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Sample records for long-term chloroquine therapy

  1. Long-term oxygen therapy.

    PubMed

    Christopher, Kent L; Porte, Phillip

    2011-02-01

    This article provides an overview of the status of long-term oxygen therapy (LTOT). In the United States, payment cutbacks are occurring as a result of congressionally mandated competitive bidding and capped rental programs. These Medicare programs are discussed. These legislative and regulatory changes may result in reduced patient access to appropriate oxygen-delivery systems that meet medical needs, including optimal ambulation. Prescribing LTOT is addressed in this article, as is the need for adequate patient education. The importance of appropriate monitoring and reassessment is presented. The use of an LTOT collaborative care model is discussed. Although the new intermittent flow oxygen-delivery systems have potential benefits, there is consensus that each patient should be tested on the specific device because of variability in delivery and patient response. Feasible locations for patient education and monitoring are identified.

  2. Extrapyramidal syndrome following chloroquine therapy.

    PubMed

    Singhi, S; Singhi, P; Singh, M

    1979-02-01

    Chloroquine is considered essentially nontoxic when used for the chemosuppression of malaria, but gastrointestinal upsets, headache, blurring of vision, pruritus, and uritcaria may occur during chloroquine therapy. Recently, Bhargava et al. and Eronini and Eronini have reported the extrapyramidal syndrome (EPS) following chloroquine therapy in adults. The clinical manifestations included upward rolling of the eyeballs, retraction of neck and back, trismus with marked difficulty in speech, and coarse tremors. Observations of 4 instances of EPS in children following chloroquine therapy for malaria are reported. A 2-1/2 year old girl was admitted to the All India Institute of Medical Sciences Hospital with a 4 day history of intermittent high grade pyrexia with chills and rigors. Following treatment with oral chloroquine in the recommended therapeutic dosage, the fever responded, but the child became drowsy and developed paroxysms of involuntary movements of the tongue, torticollis, torsion dystonia of the limbs, and parosysms of tonic muscular spasms. She completely recovered spontaneously within 48 hours. The 2nd case was that of a 12-year old female brought to the hospital with a 15-day history of intermittent high grade fever with chills and rigors. The patient was started on chloroquine sulfate in the recommended therapeutic dose. After an interval of 4 days she developed coarse tremors of the hands, upward rolling of the eyeballs, episodic deviation of the angle of the mouth towards the left, and trismus. These symptoms disappeared spontaneously within 8 hours. A 6-year old girl, the 3rd case, developed episodes of opisthotonous, upward rolling of the eyeballs, protrusions of the tongue, intermittent writhing movements of the upper limbs, and drowsiness following the ingestion of 6 tablets of chloroquine sulfate for suspected diagnosis of malaria. She spontaneously recovered from EPS over a period of about 48 hours. The 4th case, a 7-year old boy, gave a history

  3. Long-term opioid therapy reconsidered.

    PubMed

    Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A; Chou, Roger

    2011-09-06

    In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment.

  4. Long term therapy of generalized anxiety disorder.

    PubMed

    Rouillon, Frédéric

    2004-04-01

    Generalized anxiety disorder (GAD) is a common (lifetime prevalence: 5.1%), recurrent condition, which often heralds other psychiatric disorders, notably depression. As by definition it is a disorder progressing over months, treatment should be designed on a long term basis. And yet, few studies have been conducted beyond the classical 6-8 weeks characterizing the acute treatment phase. This is especially true of anxiolytics, but also of antidepressants, with the exception of paroxetine and venlafaxine, which are the only drugs approved in this indication in Western countries. The efficacy of psychotherapy, notably relaxation and cognitive-behavioral therapy, is established in the treatment of GAD, but its preferred indications and possible combination with antidepressants are still to be specified. Long term, not to say very long term studies of GAD, as well as depression, will still be required in the future to improve its management and specify therapeutic modalities (combination treatment, optimal duration, continuous or intermittent therapy, choice of psychotherapeutic techniques or agents, em leader ). Early and adequately prolonged treatment should not only result in more numerous remission periods, but also in decreased frequency of co-morbidities whether depressive, addictive, or of another nature, and should also reduce the social impact of GAD.

  5. Chloroquine

    MedlinePlus

    Chloroquine phosphate is in a class of drugs called antimalarials and amebicides. It is used to prevent and treat ... Chloroquine phosphate comes as a tablet to take by mouth. For prevention of malaria in adults, one dose is ...

  6. Viability of long-term gene therapy in the cochlea.

    PubMed

    Atkinson, Patrick J; Wise, Andrew K; Flynn, Brianna O; Nayagam, Bryony A; Richardson, Rachael T

    2014-04-22

    Gene therapy has been investigated as a way to introduce a variety of genes to treat neurological disorders. An important clinical consideration is its long-term effectiveness. This research aims to study the long-term expression and effectiveness of gene therapy in promoting spiral ganglion neuron survival after deafness. Adenoviral vectors modified to express brain derived neurotrophic factor or neurotrophin-3 were unilaterally injected into the guinea pig cochlea one week post ototoxic deafening. After six months, persistence of gene expression and significantly greater neuronal survival in neurotrophin-treated cochleae compared to the contralateral cochleae were observed. The long-term gene expression observed indicates that gene therapy is potentially viable; however the degeneration of the transduced cells as a result of the original ototoxic insult may limit clinical effectiveness. With further research aimed at transducing stable cochlear cells, gene therapy may be an efficacious way to introduce neurotrophins to promote neuronal survival after hearing loss.

  7. Long Term Treatment Concepts and Proactive Therapy for Atopic Eczema

    PubMed Central

    Ehmann, Laura Maximiliane

    2012-01-01

    Atopic eczema, also known as atopic dermatitis, is a frequent, highly pruritic, chronic skin disease, which is typically running in flares. The traditional treatment mainly consists of the reactive application of topical anti-inflammatory agents such as topical corticosteroids and topical calcineurin inhibitors. The short term benefit of this approach is well known, but long term remission between flares is difficult to achieve. Therefore, innovative long-term treatment strategies targeting flare prevention and skin barrier stabilization are needed. We and others have shown that normal looking, non-lesional skin of atopic dermatitis patients is immunobiologially not normal but characterized by an invisible inflammation and barrier defect. This has led to the novel concept of proactive therapy, which is defined as long-term, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin, together with an ongoing emollient treatment of unaffected skin. This review article describes the most important long-term treatment options for atopic dermatitis, which includes emollient therapy, the novel concept of proactive treatment, the different ultraviolet light modalities and a selection of systemic immunosuppressive drugs and biologics. Current trial data, licensed indications, off-label use and relevant side effects of the different treatment modalities are summarized. PMID:22879707

  8. [Renal side effects of long-term lithium therapy].

    PubMed

    Ibbeken, C; Becker, J U; Baumgärtel, M W

    2012-01-01

    Lithium is widely used in the treatment of bipolar disorders. Long-term administration of lithium often leads to side effects concerning the subjects: nephrology, endocrinology and surgery. This review emphasizes nephrotoxicity.Lithium treatment may disturb responsiveness to antidiuretic hormone (ADH), causing a nephrogenic diabetes insipidus. Furthermore long-term lithium therapy may trigger hyperparathyreoidism with hypercalcemia and chronic interstitial nephritis with development of microcysts. Long-term patients have an increased risk to develop impaired renal function. Lithium-induced endstage renal disease is rare. Termination of lithium treatment may decrease the risk of progression.To ensure security of lithium treatment regular controls of urine osmolarity, lithium-, creatinine- , thyroid stimulating hormone- and calcium-levels are essential. Patients with decreased renal function should be referred to a specialist early.

  9. Long-term management of gout: nonpharmacologic and pharmacologic therapies.

    PubMed

    Chaichian, Yashaar; Chohan, Saima; Becker, Michael A

    2014-05-01

    Gout is a common disorder with clinical signs and symptoms resulting from inflammatory responses to monosodium urate crystals deposited in tissues from extracellular fluids saturated for urate. Long-term management of gout focuses on nonpharmacologic and pharmacologic means to achieve and maintain serum urate levels in a subsaturating range. Despite a firm understanding of gout pathophysiology, means to achieve certain diagnosis, and a variety of effective therapies, treatment outcomes remain suboptimal. In this review, available nonpharmacologic and pharmacologic therapies for chronic gout are discussed and a framework is provided for successful achievement and maintenance of goal-range serum urate levels. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Supramolecular hydrogels for long-term bioengineered stem cell therapy.

    PubMed

    Yeom, Junseok; Kim, Su Jin; Jung, Hyuntae; Namkoong, Hong; Yang, Jeonga; Hwang, Byung Woo; Oh, Kyunghoon; Kim, Kimoon; Sung, Young Chul; Hahn, Sei Kwang

    2015-01-28

    Synthetic hydrogels have been extensively investigated as artificial extracellular matrices (ECMs) for tissue engineering in vitro and in vivo. Crucial challenges for such hydrogels are sustaining long-term cytocompatible encapsulation and providing appropriate cues at the right place and time for spatio-temporal control of the cells. Here, in situ supramolecularly assembled and modularly modified hydrogels for long-term engineered mesenchymal stem cell (eMSC) therapy are reported using cucurbit[6]uril-conjugated hyaluronic acid (CB[6]-HA), diaminohexane conjugated HA (DAH-HA), and drug-conjugated CB[6] (drug-CB[6]). The eMSCs producing enhanced green fluorescence protein (EGFP) remain alive and emit the fluorescence within CB[6]/DAH-HA hydrogels in mice for more than 60 d. Furthermore, the long-term expression of mutant interleukin-12 (IL-12M) by eMSCs within the supramolecular hydrogels results in effective inhibition of tumor growth with a significantly enhanced survival rate. Taken together, these findings confirm the feasibility of supramolecular HA hydrogels as 3D artificial ECMs for cell therapies and tissue engineering applications.

  11. Long-term results after acute therapy of obstructive pyelonephritis.

    PubMed

    Vahlensieck, Winfried; Friess, Doris; Fabry, Werner; Waidelich, Raphaela; Bschleipfer, Thomas

    2015-01-01

    To evaluate therapeutic results till 5 years after therapy of obstructive pyelonephritis (OPN) emphasizing regular follow-up. During 5 years, 57 patients with OPN were treated. The patients' charts were reviewed retrospectively for clinical data. These were completed by a questionnaire. In the group of 57 patients (average age 56 years), about two third were women. Urolithiasis (65%) and tumors (21%) were the main causes of obstruction; fever (91%) and loin pain (86%) the main symptoms. Three fourth of the patients showed renal insufficiency and nearly 50% anemia. E. coli and Proteus spp. were the dominating organisms. Sonography detected obstruction in 93% cases. In one third of cases, CT scan was added; 81% percutaneous nephrostomy and 19% ureteral stenting were the initial methods of urinary drainage. During therapy, 23% nephrectomies (19% complete, 4% partial) were performed. Long-term follow-up showed 11% recurrent OPN and 33% recurrent UTI. After diagnosis of OPN, primary nephrostomy or ureteral stenting and antibiotic therapy are the first measures. If recurrent urinary tract infections or OPN occur, long-term follow-up and low-dose antibiotic prophylaxis may be discussed. © 2015 S. Karger AG, Basel.

  12. A case of paracoccidioidomycosis: experience with long-term therapy.

    PubMed

    Borgia, G; Reynaud, L; Cerini, R; Ciampi, R; Schioppa, O; Dello Russo, M; Gentile, I; Piazza, M

    2000-01-01

    We describe long-term therapy for paracoccidioidomycosis occurring in a 61-year-old house-painter from Venezuela. The diagnostic examinations made in South America had shown pulmonary granulomatous lesions and an osteolytic pattern of the left knee that had been considered suspect of malignant disease with an indication for limb amputation. With the aid of fine needle aspiration biopsy (FNAB) and culture examination we diagnosed an osteomyelitis by Paracoccidioides brasiliensis and initiated therapy with itraconazole, 400 mg per day, reduced to 200 mg per day after 2 months. At the end of 2 years of drug therapy, we observed complete regression of the pulmonary lesions and of the osteolytic area of the left knee. Moreover, we have periodically observed our patient to verify his clinical development and he is still in good health. We suggest that this pathology be considered in differential diagnosis of leprosy, tuberculosis, leishmaniasis, and systemic mycoses, even in non-endemic areas.

  13. [Osteonecrosis of the jaws by long term therapy with bisphosphonates].

    PubMed

    Piesold, Jörn-Uwe; Al-Nawas, Bilal; Grötz, Knut A

    2006-09-01

    For several decades bisphosphonates have been used to reduce skeletal related events in patients with both osteoporosis or bone metastases. Under long term application, besides the known therapy side effects, a new clinical picture has been described within the last few years. This is osteonecrosis of the jaws, which is characterized by its difficulty in treatment. Besides exposed jaw bone, the start of the disease usually lacks any symptoms. The typical clinical symptoms then are foetor ex ore, swelling, exsudation, loosening of teeth, pain or paresthesia. Later oro-antral/nasal or oro-cutaneous fistula can develop. The X-ray shows persisting tooth sockets after extractions and later cloudy radio-lucency, sequestra or fractures. The patient exposed to bisphosphonate can be grouped according to the risk for osteonecrosis: high risk patients with intravenous bisphosphonate therapy and additional chemo-, radiation or corticoid therapy--predominantly patients with a malignant underlying disease and bone metastases low risk patients with an oral bisphosphonate therapy without additional chemo-, radiation or corticoid therapy--preferably patients with non-corticoid-induced osteoporosis. Before starting a bisphosphonate therapy possible causes of infection should be treated and risk of injuries to the mucosa should be reduced according to the individual risk profile. This is supplemented by information of the patient about the risk of necrosis and the possibilities for prevention. Regular dental recall under bisphophonate therapy is emphasised for early recognition of possible problems. Prophylaxis is recommended for the prevention of periodontal infection combined with a follow up of removable denture for possible ulcera. Generally, conservative treatment measures are preferred to surgical ones. Inevitable operations are carried out non-traumatically using broad spectrum antibiotic prophylaxis until the day of suture removal (not before day 10). Long term follow up

  14. Long-term Effectiveness of Intensive Therapy in Chronic Stroke.

    PubMed

    Wu, Xiaotian; Guarino, Peter; Lo, Albert C; Peduzzi, Peter; Wininger, Michael

    2016-07-01

    Background While recent clinical trials involving robot-assisted therapy have failed to show clinically significant improvement versus conventional therapy, it is possible that a broader strategy of intensive therapy-to include robot-assisted rehabilitation-may yield clinically meaningful outcomes. Objective To test the immediate and sustained effects of intensive therapy (robot-assisted therapy plus intensive conventional therapy) on outcomes in a chronic stroke population. Methods A multivariate mixed-effects model adjusted for important covariates was established to measure the effect of intensive therapy versus usual care. A total of 127 chronic stroke patients from 4 Veterans Affairs medical centers were randomized to either robot-assisted therapy (n = 49), intensive comparison therapy (n = 50), or usual care (n = 28), in the VA-ROBOTICS randomized clinical trial. Patients were at least 6 months poststroke, of moderate-to-severe upper limb impairment. The primary outcome measure was the Fugl-Meyer Assessment at 12 and 36 weeks. Results There was significant benefit of intensive therapy over usual care on the Fugl-Meyer Assessment at 12 weeks with a mean difference of 4.0 points (95% CI = 1.3-6.7); P = .005; however, by 36 weeks, the benefit was attenuated (mean difference 3.4; 95% CI = -0.02 to 6.9; P = .05). Subgroup analyses showed significant interactions between treatment and age, treatment and time since stroke. Conclusions Motor benefits from intensive therapy compared with usual care were observed at 12 and 36 weeks posttherapy; however, this difference was attenuated at 36 weeks. Subgroups analysis showed that younger age, and a shorter time since stroke were associated with greater immediate and long-term improvement of motor function. © The Author(s) 2015.

  15. [Compliance with long-term home oxygen therapy].

    PubMed

    Hayashi, A; Tatsumi, K; Kato, K; Sakuma, T; Okada, O; Kimura, H; Kuriyama, T

    1996-01-01

    Long-term home oxygen therapy has been shown to benefit patients with hypoxemic chronic obstructive pulmonary disease. However, to obtain the expected maximal benefit it is important for the oxygen to be used correctly and for a sufficient length of time. We examined compliance with home oxygen therapy in patients with chronic obstructive pulmonary disease, pulmonary fibrosis, late sequelae of pulmonary tuberculosis, and pulmonary hypertension who used oxygen concentrations. Compliance was defined as the ratio of the amount of oxygen used to the amount prescribed. The average daily length of time the concentrator actually ran was measured from the concentrator meters. These were read every 6 months by an engineer from the company that installed the concentrator. Factors thought to affect compliance were studied. These factors included age, the degree of dyspnea, arterial blood gases, and pulmonary function. Weak positive correlations were found between compliance and age and between compliance and PaCO2. A weak negative correlation was observed between compliance and PaO2. Compliance in patients with chronic obstructive pulmonary disease was higher than in patients with pulmonary fibrosis or pulmonary hypertension. Among those given prescriptions for 24-hr oxygen therapy, compliant patients had more severe dyspnea on excertion than did noncompliant patients. These data suggest that the compliant patients had more severe gas exchange problems.

  16. [Argentine Consensus of home long term oxygen therapy].

    PubMed

    Rhodius, E; Caneva, J; Sivori, M

    1998-01-01

    A national meeting of specialists in Respiratory Medicine took place with the aim of updating in a consensus the indicating criteria, source and ways of administering Long Term Oxygen Therapy (LTOT). This is the only therapeutic intervention which improves the survival of patients with severe chronic obstructive pulmonary disease and respiratory insufficiency. We regulate its indication in patients with COPD, other obstructive and restrictive diseases, primary and secondary pulmonary hypertension with: 1) PaO2 lower or equal to 55 mmHg breathing air at rest; 2) PaO2 between 56 and 60 mmHg with polyglobulia, cor pulmonale or primary and secondary pulmonary hypertension evaluated in clinical stability by taking two samples of arterial blood gases, with two weeks' difference between them and more than one month after a new acute condition. Patients should receive this therapy more than 15 hours per day (better 24 hours) including sleeping time. Norms of study and indication, were established to set up the requirements of O2 during sleep and exercise. With respect to the sources it was concluded that the O2 concentrator is indicated for patients with very little home movements, and the sources, of O2 liquid for those with active social life. Indications for conventional and non conventional O2 administration were established. Complications and an algorithm of therapeutic failure were determined. Principles which should be contained in a future national law of OCD were delineated.

  17. Long-term oxygen therapy: Are we prescribing appropriately?

    PubMed Central

    Güell Rous, Ma Rosa

    2008-01-01

    Long-term oxygen therapy (LTOT) is the treatment proven to improve survival in chronic obstructive pulmonary disease (COPD) patients with chronic respiratory failure. It also appears to reduce the number of hospitalizations, increase effort capacity, and improve health-related quality of life. Standard LTOT criteria are related to COPD patients who have PaO2 <60 mmHg, are in a clinical stable situation, and are receiving optimal pharmacological treatment. According to LTOT guidelines, oxygen should be prescribed for at least 18 hours per day although some authors consider 24 hours would be more beneficial. The benefits of LTOT depend on correction of hypoxemia. Arterial blood gases should be measured at rest. During exercise, an effort test should be done to assure adequate SaO2. During sleep, continuous monitoring of SaO2 and PaCO2 should be performed to confirm correction of SaO2 overnight. An arterial blood gas sample should be taken at awakening to assess PaCO2 in order to prevent hypoventilation from the oxygen therapy. Several issues that need to be addressed are the use of LTOT in COPD patients with moderate hypoxemia, the efficacy of LTOT in patients who desaturate during exercise or during sleep, the optimal dosage of oxygen supplementation, LTOT compliance, and the LTOT prescription in diseases other than COPD. PMID:18686732

  18. Socioeconomics of long-term glaucoma therapy in India

    PubMed Central

    Nayak, Bhagabat; Gupta, Shikha; Kumar, Guresh; Dada, Tanuj; Gupta, Viney; Sihota, Ramanjit

    2015-01-01

    Purpose: To determine the socioeconomic impact of long-term glaucoma therapy. Materials and Methods: One hundred and fifty consecutive glaucoma patients on medical therapy, following up at our glaucoma service for at least 6 months were recruited. A questionnaire regarding monthly income, cost of glaucoma medications prescribed, availability of medications, travel time, time spent in review clinics, compliance, education status, medical insurance and systemic or local side-effects was administered. Results: The patients seen at the tertiary government hospital had an average monthly income of Rs. 10,912/- (range: Rs. 500/- to Rs. 50,000/-) with approximately 56% of the patients having an income of less than Rs. 5000/month. The expenditure on anti-glaucoma medications ranged from 0.3% in high income group to 123% of their monthly gross income in low income group (P < 0.0001). The total expenditure including travel, stay, and loss of wages of patients and accompanying persons ranged from 1.6% in high income group to 137% of the monthly income in low income group (P < 0.0001). Mean time required for a glaucoma clinic visit was 15.66 h, (range: 6–96 h/month). About 2.7% experienced systemic side-effects and 21.3% had complaints of ocular adverse effects. About 90% of the patients were compliant. 92% were not covered by any insurance plan/government reimbursement for their treatment. Conclusions: Medical therapy for glaucoma is an economic burden to many patients and should be individualized, according to the socioeconomic status, availability of drugs and the required distance to travel to reach the specialist clinics. PMID:25686057

  19. Can Technology Improve Adherence to Long-Term Therapies?

    PubMed Central

    Reach, Gérard

    2009-01-01

    Background Therapeutic nonadherence is defined as the lack of equivalence between the behavior of the patients and their prescribed medical treatment. Consequences of nonadherence include not only health outcomes, but also cost saving. Thus, this issue gets paramount importance in contemporary medicine. Method The aim of this article is to discuss the relationships between technology and adherence by asking the following three questions. (1) How can technology be used to monitor patient adherence? (2) Considering the mechanisms of nonadherence in chronic diseases, is there room for technology in interventions aimed to improve patient adherence? (3) What about adherence to technology in diabetes care? Results and Conclusion Technology may help improve adherence to long-term therapies by (1) giving a concrete representation of adherence rewards, (2) overcoming immediate obstacles to adherence, such as the fear of hypoglycemia, and (3) providing an opportunity for patient–doctor conversations. This assumes, however, that both the patient and the doctor are convinced that technologies are useful. PMID:20144287

  20. Long-term beclomethasone dipropionate aerosol therapy in juvenile asthma.

    PubMed

    Francis, R S

    1976-06-01

    Following a short-term clinical trial reported elsewhere, beclomethasone dipropionate aerosol has been given to 15 children with asthma for between 2 1/2 and 3 years except for a short placebo period after the first year. Month-by-month records of wheezing, peak flow rate, and other treatments used are presented for the first 17 months, adrenocortical function tests are reported for the first 2 years, and growth is recorded for 2 1/2-3 years. The short-term clinical benefits of the treatment are confirmed in the longer term, adrenocortical function appears to be unchanged, and growth proceeds along expected lines. The main disadvantage seems to be worsening of eczema and allergic rhinitis in those children who have ceased using corticotrophin or oral steroids for the control of asthma. It is concluded that in the long term beclomethasone dipropionate aerosol provides safe and effective day-to-day control of asthma in children, although occasional recourse to systemic steroid therapy cannot be avoided. Oral candidasis has not been a clinical problem.

  1. Long-term beclomethasone dipropionate aerosol therapy in juvenile asthma.

    PubMed Central

    Francis, R S

    1976-01-01

    Following a short-term clinical trial reported elsewhere, beclomethasone dipropionate aerosol has been given to 15 children with asthma for between 2 1/2 and 3 years except for a short placebo period after the first year. Month-by-month records of wheezing, peak flow rate, and other treatments used are presented for the first 17 months, adrenocortical function tests are reported for the first 2 years, and growth is recorded for 2 1/2-3 years. The short-term clinical benefits of the treatment are confirmed in the longer term, adrenocortical function appears to be unchanged, and growth proceeds along expected lines. The main disadvantage seems to be worsening of eczema and allergic rhinitis in those children who have ceased using corticotrophin or oral steroids for the control of asthma. It is concluded that in the long term beclomethasone dipropionate aerosol provides safe and effective day-to-day control of asthma in children, although occasional recourse to systemic steroid therapy cannot be avoided. Oral candidasis has not been a clinical problem. Images PMID:781906

  2. Safety of electroconvulsive therapy in patients receiving long-term warfarin therapy.

    PubMed

    Mehta, Vinay; Mueller, Paul S; Gonzalez-Arriaza, Heydy L; Pankratz, V Shane; Rummans, Teresa A

    2004-11-01

    To investigate the safety of electroconvulsive therapy (ECT) in patients receiving long-term warfarin therapy. Retrospective data were reviewed for 35 consecutively hospitalized patients who received long-term warfarin therapy and ECT at the Mayo Clinic in Rochester, Minn, between January 1, 1994, and December 31, 2001. A total of 300 ECT treatments were administered to the 35 patients. Of 284 ECT treatments for which data were available, no ECT-related complications due to anticoagulation occurred despite increases in blood pressure and pulse rate. One patient experienced ventricular tachycardia, resulting in transfer to a cardiology service for temporary monitoring. No other serious ECT-related adverse effects were noted. The rate of intertreatment delirium was similar to that reported in other studies. Electroconvulsive therapy in patients receiving long-term warfarin therapy appears to be safe. Although no major adverse effects were identified in our case series, additional prospective evaluation is warranted.

  3. Long-term hormone therapy for perimenopausal and postmenopausal women.

    PubMed

    Marjoribanks, Jane; Farquhar, Cindy; Roberts, Helen; Lethaby, Anne; Lee, Jasmine

    2017-01-17

    BACKGROUND: Hormone therapy (HT) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess effects of long-term HT (at least 1 year's duration) on mortality, cardiovascular outcomes, cancer, gallbladder disease, fracture and cognition in perimenopausal and postmenopausal women during and after cessation of treatment. SEARCH METHODS: We searched the following databases to September 2016: Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO. We searched the registers of ongoing trials and reference lists provided in previous studies and systematic reviews. SELECTION CRITERIA: We included randomised double-blinded studies of HT versus placebo, taken for at least 1 year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via the oral, transdermal, subcutaneous or intranasal route. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the quality of the evidence by using GRADE methods. MAIN RESULTS: We included 22 studies involving 43,637 women. We derived nearly 70% of the data from two well-conducted studies (HERS 1998; WHI 1998). Most participants were postmenopausal American women with at least some degree of comorbidity, and mean participant age in most studies was over 60 years. None of the studies focused on perimenopausal women.In relatively healthy postmenopausal women (i.e. generally fit, without overt disease), combined continuous HT increased the risk of a coronary event (after 1 year's use

  4. Long term differential consequences of miglustat therapy on intestinal disaccharidases.

    PubMed

    Amiri, Mahdi; Naim, Hassan Y

    2014-11-01

    Miglustat is an oral medication for treatment of lysosomal storage diseases such as Gaucher disease type I and Niemann Pick disease type C. In many cases application of Miglustat is associated with symptoms similar to those observed in intestinal carbohydrate malabsorption. Previously, we have demonstrated that intestinal disaccharidases are inhibited immediately by Miglustat in the intestinal lumen. Nevertheless, the multiple functions of Miglustat hypothesize long term effects of Miglustat on intracellular mechanisms, including glycosylation, maturation and trafficking of the intestinal disaccharidases. Our data show that a major long term effect of Miglustat is its interference with N-glycosylation of the proteins in the ER leading to a delay in the trafficking of sucrase-isomaltase. Also association with lipid rafts and plausibly apical targeting of this protein is partly affected in the presence of Miglustat. More drastic is the effect of Miglustat on lactase-phlorizin hydrolase which is partially blocked intracellularly. The de novo synthesized SI and LPH in the presence of Miglustat show reduced functional efficiencies according to altered posttranslational processing of these proteins. However, at physiological concentrations of Miglustat (≤50 μM) a major part of the activity of these disaccharidases is found to be still preserved, which puts the charge of the observed carbohydrate maldigestion mostly on the direct inhibition of disaccharidases in the intestinal lumen by Miglustat as the immediate side effect.

  5. Long term azathioprine maintenance therapy in ANCA-associated vasculitis: combined results of long-term follow-up data.

    PubMed

    de Joode, Anoek A E; Sanders, Jan Stephan F; Puéchal, Xavier; Guillevin, Loic P; Hiemstra, Thomas F; Flossmann, Oliver; Rasmussen, Nils; Westman, Kerstin; Jayne, David R; Stegeman, Coen A

    2017-08-03

    We studied whether in ANCA-associated vasculitis patients, duration of AZA maintenance influenced relapse rate during long-term follow-up. Three hundred and eighty newly diagnosed ANCA-associated vasculitis patients from six European multicentre studies treated with AZA maintenance were included; 58% were male, median age at diagnosis 59.4 years (interquartile range: 48.3-68.2 years); granulomatosis with polyangiitis, n = 236; microscopic polyangiitis, n = 132; or renal limited vasculitis, n = 12. Patients were grouped according to the duration of AZA maintenance after remission induction: ⩽18 months, ⩽24 months, ⩽36 months, ⩽48 months or > 48 months. Primary outcome was relapse-free survival at 60 months. During follow-up, 84 first relapses occurred during AZA-maintenance therapy (1 relapse per 117 patient months) and 71 after withdrawal of AZA (1 relapse/113 months). During the first 12 months after withdrawal, 20 relapses occurred (1 relapse/119 months) and 29 relapses >12 months after withdrawal (1 relapse/186 months). Relapse-free survival at 60 months was 65.3% for patients receiving AZA maintenance >18 months after diagnosis vs 55% for those who discontinued maintenance ⩽18 months (P = 0.11). Relapse-free survival was associated with induction therapy (i.v. vs oral) and ANCA specificity (PR3-ANCA vs MPO-ANCA/negative). Post hoc analysis of combined trial data suggest that stopping AZA maintenance therapy does not lead to a significant increase in relapse rate and AZA maintenance for more than 18 months after diagnosis does not significantly influence relapse-free survival. ANCA specificity has more effect on relapse-free survival than duration of maintenance therapy and should be used to tailor therapy individually.

  6. Current and long-term technologies of laser therapy

    NASA Astrophysics Data System (ADS)

    Ulashcyk, Vladimir S.; Volotovskaya, Anna V.

    2007-06-01

    Laser therapy, using low-energy laser radiation, is being more and more applied. The most applied technology is transcutaneous radiation of tissues by laser radiation. Originally, a direct action on a pathological site was mostly used, but recently more attention is given to reflexogenic areas, acupuncture points, and endocrine organ projection sites. The development of light-conductive engineering made it possible to practically apply intraorgan laser therapy. This technology is widely spread in gynecology, otorhinolaryngology, urology, gastroenterology, etc. Close to it are different versions of intratissue laser therapy (intraosteal, periosteal, myofascial). A special kind of laser therapy is laser hemotherapy. Depending on the techniques and protocol of its application, there are extracorporeal, intravascular, and supravenous ways of action. According to our comparative investigations, supravenous hemotherapy by its therapeutic efficacy and major medicinal effects can be well compared with intravascular laser hemotherapy. With good prospects and efficiency is laser therapy as a combination of laser and other physical factors. Magnetolaser therapy has been scientifically substantiated and practically applied so far. Theoretically and experimentally substantiated is a combined application of laser radiation and physical factors such as ultrasound, direct current field, vacuum, cryotherapy, etc. Experimental research and few so far clinical observations are indicative of prospects of a complex application of laser radiation and drugs. To improve light absorption, laser radiation is combined with different dyes. Photodynamic therapy, originally used in oncology, is applied today in treating different diseases. We showed a possibility of using a number of drugs possessing simultaneously photosensitizing properties to this end. Laser radiation significantly influences pharmacokinetics and pharmacodynamics of drugs, which gives reason to practically implement laser

  7. [Current aspects of ambulatory long-term oxygen therapy].

    PubMed

    Russi, W

    1988-03-19

    Longterm O2-therapy increases life expectancy in hypoxemic patients suffering from chronic obstructive pulmonary disease and may improve their quality of life as well. The efficiency of this treatment modality depends upon the duration of oxygen administration within 24 hours. Measures which prolong mobility through a long-lasting oxygen source improve patient compliance. Transtracheal oxygen delivery is a genuine advance in longterm O2-therapy. Other oxygen-conserving methods are of interest, but experience is lacking to assess their efficiency in longterm practice.

  8. Atypical periprosthetic acetabular fracture in long-term alendronate therapy

    PubMed Central

    Marongiu, Giuseppe; Capone, Antonio

    2016-01-01

    Summary Bisphosphonates have been commonly used in the treatment of osteoporosis, demonstrating its efficacy in fracture risk reduction. However, even if are generally safe and well tolerated, concerns have emerged about atypical fractures related to its prolonged use. Although atypical femoral fracture are more common, case reports demonstrated that even other skeletal areas can be involved by unusual pattern of fracture. We report a atypical acetabular periprosthetic fracture in a 83-year-old female patient after prolonged alendronate treatment for osteoporosis and isolated acetabular revision surgery. The patient underwent to clinical, bioumoral and radiological evaluation and all the history cases were fully reported. We believe this periprosthetic fracture, according to the available data, may have similar underlying pathology to atypical femoral fractures. Awareness of symptoms, in addition to a regular radiographic survey may facilitate early diagnosis and possible prevention of spontaneous periprosthetic fractures, in patients receiving bisphosphonate therapy beyond 5 years. The treatment of this atypical periprosthetic fracture should include both surgical than pharmacological therapy to obtained bone healing. PMID:28228784

  9. Atypical periprosthetic acetabular fracture in long-term alendronate therapy.

    PubMed

    Marongiu, Giuseppe; Capone, Antonio

    2016-01-01

    Bisphosphonates have been commonly used in the treatment of osteoporosis, demonstrating its efficacy in fracture risk reduction. However, even if are generally safe and well tolerated, concerns have emerged about atypical fractures related to its prolonged use. Although atypical femoral fracture are more common, case reports demonstrated that even other skeletal areas can be involved by unusual pattern of fracture. We report a atypical acetabular periprosthetic fracture in a 83-year-old female patient after prolonged alendronate treatment for osteoporosis and isolated acetabular revision surgery. The patient underwent to clinical, bioumoral and radiological evaluation and all the history cases were fully reported. We believe this periprosthetic fracture, according to the available data, may have similar underlying pathology to atypical femoral fractures. Awareness of symptoms, in addition to a regular radiographic survey may facilitate early diagnosis and possible prevention of spontaneous periprosthetic fractures, in patients receiving bisphosphonate therapy beyond 5 years. The treatment of this atypical periprosthetic fracture should include both surgical than pharmacological therapy to obtained bone healing.

  10. Long-term patient adherence to antiretroviral therapy.

    PubMed

    Ostrop, N J; Hallett, K A; Gill, M J

    2000-06-01

    To measure patient adherence to antiretroviral therapy over a two-year period and to identify factors impacting adherence. In a regional HIV treatment center, 100 consecutive patients starting any new antiretroviral agent were enrolled in this study, which consisted of a one-year retrospective data review and a one-year prospective component. The tools used for evaluating adherence were the monthly prescription refill data and a patient questionnaire. Data analyzed included overall adherence, adherence to individual antiretrovirals, and change in adherence over time, as well as factors reported as influencing adherence. Greater than 80% adherence in taking prescribed doses was seen in 75% of patients during the retrospective phase of the study; adherence increased to 84% in the prospective phase. Throughout the prospective phase of the study, monthly median adherence rates were 98-100%. Suboptimal adherence secondary to pill fatigue or number of daily pills did not occur. Reported nonadherence to dietary restrictions varied among drugs. The primary cause given for poor adherence was difficulty remembering followed by inconvenient dosing schedule and difficulty scheduling administration times around meals. At least one adherence tool was used by 61% of patients. A diagnosis of AIDS was associated with lower adherence in our patient population (p = 0.039); substance abuse and psychiatric history had no influence. Adherence to antiretroviral treatment regimens did not diminish over the two years studied. Several patients with poor adherence were identified, emphasizing the importance of addressing this issue both prior to and throughout treatment. A personalized approach by healthcare providers can optimize patient adherence to antiretroviral therapy by providing careful drug selection in addition to routine follow-up and the provision of information, feedback, and reminder systems.

  11. The Long Term Effectiveness of Intensive Stuttering Therapy: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-01-01

    Purpose: The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. Methods: The…

  12. The Long Term Effectiveness of Intensive Stuttering Therapy: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-01-01

    Purpose: The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. Methods: The…

  13. [Long-term efficacy of multimodal pain therapy for chronic back pain].

    PubMed

    Zhuk, A; Schiltenwolf, M; Neubauer, E

    2017-08-22

    The day clinic for pain therapy at the Orthopedic Clinic of the University Heidelberg has been in existence since 2001. In the context of multimodal pain therapy patients with chronic and chronically recurring pain of the musculoskeletal system are treated. The present prospective long-term study investigated the effects of therapy using the following outcome parameters: pain intensity, disability, depression, functional capacity and vitality. For this purpose patients with low back pain (n = 59) were questioned in writing at four measurement times: start of therapy (t0), completion of therapy (t1), 6 months (t2) and 10 years (t3) following therapy. Of the examined patients 78% were in chronification stages I and II, according to the Mainz pain staging system (MPSS) of Gerbershagen. The main aim of the study was to examine the effects of multimodal pain therapy in the long term. In the short, medium and long term significant differences were found in the outcome parameters with low to high effect sizes (d = 0.36-1.85). There was a continuous improvement of the pain intensity in the long term, and 10 years after pain therapy the effect size for the currently asked pain intensity was d = 1.28. Multimodal pain therapy is an effective method for the treatment of chronic back pain. It not only leads to short and medium-term improvements but also proves to be efficient in the long term. This form of pain therapy seems to lead to long-term success, particularly for patients with low-grade chronification.

  14. Assessment of the appropriateness of naloxone administration to patients receiving long-term opioid therapy.

    PubMed

    Facey, Caroline; Brooks, David; Boland, Jason W

    2016-01-01

    The most dangerous adverse effect of opioids is respiratory depression. Naloxone is used to reverse this, although in patients receiving long-term opioid therapy it can cause acute opioid withdrawal and opioid-refractory pain. To determine if naloxone is appropriately administered to patients receiving long-term opioid therapy. This retrospective case series based on chart reviews systematically identified patients over one year in a district general hospital. All patients aged 18 years or older receiving long-term opioid therapy admitted to medicine, surgery or the high dependency unit who were administered naloxone during their admission were included. A total of 1206 patient drug administration records were reviewed. Sixteen patients receiving long-term opioid therapy were administered naloxone. Twelve of these did not have opioid-induced respiratory depression and four did not have respiratory rate and oxygen saturations documented in the medical notes. All naloxone doses administered were higher than those recommended by national guidelines for this patient group. No patient receiving long-term opioid therapy who was administered naloxone had evidence of respiratory depression. More thorough assessment and documentation are needed. Verbal and physical stimulation as well as oxygenation should be considered prior to naloxone administration; this should be followed by close observation, hydration, renal function tests and opioid dose review.

  15. Medical and Psychological Risks and Consequences of Long-Term Opioid Therapy in Women

    PubMed Central

    Darnall, Beth D.; Stacey, Brett R.; Chou, Roger

    2016-01-01

    Background Long-term opioid use has increased substantially over the past decade for U.S. women. Women are more likely than men to have a chronic pain condition, to be treated with opioids, and may receive higher doses. Prescribing trends persist despite limited evidence to support the long-term benefit of this pain treatment approach. Purpose To review the medical and psychological risks and consequences of long-term opioid therapy in women. Method Scientific literature containing relevant keywords and content were reviewed. Results and Conclusions Long-term opioid use exposes women to unique risks, including endocrinopathy, reduced fertility, neonatal risks, as well as greater risk for polypharmacy, cardiac risks, poisoning and unintentional overdose, among other risks. Risks for women appear to vary by age and psychosocial factors may be bidirectionally related to opioid use. Gaps in understanding and priorities for future research are highlighted. PMID:22905834

  16. Generalised stunting of roots in an epileptic child: is long-term phenytoin therapy the cause?

    PubMed Central

    Jindal, Garima; Pandey, Ramesh K; Kumar, Dipanshu

    2012-01-01

    Long-term phenytoin therapy is known to cause disturbance in calcium and bone homeostasis. Dental tissues being calcified tissues can also be affected by this derangement of mineral metabolism, especially during developmental phases. This report describes a case of an epileptic child who presented with short roots, enlarged pulp chambers, blunt apices and delayed eruption of permanent dentition, which might be attributed to long-term phenytoin therapy. The purpose of this case report is to increase awareness among the clinicians about its possible dental implications and emphasise upon the need of regular dental check-ups in epileptic children. PMID:22761220

  17. Generalised stunting of roots in an epileptic child: is long-term phenytoin therapy the cause?

    PubMed

    Jindal, Garima; Pandey, Ramesh K; Kumar, Dipanshu

    2012-07-03

    Long-term phenytoin therapy is known to cause disturbance in calcium and bone homeostasis. Dental tissues being calcified tissues can also be affected by this derangement of mineral metabolism, especially during developmental phases. This report describes a case of an epileptic child who presented with short roots, enlarged pulp chambers, blunt apices and delayed eruption of permanent dentition, which might be attributed to long-term phenytoin therapy. The purpose of this case report is to increase awareness among the clinicians about its possible dental implications and emphasise upon the need of regular dental check-ups in epileptic children.

  18. Oxygen therapy for patients with COPD: current evidence and the long-term oxygen treatment trial.

    PubMed

    Stoller, James K; Panos, Ralph J; Krachman, Samuel; Doherty, Dennis E; Make, Barry

    2010-07-01

    Long-term use of supplemental oxygen improves survival in patients with COPD and severe resting hypoxemia. However, the role of oxygen in symptomatic patients with COPD and more moderate hypoxemia at rest and desaturation with activity is unclear. The few long-term reports of supplemental oxygen in this group have been of small size and insufficient to demonstrate a survival benefit. Short-term trials have suggested beneficial effects other than survival in patients with COPD and moderate hypoxemia at rest. In addition, supplemental oxygen appeared to improve exercise performance in small short-term investigations of patients with COPD and moderate hypoxemia at rest and desaturation with exercise, but long-term trials evaluating patient-reported outcomes are lacking. This article reviews the evidence for long-term use of supplemental oxygen therapy and provides a rationale for the National Heart, Lung, and Blood Institute Long-term Oxygen Treatment Trial. The trial plans to enroll subjects with COPD with moderate hypoxemia at rest or desaturation with exercise and compare tailored oxygen therapy to no oxygen therapy.

  19. Long-term Metformin Therapy and Monitoring for Vitamin B12 Deficiency Among Older Veterans.

    PubMed

    Kancherla, Vijaya; Elliott, John L; Patel, Birju B; Holland, N Wilson; Johnson, Theodore M; Khakharia, Anjali; Phillips, Lawrence S; Oakley, Godfrey P; Vaughan, Camille P

    2017-05-01

    To examine the association between long-term metformin therapy and serum vitamin B12 monitoring. Retrospective cohort study. A single Veterans Affairs Medical Center (VAMC), 2002-2012. Veterans 50 years or older with either type 2 diabetes and long-term metformin therapy (n = 3,687) or without diabetes and no prescription for metformin (n = 13,258). We determined diabetes status from outpatient visits, and defined long-term metformin therapy as a prescription ≥500 mg/d for at least six consecutive months. We estimated the proportion of participants who received a serum B12 test and used multivariable logistic regression, stratified by age, to evaluate the association between metformin use and serum B12 testing. Only 37% of older adults with diabetes receiving metformin were tested for vitamin B12 status after long-term metformin prescription. The mean B12 concentration was significantly lower in the metformin-exposed group (439.2 pg/dL) compared to those without diabetes (522.4 pg/dL) (P = .0015). About 7% of persons with diabetes receiving metformin were vitamin B12 deficient (<170 pg/dL) compared to 3% of persons without diabetes or metformin use (P = .0001). Depending on their age, metformin users were two to three times more likely not to receive vitamin B12 testing compared to those without metformin exposure, after adjusting for sex, race and ethnicity, body mass index, and number of years treated at the VAMC. Long-term metformin therapy is significantly associated with lower serum vitamin B12 concentration, yet those at risk are often not monitored for B12 deficiency. Because metformin is first line therapy for type 2 diabetes, clinical decision support should be considered to promote serum B12 monitoring among long-term metformin users for timely identification of the potential need for B12 replacement. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  20. Making music, making friends: Long-term music therapy with young adults with severe learning disabilities.

    PubMed

    Pavlicevic, Mercédès; O'Neil, Nicky; Powell, Harriet; Jones, Oonagh; Sampathianaki, Ergina

    2014-03-01

    This collaborative practitioner research study emerged from music therapists' concerns about the value of improvisational, music-centred music therapy for young adults with severe learning disabilities (SLDs), given the long-term nature of such work. Concerns included the relevance, in this context, of formulating, and reporting on, therapeutic aims, development, change; and working in 'goal-oriented' way. Focus groups with the young adults' families and a range of professionals suggest that, rather than leading to developmental change, long-term shared therapeutic musicking provides young adults with ongoing opportunities for experiencing confidence and self-esteem, with feelings of shared acceptance and success, and also provides young adults and their families with opportunities for developing and sustaining friendships. In addition, families experienced meeting other parents and carers in the communal reception area as supportive and countering their isolation. Focus groups assigned intrapersonal, relational and social values to long-term music therapy for young adults with SLDs.

  1. Recurrence rate after discontinuation of long-term mebendazole therapy in alveolar echinococcosis (preliminary results).

    PubMed

    Ammann, R W; Hirsbrunner, R; Cotting, J; Steiger, U; Jacquier, P; Eckert, J

    1990-11-01

    The recurrence rate was investigated in 19 patients with non-resectable alveolar echinococcosis after discontinuation of a long-term therapy with mebendazole (average treatment 4.3 years). A control group consisted of 14 patients who underwent radical surgery and finished a course of prophylactic postoperative mebendazole treatment of 2 years. In the controls, no recurrence was observed after a post-therapy period averaging 3.5 years. In contrast, recurrence occurred in 7/19 patients (37%) with non-resectable alveolar echinococcosis an average of 1.6 years after discontinuation of the long-term mebendazole therapy. The absence of clinically detectable recurrence in the remaining 12 patients seems to be due either to spontaneous inactivation of alveolar echinococcosis preceding chemotherapy or too short post-therapy surveillance. The patients with recurrence responded favorably to reintroduction of chemotherapy. The data indicate that mebendazole therapy is parasitostatic rather than parasiticidal.

  2. Effect of Short- and Long-Term Play Therapy Services on Teacher-Child Relationship Stress

    ERIC Educational Resources Information Center

    Ray, Dee C.; Henson, Robin K.; Schottelkorb, April A.; Brown, April Garofano; Muro, Joel

    2008-01-01

    The purpose of the present study was to explore the effect of both short- and long term Child-Centered Play Therapy on teacher-student relationship stress. Teachers identified 58 students exhibiting emotional and behavioral difficulties who were randomly assigned to one of two treatment groups. Students in the short-term intensive play therapy…

  3. Comparison of Long-Term Outcomes in Adolescents with Anorexia Nervosa Treated with Family Therapy

    ERIC Educational Resources Information Center

    Lock, James; Couturier, Jennifer; Agras, W. Stewart

    2006-01-01

    Objective: To describe the relative effectiveness of a short versus long course of family-based therapy (FBT) for adolescent anorexia nervosa at long-term follow-up. Method: This study used clinical and structured interviews to assess psychological and psychosocial outcomes of adolescents (ages 12-18 years at baseline) who were previously treated…

  4. Making Music, Making Friends: Long-Term Music Therapy with Young Adults with Severe Learning Disabilities

    ERIC Educational Resources Information Center

    Pavlicevic, Mercédès; O'Neil, Nicky; Powell, Harriet; Jones, Oonagh; Sampathianaki, Ergina

    2014-01-01

    This collaborative practitioner research study emerged from music therapists' concerns about the value of improvisational, music-centred music therapy for young adults with severe learning disabilities (SLDs), given the long-term nature of such work. Concerns included the relevance, in this context, of formulating, and reporting on, therapeutic…

  5. Ethnic Similarity, Therapist Adherence, and Long-Term Multisystemic Therapy Outcomes

    ERIC Educational Resources Information Center

    Chapman, Jason E.; Schoenwald, Sonja K.

    2011-01-01

    The current study investigated relations among ethnic similarity in caregiver-therapist pairs of youth participating in Multisystemic Therapy, therapist adherence, and youth long-term behavioral and criminal outcomes. Participants were 1,979 youth and families treated by 429 therapists across provider organizations in 45 sites. Relations were…

  6. The Effect of Long-Term Outcome Studies on the Therapy of Schizophrenia: A Critique.

    ERIC Educational Resources Information Center

    Stein, Leonard I.

    1989-01-01

    Comments on Haley's paper "The Effect of Long-Term Outcome Studies on the Therapy of Schizophrenia." Criticizes Haley for making gratuitous, demeaning remarks about psychiatry; concluding that schizophrenia is a psychological and social problem; recommending ineffective treatments for the psychotic phase; and recommending psychotherapy without…

  7. The Effect of Long-Term Outcome Studies on the Therapy of Schizophrenia: A Critique.

    ERIC Educational Resources Information Center

    Stein, Leonard I.

    1989-01-01

    Comments on Haley's paper "The Effect of Long-Term Outcome Studies on the Therapy of Schizophrenia." Criticizes Haley for making gratuitous, demeaning remarks about psychiatry; concluding that schizophrenia is a psychological and social problem; recommending ineffective treatments for the psychotic phase; and recommending psychotherapy without…

  8. The Effect of Long-Term Outcome Studies on the Therapy of Schizophrenia.

    ERIC Educational Resources Information Center

    Haley, Jay

    1989-01-01

    Claims since schizophrenia is reversible, professions involved in social control and those doing therapy face new responsibilities. Notes therapists can approach psychotic symptoms expecting the person to become normal. Describes goal as being to help people past periods of acute disturbance without doing them long-term harm. (Author/ABL)

  9. The Effect of Long-Term Outcome Studies on the Therapy of Schizophrenia.

    ERIC Educational Resources Information Center

    Haley, Jay

    1989-01-01

    Claims since schizophrenia is reversible, professions involved in social control and those doing therapy face new responsibilities. Notes therapists can approach psychotic symptoms expecting the person to become normal. Describes goal as being to help people past periods of acute disturbance without doing them long-term harm. (Author/ABL)

  10. Making Music, Making Friends: Long-Term Music Therapy with Young Adults with Severe Learning Disabilities

    ERIC Educational Resources Information Center

    Pavlicevic, Mercédès; O'Neil, Nicky; Powell, Harriet; Jones, Oonagh; Sampathianaki, Ergina

    2014-01-01

    This collaborative practitioner research study emerged from music therapists' concerns about the value of improvisational, music-centred music therapy for young adults with severe learning disabilities (SLDs), given the long-term nature of such work. Concerns included the relevance, in this context, of formulating, and reporting on, therapeutic…

  11. Comparison of Long-Term Outcomes in Adolescents with Anorexia Nervosa Treated with Family Therapy

    ERIC Educational Resources Information Center

    Lock, James; Couturier, Jennifer; Agras, W. Stewart

    2006-01-01

    Objective: To describe the relative effectiveness of a short versus long course of family-based therapy (FBT) for adolescent anorexia nervosa at long-term follow-up. Method: This study used clinical and structured interviews to assess psychological and psychosocial outcomes of adolescents (ages 12-18 years at baseline) who were previously treated…

  12. Hyperbaric Oxygen Therapy in Treating Long-Term Gastrointestinal Adverse Effects Caused by Radiation Therapy in Patients With Pelvic Cancer

    ClinicalTrials.gov

    2011-07-14

    Bladder Cancer; Cervical Cancer; Colorectal Cancer; Endometrial Cancer; Gastrointestinal Complications; Long-term Effects Secondary to Cancer Therapy in Adults; Ovarian Cancer; Prostate Cancer; Radiation Toxicity; Sarcoma; Testicular Germ Cell Tumor; Vaginal Cancer

  13. Metastatic lung cancer in the age of targeted therapy: improving long-term survival

    PubMed Central

    Del Rivero, Jaydira; Thomas, Anish

    2016-01-01

    Epidermal growth factor receptor (EGFR) mutations are the most frequent targetable genetic abnormality observed in non-small cell lung cancer (NSCLC). More than a decade after EGFR mutations were shown to predict sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKI), retrospective cohort studies are now identifying and characterizing 5-year survivors. While these studies indicate subsets of patients achieving long-term survival, there is paucity of data pertaining to the long-term survival benefits of these targeted therapies at a population level. Improving access to molecular testing and treatment are key to maximizing the survival benefits at a population level. PMID:28149768

  14. The treatment of anorgasmia: long-term effectiveness of a short-term behavioral group therapy.

    PubMed

    Kuriansky, J B; Sharpe, L; O'Connor, D

    1982-01-01

    A long-term follow-up of 19 women who participated in short-term group therapy for anorgasmia using masturbation and assertiveness training showed that the majority of women maintained treatment gains and progressed further in orgasm response and other aspects of sexual functioning, including assertiveness and liberalness of sexual attitudes. However, several women regressed, and four additional women who dropped out of treatment also improved dramatically in orgasm response, suggesting that other patient characteristics and factors affect apparent treatment outcome. Independent evaluations, standardized assessment scales, long-term, in-person follow-ups and multidimensional assessment are useful in evaluating treatment effectiveness.

  15. Natural history of multiple sclerosis: have available therapies impacted long-term prognosis?

    PubMed

    Trojano, Maria; Paolicelli, Damiano; Tortorella, Carla; Iaffaldano, Piero; Lucchese, Guglielmo; Di Renzo, Vita; D'Onghia, Mariangela

    2011-05-01

    Since the mid-1990s several disease-modifying drugs (DMDs), such as β-interferons and glatiramer acetate, have become available to treat patients with relapse-remitting multiple sclerosis (MS). These therapies have known short- and medium-term benefit in reducing relapses, disability progression, and accrual of new inflammatory lesions. However, the short duration of the randomized pivotal MS trials have provided little to no information about benefit from such treatment over periods of extended (>5 years) use. Whether DMDs may significantly alter the development of long-term disability remains uncertain, thus it remains challenging how to best approach the issue of long-term benefits from these treatments.

  16. Long-Term Anticoagulant Therapy of Patients with Venous Thromboembolism. What Are the Practices?

    PubMed Central

    Mahé, Isabelle; Sterpu, Raluca; Bertoletti, Laurent; López-Jiménez, Luciano; Mellado Joan, Meritxell; Trujillo-Santos, Javier; Ballaz, Aitor; Hernández Blasco, Luis Manuel; Marchena, Pablo Javier; Monreal, Manuel

    2015-01-01

    Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26–3.23), age >70 years (OR 1.15, 95% CI 1.06–1.24), immobility (OR 2.06, 95% CI 1.93–2.19), renal insufficiency (OR 2.42, 95% CI 2.15–2.71) and anemia (OR 1.75, 95% CI 1.65–1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64–2.06), immobility (OR 1.51, 95% CI 1.30–1.76) and metastases (OR 3.22, 95% CI 2.87–3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision. PMID:26076483

  17. Long-term immunosuppressive therapy with cyclosporine plus prednisolone for necrotizing meningoencephalitis in a Pekingese dog.

    PubMed

    Jung, Dong-In; Kim, Ju-Won; Park, Hee-Myung

    2012-06-01

    A 4-year-old intact female Pekingese dog was presented with ataxia and seizure episodes. Based on magnetic resonance imaging and cerebrospinal fluid analysis results, meningoencephalitis of unknown etiology was suspected. The present case survived for 1,096 days under cyclosporine plus prednisolone therapy and was definitively diagnosed with necrotizing meningoencephalitis. This report describes the clinical findings, serial magnetic resonance imaging characteristics and pathologic features of a necrotizing meningoencephalitis and long-term survival after cyclosporine with prednisolone therapy.

  18. Quality of life in Brazilian obese adolescents: effects of a long-term multidisciplinary lifestyle therapy

    PubMed Central

    Lofrano-Prado, Mara Cristina; Antunes, Hanna Karen Moreira; Prado, Wagner Luiz do; de Piano, Aline; Caranti, Danielle Arisa; Tock, Lian; Carnier, June; Tufik, Sergio; de Mello, Marco Túlio; Dâmaso, Ana R

    2009-01-01

    Background Obesity has adverse physical, social, and economic consequences that can negatively affect quality of life (QOL). Thus the aim of this study was to verify the effects of a long-term multidisciplinary lifestyle intervention on QOL, body image, anxiety, depression and binge eating in obese adolescents. Methods Sixty-six obese adolescents (41 girls and 25 boys; BMI: 35.62 ± 4.18 kg/m2) were recruited from the Multidisciplinary Obesity Intervention Program outpatient clinic, and were submitted to a multidisciplinary lifestyle therapy (short-term = 12 weeks and long-term = 24 weeks), composed of medical, dietary, exercise and psychological programs. Validated self-report questionnaires were used to assess symptoms of anxiety Trait/State (STAI); depression (BDI); binge eating (BES), body image dissatisfaction (BSQ) and QOL (SF-36). Data were analyzed by means of scores; comparisons were made by ANOVA for repeated measures, and Tukey's test as post-hoc and Students T test. Results Long-term therapy decreased depression and binge eating symptoms, body image dissatisfaction, and improved QOL in girls, whereas, for boys, 24 weeks, were effective to reduce anxiety trait/state and symptoms of binge eating, and to improve means of dimensions of QOL (p < .05). Conclusion A long-term multidisciplinary lifestyle therapy is effective to control psychological aspects and to improve QOL in obese adolescents. PMID:19575801

  19. [Long-term digitalis therapy of elderly patients. Is digitalization unnecessary in the majority of cases?].

    PubMed

    Häcki, M A; Angehrn, W; Cavegn, H R; Brändli, O

    1982-12-18

    More than 40% of patients hospitalized in the Wald Altitude Clinic of Zürich are already on long-term digitalis therapy upon admission. During a 6 month period long-term digoxin therapy was discontinued in 97 patients (age 74 +/- 9 years) with stable cardiac insufficiency (NYHA class I-III) and sinus rhythm. During the hospitalization (37 +/- 20 days), clinical signs and symptoms, body weight, radiological heart size, and systolic time intervals were monitored. After an observation period of one week, digoxin was discontinued in all patients. Body weight, cardio-thoracic ratio and left ventricular ejection time remained unchanged after cessation of digoxin therapy during hospitalization. The pre-ejection period showed a significant increase from 89 +/- 17 to 95 +/- 19 msec. Six patients were re-instituted on digoxin therapy, 3 due to progressive cardiac insufficiency, 2 due to atrial fibrillation, and 1 at his own request. After telephone follow-up six months later with the family physician an additional 20 patients were put back on digitalis. Among the total of 26 patients requiring further digitalization an absolute indication was found only in 12 (14%), 8 due to progressive cardiac insufficiency and 4 due to atrial fibrillation. In this study digitalis therapy could be discontinued without ill effects in 86% of elderly clinically stable patients in sinus rhythm. The authors therefore recommend a more cautious use of long-term digitalis therapy and, in already digitalized patients in sinus rhythm, a controlled trial period of discontinuation.

