]

To present oncological results with intermittent androgen deprivation (IAD) in a single center. Between 1992 and 2008, 566 patients with prostate cancer (PC) were selected for a non-randomized study of IAD. Two hundred and eighteen patients had biochemical recurrence (BCR) after local treatment for PC and 348 patients had micro- or macro-metastatic disease. On-treatment period (ONTP) consisted of three-monthly injections of gonadatropin-releasing hormone (GnRH) agonist combined with daily oral androgen receptor antagonist. Off-treatment period (OFTP) was indicated when prostate-specific antigen (PSA) was <4 ng/ml. Criteria for resumption of hormonal therapy were PSA >20 ng/ml or clinical symptoms. Cancer specific survival curves were computed according to the Kaplan–Meier method. Median follow-up was 81 months (12–230). Median age was 74.7 years (52–92). Median Gleason score at diagnosis was 7 (3–9). Median initial PSA was 17 ng/ml (0.4–433). Cycle duration decreased progressively from 23 months for the 1st cycle to 10 months at 12th cycle. The number of patients who became hormone resistant was 182 (32%). Median cancer specific survival probability for the series is 12 (10.8–infinity) years. No previous treatment group showed a higher cancer specific survival probability (log rank test, CI 95%, P = 0.003) versus BCR group. Multivariate analysis of cancer specific survival demonstrates age, initial Gleason score and initial PSA level as significant factors affecting mortality ( P < 0.05). Intermittent androgen deprivation is an acceptable treatment in different stages of PC. Duration of cycle decreased progressively during therapy. Age, Gleason score and PSA are factors predicting mortality. [ABSTRACT FROM AUTHOR]

Abstract: Background: Few randomised studies have compared intermittent hormonal therapy (IHT) with continuous therapy for the treatment of advanced prostate cancer (PCa). Objective: To determine whether intermittent therapy is associated with a shorter time to progression. Design, setting, and participants: 766 patients with locally advanced or metastatic PCa received a 3-mo induction treatment. The 626 patients whose prostate-specific antigen (PSA) level decreased to <4ng/ml or to 80% below the initial value were randomised. Intervention: Patients received cyproterone acetate (CPA) 200mg for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH) analogue plus 200mg of CPA daily during induction. Patients randomised to the intermittent arm ceased treatment, while those randomised to the continuous arm received 200mg of CPA daily plus an LHRH analogue. Measurements: Primary outcome measurement was time to subjective or objective progression. Secondary outcomes were survival and quality of life (QoL). Time off therapy in the intermittent arm was also recorded. Results and limitations: 127 patients from the intermittent arm and 107 patients from the continuous arm progressed, with a hazard ratio (HR) of 0.81 (95% confidence interval [CI]: 0.63–1.05, p =0.11). There was no difference in survival, with an HR of 0.99 (95% CI: 0.80–1.23) and 170 deaths in the intermittent arm and 169 deaths in the continuous arm. The greater number of cancer deaths in the intermittent treatment arm (106 vs 84) was balanced by a greater number of cardiovascular deaths in the continuous arm (52 vs 41). Side-effects were more pronounced in the continuous arm. Men treated with intermittent therapy reported better sexual function. Median time off therapy for the intermittent patients was 52 wk (95% CI: 39.4–65.7). Conclusions: IHT should be considered for use in routine practice because it is associated with no reduction in survival, no clinically meaningful impairment in QoL, better sexual activity, and considerable economic benefit to the individual and the community. [Copyright &y& Elsevier]

The aim of palliative chemotherapy is to increase survival whilst maintaining maximum quality of life for the individual concerned. It is evident that the survival advantage offered by palliative chemotherapy for metastatic colorectal cancer has increased incrementally with the addition of each newly licensed therapeutic agent. More recently, advances in the field have led to the introduction of targeted monoclonal antibodies, whose benefits are documented in clinical trials and are acknowledged in their approval and licensing Whilst we are continuing to explore the optimum use of the more traditional chemotherapy agents, with respect to both quantity and quality of life, these novel agents are battling to find their optimum place in the armamentarium. It is evident that a continuing add-one-in policy is likely to be detrimental to both patient and budget. Defining the positioning and duration of these combination therapies has become the subject of much debate and numerous current clinical trials. The Medical Research Council COIN trial is one of these trials, with a remit to explore further the optimum use of both standard agents and novel agents in the first-line setting for metastatic colorectal cancer. [ABSTRACT FROM AUTHOR]