  20. Short and long-term effect of spa therapy in chronic low back pain.

    PubMed

    Guillemin, F; Constant, F; Collin, J F; Boulange, M

    1994-02-01

    The effect of spa therapy on chronic low back pain (LBP) was assessed in a randomized trial comparing patients undergoing a 3-week therapy programme in a spa resort in France (n = 50) with patients receiving ambulatory care (n = 52). After 3 weeks, patients in the spa group had significant improvement in their spine mobility and functional score (Waddell index) and a reduction in their daily duration of pain, pain intensity and drug consumption. The long-term effect was assessed after 9 months and showed continued reduction in pain and drug consumption, and improvement in spine mobility but no longer in functional score which returned to baseline level. It is concluded that spa therapy has a positive short-term and a moderate long-term effectiveness on chronic LBP.

  1. Predictors of atypical femoral fractures during long term bisphosphonate therapy: a case series & review of literature.

    PubMed

    Bhadada, Sanjay Kumar; Sridhar, Subbiah; Muthukrishnan, Jeyaram; Mithal, Ambrish; Sharma, Dinesh C; Bhansali, Anil; Dhiman, Vandana

    2014-07-01

    Bisphosphonates (BPs) are the most widely prescribed medicines for the treatment of osteoporosis because of their efficacy and favourable safety profile. There have been, several reports on an increased incidence of atypical femoral fractures after long term treatment with BPs. The objective of this study was to evaluate the clinical presentation including prodromal symptoms, skeletal radiograph findings, type and duration of BPs received and treatment outcome of patients who developed atypical femoral fractures during bisphosphonate therapy. In this retrospective study, eight patients with atypical femoral fractures were analysed based on clinical features, biochemical and radiological investigations. Of the eight patients, who sustained atypical femoral fractures, six were on alendronate and two were on zoledronate therapy before the fractures. In addition to BPs, two patients were on long term corticosteroid therapy for rheumatoid arthritis and Addison's disease. Three patients had bilateral atypical femoral fractures. Except one, all of them had prodromal symptoms prior to fracture. Skeletal radiograph showed cortical thickening, pointed (beaking of) cortical margin and transverse fracture in meta-diaphyseal location. Serum calcium, phosphate, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) concentrations were within the reference range in all patients. Long term bisphosphonate therapy may increase the risk of atypical femoral fractures. Presence of prodromal pain, thickened cortex with cortical beaking may be an early clue for predicting the atypical fractures. High risk patients need periodical skeletal survey and a close follow up for early detection of cases.

  2. Tapering Long-term Opioid Therapy in Chronic Noncancer Pain: Evidence and Recommendations for Everyday Practice.

    PubMed

    Berna, Chantal; Kulich, Ronald J; Rathmell, James P

    2015-06-01

    Increasing concern about the risks and limited evidence supporting the therapeutic benefit of long-term opioid therapy for chronic noncancer pain are leading prescribers to consider discontinuing the use of opioids. In addition to overt addiction or diversion, the presence of adverse effects, diminishing analgesia, reduced function and quality of life, or the absence of progress toward functional goals can justify an attempt at weaning patients from long-term opioid therapy. However, discontinuing opioid therapy is often hindered by patients' psychiatric comorbidities and poor coping skills, as well as the lack of formal guidelines for the prescribers. The aim of this article is to review the existing literature and formulate recommendations for practitioners aiming to discontinue long-term opioid therapy. Specifically, this review aims to answer the following questions: What is an optimal opioid tapering regimen? How can the risks involved in a taper be managed? What are the alternatives to an opioid taper? A PubMed literature search was conducted using the keywords chronic pain combined with opioid withdrawal, taper, wean and detoxification. Six hundred ninety-five documents were identified and screened; 117 were deemed directly relevant and are included. On the base of this literature review, this article proposes evidence-based recommendations and expert-based suggestions for clinical practice. Furthermore, areas of lack of evidence are identified, providing opportunities for further research.

  3. Long-term efficacy of simple behavioral therapy for daytime wetting in children.

    PubMed

    Wiener, J S; Scales, M T; Hampton, J; King, L R; Surwit, R; Edwards, C L

    2000-09-01

    Behavioral therapy has proved benefit for children with daytime wetting but most studies have used biofeedback techniques and provide no long-term assessment of results. We previously reported similar results using simple behavioral therapy without biofeedback. We report the long-term efficacy of behavioral therapy for daytime wetting. Our program of behavioral therapy included timed voiding, modification of fluid intake, positive reinforcement techniques and pelvic floor (Kegel) exercises to promote pelvic floor strengthening and relaxation. Questionnaires to assess therapeutic efficacy were mailed to patients who had completed therapy more than 1 year previously. A total of 48 patients responded. Mean ages at the time of the initial clinic visit and questionnaire were 8.2 and 12.9 years, respectively. Improvement in symptoms was noted in approximately 74% of the cases during the first year following therapy. At a mean of 4. 7 years after treatment 59.4% of the patients had improved daytime urinary control, 51.1% improved daytime urinary frequency and 45.6% improved daytime urinary urgency. The frequency of urinary tract infections decreased in 56.4% of the cases. Measures of psychological well-being were also noted to be improved in a majority of patients. A total of 77.3% of the patients stated that they would recommend the program to others. Simple behavioral therapy without biofeedback techniques is an effective and durable first line therapy for children with daytime wetting.

  4. How Eye-Preserving Therapy Affects Long-Term Overall Survival in Heritable Retinoblastoma Survivors.

    PubMed

    Temming, Petra; Arendt, Marina; Viehmann, Anja; Eisele, Lewin; Le Guin, Claudia H D; Schündeln, Michael M; Biewald, Eva; Mäusert, Jennifer; Wieland, Regina; Bornfeld, Norbert; Sauerwein, Wolfgang; Eggert, Angelika; Lohmann, Dietmar R; Jöckel, Karl-Heinz

    2016-09-10

    Intraocular retinoblastoma is curable, but survivors with a heritable predisposition are at high risk for second malignancies. Because second malignancies are associated with high mortality, prognostic factors for second malignancy influence long-term overall survival. This study investigates the impact of all types of eye-preserving therapies on long-term survival in the complete German cohort of patients with heritable retinoblastoma. Overall survival, disease staging using international scales, time period of diagnosis, and treatment type were analyzed in the 633 German children treated at the national reference center for heritable retinoblastoma. The 5-year overall survival of children diagnosed in Germany with heritable retinoblastoma between 1940 and 2008 was 93.2% (95% CI, 91.2% to 95.1%), but long-term mortality was increased compared with patients with nonheritable disease. Overall survival correlated with tumor staging, and 92% of patients were diagnosed with a favorable tumor stage (International Retinoblastoma Staging System stage 0 or I). Despite a 5-year overall survival of 97.4% (95% CI, 96.0% to 98.8%) in patients with stage 0 or I, only 79.5% (95% CI, 74.2% to 84.8%) of these patients survived 40 years after diagnosis. Long-term overall survival was reduced in children treated with eye-preserving radiotherapy compared with enucleation alone, and adding chemotherapy aggravated this effect. The benefits of preserving vision must be balanced with the impact of eye-preserving treatments on long-term survival in heritable retinoblastoma, and the genetic background of the patient influences choice of eye-preserving treatment. Germline RB1 genetic analysis is important to identify heritable retinoblastoma among unilateral retinoblastoma cases. Eye-preserving radiotherapy should be carefully considered in patients with germline RB1 mutations. Life-long oncologic follow-up is crucial for all retinoblastoma survivors, and less detrimental eye

  5. Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy.

    PubMed

    Sehgal, Nalini; Colson, James; Smith, Howard S

    2013-11-01

    Chronic non-cancer pain (CNCP) is a disabling chronic condition with a high prevalence rate around the world. Opioids are routinely prescribed for treatment of chronic pain (CP). In the past two decades there has been a massive increase in the number of opioid prescriptions, prescribed daily opioid doses and overall opioid availability. Many more patients with CNCP receive high doses of long-acting opioids on a long-term basis. Yet CP and related disability rates remain high, and majority of the patients with CNCP are dissatisfied with their treatments. Intersecting with the upward trajectory in opioid use are the increasing trends in opioid related adverse effects, especially prescription drug abuse, addiction and overdose deaths. This complex situation raises questions on the relevance of opioid therapy in the treatment of CNCP. This article reviews current evidence on opioid effectiveness, the benefits and harms of long-term therapy in CNCP.

  6. Group therapy with WWII ex-POW's: long-term posttraumatic adjustment in a geriatric population.

    PubMed

    Boehnlein, J K; Sparr, L F

    1993-01-01

    In this assessment of group therapy with WWII ex-POWs, the small cohort limits generalizations; however, we offer a longitudinal perspective on group process. Posttraumatic suppression and denial of emotions appears to be adaptive for time-limited periods but is not a long-term solution. More lasting changes in self-esteem and social interaction may be partially achieved through a supportive group environment that fosters cognitive synthesis and reorganization.

  7. Periocular accumulation of timolol and betaxolol in glaucoma patients under long-term therapy.

    PubMed

    Sponsel, W E; Terry, S; Khuu, H D; Lam, K W; Frenzel, H

    1999-06-01

    To determine if betaxolol or timolol is present in measurable concentration in the Tenon capsule in patients under long-term topical therapy. Small (1-cc) specimens of Tenon capsule were removed at the time of filtering surgery from 15 glaucoma patients under long-term preoperative topical therapy, nine of whom had been treated with timolol and six of whom had been receiving betaxolol. Methanol extracts of these tissue samples were analyzed quantitatively for the presence of either beta-adrenergic antagonist by high-performance liquid chromatography. Drug was detected in every specimen. A mean total of 2.6 (range, 0.1-30.0) microg of betaxolol was detected per 1-cc specimen. Timolol and betaxolol penetrate the conjunctiva and accumulate in the Tenon capsule. In patients under long-term therapy, the periocular tissue can accumulate a greater quantity of beta-antagonist than is present in a daily dosage of applied eyedrops, manyfold higher than the maximal intraocular concentration.

  8. LONG TERM EFFICACY OF BIOFEEDBACK THERAPY FOR DYSSYNERGIA -RANDOMIZED CONTROLLED TRIAL

    PubMed Central

    Rao, Satish SC; Valestin, Jessica; Brown, C Kice; Zimmerman, Bridget; Schulze, Konrad

    2013-01-01

    Objectives Although biofeedback therapy is effective in the short term management of dyssynergic defecation, its long term efficacy is unknown. Our aim was to compare the one year outcome of biofeedback (manometric- assisted pelvic relaxation, and simulated defecation training), with standard therapy (diet, exercise, laxatives) in patients who completed 3 months of either therapy. Methods Stool diaries, visual analog scales (VAS), colonic transit, anorectal manometry, and balloon expulsion time were assessed at baseline, and at one year after each treatment. All subjects were seen at 3 month intervals and received reinforcement. Primary outcome measure (ITT analysis) was a change in the number of complete spontaneous bowel movements (CSBM) per week. Secondary outcome measures included bowel symptoms, changes in dyssynergia and anorectal function. Results Of 44 eligible patients with dyssynergic defecation, 26 agreed to participate in the long term study. All 13 subjects who received biofeedback, and 7 of 13 who received standard therapy completed one year; 6 failed standard therapy. The number of CSBMs/week increased significantly (p<0.001) in the biofeedback but not in the standard group. Dyssynergia pattern normalized (p<0.001), balloon expulsion time improved (p=0.0009), defecation index increased (p<0.001) and colonic transit time normalized (p=0.01) only in the biofeedback group. Conclusions Biofeedback therapy provided sustained improvement of bowel symptoms and anorectal function in constipated subjects with dyssynergic defecation while standard therapy was largely ineffective. PMID:20179692

  9. Long-Term Echocardiographic Response to Cardiac Resynchronization Therapy in Initial Nonresponders.

    PubMed

    Burns, Kevin V; Gage, Ryan M; Curtin, Antonia E; Bank, Alan J

    2015-12-01

    The aim of this study was to investigate the frequency and clinical implications of a delayed echocardiographic response to cardiac resynchronization therapy (CRT). Long-term prognosis for CRT patients is routinely based on the assessment of echocardiograms after 6 to 12 months of therapy. Some patients, however, may require a longer period of therapy before echocardiographic improvements are detectable. This observational study included all patients with heart failure (HF) receiving a CRT device at a single center from 2003 to 2011. Eligible patients met current indications and had technically adequate echocardiograms from before implantation, approximately 1 year after implantation (mid-term), and ≥3 years after implantation (long-term). A positive echocardiographic response to CRT was defined as a reduction in left ventricular end-systolic volume ≥15%. All-cause mortality was compared for patients in 3 response groups: mid-term responders, long-term responders, and nonresponders. During this study, 294 patients met the study criteria. Of the 120 patients who were nonresponders after 1 year, 52 (43%) experienced a delayed positive response. Delayed, long-term responders had mortality and hospitalization rates similar to mid-term responders and significantly lower than nonresponders. Among patients surviving at least 3 years after implantation of a CRT device and with echocardiographic follow-up, a significant portion of nonresponders after 1 year of CRT experience a delayed echocardiographic response after a longer period of time. Survival and hospitalization rates were similar for all echocardiographic responders, regardless of the time at which the response occurred. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Long-term dentoskeletal effects and facial profile changes induced by bionator therapy.

    PubMed

    Malta, Luciana Abrao; Baccetti, Tiziano; Franchi, Lorenzo; Faltin, Kurt; McNamara, James A

    2010-01-01

    To evaluate the long-term skeletal and soft tissue changes induced by the bionator in Class II subjects. The treatment sample consisted of 20 Class II patients (6 males and 14 females) treated consecutively with the bionator. The sample was evaluated at T1, start of treatment; T2, end of bionator therapy; and T3, long-term observation (including fixed appliances). Mean age at the start of treatment was 10 years 2 months (T1); at posttreatment, 12 years 4 months (T2); and at long-term follow-up, 18 years 11 months (CS 6). The control group consisted of 20 subjects (8 males and 12 females) with untreated Class II malocclusions. Lateral cephalograms were analyzed at the three time points for all groups. Student's t-tests were used for comparisons of starting forms, and of the T1-T2 and T1-T3 changes between groups. The bionator group showed significant, favorable T1-T2 changes both at the skeletal and dentoalveolar levels. The vertical dimension was increased. Significant modifications were assessed for the soft tissues as well. The treated group showed a final improvement in soft tissue pogonion of about 2.5 mm. Significant mandibular changes were noted in the treated group, with a net average 3.3 mm long-term increase in mandibular length compared with untreated Class II controls. This study suggests that bionator treatment of Class II malocclusion maintains favorable results over the long-term with a combination of skeletal, dentoalveolar, and soft tissue changes.

  11. Changes in Corneal Biomechanical Properties after Long-Term Topical Prostaglandin Therapy.

    PubMed

    Wu, Na; Chen, Yuhong; Yu, Xiaobo; Li, Mengwei; Wen, Wen; Sun, Xinghuai

    2016-01-01

    To compare corneal biomechanical properties, measured by a newly developed tonometer (Corneal Visualization Scheimpflug Technology, Corvis ST), in untreated primary open angle glaucoma (POAG) patients, POAG patients with long-term topical prostaglandin analog (PGA) therapy and in normal controls. Further is to investigate the potential effects of PGA on corneal biomechanics. In this case-control study, 35 consecutive medication naïve eyes with POAG, 34 POAG eyes with at least 2 years treatment by PGA and 19 normal eyes were included. Intraocular pressure (IOP), central corneal thickness (CCT) and corneal biomechanical parameters, including deformation amplitude (DA), applanation time (AT1 and AT2), applanation length (AL1 and AL2), applanation velocity (AV1 and AV2), and peak distance and radius were measured using Corvis ST. Axial length and corneal curvature were measured with partial coherence interferometry (IOLMaster, Zeiss, Germany). General linear model analysis was performed to investigate the corneal biomechanical property changes among the normal controls, newly diagnosed POAG patients and POAG patients with long-term PGA treatment, and among the subgroups of different types of PGA treatment, including bimatoprost, latanoprost and travoprost. Furthermore, pairwise comparisons using Bonferroni correction for least squares means were employed. AT1 (p<0.0001), AV1 (p<0.0001), AT2 (p = 0.0001), AV2 (p<0.0001) and DA (p = 0.0004) in newly diagnosed glaucoma patients were significantly different from those in normal subjects and in patients underwent at least 2 years topical PGA therapy after adjusting for age and gender. After adjusting for age, gender, IOP, CCT, axial length and corneal curvature, a significant difference was detected for DA between glaucoma patients without PGA treatment and patients with long-term PGA therapy (p = 0.0387). Furthermore, there were no statistical significant differences in all of the corneal biomechanical parameters among

  12. Hepatitis B virus long-term impact of antiviral therapy nucleot(s)ide analogues (NUCs).

    PubMed

    Grossi, Glenda; Viganò, Mauro; Loglio, Alessandro; Lampertico, Pietro

    2017-01-01

    The goal of antiviral therapy is to improve the quality of life and survival of patients with chronic hepatitis B (CHB) by halting the progression to cirrhosis, end-stage liver disease or hepatocellular carcinoma (HCC), thus preventing anticipated liver-related death. Oral administration of potent and less resistance-prone nucleot(s)ide analogues (NUCs), such as entecavir (ETV) and tenofovir disoproxil fumarate (TDF) has become the most popular treatment strategy worldwide because of their excellent efficacy and safety profile as well as easy management confirmed in both registration trials and in clinical practice studies. Long-term administration of ETV or TDF suppresses HBV replication in >95% of patients, resulting in biochemical remission, histological improvement including the regression of cirrhosis and prevention or reversal of clinical decompensation but not the development of HCC, particularly in patients with cirrhosis. Moreover, NUCs can be administered to all patients including those with severe liver disease, the elderly and in those who do not respond, are unwilling to take or have contraindications to interferon. The need for long-term, perhaps indefinite, treatment is the main limitation of NUCs therapy with the associated costs, unknown long-term safety and the low rates of hepatitis B surface antigen (HBsAg) seroclearance, which is still the best stopping rule for NUCs-treated patients with cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Physical therapy in Parkinson's disease: an open long-term rehabilitation trial.

    PubMed

    Pellecchia, M T; Grasso, A; Biancardi, L G; Squillante, M; Bonavita, V; Barone, P

    2004-05-01

    The aim of this study was to evaluate the effects of prolonged physical therapy on disability in patients with Parkinson's disease. The study was designed as an open long-term trial over 20 weeks. Twenty slightly to moderately affected parkinsonian patients were included (Hoehn & Yahr stages: 1.5-3). A comprehensive rehabilitation program was applied three times a week in all patients. Pharmacological treatment was kept stable. Evaluations were performed at baseline, at the end of treatment and after 3 months. Following physical rehabilitation, there was a significant improvement in UPDRS (ADL and motor sections) scores, Self-assessment Parkinson's disease Disability Scale, Ten-Meter Walk test and Zung scale for depression. At 3-month follow-up clinical improvements were largely maintained. A sustained improvement of motor skills in PD patients can be achieved with a long-term comprehensive rehabilitation program.

  14. Specific Therapy Regimes Could Lead to Long-Term Immunological Control of HIV

    NASA Astrophysics Data System (ADS)

    Wodarz, Dominik; Nowak, Martin A.

    1999-12-01

    We use mathematical models to study the relationship between HIV and the immune system during the natural course of infection and in the context of different antiviral treatment regimes. The models suggest that an efficient cytotoxic T lymphocyte (CTL) memory response is required to control the virus. We define CTL memory as long-term persistence of CTL precursors in the absence of antigen. Infection and depletion of CD4+ T helper cells interfere with CTL memory generation, resulting in persistent viral replication and disease progression. We find that antiviral drug therapy during primary infection can enable the development of CTL memory. In chronically infected patients, specific treatment schedules, either including deliberate drug holidays or antigenic boosts of the immune system, can lead to a re-establishment of CTL memory. Whether such treatment regimes would lead to long-term immunologic control deserves investigation under carefully controlled conditions.

  15. Melanoma associated with long-term voriconazole therapy: a new manifestation of chronic photosensitivity.

    PubMed

    Miller, Daniel D; Cowen, Edward W; Nguyen, Josephine C; McCalmont, Timothy H; Fox, Lindy P

    2010-03-01

    Voriconazole is a triazole antifungal agent approved by the US Food and Drug Administration for serious fungal infections, including with Aspergillus, Fusarium, Pseudallescheria, and Scedosporium species. In initial clinical trials, approximately 2% of patients developed cutaneous reactions, including photosensitivity, cheilitis, and xerosis. Subsequent reports have implicated voriconazole as a cause of severe photosensitivity and accelerated photoaging, pseudoporphyria cutanea tarda, and aggressive squamous cell carcinoma. We report 5 melanoma in situ lesions in the setting of extreme photosensitivity associated with long-term voriconazole therapy. We recommend surveillance for skin cancer formation in all patients who require long-term voriconazole treatment, particularly those who manifest signs or symptoms of photosensitivity or chronic photodamage. Further study of the mechanism underlying voriconazole photosensitivity and oncogenesis is warranted.

  16. Qigong and exercise therapy in patients with long-term neck pain: a prospective randomized trial.

    PubMed

    Lansinger, Birgitta; Larsson, Elisabeth; Persson, Liselott C; Carlsson, Jane Y

    2007-10-15

    A randomized, controlled, multicenter trial: 1-year follow-up. To compare the effectiveness of qigong and exercise therapy in subjects with long-term nonspecific neck pain. The evidence for the benefit of treatment programs focusing on persons with long-term, nonspecific neck pain is conflicting. Several studies have shown support for exercise therapy, but the efficacy of qigong has not been scientifically evaluated. A total of 122 patients were randomly assigned to receive either qigong (n = 60) or exercise therapy (n = 62). Most of them were women (70%), and the mean age was 44 years. A maximum of 12 treatments were given over a period of 3 months. Neck pain frequency and intensity, neck disability (NDI), grip strength, and cervical range of motion were recorded before and immediately after, at 6 months, and at 12 months after the treatment period. Changes in outcome variables were analyzed and dichotomized as improved or unchanged/deteriorated. Clinical and demographic characteristics were similar among groups at baseline. No differences were found between the 2 interventions: qigong and exercise therapy. Both groups significantly improved immediately after treatment and this was maintained at the 6- and 12-month follow-ups in 5 of 8 outcome variables: average neck pain in the most recent week, current neck pain (with exception for immediately after treatment period), neck pain diary, NDI, and cervical range of motion in rotation. These results indicate that treatments including supervised qigong or exercise therapy resulting in reduced pain and disability can be recommended for persons with long-term nonspecific neck pain.

  17. Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in Two Age Groups.

    PubMed

    Espeland, Mark A; Rapp, Stephen R; Manson, JoAnn E; Goveas, Joseph S; Shumaker, Sally A; Hayden, Kathleen M; Weitlauf, Julie C; Gaussoin, Sarah A; Baker, Laura D; Padula, Claudia B; Hou, Lifang; Resnick, Susan M

    2017-06-01

    Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age. Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos. Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p < .05. These decrements were relatively stable over time. Findings did not vary depending on the hormone therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase. CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years.

  18. Association of Long-term Opioid Therapy With Functional Status, Adverse Outcomes, and Mortality Among Patients With Polyneuropathy.

    PubMed

    Hoffman, E Matthew; Watson, James C; St Sauver, Jennifer; Staff, Nathan P; Klein, Christopher J

    2017-07-01

    Polyneuropathy is one of the most common painful conditions managed within general and specialty clinics. Neuropathic pain frequently leads to decisions about using long-term opioid therapy. Understanding the association of long-term opioid use with functional status, adverse outcomes, and mortality among patients with polyneuropathy could influence disease-specific decisions about opioid treatment. To quantify the prevalence of long-term opioid use among patients with polyneuropathy and to assess the association of long-term opioid use with functional status, adverse outcomes, and mortality. A retrospective population-based cohort study was conducted of prescriptions given to patients with polyneuropathy and to controls in ambulatory practice between January 1, 2006, and December 31, 2010, to determine exposure to long-term opioid use as well as other outcomes. The latest follow-up was conducted through November 25, 2016. Long-term opioid therapy, defined by 1 or multiple consecutive opioid prescriptions resulting in 90 continuous days or more of opioid use. Prevalence of long-term opioid therapy among patients with polyneuropathy and controls. Patient-reported functional status, documented adverse outcomes, and mortality were compared between patients with polyneuropathy receiving long-term opioid therapy (≥90 days) and patients with polyneuropathy receiving shorter durations of opioid therapy. Among the 2892 patients with polyneuropathy (1364 women and 1528 men; mean [SD] age, 67.5 [16.6] years) and the 14 435 controls (6827 women and 7608 men; mean [SD] age, 67.5 [16.5] years), patients with polyneuropathy received long-term opioids more often than did controls (545 [18.8%] vs 780 [5.4%]). Patients with polyneuropathy who were receiving long-term opioids had multiple functional status markers that were modestly poorer even after adjusting for medical comorbidity, including increased reliance on gait aids (adjusted odds ratio, 1.9; 95% CI, 1.4-2.6); no

  19. Therapy duration and long-term outcomes in extra-pulmonary tuberculosis

    PubMed Central

    2014-01-01

    Background Tuberculosis is classified as either pulmonary or extra-pulmonary (EPTB). While much focus has been paid to pulmonary tuberculosis, EPTB has received scant attention. Moreover, EPTB is viewed as one wastebasket diagnosis, as “the other” which is not pulmonary. Methods This is a retrospective cohort study of all patients treated for EPTB in the state of Texas between January 2000 and December 2005, who had no pulmonary disease. Clinical and epidemiological factors were abstracted from electronic records of the Report of Verified Case of Tuberculosis. The long-term outcome, which is death by December 2011, was established using the Social Security Administration Death Master File database. Survival in EPTB patients was compared to those with latent tuberculosis, as well as between different types of EPTB, using Cox proportional hazard models. A hybrid of the machine learning method of classification and regression tree analyses and standard regression models was used to identify high-order interactions and clinical factors predictive of long-term all-cause mortality. Results Four hundred and thirty eight patients met study criteria; the median study follow-up period for the cohort was 7.8 (inter-quartile range 6.0-10.1) years. The overall all-cause mortality rate was 0.025 (95% confidence interval [CI]: 0.021-0.030) per 100 person-year of follow-up. The significant predictors of poor long-term outcome were age (hazard ratio [HR] for each year of age-at-diagnosis was 1.05 [CI: 1.04-1.06], treatment duration, type of EPTB and HIV-infection (HR = 2.16; CI: 1.22, 3.83). Mortality in genitourinary tuberculosis was no different from latent tuberculosis, while meningitis had the poorest long-term outcome of 46.2%. Compared to meningitis the HR for death was 0.50 (CI: 0.27-0.91) for lymphatic disease, 0.42 (CI: 0.21-0.81) for bone/joint disease, and 0.59 (CI: 0.27-1.31) for peritonitis. The relationship between mortality and therapy duration for each type

  20. Cognitive and Guided Mastery Therapies for Panic Disorder with Agoraphobia: 18-Year Long-Term Outcome and Predictors of Long-Term Change.

    PubMed

    Hoffart, Asle; Hedley, Liv M; Svanøe, Karol; Sexton, Harold

    2016-01-01

    In this study, we wished to compare the long-term outcome of (medication-free) panic disorder with agoraphobia patients randomized to cognitive or guided mastery therapy. Thirty-one (67.4%) of 46 patients who had completed treatment were followed up about 18 years after end of treatment. In the combined sample and using intent-to-follow-up analyses, there were large within-group effect sizes of -1.79 and -1.63 on the primary interview-based and self-report outcome measures of avoidance of situations when alone, and 56.5% no longer had a panic disorder and/or agoraphobia diagnosis. No outcome differences between the two treatments emerged. Guided mastery was associated with greater beneficial changes in catastrophic beliefs and self-efficacy. For two of five outcome measures, more reduction in panic-related beliefs about physical and mental catastrophes from pre- to post-treatment predicted lower level of anxiety from post-treatment to 18-year follow-up when the effect of treatment changes in (a) self-efficacy and (b) anxiety was controlled. However, for one of the outcome measures, this effect attenuated with time. Copyright © 2014 John Wiley & Sons, Ltd. The results suggest that the very-long-term outcome of both cognitive therapy and guided mastery therapy for agoraphobia is positive. The results support the role of catastrophic beliefs as mediator of change. The pattern of results suggests that learning processes other than catastrophic beliefs may be important for long-term outcome as well. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Long-term anti-hypertensive therapy with benidipine improves arterial stiffness over blood pressure lowering.

    PubMed

    Kita, Toshihiro; Suzuki, Yoshihiko; Eto, Tanenao; Kitamura, Kazuo

    2005-12-01

    Pulse wave velocity (PWV) reflects arterial stiffness and is an independent predictor of cardiovascular mortality and morbidity. However, because it is closely related to blood pressure (BP), PWV is an imperfect measure for evaluating the effects of anti-hypertensive drugs on arterial wall properties. To clarify the effect of benidipine on arterial properties, we first derived the regression line between BP and PWV changes in a short-term experiment. Using this line, we evaluated the long-term effect of benidipine on PWV changes. In the short-term experiment, 29 participants were intravenously administered nicardipine for 90 min. Maximum decreases of brachial-ankle PWV (baPWV) were plotted against the corresponding decreases in BP. In the long-term experiment, 9 hypertensive patients were treated with benidipine for 1 year, during which BP and baPWV were monitored. After 1 year, benidipine was suspended for 2 weeks, and BP and baPWV were reevaluated. In the short-term experiment, PWV was dependent on BP only, and the equation of the regression line was deltaPWV (cm/s) =10.114 x deltaMBP (mmHg) (r=0.913) or deltaPWV (%) =0.719 x deltaMBP (%) (r=0.926). In the long-term therapy, benidipine treatment achieved stable BP control within 3 months; the real PWV decreases (r-PWV) were almost identical to the PWV decrease estimated (e-PWV) from BP lowering at 3 months. However, r-PWV exceeded e-PWV after 6 months. Relative BP and PWV improvements compared to the control were maintained 2 weeks after suspension of benidipine. In conclusion, long-term benidipine administration improves arterial wall properties beyond what can be accounted for by changes in BP.

  2. A randomized multicenter study evaluating Xolair persistence of response after long-term therapy.

    PubMed

    Ledford, Dennis; Busse, William; Trzaskoma, Benjamin; Omachi, Theodore A; Rosén, Karin; Chipps, Bradley E; Luskin, Allan T; Solari, Paul G

    2017-07-01

    Few data are available to assist clinicians with decisions regarding long-term use of asthma therapies, including omalizumab. We sought to evaluate the benefit and persistence of response in subjects continuing or withdrawing from long-term omalizumab treatment. Evaluating the Xolair Persistency Of Response After Long-Term Therapy (XPORT) was a randomized, double-blind, placebo-controlled withdrawal study that included subjects with moderate-to-severe persistent asthma receiving long-term omalizumab. Subjects were randomized by using a hierarchical dynamic randomization scheme to continue their same dose of omalizumab or withdraw to placebo and were then followed every 4 weeks for 1 year. The primary outcome was any protocol-defined severe asthma exacerbation. The secondary outcome was time to first protocol-defined severe asthma exacerbation. Exploratory outcomes included changes in Asthma Control Questionnaire and Asthma Control Test scores. Significantly more subjects in the omalizumab group (67%) had no protocol-defined exacerbation than in the placebo group (47.7%); an absolute difference of 19.3% (95% CI, 5.0%, 33.6%) represents a 40.1% relative difference. Time to first protocol-defined exacerbation analysis revealed a significantly different between-group exacerbation pattern that was consistent with the primary analysis. Subjects continuing omalizumab had significantly better asthma control (mean [SD] change from baseline to week 52: Asthma Control Test score, -1.16 [4.14] vs placebo, -2.88 [5.38], P = .0188; Asthma Control Questionnaire score, 0.22 [0.66] vs placebo, 0.63 [1.13], P = .0039). Discontinuation of omalizumab was associated with an increase in free IgE levels and an increase in basophil expression of the high-affinity IgE receptor. No safety concerns were noted. Continuation of omalizumab after long-term treatment results in continued benefit, as evidenced by improved symptom control and reduced exacerbation risk. Copyright © 2016 The

  3. A novel conceptual framework for understanding the mechanism of adherence to long term therapies.

    PubMed

    Reach, Gérard

    2008-02-02

    The World Health Organization claimed recently that improving patient adherence to long term therapies would be more beneficial than any biomedical progress. First, however, we must understand its mechanisms. In this paper I propose a novel approach using concepts elaborated in a field rarely explored in medicine, the philosophy of mind. While conventional psychological models (eg, the Health Belief Model) provide explanations and predictions which have only a statistical value, the philosophical assumption that mental states (eg, beliefs) are causally efficient (mental causation) can provide the basis for a causal theory of health behaviors. This paper shows that nonadherence to long term therapies can be described as the medical expression of a philosophical concept, that is, weakness of will. I use philosophical explanations of this concept to suggest a mechanistic explanation of nonadherence. I propose that it results from the failure of two principles of rationality. First, a principle of continence, described by the philosopher Donald Davidson in his explanation of weakness of will. This principle exhorts us to act after having considered all available arguments and according to which option we consider best. However, patients conforming to this principle of continence should rationally be nonadherent. Indeed, when patients face a choice between adherence and nonadherence, they must decide, in general, between a large, but delayed reward (eg, health) and a small, but immediate reward (eg, smoking a cigarette). According to concepts elaborated by George Ainslie and Jon Elster, the force of our desires is strongly influenced by the proximity of reward. This inter-temporal choice theory on one hand, and the mere principle of continence on the other, should therefore lead to nonadherence. Nevertheless, adherence to long term therapies is possible, as a result of the intervention of an additional principle, the principle of foresight, which tells us to give

  4. Long-term azithromycin therapy in patients with severe COPD and repeated exacerbations

    PubMed Central

    Pomares, Xavier; Montón, Concepción; Espasa, Mateu; Casabon, Jordi; Monsó, Eduard; Gallego, Miguel

    2011-01-01

    Background The aim of this study was to determine whether long-term intermittent azithromycin therapy reduces the frequency of exacerbation in severe chronic obstructive pulmonary disease (COPD). Methods We retrospectively investigated the clinical benefits of long-term azithromycin (500 mg orally three times per week) over 12 months in patients with severe COPD and a minimum of four acute exacerbations (AECOPD) per year or chronic bronchial colonization by Pseudomonas aeruginosa, comparing the number of AECOPD, hospitalizations due to respiratory disease, days of hospital stay, and bacterial infections during azithromycin treatment and in the year prior to this therapy. Results Twenty patients who completed the 12-month treatment period were analyzed. No clinically significant adverse events were observed during azithromycin treatment. Compared with baseline data, azithromycin therapy significantly reduced the number of AECOPD (2.8 ± 2.5 versus 6.8 ± 2.8, P < 0.001), hospitalizations (1.4 ± 1.5 versus 3.6 ± 1.4, P < 0.001), and cumulative annual days of hospital stay (25 ± 32.2 versus 43.7 ± 21.4, P = 0.01). The improvement was particularly significant in patients with exacerbations caused by common potentially pathogenic microorganisms, who had 70% fewer AECOPD and hospitalizations. Patients colonized by P. aeruginosa had reductions of 43% in AECOPD and 47% in hospitalizations. Conclusion Long-term azithromycin is well tolerated and associated with significant reductions in AECOPD, hospitalizations, and length of hospital stay in patients with severe COPD. PMID:22003290

  5. Short- and Long-Term Effects of Inhaled Iloprost Therapy in Children With Pulmonary Arterial Hypertension

    PubMed Central

    Ivy, D. Dunbar; Doran, Aimee K.; Smith, Kelly J.; Mallory, George B.; Beghetti, Maurice; Barst, Robyn J.; Brady, Daniela; Law, Yuk; Parker, Donna; Claussen, Lori; Abman, Steven H.

    2011-01-01

    Objectives This study investigated the short- and long-term outcome of children with pulmonary arterial hypertension (PAH) treated with inhaled iloprost. Background Inhaled iloprost has been approved for the treatment of adults with PAH, but little is known about the effects in children with PAH. Methods We evaluated the acute effects of inhaled iloprost on hemodynamic status and lung function and the response to long-term therapy in 22 children (range 4.5 to 17.7 years) with PAH (idiopathic, n = 12; congenital heart disease, n = 10). Cardiac catheterization, standard lung function testing before and after iloprost inhalation, 6-min walk test, World Health Organization functional class, and hemodynamic parameters were monitored. Results Acute administration of inhaled iloprost lowered mean pulmonary artery pressure equivalent to the response to inhaled nitric oxide with oxygen. Acute iloprost inhalation reduced forced expiratory volume in 1 s and mid-volume forced expiratory flow by 5% and 10%, respectively, consistent with acute bronchoconstriction. At 6 months, functional class improved in 35%, decreased in 15%, and remained unchanged in 50% of children. Sixty-four percent of patients continued receiving long-term iloprost therapy, 36% stopped iloprost, due to lower airway reactivity, clinical deterioration, or death. In 9 patients on chronic intravenous prostanoids, 8 transitioned from intravenous prostanoids to inhaled iloprost, which continued during follow-up. Conclusions Inhaled iloprost caused sustained functional improvement in some children with PAH, although inhaled iloprost occasionally induced bronchoconstriction. Most patients tolerated the transition from intravenous to inhaled prostanoid therapy. Clinical deterioration, side effects, and poor compliance, owing to the frequency of treatments, could limit chronic treatment in children. PMID:18191742

  6. A novel conceptual framework for understanding the mechanism of adherence to long term therapies

    PubMed Central

    Reach, Gérard

    2008-01-01

    The World Health Organization claimed recently that improving patient adherence to long term therapies would be more beneficial than any biomedical progress. First, however, we must understand its mechanisms. In this paper I propose a novel approach using concepts elaborated in a field rarely explored in medicine, the philosophy of mind. While conventional psychological models (eg, the Health Belief Model) provide explanations and predictions which have only a statistical value, the philosophical assumption that mental states (eg, beliefs) are causally efficient (mental causation) can provide the basis for a causal theory of health behaviors. This paper shows that nonadherence to long term therapies can be described as the medical expression of a philosophical concept, that is, weakness of will. I use philosophical explanations of this concept to suggest a mechanistic explanation of nonadherence. I propose that it results from the failure of two principles of rationality. First, a principle of continence, described by the philosopher Donald Davidson in his explanation of weakness of will. This principle exhorts us to act after having considered all available arguments and according to which option we consider best. However, patients conforming to this principle of continence should rationally be nonadherent. Indeed, when patients face a choice between adherence and nonadherence, they must decide, in general, between a large, but delayed reward (eg, health) and a small, but immediate reward (eg, smoking a cigarette). According to concepts elaborated by George Ainslie and Jon Elster, the force of our desires is strongly influenced by the proximity of reward. This inter-temporal choice theory on one hand, and the mere principle of continence on the other, should therefore lead to nonadherence. Nevertheless, adherence to long term therapies is possible, as a result of the intervention of an additional principle, the principle of foresight, which tells us to give

  7. Long-term effects of music therapy on elderly with moderate/severe dementia.

    PubMed

    Takahashi, Takiko; Matsushita, Hiroko

    2006-01-01

    Over a period of 2 years we assessed the long-term effects of group music therapy carried out once weekly on the elderly (mean age: 83 years) suffering from moderate or severe dementia by observing changes in the cortisol level in saliva and in blood pressure and by an intelligence assessment. Systolic blood pressure determined 1 and 2 years after the start of therapy increased significantly in the nonmusic therapy group compared with that in music therapy group (p < .05). Systolic blood pressure increases with aging; the systolic blood pressure was significantly lower in participants who received music therapy. No significant differences in cortisol level in saliva or intelligence assessment score were observed, but the music therapy group maintained their physical and mental states during the 2-year period better than the nonmusic therapy group. This result indicates the lasting effect of once-a-week continuous music therapy. Even the elderly with moderate or severe dementia were able to participate in the group music therapy, and results suggest that enjoying singing and playing musical instruments in a concert was effective in preventing cardiac and cerebral diseases.

  8. Evaluation of thyroid and parathyroid functions in children receiving long-term carbamazepine therapy.

    PubMed

    Caksen, Huseyin; Dulger, Haluk; Cesur, Yasar; Atas, Bulent; Tuncer, Oguz; Odabas, Dursun

    2003-09-01

    We studied serum calcium, phosphorus, alkaline phosphatase (ALP), thyroid hormones (total thyroxine [TT4], free thyroxine [FT4], thyroid-stimulating hormone [TSH]), parathyroid hormone (PH), and osteocalcine levels in children with epilepsy who had been receiving long-term carbamazepine (CBZ) therapy to determine whether there was any effect of CBZ therapy on these hormones. The study included 18 patients with epilepsy receiving CBZ and 16 healthy age-matched controls. The age ranged from 4-18 years (11.26 +/- 3.59 years) and 4.5-17 years (11.16 +/- 3.13 years) in the study and control group, respectively. The duration of CBZ use was between 10 months-5 years (3.12 +/- 1.09 years). When comparing the results we did not find any significant difference in serum calcium, phosphorus, ALP, osteocalcine and TSH and PH levels between the groups (p >.05). However, serum TT4 and FT4 levels were found to be significantly lower in the study group than those of control group (p <.05). However, we observed no clinical signs of hypothyroidism in all subjects. To these findings we suggest that serum thyroid hormone levels should be monitored in children receiving long-term CBZ therapy.

  9. Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura.

    PubMed

    Emilia, Giovanni; Morselli, Monica; Luppi, Mario; Longo, Giuseppe; Marasca, Roberto; Gandini, Giovanna; Ferrara, Leonardo; D'Apollo, Nicola; Potenza, Leonardo; Bertesi, Marcello; Torelli, Giuseppe

    2002-02-15

    Treatment of severe, chronic idiopathic thrombocytopenic purpura (ITP) refractory to most usual therapies is a difficult challenge. Little information exists on the clinical use of cyclosporin A (CyA) in the treatment of ITP. This report describes long-term treatment with CyA (median, 40 months) and follow-up (median, 36.8 months) in 12 adult patients with resistant ITP. CyA used in relatively low doses (2.5-3 mg/kg of body weight per day) led to a clinical improvement in 10 patients (83.3%). Five had a complete response (41.1%), 4 a complete response to maintenance therapy (33.3%), and one a partial response (8.3%). Two patients had no response. Most patients with a response (60%) had a long-term remission (mean, 28.6 months) after discontinuation of CyA. One patient had a relapse of ITP 4 years after CyA therapy was stopped. Side effects were moderate and transient, even in patients dependent on continued CyA treatment. CyA seems to represent reasonable salvage treatment in severe, potentially life-threatening, refractory ITP.

  10. Is long-term bisphosphonate therapy associated with benefits to the periodontium in postmenopausal women?

    PubMed

    Palomo, Leena; Buencamino-Francisco, Maria Clarinda A; Carey, John J; Sivanandy, Mala; Thacker, Holly

    2011-02-01

    The aim of this study was to compare the periodontium of postmenopausal women with known low bone mineral density who are receiving long-term bisphosphonate therapy with those who are not. The periodontal status of 28 white postmenopausal women with low bone density using bisphosphonate therapy for at least 2 years was compared with that of a matching group not using such therapy. All women underwent a cone-beam CT scan of the jaw and a complete periodontal examination evaluating for plaque score, periodontal probing depth, clinical attachment loss, bleeding on probing, and alveolar bone height. Bisphosphonate users had higher plaque score, lower probing depth, and lesser clinical attachment loss compared with the controls. These differences were determined to be significant by both t test and Wilcoxon's tests. Bleeding on probing was lower and the alveolar bone height was higher in the bisphosphonate group than in controls, but these differences were not statistically significant. Linear models showed no significant interactions between plaque score and bisphosphonate use, suggesting that the association of periodontal status and outcome measures was constant across all levels of plaque scores. Bisphosphonate use was a significant factor for probing depth but was not significant for the other parameters when adjusted for plaque score. Long-term bisphosphonate use seems to have some beneficial effects on the periodontium of postmenopausal women with low bone density, across all levels of plaque score.

  11. Hepatitis B reactivation in a long-term nonprogressor due to nivolumab therapy.

    PubMed

    Lake, Adam C

    2017-09-24

    : Hepatitis B virus (HBV) reactivation has been documented in association with multiple immunotherapy regimens . These reactivations can be life-threatening and result in fulminant hepatic failure. There are currently no reports of HBV reactivation on nivolumab treatment. This is a case of a patient with known HIV infection and previous HBV workup that revealed him to be anti-hepatitis B core antibody positive, hepatitis B surface antigen negative, and HBV DNA negative. He experienced a HBV reactivation while on therapy with nivolumab for stage IIIa poorly differentiated carcinoma of the lung, which was a recurrence from a prior surgically resected stage Ia well differentiated adenocarcinoma of the lung. He is a long-term nonprogressor in regards to his HIV and had previously had a negative HBV DNA level and had declined antiretroviral therapy until just prior to starting nivolumab. This case is also of interest as antiprogrammed death-1 receptors are involved in CD4-related HIV control , and the effects of nivolumab in a patient who was an HIV long-term nonprogressor are unknown. There was concern that he would develop increased HIV viremia and CD4-related immune dysfunction without antiretroviral therapy, and thus, he agreed to treatment prior to starting antineoplastic immunotherapy.

  12. The long-term effects of radiation therapy on patients with ovarian dysgerminoma

    SciTech Connect

    Mitchell, M.F.; Gershenson, D.M.; Soeters, R.P.; Eifel, P.J.; Delclos, L.; Wharton, J.T. )

    1991-02-15

    A retrospective chart review and questionnaire study was undertaken to look at the long-term effects of radiation therapy in ovarian dysgerminoma patients. Forty-three patients and 55 controls responded to a questionnaire that detailed bowel, bladder, thyroid, menstrual, reproductive, sexual, and growth function. Statistically significant differences in the number of bowel movements were noticed when comparing patients with controls. The authors noticed no significant differences between cases and controls in bladder function. No thyroid disorders were attributable to mediastinal radiation therapy. Most patients with intact uteri bleed monthly on hormonal replacement. Three patients with a remaining ovary and uterus resumed menstrual function after substantial doses of abdominopelvic radiation therapy. No patients have conceived. The authors noticed a slight increase in dyspareunia in the treated group, but most patients were satisfied with their sexual function. One premenarchal patient exhibited a growth disorder.

  13. Using music therapy to help a client with Alzheimer's disease adapt to long-term care.

    PubMed

    Kydd, P

    2001-01-01

    The purpose of this case study is to illustrate how music therapy can be used to help the elderly successfully adjust to living in a long-term care (LTC) facility. LTC residents, particularly those with Alzheimer's disease or related dementia, may exhibit behaviors such as depression, withdrawal, anxiety, emotional liability, confusion, and memory difficulties, frequently related to the disorder, but often exacerbated by difficulty in adjustment to the change in lifestyle. The subject of this case study demonstrated these symptoms. Music therapy helped him adjust to life in a LTC setting by improving his quality of life and enhancing his relationships with those around him. As chronicled in this study, music therapy may facilitate a resident's adjustment to life in a LTC facility. N.B. Names and identifying information have been changed to protect privacy.

  14. Long-Term Outcomes on Antiretroviral Therapy in a Large Scale-Up Program in Nigeria

    PubMed Central

    Meloni, Seema T.; Chang, Charlotte A.; Eisen, Geoffrey; Jolayemi, Toyin; Banigbe, Bolanle; Okonkwo, Prosper I.; Kanki, Phyllis J.

    2016-01-01

    Background While there has been a rapid global scale-up of antiretroviral therapy programs over the past decade, there are limited data on long-term outcomes from large cohorts in resource-constrained settings. Our objective in this evaluation was to measure multiple outcomes during first-line antiretroviral therapy in a large treatment program in Nigeria. Methods We conducted a retrospective multi-site program evaluation of adult patients (age ≥15 years) initiating antiretroviral therapy between June 2004 and February 2012 in Nigeria. The baseline characteristics of patients were described and longitudinal analyses using primary endpoints of immunologic recovery, virologic rebound, treatment failure and long-term adherence patterns were conducted. Results Of 70,002 patients, 65.2% were female and median age was 35 (IQR: 29–41) years; 54.7% were started on a zidovudine-containing and 40% on a tenofovir-containing first-line regimen. Median CD4+ cell counts for the cohort started at 149 cells/mm3 (IQR: 78–220) and increased over duration of ART. Of the 70,002 patients, 1.8% were reported as having died, 30.1% were lost to follow-up, and 0.1% withdrew from treatment. Overall, of those patients retained and with viral load data, 85.4% achieved viral suppression, with 69.3% achieving suppression by month 6. Of 30,792 patients evaluated for virologic failure, 24.4% met criteria for failure and of 45,130 evaluated for immunologic failure, 34.0% met criteria for immunologic failure, with immunologic criteria poorly predicting virologic failure. In adjusted analyses, older age, ART regimen, lower CD4+ cell count, higher viral load, and inadequate adherence were all predictors of virologic failure. Predictors of immunologic failure differed slightly, with age no longer predictive, but female sex as protective; additionally, higher baseline CD4+ cell count was also predictive of failure. Evaluation of long-term adherence patterns revealed that the majority of patients

  15. Long-term antiplatelet therapy following myocardial infarction: implications of PEGASUS-TIMI 54.

    PubMed

    Parker, William A E; Storey, Robert F

    2016-05-15

    Dual antiplatelet therapy (DAPT) is standard treatment for patients with acute coronary syndromes (ACS), typically comprising the use of aspirin with either an irreversible thienopyridine P2Y12 inhibitor, clopidogrel or prasugrel, or reversibly binding ticagrelor. Pivotal studies led to guidelines recommending DAPT for up to 12 months post-ACS. Despite this, there remains a significant burden of coronary artery disease (CAD)-related events up to and after this period. Recent meta-analyses, including both patients with ACS and patients with stable CAD treated with DAPT following percutaneous coronary intervention, have suggested that long-term thienopyridine-based DAPT reduces the risks of myocardial infarction (MI) and stent thrombosis but may paradoxically increase all-cause mortality risk. The PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 54) study examined the effects of long-term DAPT with aspirin and ticagrelor, compared with aspirin alone, on major adverse cardiovascular events (MACE) and complications, including bleeding in patients with prior history of MI. It showed that, over a 3-year period, ticagrelor reduced the risk of MACE but increased non-fatal bleeding risk. Overall, the PEGASUS-TIMI 54 results demonstrate that patients with a history of ACS deemed to be at high risk of further ischaemic events, particularly those in whom the risks of ischaemic events and cardiovascular death outweigh the risk of life-threatening bleeding, may benefit from prolonged ticagrelor-based DAPT. Guidelines are emerging which reflect this. The relationship between aspirin and ticagrelor, particularly with regard to aspirin dosing, remains to be fully elucidated and attention has recently been turned to the option of ticagrelor monotherapy. Future studies will explore optimal individualised strategies for long-term

  16. Racial differences in long-term adherence to oral antidiabetic drug therapy: a longitudinal cohort study

    PubMed Central

    Trinacty, Connie M; Adams, Alyce S; Soumerai, Stephen B; Zhang, Fang; Meigs, James B; Piette, John D; Ross-Degnan, Dennis

    2009-01-01

    Background Adherence to oral antidiabetic medications is often suboptimal. Adherence differences may contribute to health disparities for black diabetes patients, including higher microvascular event rates, greater complication-related disability, and earlier mortality. Methods In this longitudinal retrospective cohort study, we used 10 years of patient-level claims and electronic medical record data (1/1/1992–12/31/2001) to assess differences in short- and long-term adherence to oral antidiabetic medication among 1906 newly diagnosed adults with diabetes (26% black, 74% white) in a managed care setting in which all members have prescription drug coverage. Four main outcome measures included: (1) time from diabetes diagnosis until first prescription of oral antidiabetic medication; (2) primary adherence (time from first prescription to prescription fill); (3) time until discontinuation of oral antidiabetic medication from first prescription; and (4) long-term adherence (amount dispensed versus amount prescribed) over a 24-month follow-up from first oral antidiabetic medication prescription. Results Black patients were as likely as whites to initiate oral therapy and fill their first prescription, but experienced higher rates of medication discontinuation (HR: 1.8, 95% CI: 1.2, 2.7) and were less adherent over time. These black-white differences increased over the first six months of therapy but stabilized thereafter for patients who initiated on sulfonylureas. Significant black-white differences in adherence levels were constant throughout follow-up for patients initiated on metformin therapy. Conclusion Racial differences in adherence to oral antidiabetic drug therapy persist even with equal access to medication. Early and continued emphasis on adherence from initiation of therapy may reduce persistent racial differences in medication use and clinical outcomes. PMID:19200387

  17. Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents

    PubMed Central

    2012-01-01

    Aim The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. Design The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15–19 y) with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR). Results The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. Conclusions The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways. PMID:22989045

  18. Effect of Long-Term Proton Pump Inhibitor Therapy on Nutritional Status in Elderly Hospitalized Patients.

    PubMed

    Nakamichi, Mariko; Wakabayashi, Hidetaka

    2016-01-01

    The purpose was to investigate the association between proton pump inhibitor (PPI) therapy and nutritional status in elderly hospitalized patients. Participants were 190 elderly patients admitted to the long-term care wards, convalescence rehabilitation wards, and community integrated care wards in January 2015. Nutritional status was assessed using the mini nutritional assessment short-form (MNA-SF). The PPI use group was compared with the PPI non-use group regarding nutrition status. Logistic regression analysis was used to examine whether the period of PPI therapy was associated independently with malnutrition following adjustment for covariates including gender, age, and serum albumin level. Forty-one patients were male (22%) and 149 patients were female (78%), with a mean age of 85.4±8.4. Fifty-three patients (28%) took PPIs (with a median prescription period of 91 d, ranging from 51 to 227). With a MNA-SF score of 7 points or lower designated as malnutrition, there was no significant difference in nutritional status between the PPI and non-PPI groups (p=0.172). The median MNA-SF scores in the PPI and non-PPI groups were 9 vs 7 points, respectively. Logistic regression analysis showed that long-term PPI therapy (odds ratio, 0.994; 95% confidence interval 0.990-0.999) was significantly associated with improved nutritional status. The presence or absence of PPI therapy is not associated with malnutrition in elderly hospitalized patients. Longer-term PPI therapy may improve nutritional status.

  19. [Long-term oxygen therapy: which form of administration can be recommended?].

    PubMed

    Tausendpfund, C; Petro, W

    1996-03-01

    A great variety of application devices for long-term-oxygen-therapy are being used. In order to find out which products can be especially recommended we conducted an inquiry among German lung specialists asking which devices they were preferring and why. Additionally, in a clinical study the efficiency of basic types of products has been compared. Data about patients' acceptance of different devices have been collected by another inquiry. As it turned out the most efficient models (e.g. oxygen catheters) are only accepted by a very small number of patients. So they can not be recommended for long-term-oxygen-therapy. Patients' acceptance concentrates on nasal oxygen cannulae having two tubes that lead into the nostrils but no foam pad. The product PARI 96.2020 is expecially favoured as it combines "tight fit", "soft material" and "easy handling", criteria most important for the patients. Similar models (PARI 96.2021 and Airlife), although following on the next two places, are only favoured by half as much patients. As obviously quite simple, functional products are preferred to very sophisticated and expensive ones, future development should also follow the demands of patients, not only theoretical considerations.

  20. Long-term follow-up after gene therapy for canavan disease.

    PubMed

    Leone, Paola; Shera, David; McPhee, Scott W J; Francis, Jeremy S; Kolodny, Edwin H; Bilaniuk, Larissa T; Wang, Dah-Jyuu; Assadi, Mitra; Goldfarb, Olga; Goldman, H Warren; Freese, Andrew; Young, Deborah; During, Matthew J; Samulski, R Jude; Janson, Christopher G

    2012-12-19

    Canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to loss of enzyme activity and increased concentrations of the substrate N-acetyl-aspartate (NAA) in the brain. Accumulation of NAA results in spongiform degeneration of white matter and severe impairment of psychomotor development. The goal of this prospective cohort study was to assess long-term safety and preliminary efficacy measures after gene therapy with an adeno-associated viral vector carrying the ASPA gene (AAV2-ASPA). Using noninvasive magnetic resonance imaging and standardized clinical rating scales, we observed Canavan disease in 28 patients, with a subset of 13 patients being treated with AAV2-ASPA. Each patient received 9 × 10(11) vector genomes via intraparenchymal delivery at six brain infusion sites. Safety data collected over a minimum 5-year follow-up period showed a lack of long-term adverse events related to the AAV2 vector. Posttreatment effects were analyzed using a generalized linear mixed model, which showed changes in predefined surrogate markers of disease progression and clinical assessment subscores. AAV2-ASPA gene therapy resulted in a decrease in elevated NAA in the brain and slowed progression of brain atrophy, with some improvement in seizure frequency and with stabilization of overall clinical status.

  1. Percutaneous Therapy of Ureteral Obstructions and Leak After Renal Transplantation: Long-Term Results

    SciTech Connect

    Aytekin, Cueneyt Boyvat, Fatih; Harman, Ali; Ozyer, Umut; Colak, Turan; Haberal, Mehmet

    2007-11-15

    The purpose of this study was to evaluate the long-term outcome of percutaneous therapy of ureteral complications after renal transplantation. Between January 2000 and June 2006 we percutaneously treated 26 renal transplant patients with ureteral obstruction (n=19) and leak (n=7). Obstructions were classified as early (<2 months after transplantation) or late (>2 months). Patients with leak were treated with nephro-ureteral catheter placement and subsequent double-J stenting. Balloon dilatation, stent placement, and basket extraction were used to treat ureteral obstructions. Patients were followed with ultrasonography. No major procedure-related complication occurred. The mean follow-up time was 34.3 months (range: 6 to 74 months). Initial clinical success was achieved in all 19 patients with obstruction and 6 of 7 patients with leak. Four of 9 early obstructions and 4 of 10 late obstructions recurred during the follow-up. All recurrences were initially managed again with percutaneous methods, including cutting balloon technique and metallic stent placement. Although there was no recurrence in patients with successfully treated leak, stricture was seen at the previous leak site in two patients. These strictures were also successfully managed percutaneously. We conclude that in the treatment of ureteral obstruction and leak following renal transplantation, percutaneous therapy is an effective alternative to surgery. However, further interventions are usually needed to maintain long-term patency.

  2. Bacteriophages of Pseudomonas aeruginosa: long-term prospects for use in phage therapy.

    PubMed

    Krylov, Victor N

    2014-01-01

    Bacteria Pseudomonas aeruginosa, being opportunistic pathogens, are the major cause of nosocomial infections and, in some cases, the primary cause of death. They are virtually untreatable with currently known antibiotics. Phage therapy is considered as one of the possible approaches to the treatment of P. aeruginosa infections. Difficulties in the implementation of phage therapy in medical practice are related, for example, to the insufficient number and diversity of virulent phages that are active against P. aeruginosa. Results of interaction of therapeutic phages with bacteria in different conditions and environments are studied insufficiently. A little is known about possible interactions of therapeutic phages with resident prophages and plasmids in clinical strains in the foci of infections. This chapter highlights the different approaches to solving these problems and possible ways to expand the diversity of therapeutic P. aeruginosa phages and organizational arrangements (as banks of phages) to ensure long-term use of phages in the treatment of P. aeruginosa infections.

  3. Long-Term Nonsense Suppression Therapy Moderates MPS I-H Disease Progression

    PubMed Central

    Gunn, Gwen; Dai, Yanying; Du, Ming; Belakhov, Valery; Kandasamy, Jeyakumar; Schoeb, Trenton R.; Baasov, Timor; Bedwell, David M.; Keeling, Kim M.

    2014-01-01

    Nonsense suppression therapy is a therapeutic approach aimed at treating genetic diseases caused by in-frame premature termination codons (PTCs; also commonly known as nonsense mutations). This approach utilizes compounds that suppress translation termination at PTCs, which allows translation to continue and partial levels of deficient protein function to be restored. We hypothesize that suppression therapy can attenuate the lysosomal storage disease mucopolysaccharidosis type I-Hurler (MPS I-H), the severe form of α-L-iduronidase deficiency. α-L-iduronidase participates in glycosaminoglycan (GAG) catabolism and its insufficiency causes progressive GAG accumulation and onset of the MPS I-H phenotype, which consists of multiple somatic and neurological defects. 60-80% of MPS I-H patients carry a nonsense mutation in the IDUA gene. We previously showed that 2-week treatment with the designer aminoglycoside NB84 restored enough α-L-iduronidase function via PTC suppression to reduce tissue GAG accumulation in the Iduatm1Kmke MPS I-H mouse model, which carries a PTC homologous to the human IDUA-W402X nonsense mutation. Here we report that long-term NB84 administration maintains α-L-iduronidase activity and GAG reduction in Iduatm1Kmke mice throughout a 28-week treatment period. Examination of more complex MPS I-H phenotypes in Iduatm1Kmke mice following 28-week NB84 treatment revealed significant moderation of the disease in multiple tissues, including the brain, heart and bone, that are resistant to current MPS I-H therapies. This study represents the first demonstration that long-term nonsense suppression therapy can moderate progression of a genetic disease. PMID:24411223

  4. Long-term nonsense suppression therapy moderates MPS I-H disease progression.

    PubMed

    Gunn, Gwen; Dai, Yanying; Du, Ming; Belakhov, Valery; Kandasamy, Jeyakumar; Schoeb, Trenton R; Baasov, Timor; Bedwell, David M; Keeling, Kim M

    2014-03-01

    Nonsense suppression therapy is a therapeutic approach aimed at treating genetic diseases caused by in-frame premature termination codons (PTCs; also commonly known as nonsense mutations). This approach utilizes compounds that suppress translation termination at PTCs, which allows translation to continue and partial levels of deficient protein function to be restored. We hypothesize that suppression therapy can attenuate the lysosomal storage disease mucopolysaccharidosis type I-Hurler (MPS I-H), the severe form of α-L-iduronidase deficiency. α-L-iduronidase participates in glycosaminoglycan (GAG) catabolism and its insufficiency causes progressive GAG accumulation and onset of the MPS I-H phenotype, which consists of multiple somatic and neurological defects. 60-80% of MPS I-H patients carry a nonsense mutation in the IDUA gene. We previously showed that 2-week treatment with the designer aminoglycoside NB84 restored enough α-L-iduronidase function via PTC suppression to reduce tissue GAG accumulation in the Idua(tm1Kmke) MPS I-H mouse model, which carries a PTC homologous to the human IDUA-W402X nonsense mutation. Here we report that long-term NB84 administration maintains α-L-iduronidase activity and GAG reduction in Idua(tm1Kmke) mice throughout a 28-week treatment period. An examination of more complex MPS I-H phenotypes in Idua(tm1Kmke) mice following 28-week NB84 treatment revealed significant moderation of the disease in multiple tissues, including the brain, heart and bone, that are resistant to current MPS I-H therapies. This study represents the first demonstration that long-term nonsense suppression therapy can moderate progression of a genetic disease. Published by Elsevier Inc.

  5. Impact of clinical and echocardiographic response to cardiac resynchronization therapy on long-term survival.

    PubMed

    Bertini, Matteo; Höke, Ulas; van Bommel, Rutger J; Ng, Arnold C T; Shanks, Miriam; Nucifora, Gaetano; Auger, Dominique; Borleffs, C Jan Willem; van Rijnsoever, Eva P M; van Erven, Lieselot; Schalij, Martin J; Marsan, Nina Ajmone; Bax, Jeroen J; Delgado, Victoria

    2013-08-01

    Clinical or echocardiographic mid-term responses to cardiac resynchronization therapy (CRT) may have a different influence on a long-term prognosis of heart failure patients treated with CRT. The aim of the evaluation was to establish which definition of response to CRT, clinical or echocardiographic, best predicts long-term prognosis. A total of 679 heart failure patients treated with CRT were included. All the patients underwent a complete history and physical examination and transthoracic echocardiogram prior to CRT implantation and at 6-month follow-up. The clinical and echocardiographic responses to CRT were defined based on clinical improvement (≥1 NYHA class) and LV reverse remodelling (reduction in LV end-systolic volume ≥15%) at 6-month follow-up, respectively. All the patients were prospectively followed up for the occurrence of death. The mean age was 65 ± 11 years and 79% of the patients were male. At 6-month follow-up, 510 (77%) patients showed clinical response to CRT and 412 (62%) patients showed echocardiographic response to CRT. During a mean follow-up of 37 ± 22 months, 140 (21%) patients died. Clinical and echocardiographic responses to CRT were both significantly related to all-cause mortality on univariable analysis. However, on multivariable Cox-regression analysis only echocardiographic response to CRT was independently associated with superior survival (hazard ratio: 0.38; 95% CI: 0.27-0.50; P < 0.001). In a large population of heart failure patients treated with CRT, the reduction in LV end-systolic volume at the mid-term follow-up demonstrated to be a better predictor of long-term survival than improvement in the clinical status.

  6. Postoperative hemorrhagic complications after elective laparoscopic cholecystectomy in patients receiving long-term anticoagulant therapy.

    PubMed

    Ercan, Metin; Bostanci, Erdal B; Ozer, Ilter; Ulas, Murat; Ozogul, Yusuf B; Teke, Zafer; Akoglu, Musa

    2010-03-01

    Among patients on long-term anticoagulant therapy who undergo laparoscopic cholecystectomy (LC), bleeding complications have not been extensively investigated. The objective of this study was therefore to investigate postoperative bleeding complications prospectively in patients on chronic oral anticoagulation. In the period of January 2002 to December 2007, 44 patients on long-term anticoagulation with warfarin, an oral anticoagulant (OAC), underwent LC in our center. Oral anticoagulant was discontinued 5 days before the planned date of surgery, and patients were admitted to the hospital 3 days before. Upon admission, bridging anticoagulation with enoxaparin, a low molecular weight heparin (LMWH), was started. When their international normalized ratio (INR) decreased to <1.5, patients underwent LC. In the absence of postoperative bleeding complications, OAC and LMWH were resumed on the evening of the day of surgery, and LMWH was continued until each patient's target INR was reached. A comparison group was comprised by 1,421 consecutively enrolled patients with no comorbid disease who underwent LC during the same period. In the comparison group, postoperative bleeding was encountered in 21 patients (1.5%). In the anticoagulation group, postoperative bleeding was encountered in 11 patients (25%) and ranged from minor oozing from a port incision in one patient to hemorrhage, sepsis, and fatality in one patient. In the anticoagulation group, no significant differences were found between patients with and without postoperative bleeding in terms of age, gender, body mass index, American Society of Anesthesiologists score, INR, or other hemostasis parameters. In patients who underwent LC with bridging anticoagulation, postoperative bleeding was markedly more frequent than expected and was not predicted by the usual coagulation parameters. This suggests a need for methods that can indicate which patients on long-term anticoagulation are at risk for postoperative bleeding.

  7. Giant cell tumor: rapid recurrence after cessation of long-term denosumab therapy.

    PubMed

    Matcuk, George R; Patel, Dakshesh B; Schein, Aaron J; White, Eric A; Menendez, Lawrence R

    2015-07-01

    We report a case of rapid recurrence of a giant cell tumor (GCT) of the distal radius in a 24-year-old woman following the cessation of long-term denosumab therapy. GCT of bone is a histologically benign tumor with multinucleated giant cells on a background of mononuclear giant cells usually presenting as a well-defined epi-metaphyseal lytic lesion without sclerotic margins. Denosumab, a monoclonal antibody to the receptor activator of nuclear factor kappa-B ligand (RANKL), has proven to be an effective neoadjuvant treatment for GCT. The tumor in this case had demonstrated a good response with sustained control for over 2 years while on denosumab therapy. However, within 2 months of cessation of therapy, the tumor demonstrated rapid recurrence and progression with growth, osteolysis, and increased soft tissue component. Despite reinitiating denosumab therapy, there was progressive tumor growth and destruction, ultimately necessitating below-the-elbow amputation. This case illustrates the need for maintenance of denosumab therapy for GCT of bone or definitive surgical treatment prior to its cessation.

  8. Long-term efficacy of endoscopic vacuum therapy for the treatment of colorectal anastomotic leaks.

    PubMed

    Arezzo, Alberto; Verra, Mauro; Passera, Roberto; Bullano, Alberto; Rapetti, Lisa; Morino, Mario

    2015-04-01

    Anastomotic leaks are a severe complication after colorectal surgery. We aimed to evaluate the long-term efficacy of endoscopic vacuum therapy for their treatment. Retrospective review of a series of post-surgical colorectal leaks treated with endoscopic vacuum therapy, with minimum follow-up of 1 year. Generalized peritonitis or haemodynamic instability was considered contraindication to endoscopic treatment. Endoscopic vacuum therapy was applied in 14 patients with colorectal leak, in 2 cases complicated by recto-vaginal fistula. Overall success rate was 79%, favoured by early beginning of treatment (90%) and presence of a stoma (100%) and no preoperative radiotherapy (86%). Median duration of treatment was 12.5 sessions (range 4-40). Median time for complete healing was 40.5 days (range 8-114), for a median cost of treatment of 3125 Euros. No complication related to endoscopic vacuum therapy was observed. Further surgery was required in 3 cases. Endoscopic vacuum therapy is a safe treatment for post-surgical leaks, with high success rates. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  9. Short- and long-term effects of spa therapy in knee osteoarthritis.

    PubMed

    Fioravanti, Antonella; Iacoponi, Francesca; Bellisai, Barbara; Cantarini, Luca; Galeazzi, Mauro

    2010-02-01

    To assess both the short- and long-term effectiveness of spa therapy in patients with primary knee osteoarthritis in a prospective, randomized, single-blinded, controlled trial. Eighty outpatients were enrolled in this study; 40 patients were treated with a combination of daily local mud packs and bicarbonate-sulfate mineral bath water from the spa center of Rapolano Terme (Siena, Italy) for 2 wks, and 40 patients continued regular, routine ambulatory care. Patients were assessed at baseline time; after 2 wks; after 3, 6, and 9 mos after the beginning of the study and were evaluated by Visual Analog Scale for spontaneous pain, Lequesne index, Western Ontario and McMaster Universities Index for gonarthrosis, Arthritis Impact Measurement Scale-1, and symptomatic drug consumption. We observed a significant improvement of all evaluated parameters at the end of the cycle of spa therapy, which persisted throughout the whole of the follow-up period, whereas in the control group no significant differences were noted. This symptomatic effect was confirmed by the significant reduction of symptomatic drug consumption. Tolerability of spa therapy seemed to be good, with light and transitory side effects. The results from our study confirm that the beneficial effects of spa therapy in patients with knee osteoarthritis lasts over time, with positive effects on the painful symptomatology and a significant improvement on functional capacities. Spa therapy can represent a useful backup to pharmacologic treatment of knee osteoarthritis or a valid alternative for patients who do not tolerate pharmacologic treatments.

  10. Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes.

    PubMed

    Abeles, Shira R; Ly, Melissa; Santiago-Rodriguez, Tasha M; Pride, David T

    2015-01-01

    Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances.

  11. Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes

    PubMed Central

    Abeles, Shira R.; Ly, Melissa; Santiago-Rodriguez, Tasha M.; Pride, David T.

    2015-01-01

    Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances. PMID:26309137

  12. Long-term results of low-fluence photodynamic therapy for chronic central serous chorioretinopathy.

    PubMed

    Leys, E; Tuttle, S; Rasquin, F; Neu, F; Postelmans, L

    2015-10-01

    To evaluate long-term results of low-fluence photodynamic therapy (PDT) with verteporfin in the treatment of chronic central serous chorioretinopathy (CCSC). Retrospective medical record review of 38 eyes (34 patients) who received low-fluence PDT for the treatment of CCSC. Visual acuity (VA), fundus biomicroscopy, fluorescein angiography (FA), indocyanine green angiography (ICG) and optical coherence tomography (OCT) were analyzed. Thirty-eight eyes (34 patients) with CCSC received low-fluence PDT. Mean follow-up after PDT was 43.97 months. Mean logMar best corrected VA (BCVA) improved significantly from 0.33 to 0.11 at the last follow-up which corresponds to a gain of 2.2 lines. At 3 months, complete resolution of central subretinal fluid was achieved on OCT after 1 PDT in 37 eyes and after 2 PDTs in 1 eye (retreated at 3 months after first PDT). One patient developed choroidal neovascularization (CNV) 4 years after his low-fluence PDT and received anti-vascular endothelial growth factor (VEGF) injections. Low-fluence PDT with verteporfin for CCSC seems efficacious and safe in the long-term. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Effect of Long-Term, Low-Dose Aspirin Therapy on Renal Graft Function.

    PubMed

    Ali, Hatem; Shaaban, Ahmed; Murtaza, Asam; Howell, Laura E; Ahmed, Aimun

    2017-08-01

    Despite improvements in immunosuppressive protocols for renal transplant, long-term success of renal transplant is still limited by the occurrence of interstitial fibrosis and tubular atrophy. Some studies have shown that aspirin decreases the severity of kidney ischemia-reperfusion injury and the development of tubular atrophy in animal models. This study aimed to assess the effects of aspirin therapy started at the time of transplant on long-term graft function. We compared renal graft function of 82 patients on low-dose aspirin 75 mg once daily who underwent renal transplant between 1 January 2000 and 31 December 2010 from a single center with 65 patients not taking aspirin. For each patient, the following measurements were collected: age, sex, creatinine level, type of donor, cold ischemia time, occurrence of acute allograft rejections, number of HLA mismatches, first transplant, intake of statins, number of antihypertensive medications, and number of days posttransplant. Patients were excluded from the study who were on aspirin before transplant or who had coronary artery disease. Multilevel modelling was used to compare renal allograft function, as measured by serum creatinine levels, between patients taking and not taking aspirin after kidney transplant. Aspirin was not significantly associated with creatinine levels (P = .59) after adjusting for other relevant variables. Low-dose aspirin started at the time of transplant has a negligible effect on renal allograft function over the 15-year study period posttransplant.

  14. Long term effects of extended adjuvant endocrine therapy on quality of life in breast cancer patients.

    PubMed

    Kool, M; Fontein, D B Y; Meershoek-Klein Kranenbarg, E; Nortier, J W R; Rutgers, E J T; Marang-van de Mheen, P J; van de Velde, C J H

    2015-06-01

    The standard treatment for hormone-receptor positive, postmenopausal early breast cancer patients is 5 years of adjuvant endocrine therapy. Previous studies demonstrate that prolonging adjuvant endocrine therapy may improve disease-free survival. However, endocrine therapy is known for its adverse events, which may negatively affect Quality of Life (QoL). The aim of this study is to assess the impact of extended adjuvant endocrine therapy on long-term QoL outcomes. 471 patients selected from the IDEAL trial were invited to complete a questionnaire 1-1.5 years after starting with extended therapy. The questionnaire consisted of the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Mean QoL outcomes were compared with EORTC reference values for stage I and II breast cancer patients and the general population. Furthermore, QoL outcomes were compared between different treatment regimens. A difference of eight points was considered clinically relevant. IDEAL patients receiving extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with reference values for stage I and II breast cancer patients (79.6 versus 64.6; p < 0.01) and the general population (79.6 versus 71.2; p < 0.01). Similar results were found for emotional function, pain, appetite loss, diarrhea and financial problems. Between treatment regimens prior to extended adjuvant endocrine therapy, differences were only found on specific QoL domains (e.g. arm symptoms). Breast cancer patients on extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with other stage I-II breast cancer patients and the general population, 6-8.5 years after diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Value of Inhaled Corticosteroid Therapy In Long-Term Asthma Management

    PubMed Central

    Beam, Donald S.

    2010-01-01

    Asthma, which affects more than 22 million people in the U.S. every year, poses a significant clinical and economic burden to our health care system. Patients, health care practitioners, and payers require a variety of resources to ensure optimal disease management and positive clinical outcomes while also managing costs. In addition, decision makers in health care must determine the most appropriate and cost-efficient therapy or class of agents to achieve asthma control. As such, payers rely on evidence-based medicine, including guidelines to determine the right therapy for the right patient. Inhaled corticosteroid (ICS) therapy plays a critical role in the management of mild-to-moderate persistent asthma. Despite national treatment guidelines that cite ICS therapy as the most effective and safest long-term treatment option for persistent asthma, ICS monotherapy continues to be underused. One retrospective claims study found that 55.2% of children with mild-to-moderate asthma received prescriptions for combination therapy (ICS and long-acting beta-agonists) as initial controller treatment. This practice is contrary to national treatment guidelines, which recommend a step-therapy approach. These prescribing patterns result in higher pharmacy costs, do not always ensure control of symptoms, and sometimes expose patients to potential safety risks. This article addresses the importance of ICS therapy in the treatment of mild-to-moderate asthma, as advocated by the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3 guidelines; the role of small airway disease in asthma pathophysiology; and the clinical and economic benefits of ICS therapy. PMID:20689625

  16. Effects of Long-Term Statin Therapy in Coronary Artery Disease Patients with or without Chronic Kidney Disease.

    PubMed

    Huang, Huiling; Zeng, Chunmei; Ma, Yuedong; Chen, Yili; Chen, Cong; Liu, Chen; Dong, Yugang

    2015-01-01

    The effect of long-term statin therapy is essential for secondary prevention of adverse clinical outcomes of coronary artery disease (CAD) patients. No study has compared the effects of long-term statin treatment in CAD patients with or without chronic kidney disease (CKD) and CKD only patients. We compared the effects of long-term statin therapy (average follow-up time 5.79 years) in terms of major adverse cardiovascular events (MACE), all-cause death, and cardiac death among 570 CAD patients with or without CKD and 147 CKD only patients. The all-cause death and cardiac death of the patients with CAD and CKD (24.4% and 20.4%) doubled those of CAD only patients (10.7% and 9.1%) (P < 0.001). Long-term statin therapy dramatically reduced the rates of both MACE and all-cause death/cardiac death (by 20.5% and 28.6%/27.7%, resp.) in CAD and CKD patients. CKD only patients had no significant adverse clinical outcomes and were not responsive to long-term statin therapy. Chinese CAD patients with CKD had dramatically high rates of adverse clinical outcomes; for them, long-term statin therapies were exceptionally effective in improving morbidity and mortality. CKD patients who had no cardiovascular disease initially can prognose good clinical outcomes and do not require statin treatment.

  17. [Using focus groups to explore the group music therapy experience of long term care elderly].

    PubMed

    Lin, Hui-Chuan; Chen, Shu-Ling

    2007-04-01

    The purpose of this study was to explore the elderly's experience and perceptions of group music therapy. The residents of a long term care institution received group music therapy for one year. Afterwards, three interviews were conducted in focus groups of between six and eight of the elderly. Their ages ranged from 64 to 90. Ninety-five percent of these elderly subjects participated in the therapy for over ten months. The tape-recorded interviews were transcribed and analyzed using content analysis. Six themes emerged regarding the elderly subjects' experiences and perceptions of group music therapy, as follows: (1) becoming more willing to participate; (2) feeling pain relief and more controlled moods; (3) getting physically better; (4) being more motivated to live; (5) learning positive personal interaction and obedience to the rules of the group; and (6) learning skills to improve personal health. This information might be used as a helpful and valuable reference in nursing education and by administrative organizations involved in the planning of therapeutic programs for the elderly.

  18. [Comparative efficacy and tolerability of paroxetine and amitriptiline in long-term therapy preventing depressive recurrences].

    PubMed

    Mosolov, S N; Kostiukova, E G; Gorodnichev, A V; Timofeev, I V

    2005-01-01

    An open comparative randomized study of paroxetine (selective inhibitor of serotonin re-uptake) and tricyclic antidepressant amitriptiline has been conducted. These drugs were used for the treatment of 43 patients with recurrent depression (RD) with frequent relapses (ICD-10 F33.0-F33.2) during 12 months. There were 2 groups matched for demographic and clinical data, one included 21 patients treated by paroxetine and the other 22 patients switched to amitriptiline. Basing on clinical records and scores on a number of scales, i.e. HAM-D, CGI, quality of life, high efficacy of the drugs was confirmed, being estimated as 90,5% responders in the paroxetine group and 69,2% in the amitriptiline one, with the marked advantage of the former medication. The better tolerability, possibility of single intake and absence of severe side-effects argue for preferable use of paroxetine during long-term therapy in RD patients with frequent relapses.

  19. [Disorders of lipid and glucose metabolism. Long-term adverse effects of antiretroviral therapy].

    PubMed

    Landauer, N; Goebel, F D

    2002-04-09

    In addition to readily controllable short-term side effects, highly active antiretroviral therapy (HAART) also has long-term side effects: lipodystrophy syndrome, hyperlipoproteinemia, insulin resistance, elevated glucose tolerance sometimes leading to diabetes mellitus and lactic acidosis. The pathogenesis remains uncertain although various hypotheses have been advanced. A number of approaches for the treatment of lipodystrophy are available, the effects of which, however, have not been confirmed by study results. Hyperlipoproteinemia probably means an increased cardiovascular risk, but a final pronouncement on this is not yet possible. Fibrates and statins are currently applied for treatment, but interactions with HAART medicaments have to be considered. HAART-induced diabetes mellitus presents clinically as type 2 diabetes, and is treated accordingly.

  20. Long-term outcome of patients after a single interruption of antiretroviral therapy: a cohort study

    PubMed Central

    2012-01-01

    Background To describe the long term outcome of patients who interrupted highly active antiretroviral therapy (HAART) once, identify the variables associated with earlier need to re-start HAART, and the response when therapy was resumed. A retrospective observational cohort of 66 adult patients with HIV-1 infection who interrupted HAART with a CD4+cell count ≥350 cells/μL and undetectable viral load (VL) was performed. The pre-established CD4+ cell count for restarting therapy was 300cells/μL. Cox regression was used to analyse the variables associated with earlier HAART reinitiation. Results The median follow-up was 209 weeks (range, 64–395). Rates of HIV-related or possible HIV-related events were 0.37 (one case of acute retroviral syndrome) and 1.49 per 100 patient-years, respectively. Two patients died after re-starting therapy and having reached undetectable VL. Three patients suffered a sexually transmitted disease while off therapy. Fifty patients (76%) resumed therapy after a median of 97 weeks (range, 17–267). Age, a nadir of CD4+ <250 cells/μL, and a mean VL during interruption of >10,000 copies/ml were independent predictors for earlier re-start. The intention-to-treat success rate of the first HAART resumed regimen was 85.4%. There were no differences by regimen used, nor between regimens that were the same as or different from the one that had been interrupted. Conclusions Our data suggest highly active antiretroviral therapy may be interrupted in selected patients because in these patients, when the HAART is restarted, the viral and clinical response may be achieved. PMID:23095460

  1. Implantable left ventricular assist devices: an evolving long-term cardiac replacement therapy.

    PubMed Central

    DeRose, J J; Argenziano, M; Sun, B C; Reemtsma, K; Oz, M C; Rose, E A

    1997-01-01

    OBJECTIVE: The authors' 8-year experience with both inpatient and outpatient left ventricular assist device (LVAD) support is presented to show the possibilities and limitations of long-term outpatient mechanical circulatory assistance. SUMMARY BACKGROUND DATA: The limitation of suitable cardiac donors has led to the use of LVADs as a temporizing measure for patients awaiting cardiac transplantation. The success of such devices in the short and medium term as a bridge to transplantation has led to their evaluation as a long-term destination therapy for end-stage heart disease. METHODS: Between August 1990 and February 1997, 85 patients with end-stage heart disease underwent insertion of implantable LVADs. Fifty-two patients underwent pneumatic device insertion and 32 patients received a vented electric device. RESULTS: Patients were supported for a mean of 109+/-13 days for an overall survival to transplant (54) or explant (3) of 73%. Nineteen patients were discharged from the hospital on a mean of postoperative day 41+/-4 (range, 17-68) for an outpatient support time of 108+/-30 days (range, 2-466). Of 12 patients supported after postcardiotomy cardiogenic shock, 10 (82%) survived to hospital discharge. Perioperative right ventricular failure was treated in most patients with inotropic agents and inhaled nitric oxide with only six patients requiring right ventricular assist device support. Thromboembolic rate was low (0.016 events/patient-month) despite minimal or no anticoagulation in all cases. CONCLUSIONS: Left ventricular assist device support has evolved to become an outpatient therapy with excellent survival rates and an acceptable morbidity. Accordingly, wearable LVADs should be studied as permanent treatment options for patients who are not transplant candidates. Images Figure 2. PMID:9351714

  2. Long-term emollient therapy improves xerosis in children with atopic dermatitis.

    PubMed

    Boralevi, F; Saint Aroman, M; Delarue, A; Raudsepp, H; Kaszuba, A; Bylaite, M; Tiplica, G S

    2014-11-01

    Hydration with topical emollients forms the backbone of treatment for mild atopic dermatitis (AD), but few randomized controlled trials have assessed their efficacy in young children. Assess the efficacy and tolerability of long-term emollient therapy in the treatment of moderate to severe xerosis in young children with AD. This was a phase III, multicentre, double-blind, randomized, vehicle-controlled trial. Children (n = 251) aged 2-6 years with AD-associated xerosis were randomized 1 : 1 to a 28-day treatment with an emollient combining glycerol and paraffin or its vehicle. Non-responders at the end of the double-blind period were treated open label with emollient until day 84. Responders stopped treatment until reassessment on day 56. Those who relapsed after stopping treatment were treated open label with emollient until day 84. During the double-blind period, xerosis score (XS) of the scoring atopic dermatitis (SCORAD) index, objective SCORAD and visual analogue score decreased and skin hydration increased more in the emollient group than in the vehicle group (P < 0.001 for all measures). More patients were responders with emollient than with vehicle (66.1% vs. 45.6%, P < 0.001). During the open-label period, stopping emollient treatment led to relapse but improvement returned if treatment was restarted with emollient. Regular use of the emollient also yielded improvement in children who did not initially respond. Adverse events were similar in the two groups, and no treatment-related severe adverse events were reported. Long-term therapy with emollient is effective and well tolerated for the treatment of xerosis in children with atopic dermatitis. © 2013 European Academy of Dermatology and Venereology.

  3. Long-term prognostic analysis of early interventional therapy for lower extremity deep venous thrombosis

    PubMed Central

    Li, Qiang; Yu, Zongxue; Wang, Jinjun; Chen, Xiao; Li, Lin

    2016-01-01

    The aim of the present study was to observe the long-term prognostic value of early interventional therapy for lower extremity deep venous thrombosis (LDVT). In total, 85 patients diagnosed with LDVT for the first time were consecutively selected (identified course of disease was <3 months), and were divided into the control group with 43 cases and the observation group with 42 cases according to different therapeutic methods. The control group received anticoagulation therapy and thrombolysis, or integrated surgical thrombectomy, a conventional open operation, while the observation group received comprehensive treatment, combining endovascular catheter-directed thrombolysis and thrombectomy. The therapeutic effects were compared. After treatment, the differences in circumference of the thigh and shank between the affected and unaffected extremities, and vein dysfunction score of the two groups were decreased compared with before treatment. In addition, the above indexes of the observation group were significantly lower than in the control group (P<0.05). The clinical effective rate and effective extent of the observation group were higher than those of the control group, and the differences were statistically significant (P<0.05). The occurrence rate of post-thrombotic syndrome in the observation group was lower than that of the control group, and there was no difference in comparison of grading. The recurrence rate and restenosis rate of the observation group were lower than in the control group, while the patency rate of the observation group was higher than that of the control group, and the differences were statistically significant (P<0.05). In conclusion, early catheter-directed invention of thrombolysis with thrombectomy for LDVT has good clinical effect in the short-term and long-term. PMID:28105087

  4. Dose Escalation during the First Year of Long-Term Opioid Therapy for Chronic Pain

    PubMed Central

    Henry, Stephen G.; Wilsey, Barth L.; Melnikow, Joy A.; Iosif, Ana-Maria

    2014-01-01

    OBJECTIVE To identify patient factors and health care utilization patterns associated with dose escalation during the first year of long-term opioid therapy for chronic pain DESIGN Retrospective cohort study using electronic health record data SETTING University health system SUBJECTS Opioid naïve adults with musculoskeletal pain who received a new outpatient opioid prescription between July 1, 2011 and June 30, 2012 and stayed on opioids for one year METHODS Mixed-effects regression was used to estimate patients’ rate of opioid dose escalation. Demographics, clinical characteristics, and healthcare utilization for patients with and without dose escalation were compared. RESULTS Twenty-three (9%) of 246 patients in the final cohort experienced dose escalation (defined as an increase in mean daily opioid dose of ≥30 mg morphine equivalents over 1 year). Compared to patients without dose escalation, patients with escalation had higher rates of substance use diagnoses (17% versus 1%, P = 0.01) and more total outpatient encounters (51 versus 35, P = 0.002) over 1 year. Differences in outpatient encounters were largely due to more non face-to-face encounters (e.g., telephone calls, emails) among patients with dose escalation. Differences in age, race, concurrent benzodiazepine use, and mental health diagnoses between patients with and without dose escalation were not statistically significant. Primary care clinicians prescribed 89% of opioid prescriptions. CONCLUSIONS Dose escalation during the first year of long-term opioid therapy is associated with higher rates of substance use disorders and more frequent outpatient encounters, especially non face-to-face encounters. PMID:25529548

  5. A long-term efficacy study of gene replacement therapy for RPGR-associated retinal degeneration

    PubMed Central

    Wu, Zhijian; Hiriyanna, Suja; Qian, Haohua; Mookherjee, Suddhasil; Campos, Maria M.; Gao, Chun; Fariss, Robert; Sieving, Paul A.; Li, Tiansen; Colosi, Peter; Swaroop, Anand

    2015-01-01

    Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene account for >70% of X-linked retinitis pigmentosa (XLRP) and 15–20% of all inherited retinal degeneration. Gene replacement therapy for RPGR-XLRP was hampered by the relatively slow disease progression in mouse models and by difficulties in cloning the full-length RPGR-ORF15 cDNA that includes a purine-rich 3′-coding region; however, its effectiveness has recently been demonstrated in four dogs with RPGR mutations. To advance the therapy to clinical stage, we generated new stable vectors in AAV8 or AAV9 carrying mouse and human full-length RPGR-ORF15-coding sequence and conducted a comprehensive long-term dose-efficacy study in Rpgr-knockout mice. After validating their ability to produce full-length proteins that localize to photoreceptor connecting cilia, we evaluated various vector doses in mice during a 2-year study. We demonstrate that eyes treated with a single injection of mouse or human RPGR-ORF15 vector at an optimal dose maintained the expression of RPGR-ORF15 throughout the study duration and exhibited higher electroretinogram amplitude, thicker photoreceptor layer and better targeting of opsins to outer segments compared with sham-treated eyes. Furthermore, mice that received treatment at an advanced age also showed remarkable preservation of retinal structure and function. Retinal toxicity was observed at high vector doses, highlighting the importance of careful dose optimization in future clinical experiments. Our long-term dose-efficacy study should facilitate the design of human trials with human RPGR-ORF15 vector as a clinical candidate. PMID:25877300

  6. Long-term therapy with low-molecular-weight heparin in cancer patients with venous thromboembolism.

    PubMed

    Marchena, Pablo Javier; Nieto, José Antonio; Guil, María; García-Bragado, Ferrán; Rabuñal, Ramón; Boccalon, Henri; Trujillo-Santos, Javier; Monreal, Manuel

    2012-01-01

    Long-term therapy with low-molecular-weight heparin (LMWH) is the treatment of choice for cancer patients with venous thromboembolism (VTE). However, the ideal doses of LMWH have not been thoroughly studied. We used the RIETE Registry data to assess the influence of the daily LMWH dosage on outcome during the first three months after VTE. We used propensity score-matching to compare patients who received <150 vs. those receiving ≥150 UI/kg/day LMWH. Up to July 2010, 3,222 cancer patients with VTE received long-term therapy with fixed doses of LMWH. Of these, 1,472 (46%) received <150 IU/kg/day (mean, 112 ± 28), and 1,750 received ≥150 IU/kg/day (mean, 184 ± 32). Results of the propensity score matching involved 1269 matched pairs. During follow-up, the incidence of pulmonary embolism (PE) recurrences was similar (1.2% vs. 1.9%), but patients receiving <150 IU/kg/day LMWH had a lower incidence of fatal PE than those treated with ≥150 IU/kg/day (0.2% vs. 1.0%; p=0.004). Multivariate analysis confirmed that patients receiving <150 IU/kg/day LMWH had a lower risk for fatal PE (odds ratio [OR]: 0.2; 95% confidence interval [CI]: 0.06-0.8) and for major bleeding (OR: 0.6; 95% CI: 0.3-1.0) than those treated with ≥150 IU/kg/day. In real life, one in every two cancer patients with VTE received lower doses of LMWH than those used in randomised trials, with large variations from patient to patient. Unexpectedly, patients treated with <150 IU/kg/day LMWH had fewer fatal PE cases and fewer major bleeding events than those receiving ≥150 IU/kg/day LMWH. This finding, however, should be validated in prospective clinical trials.

  7. The Efficacy of Short- and Long-Term Therapy in the Treatment of Childhood Sexual Abuse: A Review of the Literature.

    ERIC Educational Resources Information Center

    Aoto-Sullivan, Stacey Y.

    This paper presents a review of the short- and long-term treatments for children who have been sexually abused. Short-term group therapy, long-term group therapy, short-term individual, and long-term individual therapy were each evaluated in terms of efficacy in alleviating symptoms associated with sexual abuse. The paper also evaluates the…

  8. Long-term results in 144 localized Ewing's sarcoma patients treated with combined therapy

    SciTech Connect

    Bacci, G.; Toni, A.; Avella, M.; Manfrini, M.; Sudanese, A.; Ciaroni, D.; Boriani, S.; Emiliani, E.; Campanacci, M.

    1989-04-15

    The results of 144 previously untreated cases of primary Ewing's sarcoma of bone are reported with a minimum follow-up of 5 years. This series was treated between 1972 and 1982 at Istituto Ortopedico Rizzoli with a combined therapy. The local control of the disease consisted of amputation (ten cases), resection followed by radiation therapy (35-45 Gy) (48 cases) and radiation therapy alone (40-60 Gy) (86 cases). Adjuvant chemotherapy, rigorously standardized, was performed according two different protocols: the first (85 cases treated in the period 1972-1978) consisted of vincristine (VCR) Adriamycin (doxorubicin) (ADM), and cyclophosphamide (EDX); the second (59 cases treated in the period 1979-1982) of VCR, ADM, EDX and dactinomycin (DACT). At a follow-up of 5 to 16 years (median, 9), 59 patients (41%) are continuously disease-free (CDF), 81 (56%) developed metastatic disease and/or local recurrence, and four (3%) had a second malignancy. Three factors seem to be correlated to prognosis: the site of the initial lesion (only 23% of the pelvic lesions are represented in the CDF group versus 46% of the other locations); the chemotherapy protocol (32% of the cases in the first protocol are CDF versus 54% in the second); the type of local treatment (60% of the patients treated with amputation or resection plus radiotherapy versus 28% of those treated with radiation therapy alone are CDF). A local recurrence was observed in 24% of the patients (8% in the group locally treated with surgery or surgery plus radiation therapy versus 36% in the group treated with radiation therapy alone). These data suggest that even though adjuvant chemotherapy can improve the long-term results in localized Ewing's sarcoma patients, this disease still represents, in a high percentage of cases, a lethal process whose final prognosis widely depends on the local control of the lesion.

  9. Trends in long-term opioid therapy for noncancer pain among persons with a history of depression.

    PubMed

    Braden, Jennifer Brennan; Sullivan, Mark D; Ray, G Thomas; Saunders, Kathleen; Merrill, Joseph; Silverberg, Michael J; Rutter, Carolyn M; Weisner, Constance; Banta-Green, Caleb; Campbell, Cynthia; Von Korff, Michael

    2009-01-01

    We report trends in long-term opioid use among patients with a history of depression from two large health plans. Using claims data, age- and gender-adjusted rates for long-term (>90 days) opioid use episodes were calculated for 1997-2005, comparing those with and without a depression diagnosis in the prior 2 years. Opioid use characteristics were calculated for those with a long-term episode in 2005. Incident and prevalent long-term opioid use rates were three times higher in those with a history of depression. Prevalent long-term use per 1000 in patients with a history of depression increased from 69.8 to 125.9 at Group Health and from 84.3 to 117.5 at Kaiser Permanente of Northern California between 1997 and 2005. Those with a history of depression were more likely to receive a higher average daily dose, greater days supply, and Schedule II opioids than nondepressed persons. Persons with a history of depression are more likely to receive long-term opioid therapy for noncancer pain than those without a history of depression. Results suggest that long-term opioid therapy for noncancer pain is being prescribed to a different population in clinical practice than the clinical trial populations where opioid efficacy has been established.

  10. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma.

    PubMed

    Jianyong, Lei; Jinjing, Zhong; Lunan, Yan; Jingqiang, Zhu; Wentao, Wang; Yong, Zeng; Bo, Li; Tianfu, Wen; Jiaying, Yang

    2017-02-03

    Combinations of transarterial chemoembolization (TACE) and radical therapies (pretransplantation, resection and radiofrequency ablation) for hepatocellular carcinoma (HCC) have been reported as controversial issues in recent years. A consecutive sample of 1560 patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B HCC who underwent solitary Radiofrequency ablation (RFA), resection or liver transplantation (LT) or adjuvant pre-operative TACE were included. The 1-, 3- and 5-year overall survival rates and tumor-free survival rates were comparable between the solitary radical therapy group and TACE combined group in the whole group and in each of the subgroups (RFA, resection and LT) (P > 0.05). In the subgroup analysis, according to BCLC stage A or B, the advantages of adjuvant TACE were also not observed (P > 0.05). A Neutrophil-lymphocyte ratio (NLR) more than 4, multiple tumor targets, BCLC stage B, and poor histological grade were significant contributors to the overall and tumor-free survival rates. In conclusions, our results indicated that preoperative adjuvant TACE did not prolong long-term overall or tumor-free survival, but LT should nevertheless be considered the first choice for BCLC stage A or B HCC patients. Radical therapies should be performed very carefully in BCLC stage B HCC patients.

  11. Long-term outcome after treatment of temporomandibular joint osteoarthritis with exercise and manual therapy.

    PubMed

    Nicolakis, Peter; Erdogmus, Celal Burak; Kollmitzer, Josef; Kerschan-Schindl, Katharina; Sengstbratl, Michaela; Nuhr, Martin; Crevenna, Richard; Fialka-Moser, Veronika

    2002-01-01

    In a previous study, exercise and manual therapy demonstrated a 90% success rate in patients with osteoarthrosis of the temporomandibular joints in the short-term. The aim of this follow-up study was to assess the long-term effect of these treatment modalities. Seventeen patients were evaluated. All patients suffered from osteoarthrosis of the temporomandibular joints with pain in the temporomandibular joint at baseline and were treated successfully in a prior short-term study. The parameters were pain at rest and at chewing, impairment in daily life, and mouth opening. At follow-up, 11 patients (65%) experienced no pain and 13 patients (76%) had no pain at rest (Fisher's Exact Test: p<0.02). Thirteen patients (76%) had a normal incisal edge clearance, and ten patients (59%) felt no impairment due to the disease (Fisher's Exact Test: p=0.01). Thirteen patients (76%), who had been treated once successfully, have not needed treatment within the three years after cessation of their therapy. Exercise therapy is an effective tool to treat osteoarthrosis of the temporomandibular joints.

  12. Long-term maintenance therapy with azathioprine in systemic lupus erythematosus.

    PubMed

    Ginzler, E; Sharon, E; Diamond, H; Kaplan, D

    1975-01-01

    One hundred ten patients with systemic lupus erythematosus (SLE) were classified into two groups, patients with central nervous system (CNS) or severe renal disease (usually associated with a poor prognosis) and patients without these manifestations, to define criteria for azathioprine therapy. Fifty-four of 68 patients with a poor prognosis received azathioprine. Azathioprine-treated patients showed improved long-term survival (72% vs 29%, P less than .005) and fewer hospitalizations (0.24/patient-years vs 0.89/patient-years, P less than .001). Azathioprine therapy in 19 of 42 patients with a good prognosis was associated with fewer hospitalizations (.02/patient-years vs .17/patient-years, P less than .05), but no decrease in maintenace prednisone requirement. Progression from a good to a poor prognosis was less frequent (1 of 20 vs 11 of 34, P = less than .05) among azathioprine-treated patients. Toxicity of azathioprine was minimal. Azathioprine therapy is indicated in patients with CNS or severe renal disease, and in patients whose prognosis was good with frequent hospitalizations or a maintenance prednisone requirement greater than 15 mg/day.

  13. Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy.

    PubMed

    Khan, Akbar; Andrews, Douglas; Blackburn, Anneke C

    2016-10-16

    Oral dichloroacetate sodium (DCA) has been investigated as a novel metabolic therapy for various cancers since 2007, based on data from Bonnet et al that DCA can trigger apoptosis of human lung, breast and brain cancer cells. Response to therapy in human studies is measured by standard RECIST definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging. However, Blackburn et al have demonstrated that DCA can also act as a cytostatic agent in vitro and in vivo, without causing apoptosis (programmed cell death). A case is presented in which oral DCA therapy resulted in tumour stabilization of stage 4 colon cancer in a 57 years old female for a period of nearly 4 years, with no serious toxicity. Since the natural history of stage 4 colon cancer consists of steady progression leading to disability and death, this case highlights a novel use of DCA as a cytostatic agent with a potential to maintain long-term stability of advanced-stage cancer.

  14. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma

    PubMed Central

    Jianyong, Lei; Jinjing, Zhong; Lunan, Yan; Jingqiang, Zhu; Wentao, Wang; Yong, Zeng; Bo, Li; Tianfu, Wen; Jiaying, Yang

    2017-01-01

    Combinations of transarterial chemoembolization (TACE) and radical therapies (pretransplantation, resection and radiofrequency ablation) for hepatocellular carcinoma (HCC) have been reported as controversial issues in recent years. A consecutive sample of 1560 patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B HCC who underwent solitary Radiofrequency ablation (RFA), resection or liver transplantation (LT) or adjuvant pre-operative TACE were included. The 1-, 3- and 5-year overall survival rates and tumor-free survival rates were comparable between the solitary radical therapy group and TACE combined group in the whole group and in each of the subgroups (RFA, resection and LT) (P > 0.05). In the subgroup analysis, according to BCLC stage A or B, the advantages of adjuvant TACE were also not observed (P > 0.05). A Neutrophil-lymphocyte ratio (NLR) more than 4, multiple tumor targets, BCLC stage B, and poor histological grade were significant contributors to the overall and tumor-free survival rates. In conclusions, our results indicated that preoperative adjuvant TACE did not prolong long-term overall or tumor-free survival, but LT should nevertheless be considered the first choice for BCLC stage A or B HCC patients. Radical therapies should be performed very carefully in BCLC stage B HCC patients. PMID:28155861

  15. Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy

    PubMed Central

    Khan, Akbar; Andrews, Douglas; Blackburn, Anneke C

    2016-01-01

    Oral dichloroacetate sodium (DCA) has been investigated as a novel metabolic therapy for various cancers since 2007, based on data from Bonnet et al that DCA can trigger apoptosis of human lung, breast and brain cancer cells. Response to therapy in human studies is measured by standard RECIST definitions, which define “response” by the degree of tumour reduction, or tumour disappearance on imaging. However, Blackburn et al have demonstrated that DCA can also act as a cytostatic agent in vitro and in vivo, without causing apoptosis (programmed cell death). A case is presented in which oral DCA therapy resulted in tumour stabilization of stage 4 colon cancer in a 57 years old female for a period of nearly 4 years, with no serious toxicity. Since the natural history of stage 4 colon cancer consists of steady progression leading to disability and death, this case highlights a novel use of DCA as a cytostatic agent with a potential to maintain long-term stability of advanced-stage cancer. PMID:27803917

  16. Long-term psychoanalytic therapy as a life-saving procedure.

    PubMed

    Chessick, Richard D

    2007-12-01

    A dramatic long-term psychoanalytic treatment of a psychotic character disorder is presented in detail. This patient began therapy with a long standing history of an eating disorder for which she had received many hospitalizations and forms of treatment without any success. She was in a deep despair and as a last resort agreed to a psychoanalytic therapy. During the many years of treatment the eating disorder completely resolved but was replaced by a series of very dangerous accidents that occurred each time she was betrayed and disappointed by a boy friend. This went on pari passu with a deepening understanding of her childhood and her psychodynamics but the middle of the therapy was very stormy and required tenacious efforts to maintain the treatment. The self-destructive behavior was traced to early and profound childhood disappointments and a sense that these were her fault because she was so unlovable and therefore deserved punishment. A dangerous stalemate developed in the treatment after a number of years. The analyst presented the case to colleagues several times and wrote it up in detail, which enabled him to understand his own countertransference and resolve it. This resulted in a dramatic change in the patient and a very favorable and happy ending to this very difficult treatment after 15 years. Although the author believes all patients in psychoanalysis should be approached with as neutral and objective a stance as possible, emphasizing free association and dream material in order to interpret the crucial childhood determinants of the patient's psychopathology, in cases such as psychotic character disorders the outcome clearly also depends on interpersonal factors. The case illustrates the deep partly conscious and partly unconscious interaction between a patient and her analyst over many years of treatment and the profound effect this has on the outcome. It underscores the importance of patients being allowed to heal in their own way and in their own

  17. Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women.

    PubMed

    Newcomb, P A; Longnecker, M P; Storer, B E; Mittendorf, R; Baron, J; Clapp, R W; Bogdan, G; Willett, W C

    1995-10-15

    Despite extensive study, concerns remain about a possible association between long-term postmenopausal hormone treatment--particularly use of combination preparations--and risk of breast cancer. The authors evaluated the use of postmenopausal hormone replacement therapy in relation to breast cancer risk in a large multicenter, population-based case-control study. Women with a new diagnosis of breast cancer were identified through statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly selected from population lists in each state. For this analysis of postmenopausal women, data were available from 3,130 breast cancer cases and 3,698 controls interviewed between 1989 and 1991. Replacement hormone use was not associated with breast cancer risk in women who had ever undergone this treatment (relative risk (RR) = 1.05, 95% confidence interval (CI) 0.93-1.18). Among women who had used replacement hormones for 15 years or more, there was no clear increase in risk, although the small sample size did not preclude the possibility of a modest association (RR = 1.11, 95% CI 0.87-1.43). Risk among women using progestins in combination with estrogens was similar to that in women using estrogens alone. Risk did not vary according to type of menopause, family history of breast cancer, history of benign breast disease, or alcohol intake. These results are consistent with the majority of reports which find no overall increased risk associated with the use of replacement hormones. However, in contrast to several other studies, this study did not find long-term use to be associated with increased risk. These results also do not support a hypothesized effect of combined progestin and estrogen use on the risk of breast cancer.

  18. Monitoring of patients on long-term glucocorticoid therapy: a population-based cohort study.

    PubMed

    Fardet, Laurence; Petersen, Irene; Nazareth, Irwin

    2015-04-01

    About 1% of the general population receives long-term systemic glucocorticoids. The monitoring provided to these patients is unknown. We conducted a population-based cohort study using The Health Improvement Network database. A total of 100,944 adult patients prescribed systemic glucocorticoids for >3 months between January 2000 and December 2012 were studied. The monitoring done before prescribing glucocorticoid therapy and during exposure to the drug was examined. This included measurement of body weight, blood pressure, lipids, glucose and potassium levels, referrals for dual-energy X-ray absorptiometry (DEXA-scan) or to an ophthalmologist/optician, and vaccinations. We assessed factors associated with the odds of being monitored before and during exposure. Before glucocorticoid initiation, weight and blood pressure were monitored in < 20% and < 50% of patients, respectively. Glucose and lipid levels were monitored in less than one-third of the patients, while DEXA-scan and eye monitoring were offered to <15% of them. Vaccination against flu and pneumococcus was given to 57% and 46% of the patients, respectively. During exposure to the drug, <60% of patients who were prescribed the drug for more than a year had their weight, glucose, or lipid levels recorded at least once and <25% of patients were referred at least once for DEXA-scan or screening for eye diseases. Overall, the odds of being monitored were higher in older patients and in those with comorbidities. There were variations in the level of monitoring provided across the UK, but the monitoring has improved over the last 12 years. Although the extent of monitoring of people on long-term glucocorticoids has improved over time, the overall monitoring provided is not satisfactory, particularly in young patients and those without comorbidities.

  19. Long-term safety and efficacy of fluticasone/formoterol combination therapy in asthma.

    PubMed

    Mansur, Adel H; Kaiser, Kirsten

    2013-08-01

    The long-term safety of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol; flutiform(®)) was assessed. In an open-label study, mild to moderate-severe asthmatics (≥12 years; N=472) were treated twice daily with fluticasone/formoterol 100/10 μg (n=224) or 250/10 μg (n=248) for 6 months (n=256) or 12 months (n=216). The primary and secondary objectives were the long-term safety and efficacy of fluticasone/formoterol, respectively. In total, 413 (87.5%) patients completed the study (of which 175 participated for 12 months). Adverse events (AEs) were reported by 174 patients (36.9%): 67 (29.9%) in the 100/10 μg group and 107 (43.1%) in the 250/10 μg group. The most common AEs (>2%) were nasopharyngitis, dyspnea, pharyngitis, and headache; the majority were mild to moderate. Only 18 (3.8%) patients reported AEs considered study drug-related. Five patients per group experienced 12 serious AEs; none was study medication-related. Asthma exacerbations were reported by 53 patients (11.2%): 46 mild to moderate and nine severe. Clinical laboratory tests and vital signs showed no abnormal trends or clinically important or dose-response-related changes. The efficacy analyses showed statistically significant improvements at every time point throughout the study period at both doses. Fluticasone/formoterol had a good safety and efficacy profile over the 6- and 12-month study periods.

  20. Long-Term Outcomes of Cognitive-Behavioral Therapy for Adolescent Body Dysmorphic Disorder.

    PubMed

    Krebs, Georgina; de la Cruz, Lorena Fernández; Monzani, Benedetta; Bowyer, Laura; Anson, Martin; Cadman, Jacinda; Heyman, Isobel; Turner, Cynthia; Veale, David; Mataix-Cols, David

    2017-07-01

    Emerging evidence suggests that cognitive-behavioral therapy (CBT) is an efficacious treatment for adolescent body dysmorphic disorder (BDD) in the short term, but longer-term outcomes remain unknown. The current study aimed to follow up a group of adolescents who had originally participated in a randomized controlled trial of CBT for BDD to determine whether treatment gains were maintained. Twenty-six adolescents (mean age = 16.2, SD = 1.6) with a primary diagnosis of BDD received a course of developmentally tailored CBT and were followed up over 12 months. Participants were assessed at baseline, midtreatment, posttreatment, 2-, 6-, and 12-month follow-up. The primary outcome measure was the clinician-rated Yale-Brown Obsessive-Compulsive Scale Modified for BDD. Secondary outcomes included measures of insight, depression, quality of life, and global functioning. BDD symptoms decreased significantly from pre- to posttreatment and remained stable over the 12-month follow-up. At this time point, 50% of participants were classified as responders and 23% as remitters. Participants remained significantly improved on all secondary outcomes at 12-month follow-up. Neither baseline insight nor baseline depression predicted long-term outcomes. The positive effects of CBT appear to be durable up to 12-month follow-up. However, the majority of patients remained symptomatic and vulnerable to a range of risks at 12-month follow-up, indicating that longer-term monitoring is advisable in this population. Future research should focus on enhancing the efficacy of CBT in order to improve long-term outcomes. Copyright © 2017. Published by Elsevier Ltd.

  1. Effectiveness of enzyme replacement therapy in Fabry disease: Long term experience in Argentina.

    PubMed

    Cabrera, Gustavo; Politei, Juan; Antongiovani, Norberto; Amartino, Hernán

    2017-06-01

    Evidence regarding long term effectiveness of enzyme replacement therapy (ERT) in Fabry disease (FD) is needed. The aim of this study was to analyze in a cohort of FD patients in Argentina, the long term effectiveness of ERT on renal, cardiac and cerebrovascular parameters. Patients with genetically proven FD were included from GADYTEF (Argentinean group for the treatment of FD) between 2001 and 2014. Renal, cardiac, and cerebral outcomes were prospectively studied in patients treated with ERT. Additionally, the occurrence of major cardiac complications, stroke, end-stage renal disease and death was analyzed during follow up. During the follow-up 8 major complications occurred in 5 patients (n = 2 deaths, n = 4 cases of end stage renal disease and n = 1 atrial fibrillation), 4 of them males and only 1 female who suffered an atrial fibrillation. Sudden death or stroke did not occur. Four (40%) of 10 males with baseline left ventricular hypertrophy (LVH) reduced left ventricular mass index (LVMI) from 163.1 ± 64.7 to 123.4 ± 49.8 g/m(2), 2 stabilized LVMI and 4 increased LVMI from157.9 ± 32.3 to 261.6 ± 48.6 g/m(2). Estimated glomerular filtration was stable in 30 patients (17 males and 13 females). We observed a few major complications during the follow up. Future studies are necessary to show the effectiveness of ERT in affected patients.

  2. Long-Term CD4+ Cell Count in Response to Combination Antiretroviral Therapy

    PubMed Central

    Luz, Paula M.; Grinsztejn, Beatriz; Velasque, Luciane; Pacheco, Antonio G.; Veloso, Valdilea G.; Moore, Richard D.; Struchiner, Claudio J.

    2014-01-01

    Objective There is a continuous debate on how to adequately evaluate long-term CD4+ cell count in response to combination antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected individuals. Our study evaluated the long-term CD4+ cell count response (up to ten years) after initiation of ART and described the differences in the CD4+ cell count response stratified by pretreatment CD4+ cell count, and other socio-demographic, behavioral, and clinical factors. Methods The study population included patients starting ART in the clinical cohorts of Rio de Janeiro, Brazil, and Baltimore, United States. Inverse probability of censoring weighting was used to estimate mean annual CD4+ cell counts while adjusting for choice of initial ART regimen, ART discontinuation and losses-to-follow-up. Results From 1997 to 2011, 3116 individuals started ART; preferred initial regimen was NNRTI-based (63%). The median follow-up time was 5 years, 10% of the individuals had nine or more years of follow-up. Observed CD4+ cell counts increased throughout the ten years of follow-up. Weighted results, in contrast, increased up to year four and plateaued thereafter with 50% of the population reaching CD4+ cell counts of 449/μL or more. Out of all stratification variables considered, only individuals with pre-treatment CD4+ cell counts ≥350/μL showed increasing CD4+ cell counts over time with 76% surpassing the CD4+ cell count >500/μL threshold at year ten. Conclusion The present study corroborates the growing body of knowledge advocating early start of ART by showing that only patients who start ART early fully recover to normal CD4+ cell counts. PMID:24695533

  3. Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy.

    PubMed

    Yang, Shuo; Ma, Si-Qi; Wan, Xing; He, Heng; Pei, Han; Zhao, Min-Jian; Chen, Chen; Wang, Dao-Wen; Dong, Xiao-Yan; Yuan, Jia-Jia; Li, Bin

    2016-08-01

    Leber's hereditary optic neuropathy (LHON) is a disease that leads to blindness. Gene therapy has been investigated with some success, and could lead to important advancements in treating LHON. This was a prospective, open-label trial involving 9 LHON patients at Tongji Hospital, Wuhan, China, from August 2011 to December 2015. The purpose of this study was to evaluate the long-term outcomes of gene therapy for LHON. Nine LHON patients voluntarily received an intravitreal injection of rAAV2-ND4. Systemic examinations and visual function tests were performed during the 36-month follow-up period to determine the safety and efficacy of this gene therapy. Based on successful experiments in an animal model of LHON, 1 subject also received an rAAV2-ND4 injection in the second eye 12months after gene therapy was administered in the first eye. Recovery of visual acuity was defined as the primary outcome of this study. Changes in the visual field, visual evoked potential (VEP), optical coherence tomography findings, liver and kidney function, and antibodies against AAV2 were defined as secondary endpoints. Eight patients (Patients 2-9) received unilateral gene therapy and visual function improvement was observed in both treated eyes (Patients 4, 6, 7, and 8) and untreated eyes (Patients 2, 3, 4, 6 and 8). Visual regression fluctuations, defined as changes in visual acuity greater than or equal to 0.3 logMAR, were observed in Patients 2 and 9. Age at disease onset, disease duration, and the amount of remaining optic nerve fibers did not have a significant effect on the visual function improvement. The visual field and pattern reversal VEP also improved. The patient (Patient 1) who received gene therapy in both eyes had improved visual acuity in the injected eye after the first treatment. Unfortunately, visual acuity in this eye decreased 3months after he received gene therapy in the second eye. Animal experiments suggested that ND4 expression remains stable in the

  4. Acquired resistance with epigenetic alterations under long-term anti-angiogenic therapy for hepatocellular carcinoma.

    PubMed

    Ohata, Yoshiteru; Shimada, Shu; Akiyama, Yoshimitsu; Mogushi, Kaoru; Nakao, Keisuke; Matsumura, Satoshi; Aihara, Arihiro; Mitsunori, Yusuke; Ban, Daisuke; Ochiai, Takanori; Kudo, Atsushi; Arii, Shigeki; Tanabe, Minoru; Tanaka, Shinji

    2017-02-28

    Anti-angiogenic therapy is initially effective for several solid tumors including hepatocellular carcinoma (HCC); however, they finally relapse and progress, resulting in poor prognosis. We here established in vivo drug-tolerant subclones of human HCC cells by long-term treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor and serial transplantation in immunocompromised mice (total 12 months), and then compared them with the parental cells in molecular and biological features. Gene expression profiles elucidated a G-actin monomer binding protein thymosin β 4 (Tβ4) as one of the genes enriched in the resistant cancer cells relative to the initially sensitive ones. Highlighting epigenetic alterations involved in drug resistance, we revealed that Tβ4 could be aberrantly expressed following demethylation of DNA and active modification of histone H3 at the promoter region. Ectopic overexpression of Tβ4 in HCC cells could significantly enhance sphere-forming capacities and infiltrating phenotypes in vitro, and promote growth of tumors refractory to the VEGFR mutltikinase inhibitor sorafenib in vivo. Clinically, sorafenib failed to improve the progression-free survival in patients with Tβ4-high HCC, indicating that Tβ4 expression could be available as a surrogate marker of susceptibility to this drug. This study suggests that Tβ4 expression triggered by epigenetic alterations could contribute to the development of resistance to anti-angiogenic therapy by the acquisition of stemness, and that epigenetic control might be one of the key targets to regulate the resistance in HCC.