This article is written to provide an overview of the past and present use of two common types of time-limited therapy. Brief (also known as ‘short term’) and intermittent therapies are explored. Using these time-limited frameworks, a structure and procedural review for conducting evidence-based intervention strategy is presented. Several popular methodologies that use a time-limited focus are reviewed. Recommendations, practice guidelines, and strategy for use of these methods are presented. [ABSTRACT FROM PUBLISHER]

Abstract: This study was one of the first to examine the in vivo levofloxacin adsorption to stent surfaces. The results demonstrated the ability of this antibiotic to adsorb to the conditioning film and to the surface of the inserted device, and showed that 1–2 weeks after the discontinuation of antibiotic administration some amount of the antibiotic still could be detected on them. The second aim of the investigation was to determine whether continuous or intermittent levofloxacin treatment is advantageous for the patients who have acute complicated urinary tract infection (UTI) caused by urinary obstruction. The results did not show any clinical or microbiological advantages of the continuous therapy. [Copyright &y& Elsevier]

Hematologic toxicity is reported as one of the most important problems connected with imatinib mesylate (IM) treatment in patients with chronic myelogenous leukemia (CML). Withholding the drug or application of growth factors is recommended in this situation. This study introduced a novel approach using intermittent dosage of IM in order to avoid prolonged interruptions in therapy, to allow spontaneous recovery in blood count and, simultaneously, to achieve intermittently therapeutic plasma drug levels. A retrospective analysis of intermittent therapy (iT) in 12 patients with CML is presented. All patients had intermediate-to-high prognostic scores. Two patients had history of autologous stem cell transplantation. Initial standard therapy with IM was indicated for resistance to interferon (eight subjects) and for accelerated phase in four cases (one of them cytogenetic) and lasted for 1 – 6 months. iT with 300 – 600 mg of IM 1 – 5 times a week was started after significant hematologic toxicity occurred. In three patients treated 3 – 5 times a week, hematologic recovery allowed reintroduction of full dose after 3 – 7 (mean 4.6) months. In three patients, one-to-three doses per week were sufficient to maintain the cytogenetic response for a mean of 30.6 months (range 29 – 33). Six patients tolerated more frequent dosage of 4 – 5 times a week for a mean of 17.8 months (range 3 – 28). Five patients improved their cytogenetic response during iT, while hematologic progression occurred in one patient. Development of a cytogenetic abnormality in a Ph-negative clone was observed in one patient. Overall, two complete and five major cytogenetic responses were achieved. The sensitivity of Bcr/Abl kinase to inhibition by IM was proved in seven patients tested by Crkl phosphorylation assay. Measurement of plasma IM concentrations in three subjects showed concentrations fully compatible with the dosage applied suggesting normal intestinal absorption. iT with IM is a feasible and safe strategy for short-time ‘bridging’ management of patients with significant hematologic toxicity after standard daily dosing. Long-term iT with IM does not seem to compromise the cytogenetic response in patients with sensitivity of Bcr/Abl kinase to IM and should be considered as a plausible treatment option in patients with persistent signs of myelotoxicity. [ABSTRACT FROM AUTHOR]

Rationale: Treatment of tuberculosis with an efficacious once-weekly regimen would be a significant achievement in improving patient adherence. Currently, the only recommended once-weekly continuation phase regimen of isoniazid plus rifapentine (10 mg/kg) is inferior to standard twice-weekly therapy with isoniazid plus rifampin and is, therefore, restricted to non-high-risk patients. The substitution of moxifloxacin, a new 8-methoxyfluoroquinolone, for isoniazid and an increase in the dose of rifapentine could augment the activity of once-weekly regimens.Methods: To test this hypothesis we evaluated the sterilizing activity of improved once-weekly rifapentine-based continuation phase regimens in a murine model that mimics the treatment of high-risk patients with tuberculosis. The bactericidal activity of standard daily therapy and standard intermittent therapy ("Denver" regimen) was also assessed to evaluate the effect of intermittent drug administration during the initial phase of therapy.Results: After 2 mo of treatment, lung colony-forming unit counts were 1 log(10) lower in mice treated with standard daily therapy than with the Denver regimen. During the continuation phase, the sterilizing activity of once-weekly moxifloxacin plus rifapentine (15 mg/kg) was significantly greater than that of the predominantly twice-weekly Denver regimen of isoniazid plus rifampin. No significant difference in sterilizing activity was detected between once-weekly isoniazid plus rifapentine (15 mg/kg) and the Denver regimen.Conclusions: These results suggest that the efficacy of the once-weekly isoniazid plus rifapentine continuation phase regimen can be increased by substituting moxifloxacin for isoniazid and by increasing the dose of rifapentine to a clinically acceptable level of 15 mg/kg. [ABSTRACT FROM AUTHOR]