  5. The long term effectiveness of intensive stuttering therapy: a mixed methods study.

    PubMed

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-09-01

    The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. The study used a mixed methods design. The core method was a phenomenological approach using semi-structured interviews. Objective clinical data was gathered concurrently. This included archival records and current measures on a variety of assessments to evaluate stuttering severity and attitudes toward communication. The major themes generated from participants' transcripts included (1) the positive effects of the Duration and Nature of the Program; (2) Speech Techniques Learned; (3) Attitude Change and Counseling; and (4) activities related to Desensitization and Transfer. The participants also reported positive effects of their personal motivation and clinician attitudes. Clinical data indicated that the participants made measurable clinical gains on all measures of stuttering severity and attitude change following the intensive clinic and these changes were maintained long after the program was completed. It appears that this intensive stuttering therapy program is effective for making positive changes in behavioral measures of speech disfluencies, and attitudes. Clients reported multiple factors directly related to the program and personal factors that contributed to treatment effectiveness. Hence, future studies should explore and report on a variety of factors related to communication attitudes and overall quality of life in addition to behavioral measures of speech. After reading this article, the learner will be able to: (a) identify the basic tenets of evidence-based practice; (b) summarize what we currently know about the effectiveness of behavioral treatments of stuttering; (c) identify factors that client report as important to

  6. Increased Numbers of Nonattached Osteoclasts After Long-Term Zoledronic Acid Therapy in Mice

    PubMed Central

    Kuroshima, Shinichiro; Go, Virginia-Arlene A.

    2012-01-01

    Osteoclasts are key players in the maintenance of bone, which is an endocrine target and organ. Bisphosphonates, used for the management of metastatic bone diseases and osteoporosis, suppress osteoclasts. However, the impact of continuously suppressed osteoclasts is unknown. In this study, mice received zoledronic acid (ZA) for 13 months, nearly half the lifespan of mice, and the effects of continual osteoclast suppression on the bone environment and oral wound healing were determined. ZA therapy suppressed osteoclasts, resulting in significantly more bone mass compared with control. Despite continuous and intense suppression of bone loss in mice receiving ZA, serum calcium levels were maintained in the normal range. No differences were noted in serum tartrate-resistant acid phosphatase (TRAP) 5b levels between ZA-treated and control mice. Histomorphometric analyses of bones revealed that ZA therapy significantly decreased osteoclasts on the bone surface but, instead, substantially increased TRAP+ mononuclear cells and osteoclasts that were not on the bone surface. When oral trauma was induced, such TRAP+ mononuclear and nonattached osteoclasts increased considerably with increased inflammatory cell infiltration in the wounds. As a result, oral wound healing was hindered at the connective tissue level. Healing of the epithelium was unaffected. These findings indicate that the continual suppression of osteoclasts does not affect serum calcium levels and that long-term ZA therapy stimulates nonattached osteoclast and TRAP+ mononuclear cell formation that are expanded rapidly in response to oral trauma. Caution should be exercised when using the serum TRAcP5b to estimate the efficacy of antiresorptive therapy. PMID:22109892

  7. Long-Term Adherence to Evidence Based Secondary Prevention Therapies after Acute Myocardial Infarction

    PubMed Central

    Bowblis, John R.; Levin, Carrie; Jan, Saira; Patel, Minalkumar; Crystal, Stephen

    2007-01-01

    BACKGROUND After acute myocardial infarction (AMI), treatment with beta-blockers and angiotensin-converting enzyme inhibitors (ACEI) is widely recognized as crucial to reduce risk of a subsequent AMI. However, many patients fail to consistently remain on these treatments over time, and long-term adherence has not been well described. OBJECTIVE To examine the duration of treatment with beta-blockers and ACEI within the 24 months after an AMI. DESIGN A retrospective, observational study using medical and pharmacy claims from a large health plan operating in the Northeastern United States. SUBJECTS Enrollees with an inpatient claim for AMI who initiated beta-blocker (N = 499) or ACEI (N = 526) therapy. MEASUREMENT Time from initiation to discontinuation was measured with pharmacy refill records. Associations between therapy discontinuation and potential predictors were estimated using a Cox proportional hazards model. RESULTS ACEI discontinuation rates were high: 7% stopped within 1 month, 22% at 6 months, 32% at 1 year and 50% at 2 years. Overall discontinuation rates for beta-blockers were similar, but predictors of discontinuation differed for the two treatment types. For beta-blockers, the risk of discontinuation was highest among males and those from low-income neighborhoods; patients with comorbid hypertension and peripheral vascular disease were less likely to discontinue therapy. These factors were not associated with ACEI discontinuation. CONCLUSION Many patients initiating evidence-based secondary prevention therapies after an AMI fail to consistently remain on these treatments. Adherence is a priority area for development of better-quality measures and quality-improvement interventions. Barriers to beta-blocker adherence for low-income populations need particular attention. PMID:17922172

  8. Swallowed Fluticasone Propionate is an Effective Long-Term Maintenance Therapy for Children with Eosinophilic Esophagitis

    PubMed Central

    Andreae, Doerthe A; Hanna, Matthew G; Magid, Margret S; Malerba, Stefano; Andreae, Michael H; Bagiella, Emilia; Chehade, Mirna

    2017-01-01

    Background and Aims While effective in the treatment of eosinophilic esophagitis (EoE) in children, limited data exists on long-term safety and efficacy of swallowed topical corticosteroids.. We investigated if long-term use of swallowed fluticasone in children with EoE leads to sustained reduction in esophageal eosinophils, and endoscopic and clinical improvement. Methods In an open-label, prospective, single center study, we offered pediatric patients with active EoE fluticasone 2 puffs to swallow twice a day (strengths in μg/puff: 2–4 years: 44, 5–11 years: 110, ≥12 years: 220). Clinical, endoscopic and histological assessments were performed at baseline and shortly after therapy. If histological remission was seen, fluticasone was continued with clinical follow-ups every 4 months, and endoscopic and histological follow-ups yearly. Clinical scores were derived from 8 symptoms (abdominal pain, nausea, vomiting, regurgitation, chest pain, dysphagia, food impaction and early satiety). Endoscopic scores were derived from 6 features (rings, exudates, furrows, edema, stricture and shearing). Scores were expressed as ratio (features present/total). In addition to peak eosinophils/HPF (primary outcome), histological features (eosinophilic microabscesses, degranulation, superficial layering, basal zone hyperplasia, dilated intercellular spaces and lamina propria fibrosis) were assessed. Median clinical and endoscopic scores and individual histologic features were compared over 4 time intervals: <4 months, 4–12 months, 13–24 months and >24 months. Growth and adverse effects were monitored. Results We enrolled 54 patients, 80% male, median age 6.5 years (range 2–17 years), 85% atopic (57% asthma, 68% allergic rhinitis, 31% atopic dermatitis) and 74% with food allergy. Mean follow-up was 20.4 months, the longest being 68 months (5.7 years). Esophageal eosinophils counts significantly decreased (median peak eosinophils/HPF at baseline 72, <4 months: 0.5, 4–12

  9. Swallowed Fluticasone Propionate Is an Effective Long-Term Maintenance Therapy for Children With Eosinophilic Esophagitis.

    PubMed

    Andreae, Doerthe A; Hanna, Matthew G; Magid, Margret S; Malerba, Stefano; Andreae, Michael H; Bagiella, Emilia; Chehade, Mirna

    2016-08-01

    Although effective in the treatment of eosinophilic esophagitis (EoE) in children, limited data exist on long-term safety and efficacy of swallowed topical corticosteroids. We investigated whether long-term use of swallowed fluticasone in children with EoE leads to sustained reduction in esophageal eosinophils, and endoscopic and clinical improvement. In an open-label, prospective, single-center study, we offered pediatric patients with active EoE fluticasone 2 puffs to swallow twice a day (strengths in μg/puff: 2-4 years: 44, 5-11 years: 110, ≥12 years: 220). Clinical, endoscopic, and histological assessments were performed at baseline and shortly after therapy. If histological remission was seen, fluticasone was continued with clinical follow-ups every 4 months and endoscopic and histological follow-ups yearly. Clinical scores were derived from eight symptoms (abdominal pain, nausea, vomiting, regurgitation, chest pain, dysphagia, food impaction, and early satiety). Endoscopic scores were derived from six features (rings, exudates, furrows, edema, stricture, and shearing). Scores were expressed as ratio (features present/total). In addition to peak eosinophils/high power field (HPF) (primary outcome), histological features (eosinophilic microabscesses, degranulation, superficial layering, basal zone hyperplasia, dilated intercellular spaces, and lamina propria fibrosis) were assessed. Median clinical and endoscopic scores and individual histologic features were compared over 4 time intervals: <4 months, 4-12 months, 13-24 months, and >24 months. Growth and adverse effects were monitored. We enrolled 54 patients, 80% male, median age 6.5 years (range 2-17 years), 85% atopic (57% asthma, 68% allergic rhinitis, and 31% atopic dermatitis), and 74% with food allergy. Mean follow-up was 20.4 months, the longest being 68 months (5.7 years). Esophageal eosinophil counts significantly decreased (median peak eosinophils/HPF at baseline 72, <4 months: 0.5, 4-12 months: 1

  10. Long-term durability of sacral nerve stimulation therapy for chronic fecal incontinence.

    PubMed

    Hull, Tracy; Giese, Chad; Wexner, Steven D; Mellgren, Anders; Devroede, Ghislain; Madoff, Robert D; Stromberg, Katherine; Coller, John A

    2013-02-01

    Limited data have been published regarding the long-term results of sacral nerve stimulation, or sacral neuromodulation, for severe fecal incontinence. The aim was to assess the outcome of sacral nerve stimulation with the use of precise tools and data collection, focusing on the long-term durability of the therapy. Five-year data were analyzed. Patients entered in a multicenter, prospective study for fecal incontinence were followed at 3, 6, and 12 months and annually after device implantation. Patients with chronic fecal incontinence in whom conservative treatments had failed or who were not candidates for more conservative treatments were selected. Patients with ≥ 50% improvement over baseline in fecal incontinence episodes per week during a 14-day test stimulation period received sacral nerve stimulation therapy. Patients were assessed with a 14-day bowel diary and Fecal Incontinence Quality of Life and Fecal Incontinence Severity Index questionnaires. Therapeutic success was defined as ≥ 50% improvement over baseline in fecal incontinence episodes per week. All adverse events were collected. A total of 120 patients (110 women; mean age, 60.5 years) underwent implantation. Seventy-six of these patients (63%) were followed a minimum of 5 years (maximum, longer than 8 years) and are the basis for this report. Fecal incontinence episodes per week decreased from a mean of 9.1 at baseline to 1.7 at 5 years, with 89% (n = 64/72) having ≥ 50% improvement (p < 0.0001) and 36% (n = 26/72) having complete continence. Fecal Incontinence Quality of Life scores also significantly improved for all 4 scales between baseline and 5 years (n = 70; p < 0.0001). Twenty-seven of the 76 (35.5%) patients required a device revision, replacement, or explant. The therapeutic effect and improved quality of life for fecal incontinence is maintained 5 years after sacral nerve stimulation implantation and beyond. Device revision, replacement, or explant rate was acceptable, but future

  11. Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD)

    PubMed Central

    2012-01-01

    Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive

  12. Long-term stability of 8-methoxypsoralen in ointments for topical PUVA therapy ('Cream-PUVA').

    PubMed

    Martens-Lobenhoffer, J; Rinke, M; Lösche, D; Gollnick, H

    1999-01-01

    8-Methoxypsoralen (8-MOP) is an established photochemotherapeutic agent for PUVA therapy. Recently, a so-called 'cream-PUVA' modality was introduced into therapy of psoriasis and other dermatoses. Little is known, however, about the stability of 8-MOP in ointments used for the topical application of this compound. Therefore, we investigated the long-term stability of 8-MOP in three different ointments, Unguentum Cordes(TM), Cold Cream Naturel(TM) and a water-containing gel on the basis of Carbopol 940. All three ointments were prepared with 8-MOP concentrations of 0.05 and 0.005%, and stored over 12 weeks at room temperature (19-20 degrees C) and at 5 degrees C. 8-MOP concentrations were measured at days 1, 8, 15, 29, 57 and 88 after preparation by thin-layer chromatography (TLC). The ointments were dissolved in an organic solvent, 10 microl were transferred onto the TLC plate and the chromatograms were developed first in toluene and then in toluene/ethyl acetate 2:1 v/v to resolve 8-MOP from the ointment constituents. The peak heights of 8-MOP were used for quantitation. The intraday variabilities are <3% for Unguentum Cordes and Cold Cream Naturel and <6% for the Carbopol 940 gel. The interday variabilities were <6.3% in all cases. In Unguentum Cordes and Cold Cream Naturel the concentrations of 8-MOP remain stable, but in Unguentum Cordes the emulsion began to break up after 8 weeks. In the Carbopol gel, only about 40% of the nominal concentrations of 8-MOP were found and they decrease significantly at storage at 5 degrees C. We conclude that the Carbopol gel seems to be unsuitable for PUVA therapy, whereas Cold Cream Naturel shows the best results.

  13. Manual therapy for cervicogenic dizziness: Long-term outcomes of a randomised trial.

    PubMed

    Reid, Susan A; Callister, Robin; Snodgrass, Suzanne J; Katekar, Michael G; Rivett, Darren A

    2015-02-01

    Manual therapy is effective for reducing cervicogenic dizziness, a disabling and persistent problem, in the short term. This study investigated the effects of sustained natural apophyseal glides (SNAGs) and passive joint mobilisations (PJMs) on cervicogenic dizziness compared to a placebo at 12 months post-treatment. Eighty-six participants (mean age 62 years, standard deviation (SD) 12.7) with chronic cervicogenic dizziness were randomised to receive SNAGs with self-SNAGs (n = 29), PJMs with range-of-motion (ROM) exercises (n = 29), or a placebo (n = 28) for 2-6 sessions over 6 weeks. Outcome measures were dizziness intensity, dizziness frequency (rated between 0 [none] and 5 [>once/day]), the Dizziness Handicap Inventory (DHI), pain intensity, head repositioning accuracy (HRA), cervical spine ROM, balance, and global perceived effect (GPE). At 12 months both manual therapy groups had less dizziness frequency (mean difference SNAGs vs placebo -0.7, 95% confidence interval (CI) -1.3, -0.2, p = 0.01; PJMs vs placebo -0.7, -1.2, -0.1, p = 0.02), lower DHI scores (mean difference SNAGs vs placebo -8.9, 95% CI -16.3, -1.6, p = 0.02; PJMs vs placebo -13.6, -20.8, -6.4, p < 0.001) and higher GPE compared to placebo, whereas there were no between-group differences in dizziness intensity, pain intensity or HRA. There was greater ROM in all six directions for the SNAG group and in four directions for the PJM group compared to placebo, and small improvements in balance for the SNAG group compared to placebo. There were no adverse effects. These results provide evidence that both forms of manual therapy have long-term beneficial effects in the treatment of chronic cervicogenic dizziness.

  14. Long-term proton pump inhibitor therapy and falls and fractures in elderly women: a prospective cohort study.

    PubMed

    Lewis, Joshua R; Barre, Deka; Zhu, Kun; Ivey, Kerry L; Lim, Ee Mun; Hughes, Jeff; Prince, Richard L

    2014-11-01

    Proton pump inhibitors (PPIs) are widely used in the elderly. Recent studies have suggested that long-term PPI therapy is associated with fractures in the elderly, however the mechanism remains unknown. We investigated the association between long-term PPI therapy ≥1 year and fracture risk factors including bone structure, falls, and balance-related function in a post hoc analysis of a longitudinal population-based prospective cohort of elderly postmenopausal women and replicated the findings in a second prospective study of falling in elderly postmenopausal women. Long-term PPI therapy was associated with increased risk of falls and fracture-related hospitalizations; adjusted odds ratio (AOR) 2.17; 95% CI, 1.25-3.77; p = 0.006 and 1.95; 95% CI, 1.20-3.16; p = 0.007, respectively. In the replication study, long-term PPI use was associated with an increased risk of self-reported falling; AOR, 1.51; 95% CI, 1.00-2.27; p = 0.049. No association of long-term PPI therapy with bone structure was observed; however, questionnaire-assessed falls-associated metrics such as limiting outdoor activity (p = 0.002) and indoor activity (p = 0.001) due to fear of falling, dizziness (p < 0.001) and numbness of feet (p = 0.017) and objective clinical measurement such as Timed Up and Go (p = 0.002) and Romberg eyes closed (p = 0.025) tests were all significantly impaired in long-term PPI users. Long-term PPI users were also more likely to have low vitamin B12 levels than non-users (50% versus 21%, p = 0.003). In conclusion, similar to previous studies, we identified an increased fracture risk in subjects on long-term PPI therapy. This increase in fracture risk in elderly women, already at high risk of fracture, appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long-term PPI therapy. © 2014 American Society for Bone and Mineral Research.

  15. TELEMOLD project: oximetry and exercise telemonitoring to improve long-term oxygen therapy.

    PubMed

    Faria, Inês; Gaspar, Carina; Zamith, Manuela; Matias, Isabel; das Neves, Rui César; Rodrigues, Fátima; Bárbara, Cristina

    2014-07-01

    Standard assessment of long-term oxygen therapy (LTOT) prescription involves hospital-based clinical tests. However, there is some evidence suggesting that oxygen demand during daily activities may not be correctly estimated by such tests, when compared with continuous ambulatory oximetry. The authors describe the results of a study aiming to evaluate the clinical relevance of a home telemonitoring system in LTOT optimization. Thirty-five chronic respiratory failure patients were monitored in real time with an oximeter sensor and an accelerometer. Signals were sent via Bluetooth(®) (Bluetooth SIG, Kirkland, WA) to a mobile phone and then via 3G or general packet radio service to a server. Continuous and secure access to data was established through an Internet site. Each patient was monitored an average of 7.6 ± 4.5 days (total, 83 ± 67 h). Valid records were on average 65 ± 24%. Records of rest, activity, and sleep time per patient were, on average, 28 ± 21%, 7 ± 6%, and 59 ± 25%, respectively. Significant desaturation during rest, activity, and sleep was found in 2, 26, and 9 patients, respectively. Patients' ratings of the user-friendliness of the equipments, assessed by questionnaire, were fairly good (76% reported it as easy/very easy). Our study suggests that a telemonitoring system combining oximetry and physical activity evaluation might contribute to a more adequate oxygen prescription, mainly during daily activities.

  16. [Long-term outcomes of children treated with continuous renal replacement therapy].

    PubMed

    Almarza, S; Bialobrzeska, K; Casellas, M M; Santiago, M J; López-Herce, J; Toledo, B; Carrillo, Á

    2015-12-01

    The objective of this study is to analyze long-term outcomes and kidney function in children requiring continuous renal replacement therapy (CRRT) after an acute kidney injury episode. A retrospective observational study was performed using a prospective database of 128 patients who required CRRT admitted to the pediatric intensive care unit between years 2006 and 2012. The subsequent outcomes were assessed in those surviving at hospital discharge. Of the 128 children who required RRT in the pediatric intensive care unit, 71 survived at hospital discharge (54.4%), of whom 66 (92.9%) were followed up. Three patients had chronic renal failure prior to admission to the NICU. Of the 63 remaining patients, 6 had prolonged or relapses of renal function disturbances, but only one patient with atypical Hemolytic Uremic Syndrome developed end-stage renal failure. The rest had normal kidney function at the last check-up. Most of surviving children that required CRRT have a positive outcome later on, presenting low mortality rates and recovery of kidney function in the medium term. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  17. Intraoperative Electron-Beam Radiation Therapy for Pediatric Ewing Sarcomas and Rhabdomyosarcomas: Long-Term Outcomes

    SciTech Connect

    Sole, Claudio V.; Calvo, Felipe A.; Polo, Alfredo; Cambeiro, Mauricio; Gonzalez, Carmen; Desco, Manuel; Martinez-Monge, Rafael

    2015-08-01

    Purpose: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). Methods and Materials: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-free survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). Conclusions: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates.

  18. Changes in spirometry over time in uremic patients receiving long-term hemodialysis therapy.

    PubMed

    Kovacević, Pedja; Stanetic, Mirko; Rajkovaca, Zvezdana; Meyer, F Joachim; Vukoja, Marija

    2011-01-01

    Complications of respiratory system in patients suffering from chronic renal failure who are treated with regular haemodialysis are well known. However, the influence of the duration of haemodialysis on pulmonary function is less understood. The aim of this study was to determine spirometry changes in patients on chronic haemodialysis over a five-year period. We tested 21 patients, out of which 11 female and 10 male, mean age of 50 (+/- 11) years. The mean duration of haemodialysis was 52.2 (+/- 44.7) months at the time of the inclusion. We performed spirometry testings in all patients, one hour before start and one hour after completion of haemodialysis. All parameters of spirometry recorded one hour after completion of haemodialysis (FVC, FEV1, FEF75, 50, 25, % of predicted), improved significantly (p < 0.01). After five years, only FVC demonstrated significant decline and none of the recorded spirometry parameters improved significantly one hour post haemodialysis compared to pre-haemodialysis period. Analysis of post-dialysis parameters of spirometry at the study onset and following five years of haemodialysis showed that all parameters, except FEF50 (p > 0.05), significantly deteriorated (p < 0.01). Patients who are on long-term haemodialysis show a significant decline in FVC following five years of treatment. Although the spirometry changes in observed population treated with chronic haemodialysis have reversible character during the first years of renal replacement therapy, five years after these changes become irreversible.

  19. Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson's disease.

    PubMed

    Mittermeyer, Gabriele; Christine, Chadwick W; Rosenbluth, Kathryn H; Baker, Suzanne L; Starr, Philip; Larson, Paul; Kaplan, Paul L; Forsayeth, John; Aminoff, Michael J; Bankiewicz, Krystof S

    2012-04-01

    We report the results of a long-term follow-up of subjects in a phase 1 study of AAV2-hAADC (adeno-associated virus type 2-human aromatic L-amino acid decarboxylase) gene therapy for the treatment of Parkinson's disease (PD). Ten patients with moderately advanced PD received bilateral putaminal infusions of either a low or a high dose of AAV2-hAADC vector. An annual positron emission tomography (PET) imaging with [(18)F]fluoro-L-m-tyrosine tracer was used for evaluation of AADC expression, and a standard clinical rating scale [Unified Parkinson's Disease Rating Scale (UPDRS)] was used to assess effect. Our previous analysis of the 6-month data suggested that this treatment was acutely safe and well tolerated. We found that the elevated PET signal observed in the first 12 months persisted over 4 years in both dose groups. A significantly increased PET value compared with the presurgery baseline was maintained over the 4-year monitoring period. The UPDRS in all patients off medication for 12 hr improved in the first 12 months, but displayed a slow deterioration in subsequent years. This analysis demonstrates that apparent efficacy continues through later years with an acceptable safety profile. These data indicate stable transgene expression over 4 years after vector delivery and continued safety, but emphasize the need for a controlled efficacy trial and the use of a higher vector dose.

  20. Changes in vertical tooth position and face height related to long term anterior repositioning splint therapy.

    PubMed

    Brown, D T; Gaudet, E L; Phillips, C

    1994-01-01

    This study evaluates whether extended full-time wear of a partial coverage mandibular anterior repositioning splint (MORA) causes intrusion of posterior teeth and determines the effect on jaw position. Sixty-four patients from two private orthodontic practices were studied using cephalometric radiographs to measure vertical change in position of the anterior and posterior teeth and the mandible. The splint wear time ranged from a minimum of one half year to a maximum of 4.8 years, with a mean of 1.33 years. No significant change was recorded in the distance from the mandibular molar to the mandibular plane. On average, the maxillary incisor and maxillary molar extruded about 1 mm, while the mandibular molar was unchanged and the mandibular incisor intruded about 0.6 mm. Posterior face height increased an average of 1.6 mm, and anterior face height increased an average of 2.7 mms. In 20% of the patients, intrusion of the mandibular molars of 1 mm or more occurred. In 41%, extrusion of the maxillary incisors of 1 mm or more was noted. Intrusion of the upper molars or extrusion of the lower incisors occurred in only 5% of the patients. The data indicates that only a very small proportion of patients having long term splint therapy using the MORA have clinically significant molar intrusion. Change in mandibular position was expressed in a vertical increase in posterior and anterior face height. Only very small changes occurred in antero-posterior position.

  1. Long-term outcome of patients treated by radiation therapy alone for salivary gland carcinomas

    SciTech Connect

    Chen, Allen M. . E-mail: achen@radonc17.ucsf.edu; Bucci, M. Kara; Quivey, Jeanne M.; Garcia, Joaquin; Eisele, David W.; Fu, Karen K.

    2006-11-15

    Purpose: To review a single-institution experience with the management of salivary gland cancers treated by radiation alone. Methods and Materials: Between 1960 and 2004, 45 patients with newly diagnosed salivary gland carcinomas were treated with definitive radiation to a median dose of 66 Gy (range, 57-74 Gy). Distribution of T-stage was: 24% T1, 18% T2, 31% T3, and 27% T4. Histology was: 14 mucoepidermoid (31%), 10 adenocarcinoma (22%), 8 adenoid cystic (18%), 4 undifferentiated (9%), 4 acinic (9%), 2 malignant mixed (4%), 2 squamous (4%), and 1 salivary duct carcinoma (2%). No patient had clinical or pathologic evidence of lymph node disease. Median follow-up was 101 months (range, 3-285 months). Results: The 5-year and 10-year rate estimates of local control were 70% and 57%, respectively. A Cox proportional hazard model identified T3-4 disease (p = 0.004) and radiation dose lower than 66 Gy (p = 0.001) as independent predictors of local recurrence. The 10-year overall survival and distant metastasis-free rates were 46% and 67%, respectively. Conclusion: Radiation therapy alone is a reasonable alternative to surgery in the definitive management of salivary gland cancers and results in long-term survival in a significant proportion of patients. Radiation dose in excess of 66 Gy is recommended.

  2. Papilla regeneration by injectable stem cell therapy with regenerative medicine: long-term clinical prognosis.

    PubMed

    Yamada, Yoichi; Nakamura, Sayaka; Ueda, Minoru; Ito, Kenji

    2015-03-01

    Black triangle (BT), an open interproximal space between teeth, can cause aesthetic concerns, food impaction, phonetic difficulties and periodontitis. The aim of this study was to determine the possibility and long-term prognosis of novel papilla regeneration with regenerative medicine, i.e. tissue-engineered papilla (TEP), and to investigate the potential of a tissue-engineering method for soft-tissue augmentation, especially aesthetic improvement of BT, with mesenchymal stem cells (MSCs) as the isolated cells, platelet-rich plasma (PRP) as the growth factor and hyaluronic acid (HA) as the scaffold. The parameters were assessed from a clinical point of view by measuring the distance from the tip of the interproximal papilla to the base of the contact area in each study region. The mean volumes, operation times and follow-up periods of TEP were 1.32 ± 0.25 ml, 2.2 ± 1.62 times and 55.3 ± 17.7 months; the mean improved BT values were 2.55 ± 0.89 mm. An aesthetic improvement was achieved. TEP was able to provide aesthetic improvement of black triangle and predictable results, and could emerge as another novel option for periodontal regenerative therapy in periodontal diseases. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Long-term testosterone therapy in hypogonadal men ameliorates elements of the metabolic syndrome: an observational, long-term registry study

    PubMed Central

    Traish, A M; Haider, A; Doros, G; Saad, F

    2014-01-01

    Aim The goal of this study was to determine if long-term testosterone (T) therapy in men with hypogonadism, henceforth referred to as testosterone deficiency (TD), ameliorates or improves metabolic syndrome (MetS) components. Methods We performed a cumulative registry study of 255 men, aged between 33 and 69 years (mean 58.02 ± 6.30) with subnormal plasma total T levels (mean: 9.93 ± 1.38; range: 5.89–12.13 nmol/l) as well as at least mild symptoms of TD assessed by the Aging Males' symptoms scale. All men received treatment with parenteral T undecanoate 1000 mg (Nebido®, Bayer Pharma, Berlin, Germany), administered at baseline and 6 weeks and thereafter every 12 weeks for up to 60 months. Lipids, glucose, liver enzymes and haemoglobin A1c analyses were carried out in a commercial laboratory. Anthropometric measurements were also made throughout the study period. Results Testosterone therapy restored physiological T levels and resulted in reductions in total cholesterol (TC) [7.29 ± 1.03 to 4.87 ± 0.29 mmol/l (281.58 ± 39.8 to 188.12 ± 11.31 mg/dl)], low-density lipoprotein cholesterol [4.24 ± 1.07 to 2.84 ± 0.92 mmol/l (163.79 ± 41.44 to 109.84 ± 35.41 mg/dl)], triglycerides [3.14 ± 0.58 to 2.16 ± 0.13 mmol/l (276.16 ± 51.32 to 189.78 ± 11.33 mg/dl)] and increased high-density lipoprotein levels [1.45 ± 0.46 to 1.52 ± 0.45 mmol/l (56.17 ± 17.79 to 58.85 ± 17.51 mg/dl)] (p < 0.0001 for all). There were marked reductions in systolic and diastolic blood pressure, blood glucose, haemoglobin A1c, C-reactive protein (6.29 ± 7.96 to 1.03 ± 1.87 U/l), alanine aminotransferase and aspartate aminotransferase (p < 0.0001 for all). Conclusions Long-term T therapy, at physiological levels, ameliorates MetS components. These findings strongly suggest that T therapy in hypogonadal men may prove useful in reducing the risk of cardiometabolic diseases. PMID:24127736

  4. Long-Term Results After Intraoperative Radiation Therapy for Gastric Cancer

    SciTech Connect

    Drognitz, Oliver Henne, Karl; Weissenberger, Christian; Bruggmoser, Gregor; Goebel, Heike; Hopt, Ulrich Theodor; Frommhold, Herrmann; Ruf, Guenther

    2008-03-01

    Purpose: We retrospectively analyzed the impact of intraoperative radiation therapy (IORT) on long-term survival in patients with resectable gastric cancer. Methods and Materials: From 1991 to 2001, a total of 84 patients with gastric neoplasms underwent gastectomy or subtotal resection with IORT (23 Gy, 6-15 MeV; IORT-positive [IORT{sup +}] group). Patients with a history of additional neoadjuvant chemotherapy, histologically confirmed R1 or R2 resection, or reoperation with curative intention after local recurrence were excluded from further analysis. The remaining 61 patients were retrospectively matched with 61 patients without IORT (IORT-negative [IORT{sup -}] group) for Union Internationale Contre le Cancer (UICC) stage, patient age, histologic grading, extent of surgery, and level of lymph node dissection. Subgroups included postoperative UICC Stages I (n = 31), II (n = 11), III (n = 14), and IV (n = 5). Results: Mean follow-up was 4.8 years in the IORT{sup +} group and 5.0 years in the IORT{sup -} group. The overall 5-year patient survival rate was 58% in the IORT{sup +} group vs. 59% in the IORT{sup -} group (p = 0.99). Subgroup analysis showed no impact of IORT on 5-year patient survival for those with UICC Stages I/II (76% vs. 80%; p = 0.87) and III/IV (21% vs. 14%, IORT{sup +} vs. IORT{sup -} group; p = 0.30). Perioperative mortality rates were 4.9% and 4.9% in the IORT{sup +} vs. IORT{sup -} group. Total surgical complications were more common in the IORT{sup +} than IORT{sup -} group (44.3% vs. 19.7%; p < 0.05). The locoregional tumor recurrence rate was 9.8% in the IORT{sup +} group. Conclusions: Use of IORT was associated with low locoregional tumor recurrence, but had no benefit on long-term survival while significantly increasing surgical morbidity in patients with curable gastric cancer.

  5. Ocular surface evaluation in eyes with chronic glaucoma on long term topical antiglaucoma therapy

    PubMed Central

    Saini, Manu; Vanathi, Murugesan; Dada, Tanuj; Agarwal, Tushar; Dhiman, Rebika; Khokhar, Sudarshan

    2017-01-01

    AIM To evaluate ocular surface changes and its correlation with the central corneal subbasal nerve fibre layer in chronic glaucoma patients. METHODS A prospective comparative study of ocular surface evaluation was performed in 50 eyes of 25 patients using two or more antiglaucoma medications for at least 6mo and 50 eyes of 25 normal subjects without any ocular problems as controls. The study parameters evaluated included visual acuity, intraocular pressure, ocular surface evaluation parameters [fluorescein break-up time (FTBUT), Schirmer's I test, ocular surface staining scores and ocular surface disease index score (OSDI)], central corneal sensation (Cochet Bonnett aesthesiometer), central subbasal nerve fiber layer density (SBNFLD) by confocal microscopy. RESULTS The mean values in the glaucoma cases and control groups respectively were as follows: OSDI score (35.89±16.07/6.02±3.84; P=0.001), Schirmer's I test score (7.63±2.64 mm/12.86±1.93 mm; P=0.001), FTBUT (9.44±2.76s/11.8±1.88s; P=0.001), corneal (5.7±2.33/ 1.1±0.58; P=0.001) and conjunctival staining score (5.06±1.94/0.84±0.46; P=0.001), corneal sensitivity (4.68±0.44/5.07±0.37; P=0.076), mean subbasal nerve fiber number (3.58±0.99/5.40±1.70; P=0.001), SBNFL length (1101.44±287.56 µm/1963.70±562.56 µm; P=0.001) and density (6883.94±1798.03 µm/mm2/12 273.15±3516.04 µm/mm2; P=0.001). Dry eye severity of level 2 and 3 was seen in 66% of glaucoma group. Corneal (R2=0.86) and conjunctival staining (R2=0.71) and OSDI score (R2=0.67) showed statistically significant negative correlation with central corneal SBNFLD while FTBUT (R2=0.84), corneal sensitivity (R2=0.52) showed positive correlation to central corneal SBNFLD in the long term topical antiglaucoma medication group. CONCLUSION Ocular surface changes and antiglaucoma therapy induced dry eye is found to be associated with decreased SBNFLD in eyes on long term topical antiglaucoma medications. PMID:28730085

  6. Ocular surface evaluation in eyes with chronic glaucoma on long term topical antiglaucoma therapy.

    PubMed

    Saini, Manu; Vanathi, Murugesan; Dada, Tanuj; Agarwal, Tushar; Dhiman, Rebika; Khokhar, Sudarshan

    2017-01-01

    To evaluate ocular surface changes and its correlation with the central corneal subbasal nerve fibre layer in chronic glaucoma patients. A prospective comparative study of ocular surface evaluation was performed in 50 eyes of 25 patients using two or more antiglaucoma medications for at least 6mo and 50 eyes of 25 normal subjects without any ocular problems as controls. The study parameters evaluated included visual acuity, intraocular pressure, ocular surface evaluation parameters [fluorescein break-up time (FTBUT), Schirmer's I test, ocular surface staining scores and ocular surface disease index score (OSDI)], central corneal sensation (Cochet Bonnett aesthesiometer), central subbasal nerve fiber layer density (SBNFLD) by confocal microscopy. The mean values in the glaucoma cases and control groups respectively were as follows: OSDI score (35.89±16.07/6.02±3.84; P=0.001), Schirmer's I test score (7.63±2.64 mm/12.86±1.93 mm; P=0.001), FTBUT (9.44±2.76s/11.8±1.88s; P=0.001), corneal (5.7±2.33/ 1.1±0.58; P=0.001) and conjunctival staining score (5.06±1.94/0.84±0.46; P=0.001), corneal sensitivity (4.68±0.44/5.07±0.37; P=0.076), mean subbasal nerve fiber number (3.58±0.99/5.40±1.70; P=0.001), SBNFL length (1101.44±287.56 µm/1963.70±562.56 µm; P=0.001) and density (6883.94±1798.03 µm/mm(2)/12 273.15±3516.04 µm/mm(2); P=0.001). Dry eye severity of level 2 and 3 was seen in 66% of glaucoma group. Corneal (R(2)=0.86) and conjunctival staining (R(2)=0.71) and OSDI score (R(2)=0.67) showed statistically significant negative correlation with central corneal SBNFLD while FTBUT (R(2)=0.84), corneal sensitivity (R(2)=0.52) showed positive correlation to central corneal SBNFLD in the long term topical antiglaucoma medication group. Ocular surface changes and antiglaucoma therapy induced dry eye is found to be associated with decreased SBNFLD in eyes on long term topical antiglaucoma medications.

  7. National study of discontinuation of long-term opioid therapy among veterans.

    PubMed

    Vanderlip, Erik R; Sullivan, Mark D; Edlund, Mark J; Martin, Bradley C; Fortney, John; Austen, Mark; Williams, James S; Hudson, Teresa

    2014-12-01

    Veterans have high rates of chronic pain and long-term opioid therapy (LTOT). Understanding predictors of discontinuation from LTOT will clarify the risks for prolonged opioid use and dependence among this population. All veterans with at least 90 days of opioid use within a 180-day period were identified using national Veteran's Health Affairs (VHA) data between 2009 and 2011. Discontinuation was defined as 6 months with no opioid prescriptions. We used Cox proportional hazards analysis to determine clinical and demographic correlates for discontinuation. A total of 550,616 veterans met criteria for LTOT. The sample was primarily male (93%) and white (74%), with a mean age of 57.8 years. The median daily morphine equivalent dose was 26 mg, and 7% received high-dose (>100mg MED) therapy. At 1 year after initiation, 7.5% (n=41,197) of the LTOT sample had discontinued opioids. Among those who discontinued (20%, n=108,601), the median time to discontinuation was 317 days. Factors significantly associated with discontinuation included both younger and older age, lower average dosage, and having received less than 90 days of opioids in the previous year. Although tobacco use disorders decreased the likelihood of discontinuation, co-morbid mental illness and substance use disorders increased the likelihood of discontinuation. LTOT is common in the VHA system and is marked by extended duration of use at relatively low daily doses with few discontinuation events. Opioid discontinuation is more likely in veterans with mental health and substance use disorders. Further research is needed to delineate causes and consequences of opioid discontinuation.

  8. Long-term Cardiac Mortality After Hypofractionated Radiation Therapy in Breast Cancer

    SciTech Connect

    Tjessem, Kristin Holm; Johansen, Safora; Reinertsen, Kristin V.; Danielsen, Turi; Fosså, Sophie D.; Fosså, Alexander

    2013-10-01

    Purpose: To explore very-long-term mortality from ischemic heart disease (IHD) after locoregional radiation therapy of breast cancer (BC) in relation to degree of hypofractionation and other treatment variables. Methods and Materials: Two hypofractionated regimens used for locoregional radiation therapy for BC from 1975 to 1991 were considered. Patients received 4.3 Gy × 2/week (10 fractions; target dose 43 Gy; n=1107) or 2.5 Gy × 5/week (20 fractions; target dose 50 Gy; n=459). To estimate cardiac doses, radiation fields were reconstructed in a planning system. Time to death from IHD was the endpoint, comparing the groups with each other and with age-matched, cancer-free control individuals, modeled with the Cox proportional hazards model. Results: Patients given 4.3 Gy × 10 had an increased risk of dying of IHD compared with both the 2.5 Gy group (hazard ratio [HR] = 2.37; 95% confidence interval [CI]: 1.06-5.32; P=.036) and the control group (HR = 1.59; 95% CI: 1.13-2.23; P=.008). Photon beams for parasternal fields gave an increased risk of dying of IHD compared with electron beams (HR = 2.56; 95% CI: 1.12-5.84; P=.025). Multivariate analysis gave an increased risk for the 4.3-Gy versus 2.5-Gy regimen with borderline significance (HR = 2.90; 95% CI: 0.97-8.79; P=.057) but not for parasternal irradiation. Conclusions: The degree of hypofractionation and parasternal photon beams contributed to increased cardiac mortality in this patient cohort. Differences emerged after 12 to 15 years, indicating the need of more studies with observation time of 2 decades.

  9. Acute prooxidant effects of vitamin C in EDTA chelation therapy and long-term antioxidant benefits of therapy.

    PubMed

    Hininger, Isabelle; Waters, Robert; Osman, Mireille; Garrel, Catherine; Fernholz, Karen; Roussel, Anne Marie; Anderson, Richard A

    2005-06-15

    Chelation therapy is thought to not only remove contaminating metals but also to decrease free radical production. EDTA chelation therapy, containing high doses of vitamin C as an antioxidant, is often used in the treatment of diseases such as diabetes and cardiovascular diseases but the effectiveness of this treatment may be variable and its efficacy has not been demonstrated conclusively. The objective of this work was to determine if the vitamin C added to standard chelation therapy cocktails was prooxidant. We administered a standard EDTA cocktail solution with or without 5 g of sodium ascorbate. One hour following the standard chelation therapy, there were highly significant prooxidant effects on lipids, proteins, and DNA associated with decreased activities of RBC glutathione peroxidase and superoxide dismutase while in the absence of sodium ascorbate, there were no acute signs of oxidative damage. After 16 sessions of standard chelation therapy, the acute prooxidant effects of vitamin C remained, but, even in the absence of nutrient supplements, there were beneficial long-term antioxidant effects of chelation therapy and plasma peroxide levels decreased. In conclusion, multiple sessions of EDTA chelation therapy protect lipids against oxidative damage. However, standard high amounts of vitamin C added to EDTA chelation solutions also display short term prooxidant effects. The added benefits of lower levels of vitamin C in chelation therapy need to be documented.

  10. Long-term efficacy and tolerability of mycophenolate mofetil therapy in diffuse scleroderma skin disease.

    PubMed

    Boulos, Daniel; Ngian, Gene-Siew; Rajadurai, Anton; Elford, Kathleen; Stevens, Wendy; Proudman, Susanna; Owen, Claire; Roddy, Janet; Nikpour, Mandana; Youssef, Peter; Hill, Catherine; Sahhar, Joanne

    2017-04-01

    To assess the long-term efficacy and tolerability of mycophenolate mofetil (MMF) in patients with diffuse cutaneous systemic sclerosis (dcSSc). Patients enrolled in the Australian Scleroderma Cohort study with dcSSc and baseline modified Rodnan skin score (mRSS) ≥ 12 who were treated for a minimum of 12 months with MMF for the primary indication of skin disease were included and their prospectively collected data retrieved. Change in mRSS, the proportion with a clinically significant improvement (reduction in mRSS ≥ 5 from baseline) and adverse effects due to therapy were determined. Seventy-four participants treated with MMF were identified and of these, 42 met inclusion criteria. The mean age was 53 ± 12 years, with mean disease duration at MMF commencement of 4.8 ± 4.3 years. Twenty-one participants (50%) commenced MMF within 2 years of disease onset and the mean duration of therapy was 2.7 ± 1.7 years. The mean mRSS at baseline was 25.9 ± 9.2 with a reduction of 3.7 ± 7.1 (P = 0.07) after 1 year of therapy, 7.6 ± 8.3 after 2 years (P = 0.01) and 10.5 ± 10.3 after 5 years (P < 0.01). Response to treatment was not affected by disease duration at MMF commencement or baseline skin score. Eighteen participants (43%) demonstrated clinically significant improvement after 1 year, increasing to 92% after 4 years. Two participants (5%) ceased MMF due to adverse effects. MMF was associated with a modest improvement in mRSS and was well tolerated in the treatment of dcSSc. Given the natural history of dcSSc where skin involvement can spontaneously improve, randomized, placebo-controlled studies are required to confirm whether improvement can be attributed to MMF therapy. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  11. Increased long-term remission after adequate medical cortisol suppression therapy as presurgical treatment in Cushing's disease.

    PubMed

    van den Bosch, O F C; Stades, A M E; Zelissen, P M J

    2014-02-01

    In the last decade, pre-operative medical cortisol suppression therapy has frequently been used in Cushing's disease to normalize cortisol concentrations pre-operatively. Our aim was to assess the efficacy of presurgical medical cortisol suppression therapy in Cushing's disease. We retrospectively assessed the medical files of all patients with Cushing's disease that received presurgical cortisol suppression therapy with ketoconazole or metyrapone and underwent subsequent transsphenoidal surgery between 1990 and 2010 at our centre. We retrieved the pretreatment regimen, adequacy of pretreatment, early postoperative serum cortisol levels, adverse effects and long-term remission status. Nineteen of 33 patients (58%) obtained long-term remission after pituitary surgery without additional postoperative therapy. Thirteen of 16 patients with adequate presurgical cortisol suppression therapy had postoperative cortisol concentrations <50 nmol/l. The 16 patients with adequate presurgical cortisol suppression had a higher long-term remission rate after primary surgery compared with the 13 patients with borderline or inadequate pretreatment (81% vs 38%; P < 0·05). Adequate presurgical cortisol suppression treatment with ketoconazole or metyrapone in Cushing's disease seems to be associated with suppressed postoperative cortisol concentrations and an increased long-term remission rate. © 2013 John Wiley & Sons Ltd.

  12. Alternobaric oxygen therapy in long-term treatment of Ménière's disease.

    PubMed

    Fattori, B; De Iaco, G; Nacci, A; Casani, A; Ursino, F

    2002-01-01

    results support the use of ABOT as a valid alternative to drugs in the long-term treatment of Ménière's disease.

  13. Long-term Course and Effectiveness of Combination Therapy in Alzheimer’s Disease

    PubMed Central

    Atri, Alireza; Shaughnessy, Lynn W.; Locascio, Joseph J.; Growdon, John H.

    2009-01-01

    Objective To compare the real-world clinical effectiveness and long-term clinical trajectory in patients with Alzheimer’s disease (AD) treated with combination (COMBO) therapy consisting of cholinesterase-inhibitor (CI) plus memantine (MEM) versus CI alone versus no treatment with either. Methods 382 subjects with Probable AD underwent serial clinical evaluations at a memory disorders unit. Cognition was assessed by the Information-Memory-Concentration subscale of the Blessed Dementia Scale (BDS) and function was assessed by the Weintraub Activities of Daily Living Scale (ADL) at six-month intervals. 144 subjects received standard care without CI or MEM (NO-RX), 122 received CI-monotherapy (CI), and 116 received combination therapy (COMBO) with CI plus MEM. Mean follow-up was 30 months (4.1 visits) and mean cumulative medication treatment time was 22.5 months. Rates of declines were analyzed using mixed-effects regression models, and Cohen’s d effect sizes were calculated annually for years 1–4. Results Covarying for baseline scores, age, education and duration of illness, the COMBO group had significantly lower mean annualized rates of deterioration in BDS and ADL scores compared to the CI (p<0.001; Cohen’s dBDS=0.10–0.34 and dADL=0.23–0.46 at 1–2 years) and NO-RX groups (p<0.001; Cohen’s dBDS=0.56–0.73 and dADL=0.32–0.48 at 1–2 years). For the COMBO group, Cohen’s d effect sizes increased with treatment duration. Similar comparisons significantly favored the CI over the NO-RX group on the BDS. Conclusions Combination therapy slows cognitive and functional decline in AD compared to CI-monotherapy and no treatment. These benefits had small-to-medium effect sizes that increased with time on treatment and were sustained for years. PMID:18580597

  14. Assessment of cognitive impairment in long-term oxygen therapy-dependent COPD patients.

    PubMed

    Karamanli, Harun; Ilik, Faik; Kayhan, Fatih; Pazarli, Ahmet Cemal

    2015-01-01

    A number of studies have shown that COPD, particularly in its later and more severe stages, is associated with various cognitive deficits. Thus, the primary goal of the present study was to elucidate the extent of cognitive impairment in patients with long-term oxygen therapy-dependent (LTOTD) COPD. In addition, this study aimed to determine the effectiveness of two cognitive screening tests, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), for COPD patients and the ability of oxygen therapy to mitigate COPD-related deficits in cognitive function. The present study enrolled 45 subjects: 24 nonuser and 21 regular-user LTOTD-COPD patients. All subjects had a similar grade of education, and there were no significant differences regarding age or sex. The MoCA (cutoff: <26 points) and MMSE (cutoff: ≤24 points) scores were compared between these two groups. The nonuser LTOTD-COPD group had a significantly lower MoCA score than that of the regular-user LTOTD-COPD group (19.38±2.99 vs 21.68±2.14, respectively) as well as a significantly lower MMSE score. Moreover, the absence of supplemental oxygen therapy increased the risk of cognitive impairment (MoCA, P=0.007 and MMSE, P=0.014), and the MoCA and MMSE scores significantly correlated with the number of emergency admissions and the number of hospitalizations in the last year. In the present study, the nonuser LTOTD-COPD group exhibited a significant decrease in cognitive status compared with the regular-user LTOTD-COPD group. This suggests that the assessment of cognitive function in nonuser LTOTD-COPD patients and the use of protective strategies, such as continuous supplemental oxygen treatment, should be considered during the management of COPD in this population. In addition, the MoCA score was superior to the MMSE score for the determination of cognitive impairment in the nonuser LTOTD-COPD patients.

  15. Long-term effect of a short interprofessional education interaction between medical and physical therapy students.

    PubMed

    Sytsma, Terin T; Haller, Elizabeth P; Youdas, James W; Krause, David A; Hellyer, Nathan J; Pawlina, Wojciech; Lachman, Nirusha

    2015-01-01

    Medicine is increasingly focused on team-based practice as interprofessional cooperation leads to better patient care. Thus, it is necessary to teach teamwork and collaboration with other health care professionals in undergraduate medical education to ensure that trainees entering the workforce are prepared to work in teams. Gross anatomy provides an opportunity to expose students to interprofessional education (IPE) early in their training. The purpose of this study is to describe an IPE experience and report if the experience has lasting influence on the participating students. The Readiness for Interprofessional Learning Scale (RIPLS) questionnaire was administered to first year medical (MD) and physical therapy (PT) students at Mayo Medical School and Mayo School of Health Sciences. Results demonstrated an openness on the part of the students to IPE. Interprofessional education experiences were incorporated into gross anatomy courses in both medical and PT curricula. The IPE experiences included a social event, peer-teaching, and collaborative clinical problem-solving sessions. These sessions enhanced gross anatomy education by reinforcing previous material and providing the opportunity to work on clinical cases from the perspective of two healthcare disciplines. After course completion, students again completed the RIPLS. Finally, one year after course completion, students were asked to provide feedback on their experience. The post-curricular RIPLS, similar to the pre-curricular RIPLS, illustrated openness to IPE from both MD and PT students. There were however, significant differences in MD and PT perceptions of roles and responsibilities. One-year follow-up indicated long-term retention of lessons learned during IPE.

  16. Long-Term Safety and Efficacy of Lowering Low-Density Lipoprotein Cholesterol With Statin Therapy

    PubMed Central

    Ford, Ian; Murray, Heather; Packard, Chris J.

    2016-01-01

    Background— Extended follow-up of statin-based low-density lipoprotein cholesterol lowering trials improves the understanding of statin safety and efficacy. Examining cumulative cardiovascular events (total burden of disease) gives a better appreciation of the clinical value of statins. This article evaluates the long-term impact of therapy on mortality and cumulative morbidity in a high-risk cohort of men. Methods and Results— The West of Scotland Coronary Prevention Study was a primary prevention trial in 45- to 64-year-old men with high low-density lipoprotein cholesterol. A total of 6595 men were randomized to receive pravastatin 40 mg once daily or placebo for an average of 4.9 years. Subsequent linkage to electronic health records permitted analysis of major incident events over 20 years. Post trial statin use was recorded for 5 years after the trial but not for the last 10 years. Men allocated to pravastatin had reduced all-cause mortality (hazard ratio, 0.87; 95% confidence interval, 0.80–0.94; P=0.0007), attributable mainly to a 21% decrease in cardiovascular death (hazard ratio, 0.79; 95% confidence interval, 0.69–0.90; P=0.0004). There was no difference in noncardiovascular or cancer death rates between groups. Cumulative hospitalization event rates were lower in the statin-treated arm: by 18% for any coronary event (P=0.002), by 24% for myocardial infarction (P=0.01), and by 35% for heart failure (P=0.002). There were no significant differences between groups in hospitalization for noncardiovascular causes. Conclusion— Statin treatment for 5 years was associated with a legacy benefit, with improved survival and a substantial reduction in cardiovascular disease outcomes over a 20-year period, supporting the wider adoption of primary prevention strategies. PMID:26864092

  17. Long-term Survival of Patients with Ischemic Cardiomyopathy Treated by CABG versus Medical Therapy

    PubMed Central

    Velazquez, Eric J.; Williams, Judson B.; Yow, Eric; Shaw, Linda K.; Lee, Kerry L.; Phillips, Harry R.; O’Connor, Christopher M.; K.Smith, Peter; Jones, Robert H.

    2013-01-01

    Background We prospectively applied the Surgical Treatment of Ischemic Cardiomyopathy (STICH) trial entry criteria to an observational database to determine whether coronary artery bypass grafting (CABG) decreases mortality compared to medical therapy (MED) for patients suffering coronary artery disease (CAD) and depressed left ventricular ejection fraction (LVEF). Methods This was a retrospective, observational, cohort study of prospectively collected data from the Duke Databank for Cardiovascular Disease. Long-term mortality was the main outcome measure. Between January 1, 1995 and July 31, 2009, 86,874 patients underwent cardiac catheterization for suspected ischemic heart disease and were evaluated for inclusion in the analysis. Results A total of 2,624 patients were found to have LVEF <35%, CAD amenable to CABG and no left main stenosis ≥50%. After exclusions including ongoing Class III angina and acute myocardial infarction, 763 patients were included for propensity score analysis including 624 who received MED and 139 CABG. Adjusted mortality curves were constructed for those patients in the three quintiles most likely to receive CABG. The curves diverged early, with risk-adjusted mortality rates at 5 years of 46% for MED versus 29% for CABG, and the survival benefit of CABG over MED continued through 10 years follow-up (hazard ratio 0.63, 95% CI 0.45 – 0.88). Conclusions Among a propensity-matched, risk-adjusted observational cohort of patients with CAD, LVEF < 35%, and no left main disease ≥ 50%, CABG is associated with a survival advantage over MED through 10 years follow-up. PMID:22269720

  18. Growth in HIV-infected children on long-term antiretroviral therapy.

    PubMed

    Feucht, Ute D; Van Bruwaene, Lore; Becker, Piet J; Kruger, Mariana

    2016-05-01

    To describe growth in HIV-infected children on long-term antiretroviral therapy (ART) and to assess social, clinical, immunological and virological factors associated with suboptimal growth. This observational cohort study included all HIV-infected children at an urban ART site in South Africa who were younger than 5 years at ART initiation and with more than 5 years of follow-up. Growth was assessed using weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ) and body mass index (BMI)-for-age Z-scores (BAZ). Children were stratified according to pre-treatment anthropometry and age. Univariate and mixed linear analysis were used to determine associations between independent variables and weight and height outcomes. The majority of the 159 children presented with advanced clinical disease (90%) and immunosuppression (89%). Before treatment underweight, stunting and wasting were common (WAZ<-2 = 50%, HAZ<-2 = 73%, BAZ<-2 = 19%). Weight and BMI improved during the initial 12 months, while height improved over the entire 5-year period. Height at study exit was significantly worse for children with growth impairment at ART initiation (P < 0.001), and infants (<1 year) demonstrated superior improvement in terms of BMI (P = 0.04). Tuberculosis was an independent risk factor for suboptimal weight (P = 0.01) and height (P = 0.02) improvement. Weight gain was also hindered by lack of electricity (P = 0.04). Immune reconstitution and virological suppression were not associated with being underweight or stunted at study endpoint. Malnutrition was a major clinical concern for this cohort of HIV-infected children. Early ART initiation, tuberculosis co-infection management and nutritional interventions are crucial to ensure optimal growth in HIV-infected children. © 2016 John Wiley & Sons Ltd.

  19. The long-term side effects of radiation therapy for benign brain tumors in adults

    SciTech Connect

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. )

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  20. Intraoperative Radiation Therapy in Resected Pancreatic Carcinoma: Long-Term Analysis

    SciTech Connect

    Valentini, Vincenzo; Morganti, Alessio G.; Macchia, Gabriella Mantini, Giovanna; Mattiucci, Gian C.; Brizi, M. Gabriella; Alfieri, Sergio; Bossola, Maurizio; Pacelli, Fabio; Sofo, Luigi; Doglietto, Giovanbattista; Cellini, Numa

    2008-03-15

    Purpose: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT + IORT). Methods and Materials: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative 'flash' RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. Results: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p = 0.019). Conclusions: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT ({approx}50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT + external RT)

  1. Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer

    PubMed Central

    Chen, Yingtai; Che, Xu; Zhang, Jianwei; Huang, Huang; Zhao, Dongbing; Tian, Yantao; Li, Yexiong; Feng, Qinfu; Zhang, Zhihui; Jiang, Qinglong; Zhang, Shuisheng; Tang, Xiaolong; Huang, Xianghui; Chu, Yunmian; Zhang, Jianghu; Sun, Yuemin; Zhang, Yawei; Wang, Chengfeng

    2016-01-01

    Abstract To assess prognostic benefits of intraoperative electron beam radiation therapy (IOERT) in patients with nonmetastatic locally advanced pancreatic cancer (LAPC) and evaluate optimal adjuvant treatment after IOERT. A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Two hundred forty-seven consecutive patients with nonmetastatic LAPC who underwent IOERT between January 2008 and May 2015 were identified and included in the study. Overall survival (OS) was calculated from the day of IOERT. Prognostic factors were examined using Cox proportional hazards models. The 1-, 2-, and 3-year actuarial survival rates were 40%, 14%, and 7.2%, respectively, with a median OS of 9.0 months. On multivariate analysis, an IOERT applicator diameter < 6 cm (hazards ratio [HR], 0.67; 95% confidence interval [CI], 0.47–0.97), no intraoperative interstitial sustained-release 5-fluorouracil chemotherapy (HR, 0.46; 95% CI, 0.32–0.66), and receipt of postoperative chemoradiotherapy followed by chemotherapy (HR, 0.11; 95% CI, 0.04–0.25) were significantly associated with improved OS. Pain relief after IOERT was achieved in 111 of the 117 patients, with complete remission in 74 and partial remission in 37. Postoperative complications rate and mortality were 14.0% and 0.4%, respectively. Nonmetastatic LAPC patients with smaller size tumors could achieve positive long-term survival outcomes with a treatment strategy incorporating IOERT and postoperative adjuvant treatment. Chemoradiotherapy followed by chemotherapy might be a recommended adjuvant treatment strategy for well-selected cases. Intraoperative interstitial sustained-release 5-fluorouracil chemotherapy should not be recommended for patients with nonmetastatic LAPC. PMID:27661028

  2. Long-Term Outcomes for Desmoid Tumors Treated With Radiation Therapy

    SciTech Connect

    Guadagnolo, B. Ashleigh Zagars, Gunar K.; Ballo, Matthew T.

    2008-06-01

    Purpose: To evaluate long-term outcomes in patients with desmoid fibromatosis treated with radiation therapy (RT), with or without surgery. Methods and Materials: Between 1965 and 2005, 115 patients with desmoid tumors were treated with RT at our institution. The median age was 29 years (range, 8-73 years). Of the patients, 41 (36%) received RT alone (median dose, 56 Gy) for gross disease, and 74 (64%) received combined-modality treatment (CMT) consisting of a combination of surgery and RT (median dose, 50.4 Gy). Results: Median follow-up was 10.1 years. Local control (LC) rates at 5 and 10 years were 75% and 74%, respectively. On univariate analysis, LC was significantly influenced by tumor size ({<=}5 cm vs. 5-10 cm vs. >10 cm) (p = 0.02) and age ({<=} 30 vs. >30 years) (p = 0.02). There was no significant difference in LC for patients treated with RT alone for gross disease vs. CMT. For patients treated with CMT, only tumor size significantly influenced LC (p = 0.02). Patients with positive margins after surgery did not have poorer LC than those with negative margins (p = 0.38). Radiation-related complications occurred in 20 (17%) of patients and were associated with dose >56 Gy (p = 0.001), age {<=}30 years (p = 0.009), and receipt of RT alone vs. CMT (p = 0.01). Conclusions: Desmoid tumors are effectively controlled with RT administered either as an adjuvant to surgery when resection margins are positive or alone for gross disease when surgical resection is not feasible. Doses >56 Gy may not be necessary to control gross disease and are associated with high rates of radiation-related complications.

  3. Overnight prescription of oxygen in long term oxygen therapy: time to reconsider the guidelines?

    PubMed

    Nisbet, M; Eaton, T; Lewis, C; Fergusson, W; Kolbe, J

    2006-09-01

    Guidelines for long term oxygen therapy (LTOT) recommend increasing oxygen flow by 1 l/min overnight. A study was undertaken in patients with COPD on LTOT to determine the prevalence of overnight desaturation if the usual oxygen flow rate is not increased at night, whether resting oxygen saturation predicts overnight desaturation, and whether overnight desaturation correlates with health related quality of life (HRQL) and sleep quality. A cross sectional prospective study was performed on consecutive patients with COPD on LTOT attending our regional outpatient oxygen service. All patients fulfilled standard criteria for LTOT, had been established on LTOT at a flow to achieve resting oxygen saturations >90%, but had not been instructed to increase oxygen flow overnight. Overnight desaturation was defined as <90% for > or =30% of the night on either of two consecutive nights. HRQL was evaluated with the SF-36 Health Survey Questionnaire, Chronic Respiratory Questionnaire, and the Pittsburgh Sleep Quality Index. Thirty eight patients (63% men) of mean (SD) age 73.5 (8.04) years and mean (SD) forced expiratory volume in 1 second 0.77 (0.35) l were evaluated. Overnight desaturation occurred in six (16%; 95% CI 4 to 27). Desaturators had mean (SD) resting oxygen saturation on room air of 88 (4.2)% compared with 90 (4.1)% in non-desaturators (p = 0.15), and corrected saturations of 93 (2.0)% versus 94 (2.0)% (p = 0.18). HRQL and sleep quality were poor but did not differ between desaturators and non-desaturators. Most patients did not exhibit overnight desaturation despite not increasing their LTOT prescription overnight. These results challenge the recommendation of routinely increasing overnight oxygen flow in patients receiving LTOT.

  4. The importance of knowing the home conditions of patients receiving long-term oxygen therapy

    PubMed Central

    Godoy, Ilda; Tanni, Suzana Erico; Hernández, Carme; Godoy, Irma

    2012-01-01

    Purpose Long-term oxygen therapy (LTOT) is one of the main treatments for patients with chronic obstructive pulmonary disease. Patients receiving LTOT may have less than optimal home conditions and this may interfere with treatment. The objective of this study was, through home visits, to identify the characteristics of patients receiving LTOT and to develop knowledge regarding the home environments of these patients. Methods Ninety-seven patients with a mean age of 69 plus or minus 10.5 years were evaluated. This study was a cross-sectional descriptive analysis. Data were collected during an initial home visit, using a questionnaire standardized for the study. The results were analyzed retrospectively. Results Seventy-five percent of the patients had chronic obstructive pulmonary disease, and 11% were active smokers. The patients’ mean pulse oximetry values were 85.9% plus or minus 4.7% on room air and 92% plus or minus 3.9% on the prescribed flow of oxygen. Most of the patients did not use the treatment as prescribed and most used a humidifier. The extension hose had a mean length of 5 plus or minus 3.9 m (range, 1.5–16 m). In the year prior to the visit, 26% of the patients received emergency medical care because of respiratory problems. Few patients reported engaging in leisure activities. Conclusion The home visit allowed us to identify problems and interventions that could improve the way LTOT is used. The most common interventions related to smoking cessation, concentrator maintenance and cleaning, use of a humidifier, and adjustments of the length of the connector hose. Therefore, the home visit is a very important tool in providing comprehensive care to patients receiving LTOT, especially those who show lack of adequate progress and those who show uncertainty about the treatment method. PMID:22848155

  5. Placental involvement by non-Hodgkin lymphoma in a Crohn disease patient on long-term thiopurine therapy.

    PubMed

    Chen, G; Crispin, P; Cherian, M; Dahlstrom, J E; Sethna, F F; Kaye, G; Pavli, P; Subramaniam, K

    2016-01-01

    We report the first published case of aggressive diffuse large B-cell (non-Hodgkin) lymphoma in a 35-year-old pregnant woman who had Crohn disease and was taking long-term thiopurine therapy: the patient developed placental insufficiency, and there was intrauterine fetal death.

  6. Pentoxifylline as adjunct therapy to long-term clinical management of a right-to-left patent ductus arteriosus

    PubMed Central

    Turner, Elizabeth

    2016-01-01

    Management of a right-to-left (“reversed”) patent ductus arteriosus (PDA) focuses on control of clinical signs associated with hyperviscosity due to erythrocytosis. Pentoxifylline therapy is presented as an adjunct to routine phlebotomies for the long-term clinical management of reversed PDA in a 10-year-old Chihuahua. PMID:27247468

  7. Acceptance and Commitment Therapy for Depression: A Preliminary Randomized Clinical Trial for Unemployed on Long-Term Sick Leave

    ERIC Educational Resources Information Center

    Folke, Fredrik; Parling, Thomas; Melin, Lennart

    2012-01-01

    This preliminary study investigated the feasibility of a brief Acceptance and Commitment Therapy (ACT) in a Swedish sample of unemployed individuals on long-term sick leave due to depression. Participants were randomized to a nonstandardized control condition (N = 16) or to the ACT condition (N = 18) consisting of 1 individual and 5 group…

  8. Pentoxifylline as adjunct therapy to long-term clinical management of a right-to-left patent ductus arteriosus.

    PubMed

    Turner, Elizabeth

    2016-06-01

    Management of a right-to-left ("reversed") patent ductus arteriosus (PDA) focuses on control of clinical signs associated with hyperviscosity due to erythrocytosis. Pentoxifylline therapy is presented as an adjunct to routine phlebotomies for the long-term clinical management of reversed PDA in a 10-year-old Chihuahua.

  9. Acceptance and Commitment Therapy for Depression: A Preliminary Randomized Clinical Trial for Unemployed on Long-Term Sick Leave

    ERIC Educational Resources Information Center

    Folke, Fredrik; Parling, Thomas; Melin, Lennart

    2012-01-01

    This preliminary study investigated the feasibility of a brief Acceptance and Commitment Therapy (ACT) in a Swedish sample of unemployed individuals on long-term sick leave due to depression. Participants were randomized to a nonstandardized control condition (N = 16) or to the ACT condition (N = 18) consisting of 1 individual and 5 group…

  10. Successful treatment of dwarfism secondary to long-term steroid therapy in steroid-dependent nephrotic syndrome.

    PubMed

    Sun, Linlin; Chen, Dongping; Zhao, Xuezhi; Xu, Chenggang; Mei, Changlin

    2010-01-01

    Prolonged steroid therapy is generally used for steroid-dependent nephrotic syndrome in pediatric patients. However, dwarfism secondary to a long-term regimen and its successful reverse is rarely reported. The underlying mechanism of dwarfism is still poorly understood, as both long-term steroid use and nephrotic syndrome may interact or independently interfere with the process of growth. Here, we present a 17-year-old patient with dwarfism and steroid-dependent nephrotic syndrome and the successful treatment by recombinant human growth factor and cyclosporine A with withdrawal of steroid. We also briefly review the current understanding and the management of dwarfism in pediatric patients with nephrotic syndrome.

  11. Long-Term Clinical Outcomes of Subcutaneous Versus Transvenous Implantable Defibrillator Therapy.

    PubMed

    Brouwer, Tom F; Yilmaz, Dilek; Lindeboom, Robert; Buiten, Maurits S; Olde Nordkamp, Louise R A; Schalij, Martin J; Wilde, Arthur A; van Erven, Lieselot; Knops, Reinoud E

    2016-11-08

    Transvenous implantable cardioverter-defibrillators (TV-ICDs) improve survival in patients at risk for sudden cardiac death, but complications remain an important drawback. The subcutaneous ICD (S-ICD) was developed to overcome lead-related complications. Comparison of clinical outcomes of both device types in previous studies was hampered by dissimilar patient characteristics. This retrospective study compares long-term clinical outcomes of S-ICD and TV-ICD therapy in a propensity-matched cohort. The authors analyzed 1,160 patients who underwent S-ICD or TV-ICD implantation in 2 high-volume hospitals in the Netherlands. Propensity matching for 16 baseline characteristics, including diagnosis, yielded 140 matched pairs. Clinical outcomes were device-related complications requiring surgical intervention, appropriate and inappropriate ICD therapy, and were reported as 5-year Kaplan-Meier rate estimates. All 16 baseline characteristics were balanced in the matched cohort of 140 patients with S-ICDs and 140 patients with TV-ICDs (median age 41 years [interquartile range: 30 to 52 years] and 40% women). The complication rate was 13.7% in the S-ICD group versus 18.0% in the TV-ICD group (p = 0.80). The infection rate was 4.1% versus 3.6% in the TV-ICD groups (p = 0.36). Lead complications were lower in the S-ICD arm compared with the TV-ICD arm, 0.8% versus 11.5%, respectively (p = 0.03). S-ICD patients had more nonlead-related complications than TV-ICD patients, 9.9% versus 2.2%, respectively (p = 0.047). Appropriate ICD intervention (antitachycardia pacing and shocks) occurred more often in the TV-ICD group (hazard ratio [HR]: 2.42; p = 0.01). The incidence of appropriate (TV-ICD HR: 1.46; p = 0.36) and inappropriate shocks (TV-ICD HR: 0.85; p = 0.64) was similar. The complication rate in patients implanted with an S-ICD or TV-ICD was similar, but their nature differed. The S-ICD reduced lead-related complications significantly, at the cost of nonlead

  12. Effectiveness of bionator therapy for Class II malocclusions: a comparative long-term study.

    PubMed

    Kochel, J; Meyer-Marcotty, P; Witt, E; Stellzig-Eisenhauer, A

    2012-04-01

    The goal of this retrospective study was to examine the effectiveness of isolated bionator therapy in Class II patients both longitudinally and over the long term. We aimed to determine whether skeletal and/or dentoalveolar reactions differ in relationship to the Angle Class (II, Division 1 vs. II, Division 2). A total of 50 juvenile patients with Class II malocclusion (♀ n = 26, ♂ n = 24) were included. A total of 24 patients presented an Angle Class II, Division 1 and 26 an Angle Class II, Division 2. We compared the patients' lateral cephalograms taken at the beginning of treatment (t1: 10.1 years), after active therapy (t2: 13.8 years), and at the end of retention (t3: 16.4 years) analyzing the following cephalometric parameters: SNA, SNB, ANB, ANB(ind), SNPog, Wits appraisal, U1-SN, U1-SpP, L1-MeGo, interincisal angle. Mean and standard deviations of each of the variables were calculated. Differences between t1-t2 and t2-t3 were tested for statistical significance. Changes in the variables were then analyzed biometrically for specific differences in terms of Angle Class (II, Division 1 vs. II, Division 2). Between t1 and t2, SNB (p = 0.000) and SNPog (p = 0.000) increased significantly, as did ANB (p = 0.000), while the difference between ANB and ANB(ind) (p = 0.000) and Wits appraisal (p = 0.000) decreased significantly. The dentoalveolar variables U1-SN, U1-SpP, and the interincisal angle changed significantly in both groups. The inclination of the upper incisors was corrected by retrusion in the Class II, Division 1 and by protrusion in the Class II, Division 2 group. Only marginal changes in all variables between t2 and t3 were observed. A significant skeletal effect (even in long-time stability) through bionator treatment could be confirmed in this study of Class II, Divisions 1 and 2 patients. The desired effect on the upper front teeth was realized, and there was no appreciable dentoalveolar compensation in the mandible.

  13. Short-term cognitive-behavioral therapy for binge eating disorder: long-term efficacy and predictors of long-term treatment success.

    PubMed

    Fischer, Sophia; Meyer, Andrea H; Dremmel, Daniela; Schlup, Barbara; Munsch, Simone

    2014-07-01

    The present study evaluates the long-term efficacy (four years after treatment) of a short-term Cognitive-Behavioral Treatment (CBT) of Binge Eating Disorder (BED). We examined patient characteristics, mostly measured at the end of treatment, for their predictive value of long-term success. Forty-one BED-patients between 18 and 70 years took part in a randomized controlled trial (RCT) for a short-term treatment and were evaluated until 4 years after treatment. Assessments comprised structured interviews on comorbid mental disorder/eating disorder pathology and questionnaires on eating disorder pathology/general psychopathology. BED core symptoms and associated psychopathology improved substantially during treatment phase and further improved or at least remained stable during the follow-up period. End of treatment predictors for long term success were elevated weight and eating concern and higher frequency of objective binges. Tailoring additional interventions to patients' individual needs could further improve treatment efficacy.

  14. Long-term cognitive and behavioral therapies, combined with augmentative communication, are related to uncinate fasciculus integrity in autism.

    PubMed

    Pardini, Matteo; Elia, Maurizio; Garaci, Francesco G; Guida, Silvia; Coniglione, Filadelfo; Krueger, Frank; Benassi, Francesca; Emberti Gialloreti, Leonardo

    2012-04-01

    Recent evidence points to white-matter abnormalities as a key factor in autism physiopathology. Using Diffusion Tensor Imaging, we studied white-matter structural properties in a convenience sample of twenty-two subjects with low-functioning autism exposed to long-term augmentative and alternative communication, combined with sessions of cognitive and behavioral therapy. Uncinate fasciculus structural properties correlated significantly with therapy length and early onset, as well as to clinical outcome, independently from IQ, age or symptoms severity at therapy onset. Moreover, adherence to therapy was linked with better clinical outcome and uncinate fasciculus structural integrity. The results point to the capability of a long-term rehabilitation of subjects with low-functioning autism to produce white-matter structural modifications, which could thus play a role in the rehabilitative outcome.

  15. An investigation of long-term effects of group music therapy on agitation levels of people with Alzheimer's Disease.

    PubMed

    Ledger, Alison J; Baker, Felicity A

    2007-05-01

    This study aimed to investigate the long-term effects of group music therapy on agitation manifested by nursing home residents with Alzheimer's disease. A non-randomised experimental design was employed with one group receiving weekly music therapy (n = 26) and another group receiving standard nursing home care (n = 19). Agitation levels were measured five times over one year using the Cohen-Mansfield Agitation Inventory (Cohen-Mansfield, J. (1989). Agitation in the elderly. In N. Billig & P. V. Rabins (Eds.), Issues in geriatric psychiatry (pp. 101-113). Basel, Switzerland: Karger). Although music therapy participants showed short-term reductions in agitation, there were no significant differences between the groups in the range, frequency, and severity of agitated behaviours manifested over time. Multiple measures of treatment efficacy are necessary to better understand the long-term effects music therapy programs have on this population.

  16. Mid- and long-term results of the joint preserving therapy of hallux rigidus.

    PubMed

    Waizy, Hazibullah; Czardybon, M Abbara; Stukenborg-Colsman, C; Wingenfeld, C; Wellmann, M; Windhagen, H; Frank, D

    2010-02-01

    The hallux rigidus is an over 100-year-known pathology. Yet an overall accepted therapy regime does not exist. The aim of this prospective study was to analyze the long-term clinical outcome and patient satisfaction of joint preserving operative care in patients with symptomatic hallux rigidus. We present a prospective study with 60 patients (60 feet) with symptomatic hallux rigidus. In cases with intraoperative dorsiflexion of less than 70 degrees after the cheilectomy, an additional Kessel-Bonney osteotomy was done. The first follow-up after 24 (10-31) months was done on 49 (81.7%) patients and the second after 96 (84-104) months on 46 (76.7%) patients. We recorded the pre- and post-operative Kitaoka score, range of motion, pain and patients satisfaction. The results were related to the operative procedure and the grade of hallux rigidus (according to Regnauld). Twenty patients were graded as I, 35 patients as II and 5 patients as III. At the follow-up, the mean dorsiflexion increased in grade I patients to about 21.7 degrees , in grade II patients about 23.7 degrees and in grade III patients about 26.3 degrees . At the first follow-up [24 (10-31) months], all patients of grade I, 63.3% patients of grade II and 75% of grade III patients had just occasional or no pain. At the second follow-up [96 (84-104) months], 77.8% of grade I and 73.9% of grade II patients had no pain. At the first (second) follow-up 53.3% (61.1%) of grade I, 43.3% (33.3%) of grade II and 50% (25%) of grade III patients were completely satisfied. In order to the operative procedure the patients were completely satisfied or satisfied: first (second) follow-up 52% (85.9%) of patients with cheilectomy and 85% (86.4%) of patients with cheilectomy and Kessel-Bonney osteotomy. In 51.4% of the patients, the Kitaoka Score was higher than 70.4 points. Four patients had a persistent hypaesthesia of the medial side of the great toe and three patients had a delayed wound healing. No revision was

  17. Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion

    PubMed Central

    Shuai, Yi; Liao, Li; Su, Xiaoxia; Yu, Yang; Shao, Bingyi; Jing, Huan; Zhang, Xinjing; Deng, Zhihong; Jin, Yan

    2016-01-01

    Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSCs therapy. Here, we report a melatonin-based strategy to improve cell therapy of in vitro cultured MSCs. Among four small molecules with anti-aging and stem cell-protection properties (rapamycin, resveratrol, quercetin and melatonin), colony forming, proliferation, and osteogenic differentiation assay showed that melatonin was the most efficient to preserve self-renewal and differentiation properties of rat bone marrow MSCs (BMMSCs) after long-term passaging. Functional assays confirmed melatonin treatment did not affect the colony forming, proliferation and osteogenic differentiation of BMMSCs cultured for 1 or 4 passages, but largely prevented the decline of self-renew and differentiation capacity of BMMSCs cultured for 15 passages in vitro. Furthermore, heterotopic osteogenesis assay, critical size calvarial defects repair assay, osteoporosis treatment and experimental colitis therapy assay strongly certified that melatonin preserved the therapeutic effect of long-term passaged BMMSCs on bone regeneration and immunotherapy in vivo. Mechanistically, melatonin functioned by activating antioxidant defense system, inhibiting the pathway of cell senescence, and preserving the expression of gene governing the stemness. Taken together, our findings showed that melatonin treatment efficiently prevented the dysfunction and therapeutic failure of BMMSCs after long-term passaging, providing a practical strategy to improve the application of BMMSCs in tissue engineering and cytotherapy. PMID:27570559

  18. Enzyme replacement therapy for mucopolysaccharidosis VI: long-term cardiac effects of galsulfase (Naglazyme®) therapy.

    PubMed

    Braunlin, E; Rosenfeld, H; Kampmann, C; Johnson, J; Beck, M; Giugliani, R; Guffon, N; Ketteridge, D; Sá Miranda, C M; Scarpa, M; Schwartz, I V; Leão Teles, E; Wraith, J E; Barrios, P; Dias da Silva, E; Kurio, G; Richardson, M; Gildengorin, G; Hopwood, J J; Imperiale, M; Schatz, A; Decker, C; Harmatz, P

    2013-03-01

    Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untreated patients with mucopolysaccharidosis type VI (MPS VI). Cardiac ultrasound was performed to investigate these findings in subjects during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB, rhN-acetylgalactosamine 4-sulfatase, galsulfase, Naglazyme®). Studies were conducted in 54 subjects before ERT was begun and at specific intervals for up to 96 weeks of weekly infusions of rhASB at 1 mg/kg during phase 1/2, phase 2, and phase 3 trials of rhASB. At baseline, mitral and aortic valve obstruction was present and was significantly greater in those ≥12 years of age. Mild mitral and trace aortic regurgitation were present, the former being significantly greater in those <12 years. Left ventricular hypertrophy, with averaged z-scores ranging from 1.6-1.9 SD greater than normal, was present for ages both <12 and ≥12 years. After 96 weeks of ERT, ventricular septal hypertrophy regressed in those <12 years. For those ≥12 years, septal hypertrophy was unchanged, and aortic regurgitation increased statistically but not physiologically. Obstructive gradients across mitral and aortic valves remained unchanged. The results suggest that long-term ERT is effective in reducing intraventricular septal hypertrophy and preventing progression of cardiac valve abnormalities when administered to those <12 years of age.

  19. The effects of light therapy on depression and sleep disruption in older adults in a long-term care facility.

    PubMed

    Wu, Mann-Chian; Sung, Huei-Chuan; Lee, Wen-Li; Smith, Graeme D

    2015-10-01

    This study aims to evaluate the effect of light therapy on depression and sleep disruption in older adults residing in a long-term care facility. Psychological morbidity is a problem commonly seen in older adults residing in long-term care facilities. Limited research has addressed the effect of light therapy on depression in this population. A quasi-experimental pretest and posttest design was used. Thirty-four participants in the experimental group received light therapy by sitting in front of a 10000-lux light box 30 min in the morning, three times a week for 4 weeks. Thirty-one participants in the control group received routine care without light therapy. Depression was measured by Geriatric Depression Scale-Short Form at baseline and week 4. After receiving 4 weeks of light therapy, the mean depression score in the experimental group decreased from 7.24 (SD3.42) at pretest to 5.91 (SD 3.40) at posttest, and had a significant reduction (t = 2.22, P = 0.03). However, there was no significant difference in depression score and sleep disruption between the experimental group and control group. Light therapy might have the potential to reduce depressive symptoms and sleep disruption and may be a viable intervention to improve mental health of older adults in the long-term care facilities.

  20. Biochemical Response to Androgen Deprivation Therapy Before External Beam Radiation Therapy Predicts Long-term Prostate Cancer Survival Outcomes

    SciTech Connect

    Zelefsky, Michael J.; Gomez, Daniel R.; Polkinghorn, William R.; Pei, Xin; Kollmeier, Marisa

    2013-07-01

    Purpose: To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5 years. Results: The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Conclusions: Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes.

  1. Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials.

    PubMed

    Mackenzie, A H

    1983-07-18

    No eye disease was detected in over 900 rheumatoid arthritis patients treated with less than 4.0 mg/kg per day of chloroquine or less than 6.5 mg/kg per day of hydroxychloroquine for a mean of about seven years. I therefore consider these dosage rates safe, since they are below the threshold of retinal toxicity. This is based on more than 6,000 patient-years of drug exposure. That dosage threshold for retinopathy appears to be 5.1 mg/kg per day for chloroquine and 7.8 mg/kg per day for hydroxychloroquine according to my studies with these compounds. The daily dosage rate, rather than total drug accumulation, seems to determine the development of eye disease. To prevent overdosage, dosing should be calculated not on the actual weight of the patient but on ideal (lean) body weight. Furthermore, the patient's renal and liver function should also be taken into account to avoid overdosage. Since exposure to light amplifies the risk of retinopathy in patients treated with antimalarials, dark sunglasses are recommended for patients spending much time in sunlight.

  2. Long-term ACTH and corticosteroid therapy in two siblings with polyneuropathy due to acute intermittent porphyria.

    PubMed

    Jusić, A; Sostarko, M; Majić, D

    1976-01-01

    The influence of long-term corticosteroid and ACTH therapy in two sisters was followed up. The periods of observation were 4 and 2 years. The high levels of corticosteroids obviously reversed the fatal progress of the disease. The relapses in the elder sister occurred during longer periods of discontinued corticosteroid therapy. In the younger the therapy was continuous. There was no relapse except for a short one appearing after the tooth extraction and discontinuation of the therapy for 10 days. Some correlation between neurological signs and symptoms and porphobilinogen androporphyrin levels were found. The question arises how it is possible to influence the genetically determined disease by corticosteroids or ACTH.

  3. The Mediating Role of Insight for Long-Term Improvements in Psychodynamic Therapy

    ERIC Educational Resources Information Center

    Johansson, Paul; Hoglend, Per; Ulberg, Randi; Amlo, Svein; Marble, Alice; Bogwald, Kjell-Petter; Sorbye, Oystein; Sjaastad, Mary Cosgrove; Heyerdahl, Oscar

    2010-01-01

    Objective: According to psychoanalytic theory, interpretation of transference leads to increased insight that again leads to improved interpersonal functioning over time. In this study, we performed a full mediational analysis to test whether insight gained during treatment mediates the long-term effects of transference interpretation in dynamic…

  4. Pilocarpine therapy in glaucoma: effects on anterior chamber depth and lens thickness in patients receiving long-term therapy.

    PubMed

    Abramson, D H; Chang, S; Coleman, J

    1976-06-01

    The effect of pilocarpine hydrochloride on the anterior chamber depth and lens thickness was measured in 20 eyes of patients with chronic open-angle glucoma who were receiving long-term glaucoma therapy with pilocarpine. Measurements were made with high-resolution ultrasonic biometry. This study demonstrated that regardless of their age (58.4 years, average) and the fact that they had been regularly using pilocarpine from two to four times a day, 85% of these patients demonstrated narrowing of the anterior chamber (AC) depth (average, 0.19 mm) and thickening of the lens (average, 0.21 mm) with each instillation of pilocarpine. In approximately 15% of eyes, a repeatable deepening of the AC depth and flattening of the lens was noted.

  5. Long-term recurrence of nonmelanoma skin cancer after topical methylaminolevulinate photodynamic therapy in a dermato-oncology department.

    PubMed

    Cabete, Joana; Rafael, Margarida; Cravo, Mariana; Moura, Cecília; Sachse, Fernanda; Pecegueiro, Manuela

    2015-01-01

    Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therapy from 2004 to 2008. Treatment protocol and clinical follow-up were standardized. The primary endpoint was clinically observed recurrence in a previous photodynamic therapy-treated area. Descriptive and survival analyses were performed. A total of 31 Bowen's disease lesions and 44 superficial basal cell carcinoma were treated, with a median follow-up of 43.5 months. Recurrence was observed in 14 Bowen's disease lesions (53.8%) and in 11 superficial basal cell carcinoma (33.3%). Significantly higher estimates for recurrence rates were found in patients with Bowen's disease (p=0.0036) or those aged under 58 years (p=0.039). The risk of recurrence was higher in patients with Bowen's disease than in those with superficial basal cell carcinoma and younger patients. Recurrence should be considered when choosing to treat non-melanoma skin cancer with photodynamic therapy. Younger age and Bowen's disease were independent predictors for long-term recurrence, suggesting the need to establish an extended period of follow-up for this subset of patients.

  6. Long-Term Efficacy of First Line Antiretroviral Therapy in Indian HIV-1 Infected Patients: A Longitudinal Cohort Study

    PubMed Central

    Neogi, Ujjwal; Heylen, Elsa; Shet, Anita; Chandy, Sara; Shamsunder, Ranjani; Sönnerborg, Anders; Ekstrand, Maria L.

    2013-01-01

    Background Short term efficacy of combination antiretroviral therapy (cART) in resource-constrained settings is comparable to that found in western studies. However, long term data are limited. India has the third largest HIV infected population in the world but the long-term outcome of first line therapy according to the national guidelines has not been evaluated yet. Therefore, we conducted a long-term longitudinal analysis of the efficacy of the national first-line therapy in India from an observational cohort of Indian patients in two different clinical settings. Methodology/Principal Findings A total 323 patients who had been on ART for a median of 23 months and achieved virological suppression <100 copies/ml by their study baseline visit, were included and followed for two years. Blood samples were collected every six months for viral load and CD4 count. Drug resistance genotyping was performed when the viral load was >2000 copies/mL. Adherence and treatment interruptions (>48 h) were assessed via self-report. In the studied patients, the median duration of viral suppression was 44 months; 15.8% of patients showed viral rebound, and 2.8% viral failure. Viral rebound or failure was significantly negatively related to perfect adherence (100% adherence and no treatment interruption >48 hrs). Virological re-suppression in the subsequent visit was observed in three patients without any change in therapy despite the presence of key mutations. Conclusion/Significance Our study reports for the first time, a good long-term response to the first line therapy for a median of nearly four years although a less than perfect adherence increases the risk for treatment failure and subsequent drug resistance development. The empirical findings in this study also indicate the overall success of the Indian ART program in two different settings which likely are representative of other clinics that operate under the national guidelines. PMID:23383185

  7. [The transrectal ultrasonography of prostate in men with congenital hypogonadism treated by long term testosterone replacement therapy].

    PubMed

    Heráček, Jiří; El Balouly, Karim; Sobotka, Vladimír; Šnajderová, Marta; Kalvachová, Božena; Urban, Michael

    2012-01-01

    The aim of the study was to evaluate prostate transrectal ultrasonography findings in men with congenital hypogonadism treated by long term testosterone replacement therapy. We have gradually included 31 men with congenital hypogonadism in period of 2001-2011. The average follow-up was 7.3 years (2 months - 10.8 years). We have used Sustanon® 250 i.m. every 3 weeks or Nebido® i.m. every 3 months for continual testosterone replacement therapy. We performed to all patients the transrectal ultrasonography of prostate and seminal vesicles by biplanar rectal probe every 6 months. During the transrectal ultrasonography we observed in 22 (71.0 %) patients changes in prostatic tissue. In case of 12 patients were diagnosed asymptomatic prostatic cysts, in 9 patients prostatolithiasis and in 5 patients changes in echogenity of prostatic tissue. In 2 patients was found simultaneous occurrence of prostatic cyst and prostolithiasis, in further 2 patients simultaneous occurrence of hyperechogenic prostatic lesion and prostatolithiasis. The above described findings were diagnosed in 5 patients in the treatment lasting from 3 to 5 years, for the other 17 men with hormone replacement therapy longer than 5 years. The study presents long term results of complex treatment in patients with disorders of sexual development, onset and progress of puberty. The long term treatment of these patients in interdisciplinary cooperation of endocrinologist and andrologist may significantly contribute to clarify an impact of testosterone replacement therapy on prostate development.

  8. Long-term efficacy of voice therapy in patients with voice problems after treatment of early glottic cancer.

    PubMed

    van Gogh, Christine D L; Verdonck-de Leeuw, Irma M; Langendijk, Johannes A; Kuik, Dirk J; Mahieu, Hans F

    2012-05-01

    The purpose of the present pilot study is to investigate whether the beneficial short-term effects of voice therapy in patients with voice problems after treatment of early glottic cancer as reported in our earlier study remain present on the long term. In this prospective study, 12 patients, selected based on a screening questionnaire about voice problems and randomly assigned for treatment with voice therapy (vs no treatment), were evaluated with a mean of 13 months after finishing voice therapy to evaluate the long-term voice effects. Voice assessment consisted of the Voice Handicap Index (VHI) and acoustic analyses (percent jitter, percent shimmer, and noise-to-harmonics ratio). Statistical analysis showed that the beneficial short-term effect on the mean VHI, percent jitter, and shimmer remained stable after more than a year of follow-up. The present study provides initial evidence that the beneficial effect of voice therapy is not just a short-lived voice improvement but may result in a better voice for a period of at least 1 year. Future long-term randomized controlled trials are needed to confirm our findings. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  9. Solution-focused brief therapy from the perspective of clients with long-term physical health conditions.

    PubMed

    Carr, Sharon M; Smith, Ian C; Simm, Rebecca

    2014-01-01

    As long-term physical health conditions are becoming increasingly prevalent in our society, interventions are needed to help individuals live as well as possible. The research explores participants' experiences of solution-focused brief therapy (SFBT) with a view to determining helpful aspects of this. Eleven service users were interviewed, and interviews were analysed using inductive thematic analysis. Participants' responsibility for change and the strengths and resources they possessed were highlighted, along with the focus within therapy on goals. A number of specific SFBT techniques that were perceived as helpful during therapy were described such as reframing, competence talk and reflectiveness, as well as other factors that enabled engagement with the psychologist.

  10. Linking Estrogen-Induced Apoptosis With Decreases in Mortality Following Long-term Adjuvant Tamoxifen Therapy

    PubMed Central

    2014-01-01

    The impressive first results of the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) and the adjuvant Tamoxifen To offer more (aTTom) trials both demonstrate that 10 years of tamoxifen is superior to five years of treatment. Tamoxifen is a nonsteroidal antiestrogen that blocks estrogen-stimulated tumor growth. Paradoxically, mortality decreases dramatically only in the decade after long-term tamoxifen is stopped. It is proposed that the evolution and clonal selection of micrometastases that acquire tamoxifen resistance now become increasingly vulnerable to endogenous estrogen-induced apoptosis. Laboratory and clinical studies confirm the concept, and supporting clinical evidence from the estrogen-alone trial in the Women’s Health Initiative (WHI), demonstrate that long-term estrogen-deprived women given exogenous physiologic estrogen have a decreased incidence of breast cancer and decreased mortality. It is proposed that a natural process of apoptosis is recruited to execute the long-term survival benefit of stopping ten years of adjuvant tamoxifen, but only after clonal selection of vulnerable breast cancer cells in an estrogen-deprived environment. PMID:25269699

  11. Effects of spiritual healing for women undergoing long-term hormone therapy for breast cancer: a qualitative investigation.

    PubMed

    Barlow, Fiona; Walker, Jan; Lewith, George

    2013-03-01

    Spiritual Healing is widely available and used, but is a neglected area for research and its biologic and psychologic mechanisms are not understood. The side-effects of long-term hormonal therapy for breast cancer are onerous and have been reported to lead to "drug holidays" that could diminish the long-term treatment benefits. It was investigated whether Spiritual Healing could support patients with breast cancer undergoing this treatment. The qualitative observation study took place in a specialist research facility in a general hospital. Spiritual Healing was provided by 4 healers registered with the National Federation of Spiritual Healers. Twelve (12) patients with breast cancer undergoing long-term hormone treatment and who found the effects onerous, self-referred themselves and were given ten weekly sessions of approximately 40 minutes each. Data collected included participant's daily records, direct observations noted by healers, the researcher's field diary and a one-to-one semi-structured interview. The positive effects of Spiritual Healing included alleviation of the physical side-effects of their treatment, increased energy levels, enhanced well-being, emotional relaxation, and re-engagement with precancer activities. Although 1 participant admitted considering a drug holiday prior to joining the study, none of the participants felt tempted to stop their hormonal treatments while receiving Spiritual Healing. These qualitative findings indicate that Spiritual Healing has the potential to support patients with breast cancer in the maintenance of their long-term orthodox treatments. Further research is needed to test Spiritual Healing as a cost-effective complementary therapy, for those undergoing long-term cancer treatments.

  12. Review of the long-term effectiveness of cognitive behavioral therapy compared to medications in panic disorder.

    PubMed

    Nadiga, Deepa N; Hensley, Paula L; Uhlenhuth, E H

    2003-01-01

    Panic disorder is a recurrent and disabling illness. It is believed that Cognitive Behavioral Therapy (CBT) has a long-term protective effect for this disorder. This would offer CBT considerable advantage over medication management of panic disorder, as patients often relapse when they are tapered off their medications. This is a review of the literature about the long-term effectiveness of CBT. We searched for follow-up studies of panic disorder using CBT. Of the 78 citations produced in the initial search, most had major methodological flaws, including ignoring losses to follow-up, not accounting for interval treatment, and unclear reporting. Three papers met strict methodological criteria, and two of these demonstrated a modest protective effect of CBT in panic disorder patients. We make recommendations for well-designed studies involving comparisons of medications and cognitive behavior therapy. Copyright 2003 Wiley-Liss, Inc.

  13. Long-term continuous positive airway pressure therapy improves cardiac autonomic tone during sleep in patients with obstructive sleep apnea.

    PubMed

    Palma, Jose-Alberto; Iriarte, Jorge; Fernandez, Secundino; Alegre, Manuel; Valencia, Miguel; Artieda, Julio; Urrestarazu, Elena

    2015-08-01

    Cardiac autonomic tone after long-term continuous positive airway pressure therapy in patients with obstructive sleep apnea remains unexplored. Thirty patients with obstructive sleep apnea (14 with moderate and 16 with severe obstructive sleep apnea) were studied during a baseline polysomnographic study, after a full night of acute continuous positive airway pressure treatment, and after long-term (~2 years) chronic continuous positive airway pressure therapy. Twenty age- and gender-matched controls with baseline sleep study were selected for comparison purposes. Cross-spectral analysis and the low-frequency (LF) and high-frequency (HF) components of the heart rate variability were computed separately over 10-min ECG epochs during rapid eye movement sleep, non-rapid eye movement sleep, and wakefulness. During the baseline study, obstructive sleep apnea patients exhibited increased LF, decreased HF, and increased LF/HF ratio during sleep when compared to controls. In a multiple regression model, the mean oxygen saturation explained the increased LF during rapid and non-rapid eye movement sleep in obstructive sleep apnea patients. Acute continuous positive airway pressure therapy decreased the LF modulations and the LF/HF ratio and increased the HF modulations during sleep in patients with severe obstructive sleep apnea. Long-term continuous positive airway pressure therapy decreased LF modulations and LF/HF ratio with increased HF modulations during sleep in patients with moderate and severe obstructive sleep apnea. Long-term continuous positive airway pressure reduces the sympathovagal imbalance in patients with moderate and severe obstructive sleep apnea, both during rapid and non-rapid eye movement sleep. Continuous positive airway pressure seems to exert its changes in cardiac autonomic modulation by decreasing the burden of nocturnal hypoxia.

  14. A systematic review of the use of Acceptance and Commitment Therapy (ACT) in chronic disease and long-term conditions.

    PubMed

    Graham, Christopher D; Gouick, Joanna; Krahé, Charlotte; Gillanders, David

    2016-06-01

    Many have proposed that Acceptance and Commitment Therapy (ACT) may be particularly effective for improving outcomes in chronic disease/long-term conditions, and ACT techniques are now being used clinically. However, reviews of ACT in this context are lacking, and the state of evidence is unclear. This systematic review aimed to: collate all ACT interventions with chronic disease/long-term conditions, evaluate their quality, and comment on efficacy. Ovid MEDLINE, EMBASE and Psych Info were searched. Studies with solely mental health or chronic pain populations were excluded. Study quality was then rated, with a proportion re-rated by a second researcher. Eighteen studies were included: eight were randomised controlled trials (RCTs), four used pre-post designs, and six were case studies. A broad range of applications was observed (e.g. improving quality of life and symptom control, reducing distress) across many diseases/conditions (e.g. HIV, cancer, epilepsy). However, study quality was generally low, and many interventions were of low intensity. The small number of RCTs per application and lower study quality emphasise that ACT is not yet a well-established intervention for chronic disease/long-term conditions. However, there was some promising data supporting certain applications: parenting of children with long-term conditions, seizure-control in epilepsy, psychological flexibility, and possibly disease self-management. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Long-term, drug-free remission of sympathetic ophthalmia with high-dose, short-term chlorambucil therapy.

    PubMed

    Patel, Sarju S; Dodds, Emilio M; Echandi, Laura V; Couto, Cristobal A; Schlaen, Ariel; Tessler, Howard H; Goldstein, Debra A

    2014-02-01

    To evaluate the safety and effectiveness of short-term, high-dose chlorambucil therapy in achieving long-term, drug-free remission in the treatment of sympathetic ophthalmia (SO). Retrospective case series. Sixteen patients with SO treated with high-dose, short-term chlorambucil therapy between 1970 and 2010. Descriptive and bivariate analyses were used to characterize disease and outcomes. Months of disease-free remission, prevalence rate of relapse, and prevalence of serious treatment-related adverse events. Sixteen patients with SO treated with short-term, high-dose chlorambucil were identified. Patients were treated with chlorambucil for a median of 14.0 weeks (mean, 14.5 weeks; range, 12.0-19.0 weeks). Median follow-up was 98.5 months (mean, 139.1 months; range, 48-441 months) from initiation of chlorambucil therapy. Control of inflammation was achieved in 100% of patients. Thirteen patients (81.3%) maintained vision of 20/40 or better in the sympathizing eye. Four patients (25%) relapsed after a median of 83 months (mean, 131 months) after cessation of systemic therapy. Seventy-five percent of relapses were controlled with topical therapy only. Conjunctival Kaposi's sarcoma developed in 1 patient. No patient demonstrated systemic malignancy. Short-term, high-dose chlorambucil therapy provides sustained periods of drug-free remission. With median follow-up of more than 8 years (mean, 11.6 years; range, 4-37 years), there was a low rate of recurrence and minimal long-term serious health consequences or adverse events. Because SO may be a lifelong condition and because chlorambucil therapy may offer long-term, drug-free remission, this treatment may be worth considering early in the decision-making process for severe sight-threatening disease. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  16. The long-term effectiveness of cognitive behavior therapy for psychosis within a routine psychological therapies service

    PubMed Central

    Peters, Emmanuelle; Crombie, Tessa; Agbedjro, Deborah; Johns, Louise C.; Stahl, Daniel; Greenwood, Kathryn; Keen, Nadine; Onwumere, Juliana; Hunter, Elaine; Smith, Laura; Kuipers, Elizabeth

    2015-01-01

    Randomised controlled trials (RCTs) have shown the efficacy of CBTp, however, few studies have considered its long-term effectiveness in routine services. This study reports the outcomes of clients seen in a psychological therapies clinic, set up following positive results obtained from an RCT (Peters et al., 2010). The aims were to evaluate the effectiveness of CBTp, using data from the service’s routine assessments for consecutive referrals over a 12 years period, and assess whether gains were maintained at a 6+ months’ follow-up. Of the 476 consenting referrals, all clients (N = 358) who received ≥5 therapy sessions were offered an assessment at four time points (baseline, pre-, mid-, and end of therapy) on measures assessing current psychosis symptoms, emotional problems, general well-being and life satisfaction. A sub-set (N = 113) was assessed at a median of 12 months after finishing therapy. Following the waiting list (median of 3 months) clients received individualized, formulation-based CBTp for a median number of 19 sessions from 121 therapists with a range of experience receiving regular supervision. Clients showed no meaningful change on any measure while on the waiting list (Cohen’s d <= 0.23). In contrast, highly significant improvements following therapy, all of which were significantly greater than changes during the waiting list, were found on all domains assessed (Cohen’s d: 0.44–0.75). All gains were maintained at follow-up (Cohen’s d: 0.29–0.82), with little change between end of therapy and follow-up (Cohen’s d <= 0.18). Drop-out rate from therapy was low (13%). These results demonstrate the positive and potentially enduring impact of psychological therapy on a range of meaningful outcomes for clients with psychosis. The follow-up assessments were conducted on only a sub-set, which may not generalize to the full sample. Nevertheless this study is the largest of its kind in psychosis, and has important implications for the

  17. [Evaluation of antianginal efficacy of long-term therapy with low dose isosorbide dinitrate in patients with stable angina pectoris].

    PubMed

    Kośmicki, M; Sadowski, Z

    2000-01-01

    The aim of this study was to evaluate two ways of long-term therapy with lower doses of oral isosorbide dinitrate (ISDN) in normal tablets and in sustained-release form (SR), in patients with stable angina. In double-blind, placebo (PL) controlled with cross-over design study 38 male patients with stable angina and angiographically proven coronary artery disease, received ISDN in normal tablets in two doses: 10 mg and 20 mg, and also two doses SR: 20 mg-SR and 40 mg-SR or PL in the first ingestion and in long-term therapy in two 7 day phases: 4-times-daily (4x) every 6 h and 3-times-daily (3x) with 12 h interval. In 3x patients received ISDN only in doses: 20 mg, 20 mg-SR and 40 mg-SR. After the first ingestion and on the last day of long-term phases, exercise stress tests on the treadmill were performed: preceding ingestion, 2 h and 6 h after. Evaluation of antianginal efficacy of ISDN was performed by analysis of walking times: total, to angina and to ischemia (WTI). 6 h after first ingestion all doses of ISDN improved significantly WTI in comparison to PL: 10 mg by 34.6% (p < 0.01), 20 mg by 49.6% (p < 0.0001), 20 mg-SR by 42.9% (p < 0.001) and 40 mg-SR by 52.5% (p < 0.0001). None of the doses improved significantly WTI in the long-term 4x phase, in 3x--only 40 mg-SR by 12.1% (p < 0.05). Tolerance to anti-anginal efficacy of ISDN in lower doses in long-term therapy 4-times-daily, every 6 h, was found. A 12-h interval is sufficient to prevent tolerance in long-term treatment of sustained-release ISDN in 40 mg dose. Intermitted dosing of nitrates, as a prevention of tolerance, and the practical results of works using other pharmacologic interventions in a clinical setting are discussed in the final section of this paper.

  18. Long-Term Effects of Caffeine Therapy for Apnea of Prematurity on Sleep at School Age

    PubMed Central

    Meltzer, Lisa J.; Roberts, Robin S.; Traylor, Joel; Dix, Joanne; D’ilario, Judy; Asztalos, Elizabeth; Opie, Gillian; Doyle, Lex W.; Biggs, Sarah N.; Nixon, Gillian M.; Narang, Indra; Bhattacharjee, Rakesh; Davey, Margot; Horne, Rosemary S. C.; Cheshire, Maureen; Gibbons, Jeremy; Costantini, Lorrie; Bradford, Ruth; Schmidt, Barbara

    2014-01-01

    Rationale: Apnea of prematurity is a common condition that is usually treated with caffeine, an adenosine receptor blocker that has powerful influences on the central nervous system. However, little is known about the long-term effects of caffeine on sleep in the developing brain. Objectives: We hypothesized that neonatal caffeine use resulted in long-term abnormalities in sleep architecture and breathing during sleep. Methods: A total of 201 ex-preterm children aged 5–12 years who participated as neonates in a double-blind, randomized, controlled clinical trial of caffeine versus placebo underwent actigraphy, polysomnography, and parental sleep questionnaires. Coprimary outcomes were total sleep time on actigraphy and apnea–hypopnea index on polysomnography. Measurements and Main Results: There were no significant differences in primary outcomes between the caffeine group and the placebo (adjusted mean difference of −6.7 [95% confidence interval (CI) = −15.3 to 2.0 min]; P = 0.13 for actigraphic total sleep time; and adjusted rate ratio [caffeine/placebo] for apnea–hypopnea index of 0.89 [95% CI = 0.55–1.43]; P = 0.63). Polysomnographic total recording time and total sleep time were longer in the caffeine group, but there was no difference in sleep efficiency between groups. The percentage of children with obstructive sleep apnea (8.2% of caffeine group versus 11.0% of placebo; P = 0.22) or elevated periodic limb movements of sleep (17.5% in caffeine group versus 11% in placebo group) was high, but did not differ significantly between groups. Conclusions: Therapeutic neonatal caffeine administration has no long-term effects on sleep duration or sleep apnea during childhood. Ex-preterm infants, regardless of caffeine status, are at risk for obstructive sleep apnea and periodic limb movements in later childhood. PMID:25171195

  19. Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age.

    PubMed

    Marcus, Carole L; Meltzer, Lisa J; Roberts, Robin S; Traylor, Joel; Dix, Joanne; D'ilario, Judy; Asztalos, Elizabeth; Opie, Gillian; Doyle, Lex W; Biggs, Sarah N; Nixon, Gillian M; Narang, Indra; Bhattacharjee, Rakesh; Davey, Margot; Horne, Rosemary S C; Cheshire, Maureen; Gibbons, Jeremy; Costantini, Lorrie; Bradford, Ruth; Schmidt, Barbara

    2014-10-01

    Apnea of prematurity is a common condition that is usually treated with caffeine, an adenosine receptor blocker that has powerful influences on the central nervous system. However, little is known about the long-term effects of caffeine on sleep in the developing brain. We hypothesized that neonatal caffeine use resulted in long-term abnormalities in sleep architecture and breathing during sleep. A total of 201 ex-preterm children aged 5-12 years who participated as neonates in a double-blind, randomized, controlled clinical trial of caffeine versus placebo underwent actigraphy, polysomnography, and parental sleep questionnaires. Coprimary outcomes were total sleep time on actigraphy and apnea-hypopnea index on polysomnography. There were no significant differences in primary outcomes between the caffeine group and the placebo (adjusted mean difference of -6.7 [95% confidence interval (CI) = -15.3 to 2.0 min]; P = 0.13 for actigraphic total sleep time; and adjusted rate ratio [caffeine/placebo] for apnea-hypopnea index of 0.89 [95% CI = 0.55-1.43]; P = 0.63). Polysomnographic total recording time and total sleep time were longer in the caffeine group, but there was no difference in sleep efficiency between groups. The percentage of children with obstructive sleep apnea (8.2% of caffeine group versus 11.0% of placebo; P = 0.22) or elevated periodic limb movements of sleep (17.5% in caffeine group versus 11% in placebo group) was high, but did not differ significantly between groups. Therapeutic neonatal caffeine administration has no long-term effects on sleep duration or sleep apnea during childhood. Ex-preterm infants, regardless of caffeine status, are at risk for obstructive sleep apnea and periodic limb movements in later childhood.

  20. Long-term effects of etelcalcetide as intravenous calcimimetic therapy in hemodialysis patients with secondary hyperparathyroidism.

    PubMed

    Shigematsu, Takashi; Fukagawa, Masafumi; Yokoyama, Keitaro; Akiba, Takashi; Fujii, Akifumi; Odani, Motoi; Akizawa, Tadao

    2017-08-23

    Secondary hyperparathyroidism (SHPT) is a serious major complication in hemodialysis patients with chronic kidney disease. Long-term maintenance of serum phosphate, calcium, and parathyroid hormone (PTH) levels in appropriate ranges in these patients is a major challenge. We investigated the efficacy and safety of long-term treatment with etelcalcetide, a novel intravenous calcimimetic, in Japanese SHPT patients on long-term hemodialysis. This study was a multicenter open-label study. A total of 191 hemodialysis patients with serum intact PTH (iPTH) > 240 pg/mL were enrolled. Etelcalcetide was administered thrice weekly for 52 weeks, with an initial dose of 5 mg and flexibility to adjust the dose between 2.5 and 15 mg and to adjust the dosing of concomitant medications for SHPT. The efficacy endpoint was the proportion of patients with serum iPTH decreased to the target range (60-240 pg/mL). Serum iPTH levels decreased immediately after etelcalcetide was started. At the end of the study, 87.5% (95% confidence interval 81.4-92.2; 140/160 patients) of patients achieved target serum iPTH levels, with control of serum calcium and phosphate levels. Adverse events, mostly mild to moderate, were reported by 96.8% of patients and led to study discontinuation in 7.4% of patients. Nausea, vomiting, and symptomatic hypocalcemia were found in 4.7, 9.5, and 1.1%, with 0.5, 1.1, and 1.1% considered treatment-related. Etelcalcetide effectively maintained serum iPTH, calcium, and phosphate levels in appropriate ranges with concomitant medications for SHPT for 52 weeks in Japanese hemodialysis patients, and was safe and well tolerated. JapicCTI-142665.

  1. Considerations for long-term anticoagulant therapy in patients with venous thromboembolism in the novel oral anticoagulant era

    PubMed Central

    Toth, Peter P

    2016-01-01

    Background Patients who have had a venous thromboembolic event are generally advised to receive anticoagulant treatment for 3 months or longer to prevent a recurrent episode. Current guidelines recommend initial heparin and an oral vitamin K antagonist (VKA) for long-term anticoagulation. However, because of the well-described disadvantages of VKAs, including extensive food and drug interactions and the need for regular anticoagulation monitoring, novel oral anticoagulants (NOACs) have become an attractive option in recent years. These agents are given at fixed doses and do not require routine coagulation-time monitoring. The NOACs are discussed in this review with regard to the needs of patients on long-term anticoagulation. Methods Current guidelines from Europe and North America that refer to the treatment of deep vein thrombosis and/or pulmonary embolism are included, as well as published randomized Phase III clinical trials of NOACs. PubMed searches were used for sourcing case studies of long-term anticoagulant treatment, and results were filtered for human application and screened for relevance. Conclusion NOAC-based therapy showed a similar efficacy and safety profile to heparins/VKAs but without the need for regular anticoagulation monitoring or dietary adjustments, and can be taken as a fixed-dose regimen once or twice daily. This represents a significant step forward in facilitating the management of long-term anticoagulation therapy. Furthermore, in the EINSTEIN studies, improved patient satisfaction was documented with the NOAC rivaroxaban, which may result in better adherence to therapy and an overall reduction in the incidence of recurrent venous thromboembolism. PMID:26929637

  2. Real-world clinical experience with long-term miglustat maintenance therapy in type 1 Gaucher disease: the ZAGAL project

    PubMed Central

    Giraldo, Pilar; Alfonso, Pilar; Atutxa, Koldo; Fernández-Galán, María A.; Barez, Abelardo; Franco, Rafael; Alonso, Dora; Martin, Alejandro; Latre, Paz; Pocovi, Miguel

    2009-01-01

    There are few published data from real-world clinical experience with miglustat (Zavesca®), an oral inhibitor of glucosylceramide synthase, in type 1 Gaucher disease. We report data from a prospective, open-label investigational study that evaluated substrate reduction therapy with miglustat 100 mg t.i.d. as a maintenance therapy in patients with Type 1 Gaucher disease who had been switched from previous enzyme replacement therapy. Long-term data on changes in organ size, blood counts, disease severity bio-markers, bone marrow infiltration, overall clinical status and safety/tolerability were analyzed from 28 patients with Type 1 Gaucher disease who were attending routine clinic visits. Assessments were performed at six, 12, 24, 36 and 48 months of therapy. Disease severity biomarkers improved up to 48 months after initiation of miglustat, while other disease parameters remained stable. Miglustat showed an acceptable profile of safety and tolerability throughout treatment. In conclusion, miglustat is an effective therapy for the long-term maintenance of patients with Type 1 Gaucher disease previously stabilized with enzyme replacement therapy. PMID:19608672

  3. Efficacy of daptomycin lock therapy in the treatment of bloodstream infections related to long-term catheter.

    PubMed

    Tatarelli, P; Parisini, A; Del Bono, V; Mikulska, M; Viscoli, C

    2015-02-01

    Concomitant systemic and intracatheter antibiotic therapy is a therapeutic option for catheter-related bloodstream infections (CRBSI) in patient fitted with long-term intravenous central catheters. CRBSI are mainly caused by Gram-positive bacteria. Daptomycin (DPT) is an antibiotic active against Gram-positive bacteria with high bactericidal activity and good biofilm penetration. To study the efficacy of DPT given systemically and as lock therapy in the treatment of CRBSI. A retrospective review was conducted of adult patients with a long-term central venous catheter (CVC) receiving both systemic intravenous and intracatheter lock therapy for CRBSI. The primary outcome was catheter maintenance, following clinical success and microbiological eradication. Eight patients who had failed previous standard therapy (vancomycin 7, cefazolin 1) were included in the study. In all but one, coagulase-negative staphylococci were repeatedly isolated. The other patient had enterococcal infection. DPT, given intravenously and as lock therapy, was successful in six of eight cases. The mean time to negative blood cultures was 2 days (range 1-6). In two cases neither clinical nor microbiological response was documented and the catheter was removed. Systemic and intracatheter therapy with DPT is feasible, carries no toxicity and is apparently effective. DPT might be a suitable therapeutic option in CRBSI to achieve CVC sterilization and preserve the catheter.

  4. Peritoneal dialysis catheter placement as a mode of renal replacement therapy: Long-term results from a tertiary academic institution.

    PubMed

    Haskins, Ivy N; Schreiber, Martin; Prabhu, Ajita S; Krpata, David M; Perez, Arielle J; Tastaldi, Luciano; Tu, Chao; Rosen, Michael J; Rosenblatt, Steven

    2017-08-31

    Peritoneal dialysis as a mode of renal replacement therapy still has not been embraced widely as an alternative to hemodialysis. Furthermore, there is marked variability in peritoneal dialysis catheter insertion techniques and perioperative management within the United States. After the publication of best-demonstrated practices for peritoneal dialysis catheter placement, the utilization of peritoneal dialysis has increased significantly at our institution. We detail the long-term success of peritoneal dialysis catheter placement after the adoption of best-demonstrated practices. Retrospective chart review was performed on all patients who underwent laparoscopic peritoneal dialysis catheter placement using the best-demonstrated practice technique from January 2005 through December 2015. Preoperative patient demographic information, intraoperative variables, 30-day morbidity and mortality, and long-term catheter durability outcomes were investigated. A total of 457 patients met inclusion criteria. Four (0.9%) patients experienced an immediate postoperative complication requiring return to the operating room. There were no perioperative mortalities. A total of 298 (65.2%) patients were available for long-term follow-up; 221 (74.2%) patients are still alive, 76 (25.6%) patients are still undergoing peritoneal dialysis, 63 (21.1%) patients transitioned from peritoneal dialysis to hemodialysis, and 88 (29.5%) patients have undergone kidney transplantation. Based on Kaplan-Meier survival plots, 30% of patients will transition from peritoneal dialysis to hemodialysis after 5.5 years of peritoneal dialysis and the median time from commencing peritoneal dialysis to kidney transplantation is 5.6 years. Based on our institutional data, the adoption of best-demonstrated practices should provide long-term and reliable access to the peritoneal cavity. We recommend the adoption of these techniques to facilitate long-term peritoneal dialysis catheter survival. Copyright © 2017

  5. Hemodynamics in pulmonary arterial hypertension (PAH): do they explain long-term clinical outcomes with PAH-specific therapy?

    PubMed Central

    2010-01-01

    Background Pulmonary arterial hypertension (PAH) has witnessed dramatic treatment advances over the past decade. However, with the exception of epoprostenol, data from short-term randomized controlled trials (RCTs) have not shown a benefit of these drugs on survival. There remains a need to differentiate between available therapies and current endpoint responses which in turn, could be used to guide treatment selection and provide long-term prognostic information for patients. Methods We performed a systematic literature search of MEDLINE and EMBASE databases for RCTs of PAH-specific therapy published between January 1980 and May 2009. Articles were selected if they contained a placebo comparator and described hemodynamic changes from baseline. We applied the weighted mean change in hemodynamic variables to the equation developed by the National Institutes of Health (NIH) Registry to estimate long-term survival with each therapy. Results Ten RCTs involving 1,635 patients met the inclusion criteria. Suitable hemodynamic data were identified for bosentan, sitaxentan, sildenafil, epoprostenol, beraprost and treprostinil. 77.6% of patients were female and the mean (SD) age was 46.5 ± 4.9 years. 55.5% of patients had idiopathic PAH (iPAH), 23.9% PAH related to connective tissue disease, and 18.2% PAH related to congenital heart disease. Based on the effects observed in short-term trials and, relative to placebo, all analyzed therapies improved survival. The estimated 1-year survival was 78.4%, 77.8%, 76.1%, 75.8%, 75.2%, and 74.1% for epoprostenol, bosentan, treprostinil, sitaxentan, sildenafil, and beraprost, respectively. These estimates are considerably lower than the 1-year observed survival reported in several open-label and registry studies with PAH-specific therapies: 88% - 97%. Conclusion When applied to the NIH Registry equation, hemodynamic changes from baseline appear to underestimate the survival benefits observed with long-term PAH therapy. PMID:20170553

  6. [The long-term therapy of familial hypercholesterolemia with heparin-induced extracorporeal LDL precipitation].

    PubMed

    Roth, R; Köster, W; Wanner, C; Andre, M; Orth, M; Wieland, H; Schollmeyer, P

    1992-07-24

    The long-term tolerance to and effectiveness of heparin-induced extracorporeal LDL precipitation (HELP) in combination with lipid reducing drugs and diet was tested in six patient (5 males, 1 female; mean age 48 +/- 4 years). Follow-up period was over 50 months, in one patient over 24 months, while one man had a sudden cardiac death 57 weeks after starting treatment. The study was divided into three phases. In phase I (24 months) treatment consisted of HELP and conventional lipid-reducing drugs; in phase II (12 months) of lovastatin (80 mg daily) and cholestyramine (12-24 g daily); and phase III (14 months) of HELP, lovastatin and cholestyramine. In phase I it was possible to lower the pre-treatment level of LDL-cholesterol from 306 +/- 18 mg/dl to 173 +/- 13 mg/dl (43.5%). A similar effect (from 307 +/- 21 mg/dl to 155 +/- 17 mg/dl [-49.5%]) was obtained in phase II. The resumption of HELP reduced the pre-treatment LDL concentration to 136 +/- 9 mg/dl (-55.7%). The various treatment regimens were well tolerated. Biochemical data remained unchanged except for iron loss requiring substitution. Thus combined HELP, lovastatin and ion exchange offer for the first time an effective and reliable means in familial hypercholesterolaemia of clearly reducing long-term the mean LDL cholesterol level below the atherosclerosis threshold of 120 mg/dl.

  7. Can ACTH therapy improve the long-term outcome of drug-resistant frontal lobe epilepsy?

    PubMed

    Gobbi, Giuseppe; Loiacono, Giulia; Boni, Antonella; Marangio, Lucia; Verrotti, Alberto

    2014-06-01

    Frontal lobe epilepsy is a common focal epilepsy in children and is often difficult to treat. Adrenocorticotropic hormone (ACTH) or steroids have been used for patients with several forms of medically intractable epilepsy. We evaluated the short, medium, and long-term evolution of patients with frontal lobe epilepsy and secondary bilateral synchrony on the EEG, who received ACTH treatment. Patients were recruited for an add-on trial during clinical practice, and data was retrospectively analysed. The study group comprised 6 patients treated with ACTH. The effects of ACTH were assessed in the short term (at the end of a 6-week period of ACTH treatment), medium term (at 6 months after the end of treatment), and long term (at 12 months after the end of treatment). At short-term follow-up, ACTH treatment was effective for all types of seizures in 5 of 6 patients and ineffective in 1 patient. All patients who were seizure-free at the end of ACTH treatment maintained an excellent outcome, remaining seizure-free at the end of follow-up. Our study demonstrates that ACTH may represent an effective treatment for frontal lobe epilepsy with secondary bilateral synchrony. Further double-blind prospective studies are required to confirm our initial findings.

  8. Long-term effectiveness of electroconvulsive therapy in adolescents with schizophrenia spectrum disorders.

    PubMed

    Flamarique, Itziar; Baeza, Inmaculada; de la Serna, Elena; Pons, Alexandre; Bernardo, Miguel; Castro-Fornieles, Josefina

    2015-05-01

    To compare a sample of adolescents with schizophrenia spectrum disorders (SSD) treated with either ECT or antipsychotics (AP) alone at long-term follow-up. Patients diagnosed with SSD (n = 21) treated with ECT due to resistance to AP or catatonia under the age of 18 years (ECT group), were compared to a randomly selected group of patients with SSD treated only with AP (non-ECT group) (n = 21) and matched for age, gender, diagnosis and duration of illness. Baseline data were gathered retrospectively from medical records. Subjects were assessed at follow-up (mean of follow-up period = 5.5 years; range 2-9 years) using several clinical scales such as the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale (CGI) and the Global Assessment of Functioning (GAF). Improvement in PANSS positive, negative, general, total and CGI and GAF scores between baseline and follow-up assessment did not differ significantly between groups. At follow-up, no differences were observed for the PANSS negative, CGI and GAF scores between groups, but patients in the ECT group still had higher PANSS total, positive and general scores. ECT treatment followed by AP medication in treatment-resistant SSD or catatonia is at least as effective in the long term as AP alone in non-resistant patients.

  9. Treatment of diabetes and long-term survival after insulin and glucokinase gene therapy.

    PubMed

    Callejas, David; Mann, Christopher J; Ayuso, Eduard; Lage, Ricardo; Grifoll, Iris; Roca, Carles; Andaluz, Anna; Ruiz-de Gopegui, Rafael; Montané, Joel; Muñoz, Sergio; Ferre, Tura; Haurigot, Virginia; Zhou, Shangzhen; Ruberte, Jesús; Mingozzi, Federico; High, Katherine A; Garcia, Felix; Bosch, Fatima

    2013-05-01

    Diabetes is associated with severe secondary complications, largely caused by poor glycemic control. Treatment with exogenous insulin fails to prevent these complications completely, leading to significant morbidity and mortality. We previously demonstrated that it is possible to generate a "glucose sensor" in skeletal muscle through coexpression of glucokinase and insulin, increasing glucose uptake and correcting hyperglycemia in diabetic mice. Here, we demonstrate long-term efficacy of this approach in a large animal model of diabetes. A one-time intramuscular administration of adeno-associated viral vectors of serotype 1 encoding for glucokinase and insulin in diabetic dogs resulted in normalization of fasting glycemia, accelerated disposal of glucose after oral challenge, and no episodes of hypoglycemia during exercise for >4 years after gene transfer. This was associated with recovery of body weight, reduced glycosylated plasma proteins levels, and long-term survival without secondary complications. Conversely, exogenous insulin or gene transfer for insulin or glucokinase alone failed to achieve complete correction of diabetes, indicating that the synergistic action of insulin and glucokinase is needed for full therapeutic effect. This study provides the first proof-of-concept in a large animal model for a gene transfer approach to treat diabetes.

  10. Complementary and alternative therapies among very long-term breast cancer survivors

    PubMed Central

    Carpenter, C. L.; Ganz, P. A.; Bernstein, L.

    2011-01-01

    Breast cancer patients may have different complementary and alternative medicine (CAM) usage rates and may turn to CAM for different reasons than healthy adults. CAM has mostly been studied in recently diagnosed women; no studies have included survivors 10 years post-diagnosis. We examined very long-term breast cancer survivors to determine whether CAM users had dissimilar patterns of association with survivorship factors. Interviews of 374 breast cancer case patients from a population-based case–control breast cancer study of young women from Los Angeles County, California, during the 1980s occurred at follow-up; 371 patients with complete information were included. CAM represented 28 herbal remedies. Quality-of-life originated from the Medical Outcomes Study Short Form 36 questionnaire (SF-36). Higher rates of CAM (59%) usage occurred compared to nationwide estimates. CAM users resembled non-users on follow-up age, exercise, original disease, treatment, smoking, body-mass index, alcohol, and fear of recurrence. CAM users had a higher prevalence of medical co-morbidities (P = 0.0005), and scored significantly lower on the SF-36 emotional well-being subscale than non-CAM users (P = 0.01). CAM users and non-users did not differ on the SF-36 physical sub-scale. Very long-term breast cancer survivors who use CAM may have poorer emotional functioning and more medical problems than non-users. PMID:18712472

  11. Pneumocystis pneumonia in patients treated with long-term steroid therapy for symptom palliation: a neglected infection in palliative care.

    PubMed

    Yamaguchi, Takashi; Nagai, Yuki; Morita, Tatsuya; Kiuchi, Daisuke; Matsumoto, Mina; Hisahara, Ko; Hisanaga, Takayuki

    2014-12-01

    We report 3 cases of pneumocystis pneumonia (PCP) in patients with advanced cancer who received palliative care. All patients received long-term steroid therapy for symptom management. A diagnosis of PCP was based on clinical symptoms and a positive Pneumocystis jiroveci polymerase chain reaction test from induced sputum specimens. Despite appropriate treatment, only 1 patient recovered from PCP. Long-term steroid, often prescribed in palliative care settings, is the most common risk factor for PCP in non-HIV patients. Pneumocystis pneumonia may cause distressing symptoms such as severe dyspnea, and the mortality rate is high. Therefore, it is important to consider PCP prophylaxis for high-risk patients and to diagnose PCP early and provide appropriate treatment to alleviate PCP-related symptoms and avert unnecessary shortening of a patient's life expectancy.

  12. The opioid epidemic and the long-term opioid therapy for chronic noncancer pain revisited: a transatlantic perspective.

    PubMed

    Häuser, Winfried; Petzke, Frank; Radbruch, Lukas; Tölle, Thomas R

    2016-01-01

    The rise of opioid prescriptions and associated deaths ('opioid epidemic') in North America has evoked worldwide discussions on the long-term efficacy and safety of long-term opioid therapy (LtOT) for chronic noncancer pain (CNCP). We discuss if the opioid epidemic is a real worldwide or a more North American phenomenon. We consider reasons of the opioid epidemic. We highlight differences in the appraisal of the evidence of recent systematic reviews on LtOT for CNCP of US and European authors. We discuss similarities and differences of recent North American and European guidelines on LtOT for chronic CNCP. We point out potential indications and contraindications of LtOT in CNCP syndromes.

  13. Prospective controlled cohort studies on long-term therapy of cervical cancer patients with a mistletoe preparation (Iscador).

    PubMed

    Grossarth-Maticek, Ronald; Ziegler, Renatus

    2007-06-01

    Mistletoe preparations such as Iscador are commonly used in complementary medication for many cancer indications, particularly solid cancers. The efficacy of this complementary therapy is still controversial. Does longterm therapy with Iscador show any effect on survival, tumor progression and psychosomatic self-regulation of patients with cervical cancer? Prospective recruitment and long-term follow-up was carried out in 3 controlled cohort studies: In a randomized matched-pair study (19 pairs), cervical cancer patients with distant metastases and no mistletoe therapy were matched for prognostic factors. By paired random allocation, one of the patients was recommended mistletoe therapy by the attending physician. In 2 non-randomized matched-pair studies, cervical cancer patients without (102) and with (66) metastases, who already received mistletoe therapy, were matched with control patients without Iscador therapy. For survival, the non-randomized studies showed significant effects in favor of Iscador therapy: hazard ratio (HR) estimate and 95% confidence interval (CI): 0.23 (0.14-0.39) and 0.37 (0.17-0.80), respectively. An effect of long-term Iscador therapy on tumor progression was not seen. Psychosomatic self-regulation in the Iscador group improved significantly within 12 months compared with the control group in the randomized as well as in 1 non-randomized study (cervical cancer without metastases): estimate of the median difference and 95% CI: 0.70 (0.15-1.05) and 0.25 (0.15-0.35), respectively. Iscador may have the effect of prolonging overall survival of cervical cancer patients. In the short term, psychosomatic self-regulation increases more markedly under complementary Iscador therapy than under conventional therapy alone.

  14. Long-term recurrence of nonmelanoma skin cancer after topical methylaminolevulinate photodynamic therapy in a dermato-oncology department*

    PubMed Central

    Cabete, Joana; Rafael, Margarida; Cravo, Mariana; Moura, Cecília; Sachse, Fernanda; Pecegueiro, Manuela

    2015-01-01

    BACKGROUND Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therapy from 2004 to 2008. Treatment protocol and clinical follow-up were standardized. The primary endpoint was clinically observed recurrence in a previous photodynamic therapy-treated area. Descriptive and survival analyses were performed. RESULTS A total of 31 Bowen's disease lesions and 44 superficial basal cell carcinoma were treated, with a median follow-up of 43.5 months. Recurrence was observed in 14 Bowen's disease lesions (53.8%) and in 11 superficial basal cell carcinoma (33.3%). Significantly higher estimates for recurrence rates were found in patients with Bowen's disease (p=0.0036) or those aged under 58 years (p=0.039). The risk of recurrence was higher in patients with Bowen's disease than in those with superficial basal cell carcinoma and younger patients. CONCLUSIONS Recurrence should be considered when choosing to treat non-melanoma skin cancer with photodynamic therapy. Younger age and Bowen's disease were independent predictors for long-term recurrence, suggesting the need to establish an extended period of follow-up for this subset of patients. PMID:26734866

  15. Organ-preserving neodymium-yttrium-aluminium-garnet laser therapy for penile carcinoma: a long-term follow-up.

    PubMed

    Schlenker, Boris; Tilki, Derya; Seitz, Michael; Bader, Markus J; Reich, Oliver; Schneede, Peter; Hungerhuber, Edwin; Stief, Christian G; Gratzke, Christian

    2010-09-01

    To retrospectively analyse the long-term follow-up of 54 patients treated with organ-preserving laser therapy for penile carcinoma, as such therapy provides excellent cosmetic and functional results, but recurrence rates are high, which might impair the oncological outcome and worsen tumour-related survival. Between 1979 and 2008, 54 patients with penile carcinoma were treated with the neodymium-doped yttrium-aluminium-garnet (Nd:YAG) laser at our institution; 11 were classified as having carcinoma in situ (Tis), 39 as T1 and four as T2. There was local recurrence in 16 patients (42%); the mean (range) time to local recurrence was 53 (9-132) months. In half the patients the time to local recurrence was >53 months, with the latest recurrence at 132 months after initial therapy of primary tumour. There was no statistically significant difference in recurrence rates with Tis or invasive penile carcinoma. In lymph-node-negative patients at initial presentation, there were no newly developed positive lymph nodes during the follow-up. Organ-preserving laser therapy showed a relatively high recurrence rate in patients with a long-term follow up, but the oncological outcome and survival were not compromised by local recurrence. Therefore, laser therapy appears to be appropriate for treating premalignant lesions and early stages of penile carcinoma. Patients should be informed about the potential for late recurrence.

  16. Long-term cardiovascular evaluation of patients with Hodgkin's disease treated by thoracic mantle radiation therapy

    SciTech Connect

    Applefeld, M.M.; Slawson, R.G.; Spicer, K.M.; Singleton, R.T.; Wesley, M.N.; Wiernik, P.H.

    1982-04-01

    The long-term cardiac effects of anterior-weighted thoracic mantle field radiotherapy were assessed in 25 patients treated for Hodgkin's disease. These patients underwent an evaluation that included a careful history and physical examination, ECG, M-mode echocardiogram, exercise ECG-gated radionuclide ventriculography, and cardiac catheterization. In these 25 patients evaluated 37-144 months (median, 96) after completion of thoracic mantle radiotherapy, eight had constrictive pericarditis; eight had occult constrictive pericarditis; three had an abnormal response to fluid challenge; three had suspected or proven occlusive coronary artery disease; and one each had a cardiomyopathy and diminished functional capacity on exercise testing. Only one patient appears to be normal after evaluation. The clinical spectrum of delayed-appearing radiation-induced cardiac disease in patients treated by anterior-weighted thoracic mantle fields and our suggestions for its treatment are discussed.

  17. Long-term follow-up after purine analogue therapy in hairy cell leukaemia.

    PubMed

    Else, Monica; Dearden, Claire E; Catovsky, Daniel

    2015-12-01

    Since 2006 when we last reviewed the literature concerning the use of purine analogues in hairy cell leukaemia (HCL), results from several new and updated series have been published. Here we examine these reports and consider their implications for patient management. The two purine analogues pentostatin and cladribine remain the first-line treatments of choice for all patients with HCL. Although they have not been compared in randomised trials, they appear to be equally effective. A complete response is important for the long-term outcome and we look at how best this can be achieved. Evidence is emerging which supports the use of either purine analogue plus an anti-CD20 monoclonal antibody after relapse, though questions remain concerning the scheduling of the monoclonal antibody. Patients refractory to the purine analogues may require alternative agents. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Long-Term Oral Bisphosphonate Therapy and Fractures in Older Women: The Women's Health Initiative.

    PubMed

    Drieling, Rebecca L; LaCroix, Andrea Z; Beresford, Shirley A A; Boudreau, Denise M; Kooperberg, Charles; Chlebowski, Rowan T; Ko, Marcia G; Heckbert, Susan R

    2017-09-01

    To examine the association between long-term bisphosphonate use and fracture in older women at high risk of fracture. Retrospective cohort. Women's Health Initiative. Older women who reported at least 2 years of bisphosphonate use in 2008-09 (N = 5,120). Exposure data were from a current medications inventory. Outcomes (hip, clinical vertebral, wrist or forearm, any clinical fracture) were ascertained annually. Using multivariate Cox proportional hazards models, the association between duration of bisphosphonate use (3-5, 6-9, 10-13 years) and fracture was estimated, using 2 years as the referent group. On average participants were 80 years old and were followed for 3.7 ± 1.2 years. There were 127 hip, 159 wrist or forearm, 235 clinical vertebral, and 1,313 clinical fractures. In multivariate-adjusted analysis, 10 to 13 years of bisphosphonate use was associated with higher risk of any clinical fracture than 2 years of use (hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.07-1.57). This association persisted in analyses limited to women with a prior fracture (HR = 1.30, 95% CI = 1.01-1.67) and women with no history of cancer (HR = 1.36, 95% CI = 1.10-1.68). The association of 10 to 13 years of use, compared with 2 years of use, was not statistically significant for hip (HR = 1.66, 95% CI = 0.81-3.40), clinical vertebral (HR = 1.65, 95% CI = 0.99-2.76), or wrist fracture (HR = 1.16, 95% CI = 0.67-2.00). In older women at high risk of fracture, 10 to 13 years of bisphosphonate use was associated with higher risk of any clinical fracture than 2 years of use. These results add to concerns about the benefit of very long-term bisphosphonate use. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  19. Long-term non-invasive ventilation therapies in children: a scoping review protocol

    PubMed Central

    Castro Codesal, Maria L; Featherstone, Robin; Martinez Carrasco, Carmen; Katz, Sherri L; Chan, Elaine Y; Bendiak, Glenda N; Almeida, Fernanda R; Young, Rochelle; Olmstead, Deborah; Waters, Karen A; Sullivan, Collin; Woolf, Vicki; Hartling, Lisa; MacLean, Joanna E

    2015-01-01

    Introduction Non-invasive ventilation (NIV) in children has become an increasingly common modality of breathing support where pressure support is delivered through a mask interface or less commonly through other non-invasive interfaces. At this time, NIV is considered a first-line option for ventilatory support of chronic respiratory insufficiency associated with a range of respiratory and sleep disorders. Previous reviews on the effectiveness, complications and adherence to NIV treatment have lacked systematic methods. The purpose of this scoping review is to provide an overview of the evidence for the use of long-term NIV in children. Methods and analysis We will use previously established scoping methodology. Ten electronic databases will be searched to identify studies in children using NIV for longer than 3 months outside an intensive care setting. Grey literature search will include conference proceedings, thesis and dissertations, unpublished trials, reports from regulatory agencies and manufacturers. Two reviewers will independently screen titles and abstracts for inclusion, followed by full-text screening of potentially relevant articles to determine final inclusion. Data synthesis will be performed at three levels: (1) an analysis of the number, publication type, publication year, and country of publication of the studies; (2) a summary of the study designs, outcomes measures used; (3) a thematic analysis of included studies by subgroups. Ethics and dissemination This study will provide a wide and rigorous overview of the evidence on the use of long-term NIV in children and provide critical information for healthcare professionals and policymakers to better care for this group of children. We will disseminate our findings through conference proceedings and publications, and evaluate the results for further systematic reviews and meta-analyses. PMID:26270951

  20. Efficacy and long-term outcome of gastritis therapy in cheetahs (Acinonyx jubatus).

    PubMed

    Citino, Scott B; Munson, Linda

    2005-09-01

    A prospective clinical trial evaluating efficacy and long-term outcome of treatments for lymphoplasmacytic gastritis in cheetahs (Acinonyx jubatus) was conducted. The study evaluated efficacy of 11 different antibiotic and antiinflammatory treatment protocols in 32 cheetahs (19 male, 13 female) for reducing gastric inflammation and Helicobacter colonization and monitored the course of disease through histologic grading of gastric biopsies. All cheetahs were biopsied up to I wk before treatment and then rebiopsied within 1 mo after treatment. Most animals were reassigned to a second treatment regimen within 6 mo. Each animal received from one to three treatments during the study period. After the trial, gastric biopsies were obtained from each cheetah annually until death or transfer from the facility to assess disease progression. The trial and follow-up period spanned 10 yr. At onset of the trial, all 32 cheetahs had some degree of gastritis, and 26 cheetahs (81%) were colonized with Helicobacter. Inflammatory lesions worsened regardless of treatment or the presence of Helicobacter. No treatment had a significant effect on inflammatory changes except the lansoprazole/clarithromycin/amoxicillin treatment group, which produced a short-term decrease in inflammation when compared to controls. Prednisone had no effect on gastric inflammation. Overall, 65% of colonized cheetahs were initially cleared of histologic evidence of Helicobacter by treatment, with short-term eradication occurring in 100% of the animals treated with omeprazole/clarithromycin/amoxicillin or tetracycline/metronidazole/Pepto-Bismol for 28 days. Long-term follow-up of treated animals in this study clearly demonstrated that these treatments had little effect on life-long progression of gastritis or on Helicobacter burden in individual cheetahs, although some treatments provided short-term reduction in gastritis and Helicobacter. These results provide evidence that Helicobacter alone is not the cause

  1. Short- and long-term beneficial effects of a multidisciplinary therapy for the control of metabolic syndrome in obese adolescents.

    PubMed

    Caranti, Danielle Arisa; de Mello, Marco Túlio; Prado, Wagner L; Tock, Lian; Siqueira, Kãli O; de Piano, Aline; Lofrano, Mara C; Cristofalo, Dejaldo M J; Lederman, Henrique; Tufik, Sérgio; Dâmaso, Ana R

    2007-09-01

    Visceral fat is highly correlated with metabolic syndrome in obese adolescents. The aims of this study were to determine the prevalence of metabolic syndrome and to assess the effect of a long-term (1 year) intervention with multidisciplinary therapy in predicting metabolic syndrome among obese adolescents, as well as to compare short- with long-term therapy. Eighty-three postpuberty obese adolescents were recruited, including 37 boys (body mass index [BMI], 36.19 +/- 3.85 kg/m(2)) and 46 girls (BMI, 35.73 +/- 4.42 kg/m(2)). Body composition was measured by plethysmography using the BOD POD body composition system (version 1.69, Life Measurement Instruments, Concord, CA), and visceral fat was analyzed by ultrasound. Metabolic syndrome was determined according to the World Health Organization criteria. Patients were assigned to a weight loss multidisciplinary intervention consisting of nutritional, exercise, psychological, and clinical therapy. At the beginning of therapy, we found that 27.16% of the obese adolescents presented metabolic syndrome, whereas only 8.3% did so after intervention. Indeed, in boys, BMI (36.19 +/- 3.85 to 32.06 +/- 5.85 kg/m(2)), visceral fat (4.88 +/- 1.35 to 3.63 +/- 1.71 cm), homeostasis model assessment of insulin resistance (4.77 +/- 3.41 to 3.18 +/- 2.33), and percentage of body fat (38.24% +/- 6.54% to 30.02% +/- 13.43%) presented a statistically significant reduction; and their fat-free mass percentage increased (62.14% +/- 5.78% to 69.17% +/- 12.37%). In girls, after long-term therapy, BMI (35.73 +/- 4.42 to 33.62 +/- 3.78 kg/m(2)), visceral fat (3.70 +/- 1.40 to 2.75 +/- 1.01 cm), and percentage of body fat (46.10% +/- 5.66% to 39.91% +/- 5.59%) showed a statistically significant reduction; and their fat-free mass increased (53.61% +/- 5.65% to 59.82% +/- 5.78%). In conclusion, long-term multidisciplinary therapy was effective in promoting beneficial changes in some predictors and decreasing the prevalence of metabolic syndrome in

  2. Long-term follow up of pediatric immunoglobulin A nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy.

    PubMed

    Kawasaki, Yukihiko; Maeda, Ryo; Kanno, Shuto; Suzuki, Yuichi; Ohara, Shinichiro; Suyama, Kazuhide; Hosoya, Mitsuaki

    2017-01-01

    The aim of this study was to clarify the long-term efficacy of tonsillectomy plus methylprednisolone pulse therapy (tonsillectomy pulse therapy [TMP]) for pediatric immunoglobulin A nephropathy (IgAN). The clinical and laboratory findings as well as the prognosis for IgAN treated with TMP at long-term follow up were evaluated. We collected data on 33 IgAN children treated with TMP. The children were retrospectively divided into two groups. Group 1 consisted of 18 children treated with TMP as the initial therapy, and group 2 consisted of 15 children treated with TMP as rescue therapy for IgAN relapse. The clinical features, and laboratory and pathological findings, including those at first and second renal biopsy as well as at the latest follow up, were analyzed for both groups. Mean urinary protein excretion, incidence of hematuria, and serum creatinine in groups 1 and 2 were all decreased significantly after TMP compared with beforehand. The percentage of glomeruli showing crescents after TMP in groups 1 and 2 was significantly lower than before TMP. At the most recent follow up, 94% of patients in group 1 and 87% in group 2 had normal urine, 6% in group 1 and 13% in group 2 had minor urinary abnormalities, and no patients in either group had active renal disease or renal insufficiency. TMP is effective in ameliorating urinary abnormalities and improving the long-term outcome of pediatric IgAN both as an initial and as a rescue treatment. © 2016 Japan Pediatric Society.

  3. Prospective controlled cohort studies on long-term therapy of breast cancer patients with a mistletoe preparation (Iscador).

    PubMed

    Grossarth-Maticek, Ronald; Ziegler, Renatus

    2006-10-01

    Mistletoe preparations such as Iscador (Weleda, Schwäbisch Gmünd, Germany) are commonly used in complementary and alternative / anthroposophic medicine for many cancer indications, particularly for solid cancers. Efficacy of this complementary therapy is still controversial. Does long-term therapy with Iscador show any effect on survival, tumor progression and psychosomatic self-regulation of patients with breast cancer? Prospective recruitment and long-term follow-up of two controlled cohort studies: (1) Randomized matched-pair study (38 pairs): breast cancer patients without any recurrences or metastases and no mistletoe therapy were matched for prognostic factors. By pairwise random allocation, one of the patients was suggested mistletoe therapy to be applied by the attending physician. (2) Non-randomized matched-pair study (84 pairs): breast cancer patients without recurrences or metastases that already received mistletoe therapy were matched to control patients without Iscador therapy. For overall survival, the nonrandomized study shows significant effects in favor of Iscador therapy: hazard ratio HR estimate and 95% confidence interval CI: 0.43 (0.27-0.68). The effect of long-term Iscador therapy on tumor progression as measured by the time to local recurrences, lymphatic or distant metastases in breast cancer patients without any such events at first diagnosis, is in most cases significant in favor of the Iscador group, in the randomized as well as in the non-randomized study. Psychosomatic self-regulation in the Iscador group improves significantly within 12 months compared with the control group in the randomized as well as in the non-randomized study: estimate of the median difference and 95% CI: 0.35 (0.05-0.60), respectively 0.20 (0-0.35). Iscador shows a clinically relevant effect on breast tumor progression as measured by overall survival as well as by the time to recurrences, lymphatic or distant metastases. In the short term, psychosomatic self

  4. Determinants of long-term response to group therapy for dysfunctional fear of progression in chronic diseases.

    PubMed

    Dinkel, Andreas; Herschbach, Peter; Berg, Petra; Waadt, Sabine; Duran, Gabriele; Engst-Hastreiter, Ursula; Henrich, Gerhard; Book, Katrin

    2012-01-01

    Prior work demonstrated that cognitive-behavioral (CBT) and supportive-experiential (SET) group interventions can reduce dysfunctional fear of progression (FoP) in patients with chronic diseases. In this secondary analysis of a randomized controlled study, we investigated determinants of long-term response to group therapy for FoP. Response to therapy after 12 months was assessed using the Reliable Change Index (RCI). Outcome data were available for 129 patients with cancer and 116 patients with chronic arthritis. 37.9% of the patients in the CBT group and 32.7% of those attending the SET group indicated response to therapy (p=.402). Educational level predicted long-term response to therapy (OR 2.53, 95% CI 1.33-4.81; p=.005). Medical patients with lower education may need additional attention in order to gain long-lasting benefit from brief group psychotherapy. However, this investigation needs to be replicated in a study that includes a broader range of psychological predictors.

  5. Long-Term Follow-up of Foamy Viral Vector-Mediated Gene Therapy for Canine Leukocyte Adhesion Deficiency

    PubMed Central

    Bauer, Thomas R; Tuschong, Laura M; Calvo, Katherine R; Shive, Heather R; Burkholder, Tanya H; Karlsson, Eleanor K; West, Robert R; Russell, David W; Hickstein, Dennis D

    2013-01-01

    The development of leukemia following gammaretroviral vector-mediated gene therapy for X-linked severe combined immunodeficiency disease and chronic granulomatous disease (CGD) has emphasized the need for long-term follow-up in animals treated with hematopoietic stem cell gene therapy. In this study, we report the long-term follow-up (4–7 years) of four dogs with canine leukocyte adhesion deficiency (CLAD) treated with foamy viral (FV) vector-mediated gene therapy. All four CLAD dogs previously received nonmyeloablative conditioning with 200 cGy total body irradiation followed by infusion of autologous, CD34+ hematopoietic stem cells transduced by a FV vector expressing canine CD18 from an internal Murine Stem Cell Virus (MSCV) promoter. CD18+ leukocyte levels were >2% following infusion of vector-transduced cells leading to ongoing reversal of the CLAD phenotype for >4 years. There was no clinical development of lymphoid or myeloid leukemia in any of the four dogs and integration site analysis did not reveal insertional oncogenesis. These results showing disease correction/amelioration of disease in CLAD without significant adverse events provide support for the use of a FV vector to treat children with leukocyte adhesion deficiency type 1 (LAD-1) in a human gene therapy clinical trial. PMID:23531552

  6. Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders.

    PubMed

    Carr, Roxanne; Wasdell, Michael B; Hamilton, Donald; Weiss, Margaret D; Freeman, Roger D; Tai, Joseph; Rietveld, Wop J; Jan, James E

    2007-11-01

    To date, there have been no prospective long-term studies of melatonin therapy in children. We report here data from a prospective follow-up study of 44 children with neurodevelopmental disabilities and treatment-resistant circadian rhythm sleep disorders (CRSD) who had participated in a placebo controlled, double blind cross-over trial of sustained-release melatonin. The follow-up study involved a structured telephone interview of caregivers every 3 months for upto 3.8 yr. The caregivers provided ratings of satisfaction, adverse effects, benefits, persistence with treatment and additional medications. Changes in melatonin dose were recorded. Open ended questions were included to capture caregivers' impressions and comments concerning melatonin therapy. Adverse reaction to melatonin therapy and development of tolerance were not evident. Better sleep was associated with reported improvement in health, behavior and learning. At the end of the study, the parental comments regarding the effectiveness of long-term melatonin therapy were highly positive. Parents whose children had sleep maintenance difficulties expressed a wish to have a commercially available controlled-release melatonin product which would promote sleep for 8-10 hr. Hypnotics for children with CRSD should be considered a second line of treatment for those who fail to respond to sleep hygiene and/or melatonin.

  7. Local steroid therapy as the first-line treatment for boys with symptomatic phimosis - a long-term prospective study.

    PubMed

    Reddy, Srinath; Jain, Viral; Dubey, Manish; Deshpande, Pankaj; Singal, Arbinder K

    2012-03-01

    Phimosis is a common paediatric urological disorder and often necessitates circumcision. We prospectively evaluated local steroid therapy (LST) as the first choice therapy for such children. Two hundred and sixty symptomatic boys up to 15 years of age (mean 34 months) with phimosis were started on betamethasone dipropionate (0.05%) application on gently stretched prepuce twice a day. Follow-up visits were arranged at the end of weeks 1, 2 and 4 and 6 months. Grade of phimosis was objectively graded. Ninety one percent of the boys showed a successful outcome at the end of 4 weeks; 72% responded in first week, further 16% responded in week 2, and only 2.6% achieved alleviation of phimosis on further application of LST beyond 2 weeks. Fourty two (17.8%) boys had a recurrence of phimosis on a long-term follow-up (mean - 25.4 months, range 6-48 months); thus, the long-term success rate was 77%, while 60 (23%) boys underwent surgery. Local steroid therapy is safe and successful in alleviating symptomatic tight foreskin in a large majority of children. The response can be seen as early as 1 week; most of the children respond by week 2 and continuing therapy further may not be very effective. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

  8. Short- and Long-Term Mortality Rates of Elderly Acute Kidney Injury Patients Who Underwent Continuous Renal Replacement Therapy

    PubMed Central

    Rhee, Harin; Jang, Keum Sook; Park, Jong Man; Kang, Jin Suk; Hwang, Na Kyoung; Kim, Il Young; Song, Sang Heon; Seong, Eun Young; Lee, Dong Won; Lee, Soo Bong; Kwak, Ihm Soo

    2016-01-01

    Background The world’s population is aging faster and the incidence of acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT) is increasing in elderly population. The outcome of AKI needing CRRT in elderly patients is known to be poor. However, the definitions of elderly used in the previous literatures were diverse and, there were few data that compared the long-term mortality rates of these patients with middle aged patients. This study was aimed to evaluate this issue. Methods This study was a single-center, retrospective cohort study of patients who underwent CRRT from January 2013 to December 2015. The patients were divided into the following four age cohorts: middle-aged (55–64), young-old (65–74), middle-old (75–84), and old-old (≥85). The short- and long-term mortality rates for each age cohort were compared. Results A total of 562 patients met the inclusion criteria. The short-term mortality rate was 57.3% in the entire cohort. Compared with the middle-aged cohort, the middle-old cohort (HR 1.48 (1.09–2.02), p = 0.012) and the old-old cohort (HR 2.33 (1.30–4.19), p = 0.005) showed an increased short-term mortality rate along with an increased SOFA score, acidemia and a prolonged prothrombin time. When we analyzed the long-term mortality rate of the 238 survived patients, the middle-old cohort (HR 3.76 (1.84–7.68), p<0.001), the old-old cohort (HR 4.40(1.20–16.10), p = 0.025), a lower BMI, the presence of liver cirrhosis, the presence of congestive heart failure and a history of sepsis were independent risk factors for the prediction of long-term mortality. Conclusion Compared with the middle-aged cohort, the middle-old and the old-old cohort showed an increased short-term and long-term mortality rate. However, in the young-old cohort, neither the short-term nor the long-term mortality rate was increased. PMID:27875571

  9. Long-term persistence to mono and combination therapies with angiotensin converting enzymes and angiotensin II receptor blockers in Australia.

    PubMed

    Gadzhanova, Svetla; Roughead, Elizabeth E; Bartlett, Louise E

    2016-06-01

    The purpose of this study was to compare the impact of initial antihypertensive therapy including angiotensin converting enzyme inhibitors (ACE) or angiotensin II receptor blockers (ARB) on long-term persistence to therapy. A retrospective cohort study using prescription claims data from the Australian Pharmaceutical Benefit Scheme (PBS). Kaplan-Meier analysis of prescription refills and cox proportional hazard models were used to compare the time on therapy (persistence) in people newly initiated to monotherapy or combination therapy including ACE or ARB, between April 2007 and March 2008. Differences in persistence to initial drug class or any antihypertensive therapy were reported at 4-year follow-up. About 119,500 persons initiated ACE or ARB: 47 % initiated ACE monotherapy; 32 % ARB monotherapy; 13 % ACE combinations; and 8 % ARB combinations. Persistence (% on treatment at 4 years) to index therapy was lower in people starting ACE and ARB combinations compared to ACE or ARB monotherapies: ACE combination (12 %) versus ACE monotherapy (25 %) and ARB combinations (22 %) versus ARB monotherapy (35 %). Persistence was higher in those initiating fixed dose combinations (FDC) versus separate pill combinations of ACEs (19 vs. 10 %) and ARBs (25 vs. 14 %). Persistence at 4 years to any antihypertensive therapy was similar between initiators to ACE or ARB monotherapy (60 and 61 %, p = 0.08), ACE or ARB combinations (56 %, p = 0.99), and was slightly higher for separate pill combinations (57-59 %) versus FDC (55 %). Choice of initial antihypertensive may have little impact on long-term persistence to therapy.

  10. Efficacy and safety of long-term prophylaxis in severe hemophilia A dogs following liver gene therapy using AAV vectors.

    PubMed

    Sabatino, Denise E; Lange, Amy M; Altynova, Ekaterina S; Sarkar, Rita; Zhou, Shangzhen; Merricks, Elizabeth P; Franck, Helen G; Nichols, Timothy C; Arruda, Valder R; Kazazian, Haig H

    2011-03-01

    Developing adeno-associated viral (AAV)-mediated gene therapy for hemophilia A (HA) has been challenging due to the large size of the factor VIII (FVIII) complementary DNA and the concern for the development of inhibitory antibodies to FVIII in HA patients. Here, we perform a systematic study in HA dogs by delivering a canine FVIII (cFVIII) transgene either as a single chain or two chains in an AAV vector. An optimized cFVIII single chain delivered using AAV serotype 8 (AAV8) by peripheral vein injection resulted in a dose-response with sustained expression of FVIII up to 7% (n = 4). Five HA dogs administered two-chain delivery using either AAV8 or AAV9 via the portal vein expressed long-term, vector dose-dependent levels of FVIII activity (up to 10%). In the two-chain approach, circulating cFVIII antigen levels were more than fivefold higher than activity. Notably, no long-term immune response to FVIII was observed in any of the dogs (1/9 dogs had a transient inhibitor). Long-term follow-up of the dogs showed a remarkable reduction (>90%) of bleeding episodes in a combined total of 24 years of observation. These data demonstrate that both approaches are safe and achieve dose-dependent therapeutic levels of FVIII expression, which supports translational studies of AAV-mediated delivery for HA.

  11. Clinical Long-Term Response to Cardiac Resynchronization Therapy Is Independent of Persisting Echocardiographic Markers of Dyssynchrony

    PubMed Central

    Naegeli, Barbara; Brunner-La Rocca, Hans-Peter; Attenhofer Jost, Christine; Fah-Gunz, Anja; Maurer, Dominik; Bertel, Osmund; Scharf, Christoph

    2014-01-01

    Background The aim of the study was to prove the concept that correction of established parameters of dyssynchrony is a requirement for favorable long-term outcome in patients with cardiac resynchronization therapy (CRT), whereas patients with persisting dyssynchrony should have a less favorable response. Methods After CRT implantation and optimization of dyssynchrony parameters, we evaluated whether correction or persistence of dyssynchrony predicted long-term outcome. Primary endpoint was a combination of cardiac mortality/heart transplantation and hospitalization due to worsening heart failure, and secondary endpoint was NYHA class. Results One hundred twenty-eight consecutive patients (mean age 68 ± 10 years) undergoing CRT with a mean left ventricular ejection fraction of 27±9% were followed for 27 ± 19 months. All cause mortality was 17.2%, cardiac mortality was 7.8% and 3.1% had to undergo heart transplantation. Rehospitalization due to worsening heart failure was observed in 14.8%. NYHA class before CRT implantation was 2.8 ± 0.8 and improved during follow-up to 2.0 ± 0.8 (P < 0.001). A clinical response was observed in 76% (n = 97) and an echocardiographic response was documented in 66% (n = 85). After individually optimized AV and VV intervals with echocardiography, atrioventricular dyssynchrony was still present in 7.2%, interventricular dyssynchrony in 13.3% and intraventricular dyssynchrony in 16.4%. Despite persistent atrioventricular, interventricular and intraventricular dyssynchrony at long-term follow-up, the combined primary and secondary endpoints did not differ compared to the group without mechanical dyssynchrony (P = ns). QRS duration with biventricular stimulation did not differ between responders vs. nonresponders. Conclusion After successful CRT implantation, clinical long-term response is independent of correction of dyssynchrony measured by echocardiographic parameters and QRS width. PMID:28352448

  12. Long-Term Effects of Two Formats of Cognitive Behavioral Therapy for Insomnia Comorbid with Breast Cancer

    PubMed Central

    Savard, Josée; Ivers, Hans; Savard, Marie-Hélène; Morin, Charles M.

    2016-01-01

    Study Objectives: The goal of this randomized controlled trial, conducted in breast cancer patients, was to assess the long-term efficacy of a video-based cognitive behavioral therapy for insomnia (VCBT-I), as compared to a professionally administered intervention (PCBT-I) and to a no-treatment group (CTL). An earlier report revealed that, at posttreatment, VCBT-I patients showed significantly greater sleep improvements than CTL, but that PCBT-I produced superior effects than VCBT-I on some sleep and secondary outcomes. In this report, long-term effects are compared. Methods: Two hundred forty-two women with breast cancer and with insomnia symptoms or using hypnotic medications participated to this three-arm randomized controlled trial: (1) PCBT-I (n = 81); (2) VCBT-I (n = 80); or (3) no treatment (CTL; n = 81) group. PCBT-I was composed of six weekly, individual sessions of approximately 50 min, whereas VCBT-I comprised a 60-min animated video and six booklets. Results: Study measures (sleep and secondary variables) were administered at pretreatment and posttreatment, and at a 3-, 6-, and 12-mo follow-up. Treatment gains were well sustained at follow-up in both PCBT-I and VCBT-I. As at posttreatment, the remission rate of insomnia at follow-up was greater in PCBT-I than in VCBT-I, which was greater than in CTL. Conclusions: Although face-to-face therapy remains the optimal format to efficaciously administer CBT for insomnia in cancer patients, a minimal intervention, such as the video-based intervention tested in this study, produces significant and sustainable treatment effects. Clinical Trial Registration: ClinicalTrials.gov identifier NCT00674830. Citation: Savard J, Ivers H, Savard MH, Morin CM. Long-term effects of two formats of cognitive behavioral therapy for insomnia comorbid with breast cancer. SLEEP 2016;39(4):813–823. PMID:26715229

  13. Beliefs about the harms of long-term use of nicotine replacement therapy: perceptions of smokers in England.

    PubMed

    Black, Andrew; Beard, Emma; Brown, Jamie; Fidler, Jenny; West, Robert

    2012-11-01

    Previous research has shown that a substantial proportion of smokers believe that nicotine causes serious diseases such as cancer, possibly deterring the use of nicotine replacement therapy (NRT) for smoking cessation or smoking reduction. This study examined beliefs about the harms specifically from long-term use of NRT and associations between these and its use for smoking cessation and smoking reduction. Data were collected from 1657 smokers and recent ex-smokers involved in the Smoking Toolkit Study, a series of monthly household surveys of English adults aged 16 and over. Participants were asked if they thought the use of NRT for a year or more was harmful, and if so, to volunteer what they believed the harms to be. They were also asked if they were using NRT for smoking reduction and/or if they had used NRT in the past year during a quit attempt. Six percent and 25% of smokers respectively, believed that the long term use of NRT was very or quit harmful to health; and a further 29% reported that they 'didn't know'. The most commonly reported harms were addiction and lung cancer. There was no association between these beliefs and use of NRT for smoking reduction or smoking cessation. A significant minority of smokers in England believe that the use of nicotine replacement therapy for a year or more is harmful. However, belief that long-term nicotine replacement therapy use can cause health harm does not appear to act as a deterrent to using it in a quit attempt or for smoking reduction. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

  14. Increased rates of long-term complications after MammoSite brachytherapy compared with whole breast radiation therapy.

    PubMed

    Rosenkranz, Kari M; Tsui, Edmund; McCabe, Elizabeth B; Gui, Jiang; Underhill, Kelly; Barth, Richard J

    2013-09-01

    Due to its short duration of therapy and low rates of local recurrence, women undergoing breast conservation are increasingly opting for partial breast irradiation with the MammoSite (Cytyc/Hologic) catheter. In early follow-up studies, few complications were reported. Few data, however, exist regarding longer-term complications. We compared the long-term local toxicities of MammoSite partial breast irradiation with those resulting from whole breast radiation. This was a retrospective study performed in a single academic medical center. All patients who underwent breast-conserving surgery between 2003 and 2008, who met institutional criteria for brachytherapy, were included. We compared women treated with MammoSite with patients treated with whole breast radiation therapy (WBRT). Endpoints included incidence of palpable masses at the lumpectomy site, telangiectasias, and local recurrence. Seventy-one MammoSite patients and 245 WBRT patients were well matched with regard to clinical characteristics. Median follow-up was 4 years. A palpable mass developed at the site of lumpectomy in 27% of the MammoSite patients compared with 7% of the WBRT patients (p < 0.0001). Telangiectasias developed more frequently in the MammoSite group than in the WBRT group (24% vs 4%, p < 0.001). Forty-two percent of patients treated with MammoSite developed a palpable mass, telangectasia, or both. Palpable masses and telangiectasias are frequent long-term complications after MammoSite brachytherapy and occur at a significantly higher rate after MammoSite brachytherapy than after WBRT. This increased rate of long-term local toxicity should be considered when counseling women on options for adjuvant radiation therapy after breast-conserving surgery. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  15. [Plasma volume expansion may explain the attenuation of antianginal activity of oral isosorbide dinitrate in long-term therapy].

    PubMed

    Kośmicki, M; Sadowski, Z

    1999-11-01

    The aim of the study was to evaluate whether tolerance to oral isosorbide dinitrate in sustained-release form (ISDN-SR) may be related to reduction in hematocrit (HCT)--an indirect indicator of plasma volume expansion. In a double blind, cross-over and placebo (P) controlled study 38 men, with mean age 52.5 +/- 7.4 years, with stable angina and angiographically proven coronary artery disease, received ISDN-SR 120 mg or P as initial dose and after 7 days of therapy: 4-times-daily (ISDN-SR 480 mg a day) and once-daily (ISDN-SR 120 mg a day). Venous HCT was measured: before treatment and after each of the 3 long-term phases. Antianginal efficacy of ISDN-SR 120 mg was evaluated by analysis of walking time to ischemia (WTI) on treadmill during stress tests performed 2 and 6 hours after drug ingestion in acute and long-term therapy. 6 hours after first ingestion of ISDN-SR 120 mg the mean walking time to ischaemia WTI was significantly improved in comparison to P by 58.4% (p < 0.0001) and after 7 days of once-daily treatment by 36.2% (p < 0.01) but not after the 4-times-daily period (NS). HCT fell from mean 43.2 +/- 3.6% before and 42.0 +/- 3.4% (NS) after P phase, to 40.5 +/- 3.0% (p < 0.05) after 4-times-daily period, but HCT remained unchanged after one week of once-daily treatment (NS). Significant reduction in hematocrit--an indirect indicator of plasma volume expansion--during oral ISDN-SR 120 mg in long-term therapy 4-times-daily, when tolerance occurred, but not once-daily (without tolerance), may contribute to the mechanism of attenuation of antianginal activity of nitrates.

  16. Increased Rates of Long-Term Complications after MammoSite Brachytherapy Compared with Whole Breast Radiation Therapy

    PubMed Central

    Rosenkranz, Kari M; Tsui, Edmund; McCabe, Elizabeth B; Gui, Jiang; Underhill, Kelly; Barth, Richard J

    2013-01-01

    BACKGROUND Due to its short duration of therapy and low rates of local recurrence, women undergoing breast conservation are increasingly opting for partial breast irradiation with the MammoSite (Cytyc/Hologic) catheter. In early follow-up studies, few complications were reported. Few data, however, exist regarding longer-term complications. We compared the long-term local toxicities of MammoSite partial breast irradiation with those resulting from whole breast radiation. STUDY DESIGN This was a retrospective study performed in a single academic medical center. All patients who underwent breast-conserving surgery between 2003 and 2008, who met institutional criteria for brachytherapy, were included. We compared women treated with MammoSite with patients treated with whole breast radiation therapy (WBRT). Endpoints included incidence of palpable masses at the lumpectomy site, telangiectasias, and local recurrence. RESULTS Seventy-one MammoSite patients and 245 WBRT patients were well matched with regard to clinical characteristics. Median follow-up was 4 years. A palpable mass developed at the site of lumpectomy in 27% of the MammoSite patients compared with 7% of the WBRT patients (p < 0.0001). Telangiectasias developed more frequently in the MammoSite group than in the WBRT group (24% vs 4%, p < 0.001). Forty-two percent of patients treated with MammoSite developed a palpable mass, telangectasia, or both. CONCLUSIONS Palpable masses and telangiectasias are frequent long-term complications after MammoSite brachytherapy and occur at a significantly higher rate after MammoSite brachytherapy than after WBRT. This increased rate of long-term local toxicity should be considered when counseling women on options for adjuvant radiation therapy after breast-conserving surgery. PMID:23830216

  17. Long term follow-up of infliximab efficacy in pulmonary and extra-pulmonary sarcoidosis refractory to conventional therapy.

    PubMed

    Russell, Eric; Luk, Francis; Manocha, Sonia; Ho, Tung; O'Connor, Carolyn; Hussain, Humaira

    2013-08-01

    Infliximab, a humanized, chimeric, monoclonal antibody against tumor necrosis alpha (TNF-α), has been shown to reduce the pulmonary and extra-pulmonary manifestations of sarcoidosis, however, there is little information regarding sustained efficacy with long-term use of infliximab. We retrospectively investigate whether a reduction in disease response is maintained, over a prolonged course of therapy (up to 85 months) with infliximab, and report on adverse events associated with its use. Subjects with multi-organ sarcoidosis were prescribed infliximab, between January 2000 to June 2010 due to failure of conventional therapy and were identified from the Drexel University College of Medicine sarcoidosis clinic. Retrospective patient reported symptom and objective clinical data analyses of pulmonary and extra-pulmonary findings were evaluated pre-infliximab and post or concurrent infliximab therapy. Any adverse events or reasons for discontinuation during infliximab therapy were reported. Twenty-six patients with biopsy proven sarcoidosis received anti-TNF therapy and met the criteria for study inclusion. Clinical evidence of sustained resolution or improvement was demonstrated in 58.5% of all organs assessed (p =<0.001). No clinical change in disease activity was seen in 35.8% of all organs evaluated. Despite infliximab treatment, 5.7% had progressive disease activity. Adverse events were seen in 57.7% of patients treated with infliximab over a 46.2 month average duration of therapy. Three (12%) patients had an adverse event that required permanent discontinuation. Infliximab is efficacious in the treatment of extra-pulmonary sarcoidosis and the efficacy is maintained with prolonged treatment. In patients with pulmonary sarcoid, sustained improvement in pulmonary imaging was seen after initiation of infliximab, however, post-treatment pulmonary function testing was not conclusive. Long-term infliximab therapy was well tolerated for our study group. Copyright © 2012

  18. Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer.

    PubMed

    Speicher, P J; Wang, X; Englum, B R; Ganapathi, A M; Yerokun, B; Hartwig, M G; D'Amico, T A; Berry, M F

    2015-01-01

    The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P < 0.001). As revealed by the propensity model, induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P < 0.001. Following propensity score matching analysis, the use of induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P < 0.001). Treatment with induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N

  19. [Long-term therapy with timolol for three years (author's transl)].

    PubMed

    Urner-Bloch, U; Bischoff, P

    1981-07-01

    From an original group of 36 Patients (15 with relatively advanced chronic open-angle glaucoma and 21 with ocular hypertension) 21 (seven glucoma and 14 ocular hypertension) were well controlled with Timolol alone or in combination with other pressure-lowering drugs after a three years' observation period. Dropouts occurred mainly in the first half of the treatment period. In most of these cases a glaucoma operation was necessary; more rarely, Timolol was discontinued due to intolerance. The overall success rate of 40% with Timolol alone (14 out of 36 patients) is lower than the 60% to 70% found in other long-term studies. If one considers only the results in the ocular hypertension group, the figure of 68% is more in line with the aforementioned results. In the light of similar studies it appears essential to take into account not only the total number of patients treated but also the degree of severity of the glaucoma. In severe glaucoma Timolol alone is seldom effective enough.

  20. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

    PubMed Central

    2011-01-01

    Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents. PMID:21443797

  1. Endovascular Therapy of Ruptured Abdominal Aortic Aneurysm: Mid- and Long-Term Results

    SciTech Connect

    Kubin, Klaus Sodeck, Gottfried H.; Teufelsbauer, H.; Nowatschka, Bernd; Kretschmer, Georg; Lammer, Johannes; Schoder, Maria

    2008-05-15

    As an alternative to open aneurysm repair, emergency endovascular aortic repair (EVAR) has emerged as a promising technique for ruptured abdominal aortic aneurysm (rAAA) within the last decade. The aim of this retrospective study is to present early and late outcomes of patients treated with EVAR for rAAA. Twenty-two patients (5 women, 17 men; mean age, 74 years) underwent EVAR for rAAA between November 2000 and April 2006. Diagnostic multislice computed tomography angiography was performed prior to stent-graft repair to evaluate anatomical characteristics and for follow-up examinations. Periprocedural patient characteristics and technical settings were evaluated. Mortality rates, hospital stay, and early and late complications, within a mean follow-up time of 744 {+-} 480 days, were also assessed. Eight of 22 patients were hemodynamically unstable at admission. Stent-graft insertion was successful in all patients. The total early complication rate was 54%, resulting in a 30-day mortality rate of 23%. The median intensive care unit stay was 2 days (range, 2-48 days), and the median hospital stay was 16 days (range, 9-210 days). During the follow-up period, three patients suffered from stent-graft-related complications. The overall mortality rate in our study group was 36%. EVAR is an acceptable, minimally invasive treatment option in patients with acute rAAA, independent of the patient's general condition. Short- and long-term outcomes are definitely comparable to those with open surgical repair procedures.

  2. Long-term insulin glargine therapy in type 2 diabetes mellitus: a focus on cardiovascular outcomes.

    PubMed

    Joseph, Joshua J; Donner, Thomas W

    2015-01-01

    Cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus. Hyperinsulinemia is associated with increased cardiovascular risk, but the effects of exogenous insulin on cardiovascular disease progression have been less well studied. Insulin has been shown to have both cardioprotective and atherosclerosis-promoting effects in laboratory animal studies. Long-term clinical trials using insulin to attain improved diabetes control in younger type 1 and type 2 diabetes patients have shown improved cardiovascular outcomes. Shorter trials of intensive diabetes control with high insulin use in higher risk patients with type 2 diabetes have shown either no cardiovascular benefit or increased all cause and cardiovascular mortality. Glargine insulin is a basal insulin analog widely used to treat patients with type 1 and type 2 diabetes. This review focuses on the effects of glargine on cardiovascular outcomes. Glargine lowers triglycerides, leads to a modest weight gain, causes less hypoglycemia when compared with intermediate-acting insulin, and has a neutral effect on blood pressure. The Outcome Reduction With Initial Glargine Intervention (ORIGIN trial), a 6.2 year dedicated cardiovascular outcomes trial of glargine demonstrated no increased cardiovascular risk.

  3. Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants.

    PubMed

    Talat, Mohamed A; Ahmed, Anwar; Mohammed, Lamia

    2015-10-01

    To evaluate the serum levels of zinc and copper in epileptic children during the long-term treatment of anticonvulsant drugs and correlate this with healthy subjects. A hospital-based group matched case-control study was conducted in the Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt between November 2013 and October 2014. Ninety patients aged 7.1 ± 3.6 years were diagnosed with epilepsy by a neurologist. The control group was selected from healthy individuals and matched to the case group. Serum zinc and copper were measured by the calorimetric method using a colorimetric method kit. The mean zinc level was 60.1 ± 22.6 ug/dl in the cases, and 102.1 ± 18 ug/dl in the controls (p<0.001). The mean copper level was 180.1 ± 32.4 ug/dl in cases compared with 114.5 ± 18.5 ug/dl in controls (p<0.001). Serum zinc levels in epileptic children under drug treatment are lower compared with healthy children. Also, serum copper levels in these patients are significantly higher than in healthy people. No significant difference in the levels of serum copper and zinc was observed in using one drug or multiple drugs in the treatment of epileptic patients.

  4. Barnidipine monotherapy and combination therapy in older patients with essential hypertension: a long-term study.

    PubMed

    Naber, F B; Häge, R; Mortelmans, J

    2000-11-01

    The long-term (2 year) safety and efficacy of barnidipine was assessed in an open-label, dose-titration, multicentre study of 236 patients aged > or = 75 years with a sitting diastolic blood pressure (DBP) > or = 95 mmHg. All eligible patients started treatment with barnidipine 10 mg once daily. After at least 4 weeks treatment, the dose of barnidipine was titrated upwards to 20 mg daily in patients who did not achieve normalisation of blood pressure (sitting DBP < 90 mmHg). After at least another 4 weeks of treatment an ACE inhibitor or diuretic was added if necessary. Barnidipine monotherapy was the final treatment in 74% of patients in the ITT population (50% barnidipine 10 mg, 24% barnidipine 20 mg). The overall response rate was 84.1% at endpoint. Overall mean sitting DBP decreased by 18.4 mmHg from 102.1 mmHg at baseline to 83.7 mmHg at endpoint. Although a total of 82.2% of patients reported at least one adverse event, only 37.4% of patients experienced an adverse event that was possibly or probably related to the study medication. Many patients experienced adverse events associated with co-existing diseases common in older people. It can be concluded that barnidipine as monotherapy or in combination with ACE inhibitors or diuretics is safe and effective in older patients with essential hypertension.

  5. Long-term efficacy of resilient appliance therapy in TMD pain patients: a randomised, controlled trial.

    PubMed

    Nilsson, Håkan; Vallon, D; Ekberg, E C

    2011-10-01

    The aim was to investigate long-term efficacy of a resilient appliance in patients with pain due to temporomandibular disorders (TMD). A randomised, controlled trial was performed in 80 recruited TMD pain patients. They were randomly allocated to one of two groups: treatment with a resilient appliance or treatment with a hard, palatal, non-occluding appliance. The primary treatment outcome was judged positive when patients' characteristic pain intensity decreased by at least 30%. Additional treatment outcomes were physical functioning, emotional functioning and headache. At the 12-month follow-up 50% of the patients in the treatment group and 42% in the control group had a 30% reduction of characteristic pain intensity, when calculated in an intent-to-treat analysis. Jaw function improved in both groups at the 6- and 12-month follow-up. Emotional functioning improved in both groups at the 6-month follow-up; an improvement concerning grade of depression was found in the control group at 12 months. Headache decreased in both groups at both follow-ups. There were no statistically significant differences found regarding primary and additional outcomes between groups at the 6- and 12-months follow-up. There was no statistically significant difference between the resilient appliance and the non-occluding control appliance in reducing TMD pain, physical functioning, emotional functioning and headache in a 12 months perspective.

  6. Adrenal response to corticotrophin and testosterone during long-term therapy with itraconazole in patients with chromoblastomycosis.

    PubMed

    Queiroz-Telles, F; Purim, K S; Boguszewski, C L; Afonso, F C; Graf, H

    1997-12-01

    In order to establish whether long-term itraconazole therapy can affect adrenal or testicular function, the adrenal response to corticotrophin and testosterone was evaluated by radioimmunoassay in 15 patients undergoing treatment for chromoblastomycosis. Mean cortisol and testosterone concentrations were 12.4 microg/dL and 454 ng/dL respectively at baseline and 15.4 microg/dL and 480 ng/dL respectively after 12.4+/-5.2 months of treatment with itraconazole (200-400 mg daily). Results were analysed using Student's t-test. There was no clinical or laboratory evidence of steroidogenic or androgenic impairment.

  7. Long-term outcomes of high-risk elderly male patients with multivessel coronary disease: optimal medical therapy versus revascularization.

    PubMed

    Tao, Tao; Wang, Hao; Wang, Shu-Xia; Guo, Yu-Tao; Zhu, Ping; Wang, Yu-Tang

    2016-02-01

    Many studies have indicated that medical therapy and percutaneous coronary intervention have similar effects in terms of the long-term prognosis of patients with stable coronary artery disease. This study investigated the effects of optimal medical therapy (OMT) and revascularization-plus-OMT in elderly patients with high-risk angina. In this prospective non-randomized study, 241 consecutive high-risk elderly male patients (65-92 years of age) with angiographically confirmed multivessel disease were enrolled in the registry from January 2004 to April 2005. Of these, 98 patients underwent OMT and 143 underwent revascularization therapy plus OMT. After 6.5 years of follow-up, we found that the rate of long-term cardiac mortality was significantly higher in patients who underwent OMT than in those who underwent revascularization (6.5-year unadjusted mortality rate, 14.3% for OMT vs. 7.0% for revascularization patients; log-rank P = 0.04). However, the overall risks of major adverse cardiac cerebrovascular events (MACCE) were similar among all patients (6.5-year unadjusted mortality rate, 29.6% for OMT vs. 27.3% for revascularization patients; log-rank P = 0.67). OMT was associated with an increase in cardiac death but a similar 6.5-year risk of MACCE compared with revascularization in high-risk elderly male patients with coronary multivessel disease.

  8. Long-term outcomes of high-risk elderly male patients with multivessel coronary disease: optimal medical therapy versus revascularization

    PubMed Central

    Tao, Tao; Wang, Hao; Wang, Shu-Xia; Guo, Yu-Tao; Zhu, Ping; Wang, Yu-Tang

    2016-01-01

    Background Many studies have indicated that medical therapy and percutaneous coronary intervention have similar effects in terms of the long-term prognosis of patients with stable coronary artery disease. This study investigated the effects of optimal medical therapy (OMT) and revascularization-plus-OMT in elderly patients with high-risk angina. Methods In this prospective non-randomized study, 241 consecutive high-risk elderly male patients (65–92 years of age) with angiographically confirmed multivessel disease were enrolled in the registry from January 2004 to April 2005. Of these, 98 patients underwent OMT and 143 underwent revascularization therapy plus OMT. Results After 6.5 years of follow-up, we found that the rate of long-term cardiac mortality was significantly higher in patients who underwent OMT than in those who underwent revascularization (6.5-year unadjusted mortality rate, 14.3% for OMT vs. 7.0% for revascularization patients; log-rank P = 0.04). However, the overall risks of major adverse cardiac cerebrovascular events (MACCE) were similar among all patients (6.5-year unadjusted mortality rate, 29.6% for OMT vs. 27.3% for revascularization patients; log-rank P = 0.67). Conclusions OMT was associated with an increase in cardiac death but a similar 6.5-year risk of MACCE compared with revascularization in high-risk elderly male patients with coronary multivessel disease. PMID:27168741

  9. The long-term safety and efficacy of intrathecal therapy using sufentanil in chronic intractable non-malignant pain.

    PubMed

    Monsivais, Jose Jesus; Monsivais, Diane Burn

    2014-07-01

    This report describes the long term safety and efficacy of intrathecal therapy using Sufentanil for the management of chronic intractable neuropathic pain in 12 chronic pain patients. Standardized psychological screening was used to determine treatment suitability. Evaluation data included the Visual Analog Scale (VAS), Wong-Baker Faces Scale, Brief Pain Inventory (BPI), Disability of Arm, Shoulder, and Hand (DASH), McGill Quality of Life Questionnaire, and complications (granulomas, toxicity, withdrawal, or deaths). SPSS version 18 was used for data analysis. Pre- and post- treatment BPI measures and pain scale scores showed a statistically significant difference. There were no complications directly related to drug toxicity, nor drug withdrawals, granulomas, or deaths. Intrathecal therapy with Sufentanil therapy offers a good treatment alternative for those cases that have failed both surgery and standard pain treatment. Strict patient selection based on psychological screening, control of co-morbidities, a proper pain management may contribute to successful outcome.

  10. The Long-Term Safety and Efficacy of Intrathecal Therapy Using Sufentanil in Chronic Intractable Non-Malignant Pain

    PubMed Central

    Monsivais, Diane Burn

    2014-01-01

    This report describes the long term safety and efficacy of intrathecal therapy using Sufentanil for the management of chronic intractable neuropathic pain in 12 chronic pain patients. Standardized psychological screening was used to determine treatment suitability. Evaluation data included the Visual Analog Scale (VAS), Wong-Baker Faces Scale, Brief Pain Inventory (BPI), Disability of Arm, Shoulder, and Hand (DASH), McGill Quality of Life Questionnaire, and complications (granulomas, toxicity, withdrawal, or deaths). SPSS version 18 was used for data analysis. Pre- and post- treatment BPI measures and pain scale scores showed a statistically significant difference. There were no complications directly related to drug toxicity, nor drug withdrawals, granulomas, or deaths. Intrathecal therapy with Sufentanil therapy offers a good treatment alternative for those cases that have failed both surgery and standard pain treatment. Strict patient selection based on psychological screening, control of co-morbidities, a proper pain management may contribute to successful outcome. PMID:25031819

  11. Cognitive-Behavioral Therapy for Child Anxiety Confers Long-Term Protection From Suicidality

    PubMed Central

    Wolk, Courtney Benjamin; Beidas, Rinad S.; Kendall, Philip C.

    2014-01-01

    Objective Evidence for an independent relationship between anxiety and suicidality has been mixed. Few studies have examined this relationship in youth seeking treatment for anxiety. The present study examined the relationship between response to treatment for an anxiety disorder in childhood and suicidal ideation, plans, and attempts at a follow-up interval of 7 to 19 years. We hypothesized that successful treatment for an anxiety disorder in childhood would be protective against later suicidality. Method The present study was a 7- to 19-year (M = 16.24; SD = 3.56) follow-up study. Adults (N = 66) completed cognitive-behavioral treatment (CBT) for anxiety as children. Information regarding suicidality at follow-up was obtained via the World Mental Health Survey Initiative Version of the World Health Organization Composite International Diagnostic Interview (CIDI) and the Beck Depression Inventory (BDI-II). Results Results indicate that participants who responded favorably to CBT during childhood were less likely to endorse lifetime, past-month, and past-two-week suicidal ideation than treatment non-responders. This was consistent across self-report and interview-report of suicidal ideation. Treatment response was not significantly associated with suicide plans or attempts, though the infrequent occurrence of both limited the ability to detect findings. Conclusion Results suggest more chronic and enduring patterns of suicidal ideation among those with anxiety in childhood that is not successfully treated. This study adds to the literature that suggests successful CBT for childhood anxiety confers long-term benefits and underscores the importance of the identification and evidence-based treatment of youth anxiety. PMID:25721182

  12. Long-term therapy with sorafenib is associated with pancreatic atrophy.

    PubMed

    Xu, Li; Zhou, Dong-Sheng; Zhao, Jing; Spolverato, Gaya; Zhang, Yao-Jun; Li, Sheng-Ping; Chen, Min-Shan; Pawlik, Timothy M

    2015-12-01

    Although the short-term adverse effects of sorafenib are well known, few data exist on long-term toxicity. The objective of the present study was to investigate the prevalence of pancreatic atrophy among a cohort of patients with hepatocellular carcinoma (HCC) who were treated with sorafenib for ≥2 y. Between March 2007 and December 2013, 31 patients with HCC who were treated with sorafenib for ≥2 y were identified. The effect of pancreatic atrophy and enhancement on incidence of adverse events, tumor response, and overall survival (OS) were assessed. Thirty-one patients with HCC were treated with sorafenib for ≥2 y and met inclusion criteria; 11 patients (35.5%) were Barcelona-clinic liver cancer stage B, whereas 20 patients (64.5%) were Barcelona-clinic liver cancer stage C. Median duration of treatment with sorafenib was 35.2 mo. Pancreatic atrophy and a decrease in pancreatic enhancement occurred in 24 patients (77.4%) and 15 patients (48.4%), respectively. On the basis of the modified response evaluation criteria in solid tumors, four patients (12.9%) had a complete response, 10 patients (32.3%) had a partial response, and 17 patients (54.8%) had stable disease. Patients treated with sorafenib with pancreatic atrophy had a median OS of 49.4 mo (95% confidence interval, 41.2-57.5 mo) compared with 31.2 mo (95% confidence interval, 25.7-36.7 mo) among patients who did not develop pancreatic atrophy (P = 0.009). In contrast, survival was not associated with decreased versus normal enhancement of the pancreas (OS, 47.7 mo versus 41.7 mo, respectively; P = 0.739). Pancreatic atrophy occurred in many HCC patients after 2 y of treatment with sorafenib. Patients who experienced pancreatic atrophy had a better tumor response and OS. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Recurrence of Hyperprolactinemia after Withdrawal of Long-Term Cabergoline Therapy

    PubMed Central

    Kharlip, J.; Salvatori, R.; Yenokyan, G.; Wand, G. S.

    2009-01-01

    Context: Recurrence of hyperprolactinemia after cabergoline withdrawal ranges widely from 36 to 80%. The Pituitary Society recommends withdrawal of cabergoline in selected patients. Objective: Our aim was to evaluate recurrence of hyperprolactinemia in patients meeting The Pituitary Society guidelines. Design: Patients were followed from the date of discontinuation to either relapse of hyperprolactinemia or the day of last prolactin test. Setting: We conducted the study at an academic medical center. Patients: Forty-six patients meeting Pituitary Society criteria (normoprolactinemic and with tumor volume reduction after 2 or more years of treatment) participated in the study. Interventions: After withdrawal, if prolactin returned above reference range, another measurement was obtained within 1 month, symptoms were assessed by questionnaire, and magnetic resonance imaging was performed. Main Outcome Measures: We measured risk of and time to recurrence estimates as well as clinical predictors of recurrence. Results: Mean age of patients was 50 ± 13 yr, and 70% were women. Thirty-one patients had microprolactinomas, 11 had macroprolactinomas, and four had nontumoral hyperprolactinemia. The overall recurrence was 54%, and the estimated risk of recurrence by 18 months was 63%. The median time to recurrence was 3 months (range, 1–18 months), with 91% of recurrences occurring within 1 yr after discontinuation. Size of tumor remnant prior to withdrawal predicted recurrence [18% increase in risk for each millimeter (95% confidence interval, 3–35; P = 0.017)]. None of the tumors enlarged in the patients experiencing recurrence, and 28% had symptoms of hypogonadism. Conclusions: Cabergoline withdrawal is practical and safe in a subset of patients as defined by The Pituitary Society guidelines; however, the average risk of long-term recurrence in our study was over 60%. Close follow-up remains important, especially within the first year. PMID:19336508

  14. Long-term treatment with thiamine as possible medical therapy for Friedreich ataxia.

    PubMed

    Costantini, Antonio; Laureti, Tiziana; Pala, Maria Immacolata; Colangeli, Marco; Cavalieri, Simona; Pozzi, Elisa; Brusco, Alfredo; Salvarani, Sandro; Serrati, Carlo; Fancellu, Roberto

    2016-11-01

    Thiamine (vitamin B1) is a cofactor of fundamental enzymes of cell energetic metabolism; its deficiency causes disorders affecting both the peripheral and central nervous system. Previous studies reported low thiamine levels in cerebrospinal fluid and pyruvate dehydrogenase dysfunction in Friedreich ataxia (FRDA). We investigated the effect of long-term treatment with thiamine in FRDA, evaluating changes in neurological symptoms, echocardiographic parameters, and plasma FXN mRNA levels. Thirty-four consecutive FRDA patients have been continuously treated with intramuscular thiamine 100 mg twice a week and have been assessed with the Scale for the Assessment and Rating of Ataxia (SARA) at baseline, after 1 month, and then every 3 months during treatment. Thiamine administration ranged from 80 to 930 days and was effective in improving total SARA scores from 26.6 ± 7.7 to 21.5 ± 6.2 (p < 0.02). Moreover, deep tendon reflexes reappeared in 57 % of patients with areflexia at baseline, and swallowing improved in 63 % of dysphagic patients. Clinical improvement was stable in all patients, who did not show worsening even after 2 years of treatment. In a subgroup of 13 patients who performed echocardiogram before and during treatment, interventricular septum thickness reduced significantly (p < 0.02). Frataxin mRNA blood levels were modestly increased in one-half of treated patients. We suppose that a focal thiamine deficiency may contribute to a selective neuronal damage in the areas involved in FRDA. Further studies are mandatory to evaluate thiamine role on FXN regulation, to exclude placebo effect, to verify our clinical results, and to confirm restorative and neuroprotective action of thiamine in FRDA.

  15. The impact of statin therapy on long-term cardiovascular outcomes in an outpatient cardiology practice

    PubMed Central

    Lai, Hoang M.; Aronow, Wilbert S.; Mercando, Anthony D.; Kalen, Phoenix; Desai, Harit V.; Gandhi, Kaushang; Sharma, Mala; Amin, Harshad; Lai, Trung M.

    2011-01-01

    Summary Background Statins reduce coronary events in patients with coronary artery disease. Material/Methods Chart reviews were performed in 305 patients (217 men and 88 women, mean age 74 years) not treated with statins during the first year of being seen in an outpatient cardiology practice but subsequently treated with statins. Based on the starting date of statins use, the long-term outcomes of myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery (CABGS) before and after statin use were compared. Results Mean follow-up was 65 months before statins use and 66 months after statins use. MI occurred in 31 of 305 patients (10%) before statins, and in 13 of 305 patients (4%) after statins (p<0.01). PCI had been performed in 66 of 305 patients (22%) before statins and was performed in 41 of 305 patients (13%) after statins (p<0.01). CABGS had been performed in 56 of 305 patients (18%) before statins and was performed in 20 of 305 patients (7%) after statins (p<0.001). Stepwise logistic regression showed statins use was an independent risk factor for MI (odds ratio=0.0207, 95% CI, 0.0082–0.0522, p<0.0001), PCI (odds ratio=0.0109, 95% CI, 0.0038–0.0315, p<0.0001), and CABGS (odds ratio=0.0177, 95% CI=0.0072–0.0431, p<0.0001) Conclusions Statins use in an outpatient cardiology practice reduces the incidence of MI, PCI, and CABGS. PMID:22129898

  16. The impact of statin therapy on long-term cardiovascular outcomes in an outpatient cardiology practice

    PubMed Central

    Lai, Hoang M.; Mercando, Anthony D.; Kalen, Phoenix; Desai, Harit V.; Gandhi, Kaushang; Sharma, Mala; Amin, Harshad; Lai, Trung M.

    2012-01-01

    Introduction Statins reduce coronary events in patients with coronary artery disease. Material and methods Chart reviews were performed in 305 patients (217 men and 88 women, mean age 74 years) not treated with statins during the first year of being seen in an outpatient cardiology practice but subsequently treated with statins. Based on the starting date of statins use, the long-term outcomes of myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery (CABGs) before and after statin use were compared. Results Mean follow-up was 65 months before statins use and 66 months after statins use. Myocardial infarction occurred in 31 of 305 patients (10%) before statins, and in 13 of 305 patients (4%) after statins (p < 0.01). Percutaneous coronary intervention had been performed in 66 of 305 patients (22%) before statins and was performed in 41 of 305 patients (13%) after statins (p < 0.01). Coronary artery bypass graft surgery had been performed in 56 of 305 patients (18%) before statins and in 20 of 305 patients (7%) after statins (p < 0.001). Stepwise logistic regression showed statins use was an independent risk factor for MI (odds ratio = 0.0207, 95% CI, 0.0082-0.0522, p < 0.0001), PCI (odds ratio = 0.0109, 95% CI, 0.0038-0.0315, p < 0.0001) and CABGs (odds ratio = 0.0177, 95% CI = 0.0072-0.0431, p < 0.0001) Conclusions Statins use in an outpatient cardiology practice reduces the incidence of MI, PCI, and CABGs. PMID:22457675

  17. A cross-sectional assessment of the long term effects of brief strategic family therapy for adolescent substance use.

    PubMed

    Horigian, Viviana E; Feaster, Daniel J; Robbins, Michael S; Brincks, Ahnalee M; Ucha, Jessica; Rohrbaugh, Michael J; Shoham, Varda; Bachrach, Ken; Miller, Michael; Burlew, A Kathleen; Hodgkins, Candace C; Carrion, Ibis S; Silverstein, Meredith; Werstlein, Robert; Szapocznik, José

    2015-10-01

    Young adult drug use and law-breaking behaviors often have roots in adolescence. These behaviors are predicted by early drug use, parental substance use disorders, and disrupted and conflict-ridden family environments. To examine long-term outcomes of Brief Strategic Family Therapy (BSFT) compared to treatment as usual (TAU) in the rates of drug use, number of arrests and externalizing behaviors in young adults who were randomized into treatment conditions as adolescents. 261 of 480 adolescents who had been randomized to BSFT or TAU in the BSFT effectiveness study were assessed at a single time, 3-7 years post randomization. Assessments of drug use, externalizing behaviors, arrests and incarcerations were conducted using Timeline Follow Back, Adult Self Report, and self-report, respectively. Drug use, arrests and incarcerations were examined using negative binomial models and externalizing behaviors were examined using linear regression. When compared with TAU, BSFT youth reported lower incidence of lifetime (IRR = 0.68, 95%CI [0.57, 0.81]) and past year (IRR = 0.54, 95%CI [0.40, 0.71]) arrests; lower rates of lifetime (IRR = 0.63, 95%CI [0.49, 0.81]) and past year (IRR = 0.70, 95%CI [0.53, 0.92]) incarcerations; and lower scores on externalizing behaviors at follow-up (B = -0.42, SE = .15, p = .005). There were no differences in drug use. BSFT may have long term effects in reducing the number of arrests, incarcerations and externalizing problems. These effects could be explained by the improvements in family functioning that occurred during the effectiveness study. This study contributes to the literature by reporting on the long term outcomes of family therapy for adolescent drug abuse. © American Academy of Addiction Psychiatry.

  18. Long-term outcome of leads and patients following robotic epicardial left ventricular lead placement for cardiac resynchronization therapy.

    PubMed

    Kamath, Ganesh S; Balaram, Sandhya; Choi, Andrew; Kuteyeva, Olga; Garikipati, Naga Vamsi; Steinberg, Jonathan S; Mittal, Suneet

    2011-02-01

    In cardiac resynchronization therapy (CRT), positive clinical response and reverse remodeling have been reported using robotically assisted left ventricular (LV) epicardial lead placement. However, the long-term performance of epicardial leads and long-term outcome of patients who undergo CRT via robotic assistance are unknown. In addition, since the LV lead placement is more invasive than a transvenous procedure, it is important to identify patients at higher risk of complications. We evaluated 78 consecutive patients (70 ± 11 years, 50 male) who underwent robotic epicardial LV lead placement. The short- (<12 months) and long-term (≥ 12 months) lead performance was determined through device interrogations. Mortality data were determined by contact with the patient's family and referring physicians and confirmed using the Social Security Death Index. All patients had successful lead placement and were discharged in stable condition. When compared to the time of implantation, there was a significant increase in pacing threshold (1.0 ± 0.5 vs 2.14 ± 1.2; P < 0.001) and decrease in lead impedance (1010 ± 240 Ω vs 491 ± 209 Ω; P < 0.001) at short-term follow-up. The pacing threshold (2.3 ± 1.2 vs 2.14 ± 1.2; P = 0.30) and lead impedance (451 ± 157 Ω vs 491 ± 209 Ω; P = 0.10) remained stable during long-term follow-up when compared to short-term values. At a follow-up of 44 ± 21 months, there were 20 deaths (26%). These patients were older (77 ± 7 vs 67 ± 11 years; P = 0.001) and had a lower ejection fraction (EF) (13 ± 7% vs 18 ± 9%; P = 0.02) than surviving patients. Robotically implanted epicardial LV leads for CRT perform well over short- and long-term follow-up. Older patients with a very low EF are at higher risk of death. The risks and benefits of this procedure should be carefully considered in these patients. ©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.

  19. Long-Term Outcome and Factors Affecting Prognosis of Extracorporeal Shockwave Therapy for Chronic Refractory Achilles Tendinopathy

    PubMed Central

    2017-01-01

    Objective To investigate the factors affecting prognosis of extracorporeal shockwave therapy (ESWT) for chronic refractory Achilles tendinopathy (AT). Methods Thirty-six patients (48 consecutive feet) with chronic AT (>6 months) and who underwent ESWT for ‘poor’ or ‘fair’ grade in Roles-Maudsley Score (RMS) after unsuccessful conservative treatment were included in the present study. A maximum of 12 sessions of ESWT were conducted until treatment success: RMS reached ‘good’ or ‘excellent’. Termination of ESWT for no response, or ‘poor’ or ‘fair’ grade was regarded as treatment failure. Immediate outcome, long-term outcome (telephone interview after mean 26 months), and factors affecting treatment success were analyzed. Results Numeric Rating Scale was significantly decreased at immediate and long-term follow-up. Success rate was 71.1% and 90.3%, respectively. Univariate logistic regression identified that immediate treatment success was associated with retrocalcaneal enthesophyte on X-ray (odds ratio [OR], 0.06; 95% confidence interval [CI], 0.01–0.28), pretreatment abnormal ultrasonography echogenicity within Achilles tendon (OR, 18.89; 95% CI, 2.08–171.96), mean duration of ‘post-treatment soreness’ (OR, 0.55; 95% CI, 0.33–0.94), and duration of ‘post-treatment soreness after first ESWT’ (OR, 0.06; 95% CI, 0.01–0.34). The duration of ‘post-treatment soreness after first ESWT’ was found to be the only factor associated with long-term success (OR, 0.32; 95% CI, 0.10–0.99). Conclusion ESWT appears to be effective in achieving long-term success in chronic refractory AT. Immediate success was associated with absence of retrocalcaneal enthesophyte on X-ray, presence of pretreatment abnormal ultrasonography echogenicity, shorter mean duration of ‘post-treatment soreness’, and shorter duration of ‘post-treatment soreness after first ESWT’. The shorter duration of ‘post-treatment soreness after first ESWT’ was

  20. The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

    PubMed

    Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2011-10-01

    The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience

  1. Evolution of Long-Term Adjuvant Anti-hormone Therapy: Consequences and Opportunities. The St. Gallen Prize Lecture

    PubMed Central

    Jordan, V. Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R.; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2012-01-01

    The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5-years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of “longer is better” for adjuvant therapy in pre-menopausal patients. One-year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five-years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten-years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective nor-epinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical

  2. Functional imaging in obese children responding to long-term sports therapy.

    PubMed

    Kinder, M; Lotze, M; Davids, S; Domin, M; Thoms, K; Wendt, J; Hirschfeld, H; Hamm, A; Lauffer, H

    2014-10-01

    Functional imaging studies on responders and non-responders to therapeutic interventions in obese children are rare. We applied fMRI before and after a one-year sports therapy in 14 obese or overweight children aged 7-16 years. During scanning, participants observed a set of standardized pictures from food categories, sports, and pleasant and neutral images. We were interested in alterations of the cerebral activation to food images in association with changes in the BMI-standard deviation score (BMI-SDS) after therapy and therefore separated the observation group into two outcome subgroups. One with reduction of BMI-SDS >0.2 (responder group) and one without (non-responder group). Before therapy fMRI-activation between groups did not differ. After therapy we found the following results: in response to food images, obese children of the responder group showed increased activation in the left putamen when compared with the non-responder group. Pleasant images evoked increased insula activation in the responder group. Only the responder group showed enhanced activity within areas known to store trained motor patterns in response to sports images. Both the putamen and the insula are involved in the processing of emotional valence and were only active for the therapy responders during the observation of food or pleasant stimuli. Elevated activity in these regions might possibly be seen in the context of an increase of dopaminergic response to emotional positive stimuli during intervention. In addition, sport images activated motor representations only in those subjects who profited from the sports therapy. Overall, an altered response to rewarding and pleasant images and an increased recruitment of motor engrams during observations of sports pictures indicates a more normal cerebral processing in response to these stimuli after successful sports therapy in obese children.

  3. A microarray gene analysis of peripheral whole blood in normal adult male rats after long-term GH gene therapy.

    PubMed

    Qin, Ying; Tian, Ya-Ping

    2010-06-01

    The main aims of this study were to determine the effects of GH gene abuse/misuse in normal animals and to discover genes that could be used as candidate biomarkers for the detection of GH gene therapy abuse/misuse in humans. We determined the global gene expression profile of peripheral whole blood from normal adult male rats after long-term GH gene therapy using CapitalBio 27 K Rat Genome Oligo Arrays. Sixty one genes were found to be differentially expressed in GH gene-treated rats 24 weeks after receiving GH gene therapy, at a two-fold higher or lower level compared to the empty vector group (p < 0.05). These genes were mainly associated with angiogenesis, oncogenesis, apoptosis, immune networks, signaling pathways, general metabolism, type I diabetes mellitus, carbon fixation, cell adhesion molecules, and cytokine-cytokine receptor interaction. The results imply that exogenous GH gene expression in normal subjects is likely to induce cellular changes in the metabolism, signal pathways and immunity. A real-time qRT-PCR analysis of a selection of the genes confirmed the microarray data. Eight differently expressed genes were selected as candidate biomarkers from among these 61 genes. These 8 showed five-fold higher or lower expression levels after the GH gene transduction (p < 0.05). They were then validated in real-time PCR experiments using 15 single-treated blood samples and 10 control blood samples. In summary, we detected the gene expression profiles of rat peripheral whole blood after long-term GH gene therapy and screened eight genes as candidate biomarkers based on the microarray data. This will contribute to an increased mechanistic understanding of the effects of chronic GH gene therapy abuse/misuse in normal subjects.

  4. Association of β-blocker therapy with long-term clinical outcomes in patients with coronary chronic total occlusion.

    PubMed

    Hwang, Jin Kyung; Yang, Jeong Hoon; Hwang, Ji-Won; Jang, Woo Jin; Song, Young Bin; Hahn, Joo-Yong; Choi, Jin-Ho; Lee, Sang Hoon; Gwon, Hyeon-Cheol; Choi, Seung-Hyuk

    2016-07-01

    There are limited data regarding the efficacy of β-blockers for secondary prevention in patients with coronary chronic total occlusion (CTO). Therefore, we investigated the association of β-blocker therapy with long-term clinical outcomes in CTO patients. From March 2003 to February 2012, a total of 2024 CTO patients treated with either medical therapy alone or revascularization were enrolled in the study. We assessed 1596 patients with stable ischemic heart disease and divided them into the β-blocker group (n = 932) and the no-β-blocker group (n = 664). The primary outcome was all-cause death. The median follow-up duration was 3.9 (interquartile range: 2.0-6.2) years. All-cause death occurred in 11.6% patients in the β-blocker group and 13.6% patients in the no-β-blocker group (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.61-1.08; P = 0.15). In the propensity score-matched population (570 pairs), all-cause death occurred in 12.3% patients in the β-blocker group and 12.8% patients in the no-β-blocker group (HR: 0.93, 95% CI: 0.67-1.29; P = 0.66). In subgroup analysis, β-blocker therapy was associated with better outcome, in terms of all-cause death, in patients with CTO of the left anterior descending coronary artery and Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) score ≥23 (P for interaction = 0.01 and 0.02, respectively). In conclusion, β-blocker therapy was not associated with favorable long-term clinical outcomes in stable CTO patients, regardless of treatment strategy. However, β-blocker therapy might be beneficial in a highly selective group of CTO patients with a high ischemic burden.

  5. Behavior Therapy for Tics in Children: Acute and Long-Term Effects on Psychiatric and Psychosocial Functioning

    PubMed Central

    Woods, Douglas W.; Piacentini, John C.; Scahill, Lawrence; Peterson, Alan L.; Wilhelm, Sabine; Chang, Susanna; Deckersbach, Thilo; McGuire, Joseph; Specht, Matt; Conelea, Christine A.; Rozenman, Michelle; Dzuria, James; Liu, Haibei; Levi-Pearl, Sue; Walkup, John T.

    2014-01-01

    Children (n = 126) ages 9 to 17 years with chronic tic or Tourette disorder were randomly assigned to receive either behavior therapy or a control treatment over 10 weeks. This study examined acute effects of behavior therapy on secondary psychiatric symptoms and psychosocial functioning and long-term effects on these measures for behavior therapy responders only. Baseline and end point assessments conducted by a masked independent evaluator assessed several secondary psychiatric symptoms and measures of psychosocial functioning. Responders to behavior therapy at the end of the acute phase were reassessed at 3-month and 6-month follow-up. Children in the behavior therapy and control conditions did not differentially improve on secondary psychiatric or psychosocial outcome measures at the end of the acute phase. At 6-month posttreatment, positive response to behavior therapy was associated with decreased anxiety, disruptive behavior, and family strain and improved social functioning. Behavior therapy is a tic-specific treatment for children with tic disorders. PMID:21555779

  6. Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke.

    PubMed

    Saver, Jeffrey L; Carroll, John D; Thaler, David E; Smalling, Richard W; MacDonald, Lee A; Marks, David S; Tirschwell, David L

    2017-09-14

    Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown. In a multicenter, randomized, open-label trial, with blinded adjudication of end-point events, we randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The results of the analysis of the primary outcome from the original trial period have been reported previously; the current analysis of data from the extended follow-up period was considered to be exploratory. We enrolled 980 patients (mean age, 45.9 years) at 69 sites. Patients were followed for a median of 5.9 years. Treatment exposure in the two groups was unequal (3141 patient-years in the PFO closure group vs. 2669 patient-years in the medical-therapy group), owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat population, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient-years, respectively (hazard ratio with PFO closure vs. medical therapy, 0.55; 95% confidence interval [CI], 0.31 to 0.999; P=0.046 by the log-rank test). Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical-therapy group (hazard ratio, 0.38; 95% CI, 0.18 to 0.79; P=0.007). Venous thromboembolism (which comprised events of pulmonary embolism and deep-vein thrombosis) was more common in the PFO closure group

  7. Comparison of the long-term effectiveness of progressive neuromuscular facilitation and continuous passive motion therapies after total knee arthroplasty

    PubMed Central

    Alaca, Nuray; Atalay, Ayçe; Güven, Zeynep

    2015-01-01

    [Purpose] The aim of this longitudinal study was to examine the long term functional effectiveness of proprioceptive neuromuscular facilitation (PNF) after total knee arthroplasty. [Subjects and Methods] We included 30 patients and they were randomly assigned to two groups. In addition to the standard rehabilitation program the PNF group received proprioceptive neuromuscular facilitation therapy and the CPM group received continuous passive motion therapy. The outcome measures included range of motion using a goniometer, pain scores using a numeric pain rating scale, days to reach functional benchmarks, the Beck depression scale and isokinetic torque and isometric strength measurements. [Results] There were no significant differences between the two groups in terms of baseline demographic data, clinical findings and length of stay. Days to reach range of motion benchmarks were similar in the two groups. Pain at the 8th week was slightly higher in the PNF group. With the exception of walking with a walker, days to reach functional benchmarks were statistically significantly fewer in patients of the PNF group despite similar isokinetic measurements. Administration of PNF resulted in earlier functional gains in patients after total knee arthroplasty. These functional accomplishments were more pronounced in the PNF group despite it having isokinetic torque measurements similar to those of the CPM group. [Conclusion] PNF techniques can positively affect functional outcomes over the long term. PMID:26696702

  8. AAV-based neonatal gene therapy for hemophilia A: long-term correction and avoidance of immune responses in mice.

    PubMed

    Hu, C; Lipshutz, G S

    2012-12-01

    Hemophilia A gene therapy has been hampered by immune responses to vector-associated antigens and by neutralizing antibodies or inhibitors against the factor VIII (FVIII) protein; these 'inhibitors' more commonly affect hemophilia A patients than those with hemophilia B. A gene replacement strategy beginning in the neonatal period may avoid the development of these immune responses and lead to prolonged expression with correction of phenotype, thereby avoiding long-term consequences. A serotype rh10 adeno-associated virus (AAV) was developed splitting the FVIII coding sequence into heavy and light chains with the chicken β-actin promoter/CMV enhancer for dual recombinant adeno-associated viral vector delivery. Virions of each FVIII chain were co-injected intravenously into mice on the second day of life. Mice express sustained levels of FVIII antigen ≥5% up to 22 months of life without development of antibodies against FVIII. Phenotypic correction was manifest in all AAV-FVIII-treated mice as demonstrated by functional assay and reduction in bleeding time. This study demonstrates the use of AAV in a gene replacement strategy in neonatal mice that establishes both long-term phenotypic correction of hemophilia A and lack of antibody development against FVIII in this disease model where AAV is administered shortly after birth. These studies support the consideration of gene replacement therapy for diseases that are diagnosed in utero or in the early neonatal period.

  9. Body composition abnormalities in children with Prader-Willi syndrome and long-term effects of growth hormone therapy.

    PubMed

    Eiholzer, U; l'Allemand, D; van der Sluis, I; Steinert, H; Gasser, T; Ellis, K

    2000-01-01

    Obesity and hypothalamic GH deficiency contribute in different ways to the disturbances of body composition in Prader-Willi syndrome (PWS); while both increase the fat compartment, the reduction of lean tissue mass has been attributed mainly to GH deficiency. Therefore, body composition measured by dual-energy X-ray absorptiometry was prospectively studied in 12 overweight children with PWS and weight for height (WfH) SDS >0 before and during 3.5 years of treatment with hGH (0.037 mg/kg/day) on average. In the long term, there is a net reduction of body fat from 3.1 to 1.2 SD, with a minimum at the end of the second year of treatment. WfH SDS correctly reflects body fat mass and its changes. The initial deficit of lean mass (-1.6 SD) is counteracted by GH only during the first year of therapy (increase to -1.25 SD). But in the long term, GH therapy does not further compensate for this deficit, when lean mass is corrected for its growth-related increase. In conclusion, exogenous GH changes the phenotype of children with PWS: fat mass becomes normal, but, at least in the setting studied, GH is not sufficient to normalize lean tissue mass. Copyright 2000 S. Karger AG, Basel

  10. Comparison of the long-term effectiveness of progressive neuromuscular facilitation and continuous passive motion therapies after total knee arthroplasty.

    PubMed

    Alaca, Nuray; Atalay, Ayçe; Güven, Zeynep

    2015-11-01

    [Purpose] The aim of this longitudinal study was to examine the long term functional effectiveness of proprioceptive neuromuscular facilitation (PNF) after total knee arthroplasty. [Subjects and Methods] We included 30 patients and they were randomly assigned to two groups. In addition to the standard rehabilitation program the PNF group received proprioceptive neuromuscular facilitation therapy and the CPM group received continuous passive motion therapy. The outcome measures included range of motion using a goniometer, pain scores using a numeric pain rating scale, days to reach functional benchmarks, the Beck depression scale and isokinetic torque and isometric strength measurements. [Results] There were no significant differences between the two groups in terms of baseline demographic data, clinical findings and length of stay. Days to reach range of motion benchmarks were similar in the two groups. Pain at the 8th week was slightly higher in the PNF group. With the exception of walking with a walker, days to reach functional benchmarks were statistically significantly fewer in patients of the PNF group despite similar isokinetic measurements. Administration of PNF resulted in earlier functional gains in patients after total knee arthroplasty. These functional accomplishments were more pronounced in the PNF group despite it having isokinetic torque measurements similar to those of the CPM group. [Conclusion] PNF techniques can positively affect functional outcomes over the long term.

  11. Oral valproic acid for epilepsy--long-term experience in therapy and side effects.

    PubMed

    Gerstner, Thorsten; Bell, Nellie; König, Stephan

    2008-02-01

    Valproic acid (VPA) is considered to be a drug of first choice and one of the most frequently-prescribed antiepileptic drugs worldwide for the therapy of generalized and focal epilepsies, including special epileptic. It is a broad-spectrum antiepileptic drug and is usually well tolerated. Rarely, serious complications may occur in some patients, including hemorrhagic pancreatitis, coagulopathies, bone marrow suppression, VPA-induced hepatotoxicity and encephalopathy, but there is still a lack of knowledge about the incidence and occurrence of these special side effects. Additionally, the consequences for VPA therapy and indication are more or less unclear. By literature review and own data this review addresses some of the challenges of VPA therapy and its side effects, which are not unique to epilepsy in childhood.

  12. Electroconvulsive Therapy for Long-term Mutism in a Case of Noncatatonic Paranoid Schizophrenia

    PubMed Central

    Singh, Priti; Gupta, Rajiv; Kundu, Savita

    2013-01-01

    We report a rare case of paranoid schizophrenia presenting with continuous mutism for about three years. This 26-year-old woman with multiple Schneiderian first-rank symptoms [‘Schneiderian’ refers to those symptoms established by the German psychiatrist Kurt Schneider for the diagnosis of schizophrenia] did not have any catatonic features, and she would fluently communicate by gesturing or writing. Since there was serious impairment in biological functions not readily correctable by antipsychotics, she was started on electroconvulsive therapy. She responded well to 14 sessions of electroconvulsive therapy along with oral haloperidol. We also discuss the cultural implications of prolonged mutism. To the best of our knowledge, this is the first case of mutism in noncatatonic paranoid schizophrenia that responded well to electroconvulsive therapy described in the literature. PMID:24062967

  13. Enhanced combination therapy effect on paclitaxel-resistant carcinoma by chloroquine co-delivery via liposomes

    PubMed Central

    Gao, Menghua; Xu, Yuzhen; Qiu, Liyan

    2015-01-01

    A novel composite liposomal system co-encapsulating paclitaxel (PTX) with chloroquine phosphate (CQ) was designed for treating PTX-resistant carcinoma. It was confirmed that liposomal CQ can sensitize PTX by means of autophagy inhibition and competitively binding with multidrug-resistance transporters. Furthermore, according to the in vitro cytotoxicity and apoptosis assay, real-time observation of cellular uptake, and in vivo tissue distribution study, co-encapsulation of PTX and CQ in liposomes was validated as superior to the mixture of PTX liposome plus CQ liposome due to the simultaneous delivery and synergetic effect of the two drugs. Consequently, this composite liposome achieved significantly stronger anticancer efficacy in vivo than the PTX liposome plus CQ liposome mixture. This study helps to guide and enlighten ongoing and future clinical trials about the optimal administration modes for drug combination therapy. PMID:26543365

  14. [Long-term intermittent renal replacement therapy at an intensive care unit].

    PubMed

    Bellomo, R; Baldwin, I; Toshio, N; Wan, L; Fealy, N; Ronco, C

    2005-01-01

    Standard intermittent hemodialysis (IHD) used for the treatment of acute renal failure (ARF) at an intensive care unit has significant biochemical and physiological drawbacks. In the past 20 years, these drawbacks have stimulated the development of continuous renal replacement therapy (CRRT) and its ever-increasing use. However, CRRT is technically complicated and requires 24-hour monitoring. In some clinics, the use of CRRT leads to that each patient is under his/her nurse's surveillance, instead 1 nurse per 2 patients as before; this change has economic consequences and may limit nursing accessibility to other patients. The procedures prolonging intermittent therapy do not require 24-hour monitoring may benefit the treatment of ARF at the intensive care therapy. In this paper the authors call such procedures for continuous intermittent renal replacement therapy. They are characterized by a number of basic principles: (1) the use of modified or standard dialysis apparatuses; (2) the application of diffuse, convection, or both; (3) a certain reduction in the rate of elimination of dissolved substances as compared with IHD; (4) more prolonged treatment: above usual 3 or 4 hours of IHD, but not more than 8-12 hours (hence the term "intermittent"); (5) the use of on-line generation dialysate or substituting fluid. Information on the effectiveness and safety of this procedure is being now compiled.

  15. Long-Term Effects of Brief Acceptance and Commitment Therapy for Psychosis

    ERIC Educational Resources Information Center

    Bach, Patricia; Hayes, Steven C.; Gallop, Robert

    2012-01-01

    A previous report explored the impact of a brief (four session) acceptance and commitment therapy (ACT) intervention as compared with treatment as usual (TAU) on rehospitalization over 4 months in a sample of 80 inpatients with psychosis. The present study extended the follow-up period to 1 year and used a more sophisticated survival analysis to…

  16. [Animal assisted therapy in a long-term care nursing home].

    PubMed

    Mudzyk, Agnés; Bourque, Monique; Guilbert, Héléne; Seguin, Anne Dahaba; Savoye, Marie-Jo

    2011-01-01

    Animal assisted therapy sessions have been set up at the Bellevaux nursing home in Besançon. The project has required a number of specific procedures and training courses to be put in place as well as the involvement of different departments. The sessions give real pleasure to the residents and produce interesting results.

  17. Long-Term Effects of Brief Acceptance and Commitment Therapy for Psychosis

    ERIC Educational Resources Information Center

    Bach, Patricia; Hayes, Steven C.; Gallop, Robert

    2012-01-01

    A previous report explored the impact of a brief (four session) acceptance and commitment therapy (ACT) intervention as compared with treatment as usual (TAU) on rehospitalization over 4 months in a sample of 80 inpatients with psychosis. The present study extended the follow-up period to 1 year and used a more sophisticated survival analysis to…

  18. A Comparison of Short- And Long-Term Family Therapy for Adolescent Anorexia Nervosa.

    ERIC Educational Resources Information Center

    Lock, James; Agras, W. Stewart; Bryson, Susan; Kraemer, Helena C.

    2005-01-01

    Objective: Research suggests that family treatment for adolescents with anorexia nervosa may be effective. This study was designed to determine the optimal length of such family therapy. Method: Eighty-six adolescents (12-18 years of age) diagnosed with anorexia nervosa were allocated at random to either a short-term (10 sessions over 6 months) or…

  19. A Comparison of Short- And Long-Term Family Therapy for Adolescent Anorexia Nervosa.

    ERIC Educational Resources Information Center

    Lock, James; Agras, W. Stewart; Bryson, Susan; Kraemer, Helena C.

    2005-01-01

    Objective: Research suggests that family treatment for adolescents with anorexia nervosa may be effective. This study was designed to determine the optimal length of such family therapy. Method: Eighty-six adolescents (12-18 years of age) diagnosed with anorexia nervosa were allocated at random to either a short-term (10 sessions over 6 months) or…

  20. [Effects of steroid therapy on long-term canal prognosis and activity in the daily life of vestibular neuronitis patients].

    PubMed

    Kitahara, T; Okumura, S; Takeda, N; Nishiike, S; Uno, A; Fukushima, M; Kubo, T

    2001-11-01

    We studied 28 patients with vestibular neuronitis treated at our hospital between 1997 and 1999. To determine the effects of steroid therapy on long-term canal prognosis and daily activity, we examined caloric tests and gave questionnaires to 12 steroid-treated and 16 nonsteroid-treated patients 2 years after onset. We found that canal improvement was 50% in the nonsteroid-treated group and 75% in the steroid-treated one. In cases with severe canal paresis (CP > or = 60%), canal improvement was 33% in the nonsteroid-treated group and 67% in the steroid-treated one. Steroid therapy at the acute stage of this disease significantly reduced the duration of spontaneous nystagmus and handicap in daily life due to dizziness induced by head and body movement, decreasing mood disturbance.

  1. Additional studies on side effects of melperone in long-term therapy for 1 to 15 years in psychiatric patients.

    PubMed

    Kirkegaard, A; Kirkegaard, G; Geismar, L; Christensen, I

    1981-01-01

    The present study which reports on the hitherto longest continuous melperone treatment recorded in the literature, was conducted in order to reveal side effects of long-term melperone therapy. 17 female and 20 male patients, aged 33-97 years, most of them with the diagnoses: schizophrenia (11 patients), dementia organica (11 patients) and dementia senilis (11 patients) were treated with melperone (Buronil) in doses of 15--800 mg/day for 1 to 15 years. The patients were examined for clinical side effects, abnormal electrocardiograms and ophthalmological diseases as well as abnormal values in sedimentation rate, hemoglobin, leucocytes, creatinine, alanine-aminotransferase, gamma-glutamyl-transferase and bilirubin. Also the thymol reaction was done. The electrocardiograms and laboratory investigations were controlled by specialists in internal medicine and the eye diseases by an ophthalmologist. We did not find any severe side effects which could be related with any certainty to melperone therapy.

  2. Bladder Function Preservation With Brachytherapy, External Beam Radiation Therapy, and Limited Surger in Bladder Cancer Patients: Long-Term Results

    SciTech Connect

    Aluwini, Shafak; Rooij, Peter H.E. van; Kirkels, Wim J.; Boormans, Joost L.; Kolkman-Deurloo, Inger-Karina K.; Wijnmaalen, Arendjan

    2014-03-01

    Purpose: To report long-term results of a bladder preservation strategy for muscle-invasive bladder cancer (MIBC) using external beam radiation therapy and brachytherapy/interstitial radiation therapy (IRT). Methods and Materials: Between May 1989 and October 2011, 192 selected patients with MIBC were treated with a combined regimen of preoperative external beam radiation therapy and subsequent surgical exploration with or without partial cystectomy and insertion of source carrier tubes for afterloading IRT using low dose rate and pulsed dose rate. Data for oncologic and functional outcomes were prospectively collected. The primary endpoints were local recurrence-free survival (LRFS), bladder function preservation survival, and salvage cystectomy-free survival. The endpoints were constructed according to the Kaplan-Meier method. Results: The mean follow-up period was 105.5 months. The LRFS rate was 80% and 73% at 5 and 10 years, respectively. Salvage cystectomy-free survival at 5 and 10 years was 93% and 85%. The 5- and 10-year overall survival rates were 65% and 46%, whereas cancer-specific survival at 5 and 10 years was 75% and 67%. The distant metastases-free survival rate was 76% and 69% at 5 and 10 years. Multivariate analysis revealed no independent predictors of LRFS. Radiation Therapy Oncology Group grade ≥3 late bladder and rectum toxicity were recorded in 11 patients (5.7%) and 2 patients (1%), respectively. Conclusions: A multimodality bladder-sparing regimen using IRT offers excellent long-term oncologic outcome in selected patients with MIBC. The late toxicity rate is low, and the majority of patients preserve their functional bladder.

  3. [Effect of long-term therapy with oral Beraprost on survival of patients with arterial and inoperable thromboembolic pulmonary hypertension].

    PubMed

    Kurzyna, Marcin; Florczyk, Michał; Fijałkowska, Anna; Kuca, Paweł; Szewczyk, Grzegorz; Burakowski, Janusz; Kober, Jarosław; Sikora, Jarosław; Wawrzyńska, Liliana; Szturmowicz, Monika; Tomkowskil, Witold; Torbicki, Adam

    2004-04-01

    Beraprost sodium (BPS)--an orally active prostacyclin analogue--improves haemodynamic parameters and quality of life in group of patients with pulmonary arterial hypertension. Effect of long-term therapy with BPS is not well defined. This study assesses influence of long-term therapy with BPS on the survival of patients with precapillary pulmonary hypertension. Studied group consisted of 25 patients with precapillary PH (18 F, 7M, aged 34 +/- 13,9 years). Sixteen patients were diagnosed with primary PH, 3 pts had PH associated with connective tissue disease, 5 pts developed PH in course of congenital systemic to pulmonary shunt, and 1 patient suffered from inoperable chronic thromboembolic PH. At time of diagnosis 15 pts presented exercise impairment of WHO class II and 10 pts were in functional class III. All studied subjects had complete hemodynamic assessment of right heart and obtained values were used for estimation of hypothetic survival using prognostic equation proposed by D'Alonzo et al. On follow-up period patients received BPS in the highest tolerated dose (80-480 mg daily). During a follow-up period (mean: 22 months) 7 patients died. Cumulative survival rate BPS group was significantly higher in BPS group comparing to hypothetical survival at 6 months (96% (95% CI: 88-104%) vs 73% (95% CI: 67-78%), p = 0.02) and 12 months (94% (95% CI: 84-104%) vs 65% (58-71%), p = 0.01), respectively. At 18 and 24 months differences between BPS virtual and hypothetical survival were not statistically significant. There was no correlation between survival and maximal achieved dose of BPS. These results suggest, that BPS improves prognosis of patients with precapillary PH during 12 months after initiation of therapy. Later effect of BPS seems to decrease, requiring changing or intensification of therapy.

  4. Rituximab therapy for chonic and refractory immune thrombocytopenic purpura: a long-term follow-up analysis

    PubMed Central

    Garcia-Chavez, Jaime; Montiel-Cervantes, Laura; Esparza, Miriam García-Ruiz; Vela-Ojeda, Jorge

    2007-01-01

    The aim of this study was to evaluate the long-term response to rituximab in patients with chronic and refractory immune thrombocytopenic purpura (ITP). Adults with ITP fail to respond to conventional therapies in almost 30% of cases, developing a refractory disease. Rituximab has been successfully used in these patients. We used rituximab at 375 mg/m2, IV, weekly for a total of four doses in 18 adult patients. Complete remission (CR) was considered if the platelet count was >100 × 109/l, partial remission (PR) if platelets were >50 × 109/l, minimal response (MR) if the platelet count was >30 × 109/l and <50 × 109/l, and no response if platelet count remained unchanged. Response was classified as sustained (SR) when it was stable for a minimum of 6 months. Median age was 43.5 years (range, 17 to 70). Median platelet count at baseline was 12.5 × 109/l (range, 3.0 to 26.3). CR was achieved in five patients (28%), PR in five (28%), MR in four (22%), and two patients were classified as therapeutic failures (11%). Two additional patients were lost to follow-up. The median time between rituximab therapy and response was 14 weeks (range, 4 to 32). SR was achieved in 12 patients (67%). There were no severe adverse events during rituximab therapy. During follow-up (median, 26 months; range, 12 to 59), no other immunosuppressive drugs were used. In conclusion, rituximab therapy is effective and safe in adult patients with chronic and refractory ITP. Overall response rate achieved is high, long term, and with no risk of adverse events. PMID:17874322

  5. Prospective controlled cohort studies on long-term therapy of ovairian cancer patients with mistletoe (Viscum album L.) extracts iscador.

    PubMed

    Grossarth-Maticek, Ronald; Ziegler, Renatus

    2007-01-01

    Mistletoe extracts such as Iscador are commonly used as complementary/anthroposophic medications for many cancer indications, particularly for solid cancers. The efficacy of this complementary therapy is still controversial. Does long-term therapy with mistletoe extracts Iscador show any effect on survival and psychosomatic self-regulation of patients with ovarian cancer? Prospective recruitment and long-term follow-up in controlled cohort studies. (1) Two randomized matched-pair studies: OvarRand (ovarian cancer patients without distant metastases; 21 pairs) and OvarMetRand (ovarian cancer patients with distant metastases; 20 pairs); patients having no mistletoe therapy were matched for prognostic factors. By paired random allocation, one of the patients of each pair was suggested therapy with mistletoe extracts Iscador to be applied by her attending physician. (2) Two non-randomized matched-pair studies: Ovar (ovarian cancer patients without distant metastases; 75 pairs) and OvarRand (ovarian cancer patients with distant metastases; 62 pairs); patients that already received therapy with mistletoe extracts Iscador were matched by the same criteria to control patients without therapy with mistletoe extracts Iscador. For overall survival in the randomized studies, the effect in favor of therapy with mistletoe extracts Iscador was significant in OvarMetRand but not in OvarRand; hazard ratio estimate and 95% confidence interval: 0.40 (0.15, 1.03) and 0.33 (0.12, 0.92), respectively. In the non-randomized studies Ovar and OvarMet, the results adjusted for relevant prognostic variables were 0.47 (0.31, 0.69) and 0.62 (0.37, 1.05). Psychosomatic self-regulation in the Iscador group increases significantly within 12 months on a scale from 1 to 6 compared with the control group in the randomized study OvarRand as well as in the non-randomized study Ovar on patients with ovarian cancer without distant metastases; estimate of the median difference and 95% confidence interval

  6. Long-term risks of psoralen and UV-A therapy for psoriasis

    SciTech Connect

    Farber, E.M.; Abel, E.A.; Cox, A.J.

    1983-05-01

    It has been more than eight years since photochemotherapy with methoxsalen and UV-A (psoralen and UV-A (PUVA)) was introduced for the treatment of psoriasis. This treatment remained under investigation until May 1982 because of concerns about possible chronic toxic effects. With recent Food and Drug Administration approval of PUVA therapy for severe psoriasis, strict drug labeling for administration and patient use and continued monitoring of side effects have become essential. The full effects of PUVA in regard to carcinogenicity, prematurelly induced aging of the skin, pigmentary changes, immunologic alterations, and ocular side effects are still unknown. A review of the risks of PUVA therapy is presented, with the aim of maintaining a proper perspective for its limited use in treating selected patients.

  7. Remission of type 2 diabetes in a hypogonadal man under long-term testosterone therapy.

    PubMed

    Haider, Ahmad; Haider, Karim S; Saad, Farid

    2017-01-01

    In daily practice, clinicians are often confronted with obese type 2 diabetes mellitus (T2DM) patients for whom the treatment plan fails and who show an inadequate glycemic control and/or no sustainable weight loss. Untreated hypogonadism can be the reason for such treatment failure. This case describes the profound impact testosterone therapy can have on a male hypogonadal patient with metabolic syndrome, resulting in a substantial and sustained loss of body weight, pronounced improvement of all critical laboratory values and finally complete remission of diabetes. Hypogonadism occurs frequently in men with T2DM.In case of pronounced abdominal fat deposition and T2DM, the male patient should be evaluated for testosterone deficiency.Untreated hypogonadism can complicate the successful treatment of patients with T2DM.Under testosterone therapy, critical laboratory values are facilitated to return back to normal ranges and even complete remission of diabetes can be achieved.

  8. Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties.

    PubMed

    Ma, Shaocheng; Goh, En Lin; Jin, Andi; Bhattacharya, Rajarshi; Boughton, Oliver R; Patel, Bhavi; Karunaratne, Angelo; Vo, Nghia T; Atwood, Robert; Cobb, Justin P; Hansen, Ulrich; Abel, Richard L

    2017-03-06

    Osteoporosis is characterised by trabecular bone loss resulting from increased osteoclast activation and unbalanced coupling between resorption and formation, which induces a thinning of trabeculae and trabecular perforations. Bisphosphonates are the frontline therapy for osteoporosis, which act by reducing bone remodelling, and are thought to prevent perforations and maintain microstructure. However, bisphosphonates may oversuppress remodelling resulting in accumulation of microcracks. This paper aims to investigate the effect of bisphosphonate treatment on microstructure and mechanical strength. Assessment of microdamage within the trabecular bone core was performed using synchrotron X-ray micro-CT linked to image analysis software. Bone from bisphosphonate-treated fracture patients exhibited fewer perforations but more numerous and larger microcracks than both fracture and non-fracture controls. Furthermore, bisphosphonate-treated bone demonstrated reduced tensile strength and Young's Modulus. These findings suggest that bisphosphonate therapy is effective at reducing perforations but may also cause microcrack accumulation, leading to a loss of microstructural integrity and consequently, reduced mechanical strength.

  9. [Interstitial lung diseases caused by long-term neurological-psychiatric drug therapy?].

    PubMed

    Liebetrau, G; Pielesch, W

    1991-03-01

    The development of alveolitis or lung fibrosis through drugs is wellknown, however rare described in the spectrum of drug side effects. In six cases of patients with neurological diseases were studied the relationship between alveolitis or lung fibrosis and a long-time therapy with especially drugs in a neurological practice. By the etiological examination of alveolitis or lung fibrosis it is necessary to pay attention to the possible relationship between drug and disease.

  10. Repair of atrial septal defect with Eisenmenger syndrome after long-term sildenafil therapy.

    PubMed

    Kim, Young-Hwue; Yu, Jeong Jin; Yun, Tae-Jin; Lee, Yonghee; Kim, Yong Beom; Choi, Hyung Soon; Jhang, Won Kyoung; Shin, Hong Ju; Park, Jeong-Jun; Seo, Dong-Man; Ko, Jae-Kon; Park, In-Sook

    2010-05-01

    We report a woman with atrial septal defect and severe pulmonary hypertension with 25.0 Wood unit.m(2) of indexed total pulmonary vascular resistance. She underwent successful corrective repair of atrial septal defect after 2 years of treatment with sildenafil, and has been monitored for 4 years after repair. This case supports a "treat and repair" approach using advanced pulmonary vasodilator therapy in selected patients with inoperable severe pulmonary hypertension associated with atrial septal defect.

  11. 101 Long-Term Survivors Who Had Metastatic Gastroesophageal Cancer and Received Local Consolidative Therapy.

    PubMed

    Mizrak Kaya, Dilsa; Wang, Xuemei; Harada, Kazuto; Blum Murphy, Mariela A; Das, Prajnan; Minsky, Bruce D; Estrella, Jeannelyn S; Lin, Quan; Amlashi, Fatemeh G; Lee, Jeffrey H; Weston, Brian; Bhutani, Manoop S; Matamoros, Aurelio; Sagebiel, Tara; Wu, Carol C; Rogers, Jane E; Thomas, Irene; Maru, Dipen M; Skinner, Heath D; Badgwell, Brian D; Hofstetter, Wayne L; Ajani, Jaffer A

    2017-01-01

    Through a multidisciplinary decision-making process, we developed a strategy of systemic therapy followed by local consolidative therapy (chemoradiation with/without surgery) in selected patients with metastatic gastroesophageal carcinoma (mGEAC). Only after a consensus during multidisciplinary discussions, local therapy was initiated. We identified 101 patients with mGEAC who had local consolidation. We evaluated the association between various clinical variables (location of the primary, location of metastases, duration of initial chemotherapy, histologic grade, and radiation dose) and overall survival (OS). Of 101 patients, 71 had a proximal primary (esophageal, Siewert type I or II), and 30 patients had a distal primary (Siewert type III or distal). The median OS was 25.7 months (95% confidence interval [CI] 22.3-32.8). The OS rates at 2 and 5 years were 53.8% (95% CI 44.7-64.8) and 20.7% (95% CI 13.4-31.9), respectively. OS was highly associated with the location of the primary (median of 22.8 months for Siewert I/II vs. 41.5 months for Siewert III or distal, p = 0.03). The duration of initial chemotherapy was highly associated with OS (median of 21.8 months for <3 months vs. 32.5 months for ≥3 months, p = 0.004). Some mGEAC patients with a favorable clinical course can achieve a ∼20% 5-year survival rate with an approach that uses initial chemotherapy followed by multidisciplinary discussion to proceed with consolidation with local therapy. Patients with distal GEAC and those who receive initial chemotherapy for ≥3 months are the maximum beneficiaries. © 2017 S. Karger AG, Basel.

  12. Long-term therapy of chronic bacterial prostatitis with trimethoprim-sulfamethoxazole.

    PubMed Central

    Meares, E. M.

    1975-01-01

    Trimethoprim (TMP) meets all of the theoretical requirements of diffusion into, and actual concentration in, human prostatic fluid. When TMP is combined with the sulfonamide sulfamethoxazole (SMX), potentiation of antibacterial activity is achieved and the development of resistant bacterial strains is less likely to occur. In our initial use of TMP-SMX in the treatment of 13 men with chronic bacterial prostatitis due to gram-negative organisms, patients were given two tablets of TMP-SMX twice daily for only 14 days. The results were that two patients (15%) were cured, nine patients (70%) were improved (sterile prostatic fluid during therapy) but eventually relapsed, and two patients (15%) were unchanged by therapy. In our present study 19 patients (31.6%) were totally cured and 9 of 23 (39.1%) gram-negative organisms were permanently cleared from prostatic fluid; 8 of the 9 patients (42.1%) were improved but eventually relapsed with the same organism; 5 of the 19 patients (26.3%) were considered unchanged by therapy. PMID:236820

  13. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy

    PubMed Central

    Hazell, Gareth; Shabanpoor, Fazel; Saleh, Amer F.; Bowerman, Melissa; Meijboom, Katharina E.; Zhou, Haiyan; Muntoni, Francesco; Talbot, Kevin; Gait, Michael J.; Wood, Matthew J. A.

    2016-01-01

    The development of antisense oligonucleotide therapy is an important advance in the identification of corrective therapy for neuromuscular diseases, such as spinal muscular atrophy (SMA). Because of difficulties of delivering single-stranded oligonucleotides to the CNS, current approaches have been restricted to using invasive intrathecal single-stranded oligonucleotide delivery. Here, we report an advanced peptide-oligonucleotide, Pip6a-morpholino phosphorodiamidate oligomer (PMO), which demonstrates potent efficacy in both the CNS and peripheral tissues in severe SMA mice following systemic administration. SMA results from reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein because of loss-of-function mutations in the SMN1 gene. Therapeutic splice-switching oligonucleotides (SSOs) modulate exon 7 splicing of the nearly identical SMN2 gene to generate functional SMN protein. Pip6a-PMO yields SMN expression at high efficiency in peripheral and CNS tissues, resulting in profound phenotypic correction at doses an order-of-magnitude lower than required by standard naked SSOs. Survival is dramatically extended from 12 d to a mean of 456 d, with improvement in neuromuscular junction morphology, down-regulation of transcripts related to programmed cell death in the spinal cord, and normalization of circulating insulin-like growth factor 1. The potent systemic efficacy of Pip6a-PMO, targeting both peripheral as well as CNS tissues, demonstrates the high clinical potential of peptide-PMO therapy for SMA. PMID:27621445

  14. [Long-term effects of combined therapy in patients with beta-thalassemia major].

    PubMed

    Bagnulo, S; Giannini, A M; Moscatelli, F; Stragapede, L; Acquafredda, A; Dammacco, A

    1998-01-01

    We evaluated therapy complications in 19 beta-thalassemia major patients (mean age from 3 years/5 months and 1 years/6 months) who were followed at II Pediatric Department-University of Bari. 3 out of 19 patients underwent allogenic BMT from matched related donor; 2 out of 19 underwent splenectomy. All of them were receiving hypertransfusion therapy and continuous chelation with DFO. In all patients we performed physical examination, laboratory assays, cardiac and endocrinologic function tests, serum HBV-HCV-HIV antibodies, otoscopy and audiometric test, fundus oculi, skeletal x-ray. 1 out of 19 patients, who was under 15, had a slight dilatation of left ventricle and arythmia. All patients were HBsAb positive. 4/19 patients were HCV Ab positive (ELISA test) with an increase in ALT-AST serum levels since at least 6 months. In 3 of them we assessed RIBA test, always positive. 3 of them underwent liver biopsy (1 iron overload 2 chronic active hepatitis). All patients were HIV Ab negative. 4/15 patients revealed low GH levels after Arginina test. 13 pre-pubescent patients had normal results with GNRH test but lower results after FSH test. 1 pubescent patient had gonadotropic hypophyseal deficit. 4 patients had subclinic hypothiroidism. We couldn't find any sequelas in bone-eyes-ears. Hypertransfusion therapy, chelation, profilaxis of infections improved length and quality of life in thalassemic patients. Hypogonadotropic hypogonadism remains a serious sequela and we think it needs to be treated.

  15. LONG-TERM MECHANICAL CIRCULATORY SUPPORT (DESTINATION THERAPY): ON TRACK TO COMPETE WITH HEART TRANSPLANTATIO?

    PubMed Central

    Kirklin, James K.; Naftel, David C.; Pagani, Francis D.; Kormos, Robert L.; Stevenson, Lynne; Miller, Marissa; Young, James B.

    2012-01-01

    Objective(s) Average two-year survival following cardiac transplantation is approximately 80%. The evolution and subsequent approval of larger pulsatile and, more recently, continuous flow mechanical circulatory support (MCS) technology for destination therapy (DT) offers the potential for triage of some patients awaiting cardiac transplantation to DT. Methods The National Heart, Lung and Blood Institute Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a national multi-institutional study of chronic mechanical circulatory support. Between June 2006 and December 2011, 127 pulsatile and 1160 continuous flow pumps (24% of total primary LVADs) carried an initial strategy of DT therapy. Results By multivariable analysis, risk factors (p<0.05) for mortality following DT included older age, larger body mass index, history of cancer, history of cardiac surgery, INTERMACS level I (cardiogenic shock), dialysis, increased BUN, use of a pulsatile flow device and use of a RVAD. Among continuous flow LVAD patients who were not in cardiogenic shock, a particularly favorable survival was associated with no cancer, patients not in cardiogenic shock, and BUN < 50, resulting in one and two year survival of 88 and 80%. Conclusions 1) Evolution from pulsatile to continuous flow technology has dramatically improved one and two year survival; 2) Destination Therapy is not appropriate for patients with rapid hemodynamic deterioration; or severe right ventricular failure 4) Important subsets of continuous flow DT patients now enjoy survival which is competitive with heart transplantation out to about two years. PMID:22795459

  16. Long-Term Persistence with Injectable Therapy in Relapsing-Remitting Multiple Sclerosis: An 18-Year Observational Cohort Study

    PubMed Central

    Zhornitsky, Simon; Greenfield, Jamie; Koch, Marcus W.; Patten, Scott B.; Harris, Colleen; Wall, Winona; Alikhani, Katayoun; Burton, Jodie; Busche, Kevin; Costello, Fiona; Davenport, Jeptha W.; Jarvis, Scott E.; Lavarato, Dina; Parpal, Helene; Patry, David G.; Yeung, Michael; Metz, Luanne M.

    2015-01-01

    Disease modifying therapies (DMTs) reduce the frequency of relapses and accumulation of disability in multiple sclerosis (MS). Long-term persistence with treatment is important to optimize treatment benefit. This long-term, cohort study was conducted at the Calgary MS Clinic. All consenting adults with relapsing-remitting MS who started either glatiramer acetate (GA) or interferon-β 1a/1b (IFN-β) between January 1st, 1996 and July 1st, 2011 were included. Follow-up continued to February 1st, 2014. Time-to-discontinuation of the initial and subsequently-prescribed DMTs (switches) was analysed using Kaplan-Meier survival analyses. Group differences were compared using log-rank tests and multivariable Cox regression models. Analysis included 1471 participants; 906 were initially prescribed GA and 565 were initially prescribed IFN-β. Follow-up information was available for 87%; 29 (2%) were lost to follow-up and 160 (11%) moved from Southern Alberta while still using DMT. Median time-to-discontinuation of all injectable DMTs was 11.1 years. Participants with greater disability at treatment initiation, those who started treatment before age 30, and those who started between 2006 and 2011 were more likely to discontinue use of all injectable DMTs. Median time-to-discontinuation of the initial DMT was 8.6 years. Those initially prescribed GA remained on treatment longer. Of 610 participants who discontinued injectable DMT, 331 (54%) started an oral DMT, or a second-line DMT, or resumed injectable DMT after 90 days. Persistence with injectable DMTs was high in this long-term population-based study. Most participants who discontinued injectable DMT did not remain untreated. Further research is required to understand treatment outcomes and outcomes after stopping DMT. PMID:25867095

  17. Assessment of bone microarchitecture in postmenopausal women on long-term bisphosphonate therapy with atypical fractures of the femur.

    PubMed

    Zanchetta, Maria Belen; Diehl, Maria; Buttazzoni, Mirena; Galich, Ana; Silveira, Fernando; Bogado, Cesar E; Zanchetta, Jose Rubén

    2014-04-01

    Reports of atypical femoral fractures (AFFs) in patients receiving long- term bisphosphonate therapy have raised concerns regarding the genesis of this rare event. Using high-resolution peripheral quantitative computed tomography (HR-pQCT), we conducted a study to evaluate bone microarchitecture in patients who had suffered an AFF during long-term bisphosphonate treatment. The aim of our study was to evaluate if bone microarchitecture assessment could help explain the pathophysiology of these fractures. We compared bone volumetric density and microarchitectural parameters measured by HR-pQCT in the radius and tibia in 20 patients with AFFs with 35 postmenopausal women who had also received long-term bisphosphonate treatment but had not experienced AFFs, and with 54 treatment-naive postmenopausal women. Control groups were similar in age, body mass index (BMI), and bone mineral density (BMD). Mean age of the 20 patients with AFFs was 71 years, mean lumbar spine T-score was -2.2, and mean femoral neck T-score was -2. Mean time on bisphosphonate treatment was 10.9 years (range, 5-20 years). None of the patients had other conditions associated with AFFs such as rheumatoid arthritis, diabetes or glucocorticoid use. There were no statistically significant differences in any of the parameters measured by HR-pQCT between postmenopausal women with or without treatment history and with or without history of atypical fractures. We could not find any distinctive microarchitecture features in the peripheral skeleton of women who had suffered an atypical fracture of the femur while receiving bisphosphonate treatment. This suggests that risk of developing an atypical fracture is not related to bone microarchitecture deterioration. Our results indicate that there may be other individual factors predisposing to atypical fractures in patients treated with bisphosphonates, and that those are independent of bone microarchitecture. In the future, identification of those factors could

  18. Echocardiographic Predictors of Long-Term Survival in Patients Undergoing Cardiac Resynchronization Therapy: What Is the Optimal Metric?

    PubMed

    Rickard, John; Baranowski, Bryan; Wilson Tang, W H; Grimm, Richard A; Niebauer, Mark; Cantillion, Daniel; Wilkoff, Bruce L; Varma, Niraj

    2017-04-01

    Multiple definitions of reverse ventricular remodeling (RVR) employing various changes in left ventricular end-systolic (LVESV) or diastolic volumes (LVEDVs) or left ventricular ejection fraction (LVEF) have been used in determining cardiac resynchronization therapy (CRT) response, making comparability across studies difficult. We compared different metrics to each other, and in combination, in terms of association with long-term outcomes. We collected clinical and echocardiographic data on 436 patients undergoing CRT. LVEF was assessed via a combined volumetric and visual assessment. Volumes were manually traced. Using a nested multivariate model of a priori determined predictors of long-term survival free of left ventricular assist device (LVAD) or heart transplant, multiple definitions of RVR were added to the model individually to determine which provided the best model fit. Over a mean follow-up of 5.4 ± 2.3 years, there were 198 endpoints (10 LVADs, 15 heart transplants, and 173 deaths). When added to a nested model controlling for multiple potential confounders, all definitions of RVR were significantly associated with improved survival. Changes in LVEF and LVESV were superior to changes in LVEDV. A combination metric of an LVEF improvement ≥ 5% and LVESV reduction ≥ 10% was the best overall metric for model fit. Changes in LVESV and LVEF are better predictors of long-term outcome following CRT compared to changes in LVEDV. Adding an assessment of LVEF to reduction in LVESV ≥ 10% provided the best overall definition for RVR in predicting CRT outcomes. © 2017 Wiley Periodicals, Inc.

  19. Paucity of Intact Non-Induced Provirus with Early, Long-Term Antiretroviral Therapy of Perinatal HIV Infection

    PubMed Central

    Watson, Douglas; Luzuriaga, Katherine; Siberry, George; Petru, Ann; Chen, YaHui; Uprety, Priyanka; Ho, Ya-Chi; Persaud, Deborah

    2017-01-01

    The latent reservoir is a major barrier to HIV eradication. Reservoir size is emerging as an important biomarker to assess the likelihood of HIV remission in the absence of antiretroviral therapy (ART) and may be reduced by earlier initiation of ART that restricts HIV spread into CD4+ T cells. Reservoir size is traditionally measured with a quantitative viral outgrowth assay (QVOA) that induces replication-competent HIV production through in vitro stimulation of resting CD4+ T cells. However, the recent identification of replication-intact, non-induced proviral genomes (NIPG) suggests the QVOA significantly underestimates (by 62-fold) latent reservoir size in chronically-infected adults. Whether formation and persistence of Intact, NIPG is thwarted by early ART initiation and long-term virologic suppression in perinatal infection is unclear. Here, we show that the latent reservoir in 11 early treated, long-term suppressed perinatally infected children and adolescents was not inducible by QVOA and dominated by defective, NIPG. Single genome analysis of 164 NIPG from 232 million cultured resting CD4+ T cells revealed no replication-intact, near-full length sequences. Forty-three (26%) NIPG contained APOBEC3G-mediated hypermutation, 115 (70%) NIPG contained large internal deletions, one NIPG contained nonsense mutations and indels, and 5 (3%) NIPG were assigned as “Not Evaluable” due to multiple failed sequencing attempts that precluded further classification. The lack of replication competent inducible provirus and intact NIPG in this cohort indicate early, long-term ART of perinatal infection leads to marked diminution of replication-competent HIV-1 reservoirs, creating a favorable state towards interventions aimed at virologic remission. PMID:28178277

  20. Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys.

    PubMed

    Olson, Erik J; Lindgren, Bruce R; Carlson, Cathy S

    2008-05-01

    The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but

  1. Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer.

    PubMed

    Cerne, Jasmina Ziva; Novakovic, Srdjan; Frkovic-Grazio, Snjezana; Pohar-Perme, Maja; Stegel, Vida; Gersak, Ksenija

    2011-08-01

    Association between long-term hormone replacement therapy (HRT) use and increased risk of breast cancer is still under debate. Functionally relevant genetic variants within the estrogen metabolic pathway may alter exposure to exogenous sex hormones and affect the risk of postmenopausal breast cancer. We investigated the associations of common polymorphisms in 4 genes encoding key proteins of the estrogen metabolic pathway, duration of HRT use and their interactions with breast cancer risk. We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Duration of HRT use was ascertained through a postal questionnaire. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695) and MnSOD (rs4880) polymorphisms by PCR-based RFLP and TaqMan® allelic discrimination method. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression analysis. HRT use was significantly associated with decreased breast cancer risk (p<0.001). None of the polymorphisms studied was associated with breast cancer risk. A significant interaction was observed between MnSOD 47T>C and HRT use (pinteraction=0.036); the risk of breast cancer associated with long-term vs. short-term HRT use was decreased in women homozygous for the wild-type allele and increased in women with at least one variant allele of the MnSOD 47T>C polymorphism. Our results suggest that MnSOD 47T>C polymorphism in interaction with long-term HRT use may modify the risk of breast cancer.

  2. Functional response to cardiac resynchronization therapy in patients with renal dysfunction and subsequent long-term mortality.

    PubMed

    Bogdan, Stefan; Klempfner, Robert; Sabbag, Avi; Luria, David; Gurevitz, Osnat; Bar-Lev, David; Lipchenca, Igor; Nof, Eyal; Kuperstein, Rafael; Goldenberg, Ilan; Eldar, Michael; Glikson, Michael; Beinart, Roy

    2014-11-01

    Renal dysfunction is associated with increased morbi-mortality in heart failure patients. Data regarding functional and clinical efficacy of cardiac resynchronization therapy (CRT) in this population are limited. We aimed to evaluate the rate of functional response to CRT in patients with renal dysfunction and its association with long-term mortality. Our study included a total of 179 consecutive patients implanted between 2007 and 2010. The rate of functional response to CRT (defined by a composite score using New York Heart Association functional class, 6-minute walk test, and quality of life) was compared between patients with and without renal dysfunction (defined as eGFR < or ≥60 mL/min/1.73 m(2) ). Survival analysis estimates were constructed according to the Kaplan-Meier method, with results comparison using the log-rank test. During a median follow-up of 4.2 years, 73 patients (40%) died. Patients with low eGFR were older (72 ± 8 years vs. 64 ± 12 years; P < 0.001), and had higher prevalence of ischemic heart disease (75% vs. 53%; P = 0.003). Functional response rates did not differ significantly between patients with and without renal dysfunction (58% and 69%, respectively; P = 0.14). Despite overall higher mortality in patients with low eGFR (53.8% vs. 22.7%; P < 0.001), the presence of functional response at 1 year among patients with renal dysfunction was still independently associated with an improved long-term survival (HR = 0.49 [95%CI: 0.28-0.83]; P = 0.009). Functional response to CRT at 1 year does not differ significantly between patients with or without kidney disease, and is an independent predictor of improved long-term survival in patients with renal dysfunction. © 2014 Wiley Periodicals, Inc.

  3. Paucity of Intact Non-Induced Provirus with Early, Long-Term Antiretroviral Therapy of Perinatal HIV Infection.

    PubMed

    Rainwater-Lovett, Kaitlin; Ziemniak, Carrie; Watson, Douglas; Luzuriaga, Katherine; Siberry, George; Petru, Ann; Chen, YaHui; Uprety, Priyanka; McManus, Margaret; Ho, Ya-Chi; Lamers, Susanna L; Persaud, Deborah

    2017-01-01

    The latent reservoir is a major barrier to HIV eradication. Reservoir size is emerging as an important biomarker to assess the likelihood of HIV remission in the absence of antiretroviral therapy (ART) and may be reduced by earlier initiation of ART that restricts HIV spread into CD4+ T cells. Reservoir size is traditionally measured with a quantitative viral outgrowth assay (QVOA) that induces replication-competent HIV production through in vitro stimulation of resting CD4+ T cells. However, the recent identification of replication-intact, non-induced proviral genomes (NIPG) suggests the QVOA significantly underestimates (by 62-fold) latent reservoir size in chronically-infected adults. Whether formation and persistence of Intact, NIPG is thwarted by early ART initiation and long-term virologic suppression in perinatal infection is unclear. Here, we show that the latent reservoir in 11 early treated, long-term suppressed perinatally infected children and adolescents was not inducible by QVOA and dominated by defective, NIPG. Single genome analysis of 164 NIPG from 232 million cultured resting CD4+ T cells revealed no replication-intact, near-full length sequences. Forty-three (26%) NIPG contained APOBEC3G-mediated hypermutation, 115 (70%) NIPG contained large internal deletions, one NIPG contained nonsense mutations and indels, and 5 (3%) NIPG were assigned as "Not Evaluable" due to multiple failed sequencing attempts that precluded further classification. The lack of replication competent inducible provirus and intact NIPG in this cohort indicate early, long-term ART of perinatal infection leads to marked diminution of replication-competent HIV-1 reservoirs, creating a favorable state towards interventions aimed at virologic remission.

  4. Long-term persistence with injectable therapy in relapsing-remitting multiple sclerosis: an 18-year observational cohort study.

    PubMed

    Zhornitsky, Simon; Greenfield, Jamie; Koch, Marcus W; Patten, Scott B; Harris, Colleen; Wall, Winona; Alikhani, Katayoun; Burton, Jodie; Busche, Kevin; Costello, Fiona; Davenport, Jeptha W; Jarvis, Scott E; Lavarato, Dina; Parpal, Helene; Patry, David G; Yeung, Michael; Metz, Luanne M

    2015-01-01

    Disease modifying therapies (DMTs) reduce the frequency of relapses and accumulation of disability in multiple sclerosis (MS). Long-term persistence with treatment is important to optimize treatment benefit. This long-term, cohort study was conducted at the Calgary MS Clinic. All consenting adults with relapsing-remitting MS who started either glatiramer acetate (GA) or interferon-β 1a/1b (IFN-β) between January 1st, 1996 and July 1st, 2011 were included. Follow-up continued to February 1st, 2014. Time-to-discontinuation of the initial and subsequently-prescribed DMTs (switches) was analysed using Kaplan-Meier survival analyses. Group differences were compared using log-rank tests and multivariable Cox regression models. Analysis included 1471 participants; 906 were initially prescribed GA and 565 were initially prescribed IFN-β. Follow-up information was available for 87%; 29 (2%) were lost to follow-up and 160 (11%) moved from Southern Alberta while still using DMT. Median time-to-discontinuation of all injectable DMTs was 11.1 years. Participants with greater disability at treatment initiation, those who started treatment before age 30, and those who started between 2006 and 2011 were more likely to discontinue use of all injectable DMTs. Median time-to-discontinuation of the initial DMT was 8.6 years. Those initially prescribed GA remained on treatment longer. Of 610 participants who discontinued injectable DMT, 331 (54%) started an oral DMT, or a second-line DMT, or resumed injectable DMT after 90 days. Persistence with injectable DMTs was high in this long-term population-based study. Most participants who discontinued injectable DMT did not remain untreated. Further research is required to understand treatment outcomes and outcomes after stopping DMT.

  5. Long-Term Fosfomycin-Tromethamine Oral Therapy for Difficult-To-Treat Chronic Bacterial Prostatitis

    PubMed Central

    Pigrau, Carles; Rodríguez-Pardo, Dolors; Fernández-Hidalgo, Nuria; Andreu, Antonia; Larrosa, Nieves; Almirante, Benito

    2015-01-01

    This is a retrospective study of 15 difficult-to-treat (i.e., exhibiting previous failure, patient side effects, or resistance to ciprofloxacin and co-trimoxazole) chronic bacterial prostatitis infections (5 patients with multidrug-resistant Enterobacteriaceae [MDRE]) receiving fosfomycin-tromethamine at a dose of 3 g per 48 to 72 h for 6 weeks. After a median follow-up of 20 months, 7 patients (47%) had a clinical response, and 8 patients (53%) had persistent microbiological eradication; 4/5 patients with MDRE isolates achieved eradication. There were no side effects. Fosfomycin-tromethamine is a possible alternative therapy for chronic bacterial prostatitis. PMID:26666924

  6. Long-Term Chinese Herbs Decoction Administration for Management of Hot Flashes Associated with Endocrine Therapy in Breast Cancer Patients

    PubMed Central

    Xue, Dong; Sun, Hong; Li, Ping-ping

    2011-01-01

    Objective To evaluate the effect of Chinese herbs decoction Shu-Gan-Liang-Xue on endocrine therapy- associated hot flashes symptom in breast cancer patients. Methods Sixty-six patients with breast cancer receiving adjuvant endocrine therapy were categorized to two groups, the control group received endocrine therapy alone, the other group is administered with Chinese herbs decoction Shu-Gan-Liang-Xue besides the endocrine therapy: Shu-Gan-Liang-Xue decoction was administered above 6 months per year for more than 2 years. Frequency of hot flashes per day was recorded, and the effect of Shu-Gan-Liang-Xue decoction on hot flashes symptom being assessed with Kupperman Scoring Index. Results Sixty cases were analyzed, 32 cases in endocrine therapy combining Chinese herbs decoction group, 28 cases in mere endocrine therapy group. For hot flashes symptom, in Chinese herbs decoction administration group, 7 cases (21.9%) reported symptom disappeared, 22 cases (68.7%) reported symptom alleviated, 3 cases (9.4%) reported symptom not changed; in endocrine therapy alone group, 5 cases (17.9%) reported symptom disappeared, 13 cases (46.4%) reported symptom alleviated, 10 cases (10/28, 35.7%) reported symptom not changed. The difference between two groups was statistically significant (P=0.013). For sleeping disorder, in Chinese herbs decoction administration group, 27 cases (84.4%) reported symptom improved, 5 cases (15.6%) reported no change; in endocrine therapy alone group, 16 cases (57.1%) symptom improved, 12 cases (42.9%) reported no change in sleeping disorder (P=0.019), the difference was also of significance statistically. Conclusion Long-term Chinese herbs decoction administration remarkably improved hot flashes symptom and sleeping disorder associated with endocrine therapy, meanwhile without definite toxicity and influence on the risk of recurrence of tumor. PMID:23467638

  7. Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy

    PubMed Central

    Le Guiner, Caroline; Servais, Laurent; Montus, Marie; Larcher, Thibaut; Fraysse, Bodvaël; Moullec, Sophie; Allais, Marine; François, Virginie; Dutilleul, Maeva; Malerba, Alberto; Koo, Taeyoung; Thibaut, Jean-Laurent; Matot, Béatrice; Devaux, Marie; Le Duff, Johanne; Deschamps, Jack-Yves; Barthelemy, Inès; Blot, Stéphane; Testault, Isabelle; Wahbi, Karim; Ederhy, Stéphane; Martin, Samia; Veron, Philippe; Georger, Christophe; Athanasopoulos, Takis; Masurier, Carole; Mingozzi, Federico; Carlier, Pierre; Gjata, Bernard; Hogrel, Jean-Yves; Adjali, Oumeya; Mavilio, Fulvio; Voit, Thomas; Moullier, Philippe; Dickson, George

    2017-01-01

    Duchenne muscular dystrophy (DMD) is an incurable X-linked muscle-wasting disease caused by mutations in the dystrophin gene. Gene therapy using highly functional microdystrophin genes and recombinant adeno-associated virus (rAAV) vectors is an attractive strategy to treat DMD. Here we show that locoregional and systemic delivery of a rAAV2/8 vector expressing a canine microdystrophin (cMD1) is effective in restoring dystrophin expression and stabilizing clinical symptoms in studies performed on a total of 12 treated golden retriever muscular dystrophy (GRMD) dogs. Locoregional delivery induces high levels of microdystrophin expression in limb musculature and significant amelioration of histological and functional parameters. Systemic intravenous administration without immunosuppression results in significant and sustained levels of microdystrophin in skeletal muscles and reduces dystrophic symptoms for over 2 years. No toxicity or adverse immune consequences of vector administration are observed. These studies indicate safety and efficacy of systemic rAAV-cMD1 delivery in a large animal model of DMD, and pave the way towards clinical trials of rAAV–microdystrophin gene therapy in DMD patients. PMID:28742067

  8. Tamoxifen as the First Targeted Long Term Adjuvant Therapy for Breast Cancer

    PubMed Central

    Jordan, V. Craig

    2014-01-01

    Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine has continued to surprise us, perform and save lives for the past 40 years. Unlike any other medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinoma in situ, male breast cancer, pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that “longer was going to be better” when tamoxifen was being considered as an adjuvant therapy (Jordan 1978 Use of the DMBA-induced rat mammary carcinoma system for the evaluation of tamoxifen as a potential adjuvant therapy Reviews in Endocrine Related Cancer. October Supplement: 49–55.). This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation with Nature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society. “Science is adventure, discovery, new horizons, insight into our world, a means of predicting the future and enormous power to help others”(Hoagland 1990).- Mahlon Hoagland, MD. Director, Worcester Foundation for Experimental Biology (1970–85) PMID:24659478

  9. Acute and long-term effects of radioiodine therapy on serum levels of calcitonin

    SciTech Connect

    Franke, A.; Oeff, K.

    1984-01-01

    The purpose of this study is to establish data on the radiosensitivity of thyroid C cells and medullary carcinoma of the thyroid (MCT) as reflected by the alterations in serum concentrations of calcitonin (Ct) after radioiodine therapy. Serum levels of Ct were measured by radioimmunoassay in 1437 patients subjected to diagnostic and therapeutic procedures for thyroid diseases. The effect of low dose and of high dose radioiodine therapy (RLO, RHI) was studied in 158 patients with hyperthyroidism and in 84 patients with thyroid cancer, respectively. RLO and RHI were followed by significant alterations in the distribution of Ct values. RLO decreased the occurrence of high values. RHI was followed by the absence of high concentrations and a substantial reduction in normal levels. The effect of RLO was confirmed in 47 patients by comparing their individual levels before and 8 weeks after RLO, the means +- SD being 24.3+-8.3 and 12.6+-5.7 pmol/l, respectively (p<0.001). In 30 patients followed up for late onset hypothyroidism who had been treated by RLO 10-25 years ago, the concentrations of Ct were almost normal (mean +- SD 16.6 +- 5.7 pmol/l).

  10. Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties

    PubMed Central

    Ma, Shaocheng; Goh, En Lin; Jin, Andi; Bhattacharya, Rajarshi; Boughton, Oliver R.; Patel, Bhavi; Karunaratne, Angelo; Vo, Nghia T.; Atwood, Robert; Cobb, Justin P.; Hansen, Ulrich; Abel, Richard L.

    2017-01-01

    Osteoporosis is characterised by trabecular bone loss resulting from increased osteoclast activation and unbalanced coupling between resorption and formation, which induces a thinning of trabeculae and trabecular perforations. Bisphosphonates are the frontline therapy for osteoporosis, which act by reducing bone remodelling, and are thought to prevent perforations and maintain microstructure. However, bisphosphonates may oversuppress remodelling resulting in accumulation of microcracks. This paper aims to investigate the effect of bisphosphonate treatment on microstructure and mechanical strength. Assessment of microdamage within the trabecular bone core was performed using synchrotron X-ray micro-CT linked to image analysis software. Bone from bisphosphonate-treated fracture patients exhibited fewer perforations but more numerous and larger microcracks than both fracture and non-fracture controls. Furthermore, bisphosphonate-treated bone demonstrated reduced tensile strength and Young’s Modulus. These findings suggest that bisphosphonate therapy is effective at reducing perforations but may also cause microcrack accumulation, leading to a loss of microstructural integrity and consequently, reduced mechanical strength. PMID:28262693

  11. Reasons for discontinuation of long-term opioid therapy in patients with and without substance use disorders.

    PubMed

    Lovejoy, Travis I; Morasco, Benjamin J; Demidenko, Michael I; Meath, Thomas H A; Frank, Joseph W; Dobscha, Steven K

    2017-03-01

    Several factors may accelerate opioid discontinuation rates, including lack of information about the long-term effectiveness of opioids for chronic pain, heightened awareness about opioid-related adverse events, closer monitoring of patients for opioid-related aberrant behaviors, and greater restrictions around opioid prescribing. Rates of discontinuation may be most pronounced in patients deemed to be at "high risk." The purpose of this study was to compare reasons for discontinuation of long-term opioid therapy (LTOT) between patients with and without substance use disorder (SUD) diagnoses receiving care within a major U.S. health care system. This retrospective cohort study assembled a cohort of Veterans Health Administration patients prescribed opioid therapy for at least 12 consecutive months who subsequently discontinued opioid therapy for at least 12 months. From this cohort, we randomly selected 300 patients with SUD diagnoses and propensity score-matched 300 patients without SUD diagnoses. A comprehensive manual review of patients' medical records ascertained reasons for LTOT discontinuation. Most patients (85%) were discontinued as a result of clinician, rather than patient, decisions. For patients whose clinicians initiated discontinuation, 75% were discontinued because of opioid-related aberrant behaviors. Relative to patients without SUD diagnoses, those with SUD diagnoses were more likely to discontinue LTOT because of aberrant behaviors (81% vs 68%), most notably abuse of alcohol or other substances. This is the first study to document reasons for discontinuation of LTOT in a sample of patients with and without SUD diagnoses. Treatments that concurrently address SUD and chronic pain are needed for this high-risk population.

  12. Age, gender, and earlier opioid requirement associations with the rate of dose escalation in long-term opioid therapy.

    PubMed

    Han, Huijun; Kass, Philip H; Wilsey, Barth L; Li, Chin-Shang

    2013-01-01

    To examine the association of risk factors, age, gender, and earlier opioid requirement with the rate of dose escalation in long-term opioid therapy. This is a retrospective cohort study of 1,922 individuals identified from California's prescription drug monitoring program database who continuously used opioids from 1999 to 2007. A linear mixed-effects model was used to examine the association of age, gender, and baseline dose requirement with the rate of subsequent opioid dose change. Because of different reporting requirements before and after January 1, 2005, the analyses were conducted separately for patients' opioid use in two periods (6 years between 1999 and 2004 and 3 years between 2005 and 2007). Both the 6-year and the 3-year data showed a significant age association, with younger patients having a higher rate of dose escalation than older patients (p = 0.021 and <0.0001, respectively). Females had a lower rate of dose escalation than males, although the result did not achieve statistical significance in the 6-year data (p = 0.165 and 0.013, respectively). The higher the dose requirement a patient had at baseline, the lower the rate of dose escalation (p < 0.0001 in both periods). Age, gender, and earlier dose requirement were associated with the rate of dose change in 9-year long-term opioid therapy. Patients aged 75-100 years, being female or having large dose requirement at an earlier stage of therapy may experience a slower dose escalation or even dose decline.

  13. A case of long-term survival of metastatic desmoplastic small round cell tumor treated with multimodal therapy.

    PubMed

    Watanabe, Tsubasa; Miyamoto, Shin'ichi; Kitagori, Koji; Horimatsu, Takahiro; Morita, Shuko; Mashimo, Yoko; Ezoe, Yasumasa; Muto, Manabu; Chiba, Tsutomu

    2012-01-01

    Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive and malignant tumor that predominantly affects young males. No standard therapy is currently available for patients with DSRCT and the prognosis remains extremely poor. In this study, we report a thought-provoking DSRCT case. A 24-year-old male was admitted to our hospital with a chief complaint of hematemesis. Computed tomography revealed a retrovesical mass with a splenic hilar tumor, multiple lung and liver tumors and marked lymph node swellings. The source of hematemesis was gastric varices caused by the compression of the splenic vein by a splenic hilar tumor. The patient was provided with a histological diagnosis of DSRCT based on needle biopsy from the liver tumors and the pelvic mass was thought to be the primary lesion. This is a long-term survival case of metastatic DSRCT treated with multimodal therapy including 15 courses of multiagent chemotherapy, radiation therapy for the hepatic portal region using 42.5 Gy, and four instances of therapeutic endoscopy. The prolonged progression-free survival period (15 months) obtained following chemotherapy suggests the chemosensitive feature of the disease. We used a modified P6 regimen (cyclophosphamide, pirarubicin, vincristine, ifosfamide and etoposide) and a modified PAVEP regimen (cyclophosphamide, pirarubicin, etoposide and cisplatin) to decrease severe adverse events and to improve the completion rate of chemotherapy. DSRCT is an aggressive but chemo-sensitive disease, and continuous chemotherapy using an appropriate regimen with possible supportive care is essential for long-term survival. This case report may represent a treatment option for this rare disease.

  14. Rescula as an alternative therapy for beta-blockers with long-term drift effect in glaucoma patients.

    PubMed

    Chen, Chang-Lin; Tseng, Hang-Yi; Wu, Kwou-Yeung

    2006-06-01

    The purpose of this study was to evaluate both the intraocular pressure (IOP)-decreasing and neuroprotective effects of Rescula (0.12% unoprostone isopropyl) as an alternative therapy to betablockers with a long-term drift effect in patients with glaucoma. Twenty-eight patients with unilateral or bilateral glaucoma were treated with Rescula instead of the original beta-blocker therapy. IOP was measured using a Goldmann applanation tonometer, and visual field defects were evaluated quantitatively by Humphrey automatic perimetry central 30-2 threshold test. The mean follow-up time was at least 1 year. Rescula achieved a significant (p = 0.00001) and long-lasting reduction in IOP (from 20.78 +/- 2.71 to 17.14 +/- 2.70 mmHg) in patients with open-angle glaucoma after 12 months of follow-up. It also demonstrated a significant (p = 0.02) IOP-reducing effect (from 20.67 +/- 3.60 to 16.36 +/- 3.67 mmHg) in patients with angle-closure glaucoma 12 months later. The mean deviation of visual field defects changed from -13.27 dB baseline to -10.64 dB at 12 months as evaluated by Humphrey field analyzer II central 30-2 threshold test after Rescula; however, there was no statistical difference (p = 0.098). Our results showed that Rescula has a significant IOP-reducing effect as an alternative therapy to beta-blockers with long-term drift effect in patients with open-angle and angle-closure glaucoma. However, a neuroprotective effect to prevent further progression of the visual field defect in patients with glaucoma was not demonstrated in this study.

  15. Long-term coital behaviour in women treated with cognitive behaviour therapy for superficial coital pain and vaginismus.

    PubMed

    Engman, Maria; Wijma, Klaas; Wijma, Barbro

    2010-01-01

    The purpose of the present study was to investigate long-term coital behaviour in women treated with cognitive behaviour therapy (CBT) for superficial coital pain and vaginismus. Data were taken from a questionnaire concerning long-term coital behaviour sent to 59 women who presented to Linköping University Hospital because of superficial coital pain, had been diagnosed with vaginismus, and had been treated with CBT. Data were also traced from therapy records: mean follow-up time was 39 months, the women had suffered for an average of almost 4 years, and required a mean of 14 treatment sessions. Forty-four of the 59 women returned the questionnaire, for a response rate of 74.6%. At follow-up, 81% of the treated women had had intercourse. A majority (61%) rated their ability to have intercourse without pain as 6 or higher (on a scale from 0-10), and 61% rated their ability to enjoy intercourse as 6 or higher (on a scale from 0-10). The proportion of women with positive treatment outcome at follow-up ranged from 81% (able to have intercourse) to 6% (able to have pain-free intercourse). An ability to have intercourse at end of therapy was maintained at follow-up. Two-thirds of the women reported high fulfillment of individual treatment goals. At follow-up, the women estimated a significantly higher self-worth as sex partners, and as women and human beings, than before treatment. Twelve per cent of the original sample had healed after a few assessment sessions and without treatment.

  16. [Combined arterial bypass operation and coumarin therapy--a concept for long-term management and its conditions].

    PubMed

    Kühnel, L; Heinrichs, C; Wache, I; Neugebauer, J

    1991-01-01

    Antithrombotics of cumarin type or with antiplatelet effect are preferred to obtain results from vascular surgical interventions in arterial occlusion disease. In our experience the combination with cumarin long term therapy seems to be the better method, especially if the following conditions can be achieved: very good compliance of patients respectively strict consideration of absolute and relative contraindications, a sufficient number of patients who are treated and a long enough experience of therapeutists followed by using the recommendations of the WHO expert committee for the worldwide application of standardization in measuring the anticoagulation effect, using reagents and calibration materials, and the expression of results in INR. Further in our anticoagulation behaviour we are used influencing risk factors, having a good cooperation between patients and doctors during secondary diseases and new drug intake. For dental surgery we prefer a Quick test between 30 and 35% activity or 1, 9 and 2, 1 INR. With Phenprocoumon (Falithrom, Markumar) we use the long term anticoagulation effect without several daily applications. Since September 1987 there has been the possibility of a computer assisted programme for dose prediction.

  17. Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy.

    PubMed

    De Castro, J; González-Larriba, J L; Vázquez, S; Massutí, B; Sanchez-Torres, J M; Dómine, M; Garrido, P; Calles, A; Artal, A; Collado, R; García, R; Sereno, M; Majem, M; Macías, J A; Juan, O; Gómez-Codina, J; Hernández, B; Lázaro, M; Ortega, A L; Cobo, M; Trigo, J M; Carcereny, E; Rolfo, C; Macia, S; Muñoz, J; Diz, P; Méndez, M; Rosillo, F; Paz-Ares, L; Cardona, J V; Isla, D

    2017-02-01

    First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors.

  18. [The long-term course of 60 patients with alveolar echinococcosis in continuous therapy with mebendazole (1976-85)].

    PubMed

    Ammann, R; Tschudi, K; von Ziegler, M; Meister, F; Cotting, J; Eckert, J; Witassek, F; Freiburghaus, A

    1988-11-01

    Since 1976 60 patients with inoperable alveolar echinococcosis caused by Echinococcus multilocularis were treated with high doses of mebendazole and examined at regular intervals prospectively according to our protocol regarding clinical course, liver function, morphology, immunologically and plasma mebendazole levels. The average duration of disease was 8(1-19) years, the average duration of chemotherapy was 4.25 (0.75-9) years. The long term results showed a correlation of the clinical course with the mean plasma mebendazole levels and the duration of chemotherapy, respectively. Death (n = 5) or transient progression of the disease process (n = 14) was observed primarily in patients with low plasma mebendazole levels in the early course and within the first two years of chemotherapy. Only 9 patients showed a decrease of the parasite mass. Immundiagnosis (total serum IgE and serum antibodies against Echinococcus antigen) gave some information with regard to therapy results, but only in the long-term course. The cumulative survival of the patients under study was 96% at 5 years and 84% at 10 years, respectively which is markedly higher compared to historical control series with a letality of greater than 90% within 10 years.

  19. Cephalometric variables predicting the long-term success or failure of combined rapid maxillary expansion and facial mask therapy.

    PubMed

    Baccetti, Tiziano; Franchi, Lorenzo; McNamara, James A

    2004-07-01

    The aim of this study was to select a model of cephalometric variables to predict the results of early treatment of Class III malocclusion with rapid maxillary expansion and facemask therapy followed by comprehensive treatment with fixed appliances. Lateral cephalograms of 42 patients (20 boys, 22 girls) with Class III malocclusion were analyzed at the start of treatment (mean age 8 years 6 months +/- 2 years, at stage I in cervical vertebral maturation). All patients were reevaluated after a mean period of 6 years 6 months (at stage IV or V in cervical vertebral maturation) that included active treatment plus retention. At this time, the sample was divided into 2 groups according to occlusal criteria: a successful group (30 patients) and an unsuccessful group (12 patients). Discriminant analysis was applied to select pretreatment predictive variables of long-term treatment outcome. Stepwise variable selection of the cephalometric measurements at the first observation identified 3 predictive variables. Orthopedic treatment of Class III malocclusion might be unfavorable over the long term when a patient's pretreatment cephalometric records exhibit a long mandibular ramus (ie, increased posterior facial height), an acute cranial base angle, and a steep mandibular plane angle. On the basis of the equation generated by the multivariate statistical method, the outcome of interceptive orthopedic treatment for each new patient with Class III malocclusion can be predicted with a probability error of 16.7%.

  20. SU-F-P-11: Long Term Dosimetric Stability of 6 TomoTherapy Systems

    SciTech Connect

    Smilowitz, J; Dunkerley, D; Geurts, M; Hill, P; Yadav, P

    2016-06-15

    Purpose: The dosimetric stability of six TomoTherapy units was analyzed to investigate changes in performance over time and with system upgrades. Methods: Energy and output were tracked using monitor chamber signal, onboard MVCT detector signal and external ion chamber measurements. The systems (and monitoring periods) include 3 Hi-Art (67, 61 and 65 mos.), 2 HDA (29 and 25 mos.) and one research unit (7 mo.). Dose Control Stability system (DCS) was installed on 4 systems. Output stability is reported as deviation from reference monitor chamber signal for all systems, and from an external chamber for 4 systems. Energy stability was monitored using the relative (center versus off-axis) MVCT detector signal and/or the ratio of chamber measurements at 2 depths. The results from the clinical systems were used to benchmark the stability of the research unit, which has the same linear accelerator but runs at a higher dose rate. Results: The output based on monitor chamber data of all six systems is very stable. Non- DCS had a standard deviation of 1.7% and 1.8%. As expected, DCS systems had improved standard deviation: 0.003–0.05%. The energy was also very stable for all units. The standard deviation in exit detector flatness was 0.02–0.3%. Ion chamber output and 20/10 cm ratios supported these results. The stability for the research system, as monitored with a variety of metrics, is on par with the existing systems. Conclusion: The output and energy of six TomoTherapy units over a total of almost 10 years is quite stable. For each system, the results are consistent between the different measurement tools and techniques, proving not only the dosimetric stability, but that these quality parameters can be confirmed with various metrics. A research unit operating at a higher dose rate performed as well as the clinical treatment units. University of Wisconsin and Accuray Inc. (vendor of TomoTherapy systems) have a research agreement which supplies funds for research to

  1. In vivo observations of chlorpromazine ocular deposits in a patient on long-term chlorpromazine therapy.

    PubMed

    Razeghinejad, Mohammad Reza; Nowroozzadeh, Mohammad Hosein; Zamani, Mohammad; Amini, Nima

    2008-08-01

    Chlorpromazine is known to deposit in ocular tissues when taken at high doses for prolonged periods. Chlorpromazine therapy in a 59-year-old schizophrenic man with a cumulative dosage exceeding 2500 g resulted in multiple white deposits in both corneas especially in the endothelium. Confocal microscopy revealed significant pleomorphism and polymegethism of endothelial cells. The anterior lens capsules opacities were star-shaped and concentrated in the centre. Because of cataract and chronic angle closure glaucoma our high-myopic patient underwent surgery, and light microscopic evaluation of the obtained anterior lens capsule during cataract surgery showed golden brown cytoplasmic deposits in the central epithelial cells and capsule. The peripheral epithelial cells of the removed capsule had no deposit. There were no sign of retinal deposits in the fundoscopy, optical coherence tomography and fluorescein angiography. In this patient chlorpromazine deposited mainly in the corneal endothelium, central anterior lens capsule and epithelial cells.

  2. Vital Pulp Therapy of a Symptomatic Immature Permanent Molar with Long-Term Success

    PubMed Central

    Sabbagh, Sedigheh; Sarraf Shirazi, Alireza; Eghbal, Mohammad Jafar

    2016-01-01

    Vital pulp therapy (VPT) is the preferred conservative treatment for preservation of symptomatic pulps in immature permanent teeth. The present case report summarizes VPT of an immature permanent molar with irreversible pulpitis associated with apical periodontitis in a 9-year-old boy. Cervical pulpotomy was performed and radicular pulp stumps were covered with calcium-enriched mixture (CEM) cement; the tooth was then restored with stainless steel crown. After a 50-month follow-up period, the pulpotomized molar was clinically functional and asymptomatic. Moreover, radiographic evaluation revealed evidence of complete root development as well as normal periodontal ligament around the roots. The successful outcome achieved through VPT using CEM biomaterial in the reported case suggests that this method may produce favorable outcome for vital immature permanent teeth with irreversible pulpitis and periapical disease. PMID:27790270

  3. Enhancement of renal excretion of uric acid during long-term thiazide therapy.

    PubMed

    Pak, C Y; Tolentino, R; Stewart, A; Galosy, R A

    1978-11-01

    The effect of thiazide (hydrochlorothiazide 100 mg per day orally in two divided doses for up to 3 years) on uric acid metabolism was examined in 21 patients with renal stones suffering from renal hypercalciuria or absorptive hypercalciuria. Serum concentration of uric acid increased during thiazide therapy in every patient. In 12 of 21 patients, there was a transient or persistent rise in urinary uric acid of more than 50 mg per day during treatment. The mean urinary uric acid produced by thiazide was positively correlated with the change in the renal clearance of uric acid. Thus, an increase in urinary uric acid was often associated with a rise in uric acid clearance. The results suggest that thiazide may either increase the production of uric acid or decrease the extrarenal disposal of uric acid, in some patients.

  4. Long-term health care costs for prostate cancer patients on androgen deprivation therapy

    PubMed Central

    Krahn, M.D.; Bremner, K.E.; Luo, J.; Tomlinson, G.; Alibhai, S.M.H.

    2016-01-01

    Background Comparing relative costs for androgen deprivation therapy (adt) protocols in prostate cancer (pca) requires an examination of all health care resources, not only those specific to pca. The objective of the present study was to use administrative data to estimate total health care costs in a population-based cohort of pca patients. Methods Patients in Ontario with pca who started 90 days or more of adt at age 66 years or older during 1995–2005 were selected from cancer registry and health care administrative databases. We classified patients (n = 21,818) by regimen (medical castration, orchiectomy, anti-androgen monotherapy, medical castration with anti-androgen, orchiectomy with anti-androgen) and indication (neoadjuvant, adjuvant, metastatic disease, biochemical recurrence, primary nonmetastatic). Using nonparametric regression methods, with inverse probability weighting to adjust for censoring, and bootstrapping, we computed mean 1-year, 5-year, and 10-year longitudinal total direct medical costs (2009 Canadian dollars). Results Mean first-year costs were highest for metastatic disease, ranging from $24,400 for orchiectomy to $32,120 for anti-androgen monotherapy. Mean first-year costs for all other indications were less than $20,000. Mean 5-year and 10-year costs were lowest for neoadjuvant treatment: approximately $43,000 and $81,000 respectively, with differences of less than $4,000 between regimens. Annual costs were highest in the first year of adt. Orchiectomy was the least costly regimen for most time periods, but was limited to primary and metastatic indications. Outpatient drugs, including pharmacologic adt, accounted for 17%–65% of total first-year costs. Conclusions Compared with combined therapies, the adt monotherapies, particularly orchiectomy when clinically feasible, are more economical. Our methods exemplified the use of algorithms to elucidate clinical information from administrative data. Our approach can be adapted for other

  5. Ultrasound aspects in therapy-naive CIDP compared to long-term treated CIDP.

    PubMed

    Grimm, Alexander; Vittore, Debora; Schubert, Victoria; Rasenack, Maria; Décard, Bernhard F; Heiling, Bianka; Hammer, Nadin; Axer, Hubertus

    2016-06-01

    To investigate the use of nerve ultrasound (NUS) along with the European Federation of Neurological Societies (EFNS) guidelines and clinical scores in untreated, recently diagnosed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) vs. long-lasting treated CIDP. NUS and nerve conduction studies (NCS) of predefined nerves/cervical roots were performed in CIDP on diagnostic onset and "chronic-CIDP" (diagnosis and therapy >6 months), compared to controls. Nerve morphology was quantified using the modified ultrasound pattern sum score mUPSS, which is the sum of 3 ultrasound scores derived at 12 predefined measurement points and the homogeneity score (HS) in ulnar, median, and tibial nerve. 21 onset-CIDP, 21 "chronic-CIDP", and 21 age-matched controls were included. No differences in clinical scores or in the number of electrophysiologically affected nerves existed between the groups. Significantly enlarged cross-sectional areas of the nerves and diameters of the roots ensued already in onset-CIDP; however, with proximal predominance, whilst in chronic-CIDP, nerve enlargement was more prominent and ubiquitous. Increased UPS scores were shown in both patient groups compared to the controls. Significant differences between the patient groups were found particularly in the peripheral nerve score UPSA. Evaluation by means of HS revealed that the nerves in onset-CIDP were mostly regionally enlarged (often sparing distal segments) whereas in chronic-CIDP, nerves were more generalized enlarged. Onset- and chronic-CIDP show enlarged nerves and therefore increased mUPSS, however, nerve enlargement shows a more generalized pattern in chronic-CIDP compared to disease onset and correlates with disease duration and delayed therapy start, but not with disability.

  6. Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy.

    PubMed

    Gnann, John W; Sköldenberg, Birgit; Hart, John; Aurelius, Elisabeth; Schliamser, Silvia; Studahl, Marie; Eriksson, Britt-Marie; Hanley, Daniel; Aoki, Fred; Jackson, Alan C; Griffiths, Paul; Miedzinski, Lil; Hanfelt-Goade, Diane; Hinthorn, Daniel; Ahlm, Clas; Aksamit, Allen; Cruz-Flores, Salvador; Dale, Ilet; Cloud, Gretchen; Jester, Penelope; Whitley, Richard J

    2015-09-01

    Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority. Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint. The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group. Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors. NCT00031486. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Effect of fixed orthodontic therapy on urinary nickel levels: a long-term retrospective cohort study.

    PubMed

    Amini, Fariborz; Rakhshan, Vahid; Sadeghi, Parisa

    2012-12-01

    Nickel constitutes about 8-60 % of orthodontic alloys. It is known as an allergenic/cytotoxic trace metal. Therefore, it should be investigated in patients undergoing orthodontic treatment which might last for 2 or 3 years. However, no controlled studies have assessed the influence of orthodontic treatments of longer than 5 months on its systemic levels. Thus, the aim of this retrospective cohort study was to evaluate systemic nickel in patients undergoing orthodontic therapy for a minimum period of 1 year. In this study, urinary nickel concentrations in 20 female and 10 male patients being treated with stainless steel appliances were measured using atomic absorption spectrophotometry. The same procedure was done on a control group of the patients' same-gender near-age siblings (n = 30). The effect of treatment and gender on urinary nickel levels were assessed using a repeated-measures two-way analysis of variance (ANOVA) and a Tukey test (α = 0.05). The mean treatment duration was 17.1 ± 6.4 months (range, 12-21). The mean nickel concentrations in male and female patients were 9.67 ± 3.25 and 9.9 ± 3.83 μg/L, respectively. These statistics for male and female control subjects were 6.65 ± 2.57 and 8.43 ± 2.94 μg/L, respectively. The ANOVA showed a statistically significant difference between the urinary nickel levels of the treatment and the control groups (P = 0.009) but not between the genders (P = 0.194). The interaction between gender and treatment was also nonsignificant (P = 0.337). The Tukey test indicated that the increase in nickel was higher in male patients, in comparison to their brothers (P < 0.05). It could be concluded that orthodontic therapy for longer durations with stainless-steel archwires might elevate slightly, but significantly, urinary nickel levels.

  8. Percutaneous therapy of low stage and grade urothelial neoplasia: long-term follow up.

    PubMed

    Montanari, Emanuele; Del Nero, Alberto; Bernardini, Paolo; Mangiarotti, Barbara; Confalonieri, Silvia; Grisotto, Massimo; Cordima, Giovanni

    2005-12-01

    endocavitary instillations were well tolerated. In our experience the percutaneous approach is safe and useful in neoplastic lesions of low grade and stage and should be considered as first line therapy in selected patients. Adjuvant topical therapy appears efficacious and some complications may be avoided by maintaining low intracavitary pressures during administration.

  9. The effectiveness of group reminiscence therapy for loneliness, anxiety and depression in older adults in long-term care: a systematic review.

    PubMed

    Syed Elias, Sharifah Munirah; Neville, Christine; Scott, Theresa

    2015-01-01

    Loneliness, anxiety and depression are common problems for older adults in long-term care. Reminiscence therapy is a non-pharmacological intervention that may be of some benefit. In comparison to individual reminiscence therapy, group reminiscence therapy is a preferred option when dealing with the resource constraints of long-term care. The aim of this paper was to systematically review the literature in order to explore the effectiveness of group reminiscence therapy for older adults with loneliness, anxiety and depression in long-term care. Results indicated that group reminiscence therapy is an effective treatment for depression in older adults, however to date, there is limited research support for its effectiveness to treat loneliness and anxiety. Further research and an improvement in methodological quality, such as using qualitative and mixed methods approaches, is recommended to help establish an evidence base and provide better understanding of the effectiveness of group reminiscence therapy.

  10. Androgen deprivation therapy for prostate cancer: long-term safety and patient outcomes

    PubMed Central

    Ahmadi, Hamed; Daneshmand, Siamak

    2014-01-01

    Androgen deprivation therapy (ADT) constitutes the first-line treatment for patients with locally advanced tumors, recurrent or metastatic disease. Given its widespread use, clinicians should be familiar with common side effects of this treatment. This review focuses on common side effects of ADT and available treatment options to control the side effects. Also, it briefly compares continuous ADT with other therapeutic approaches for androgen deprivation in prostate cancer patients. Similar to hormonal medications, newer non-hormonal therapeutic options including gabapentin and acupuncture have at best moderate effect in controlling hot flashes in patients on ADT. Supervised and/or home exercise programs significantly improve ADT-related fatigue, metabolic/cardiovascular side effects, and cognitive dysfunction. Denosumab, a human monoclonal antibody against RANK-L, is more effective than bisphosphonates in preventing skeletal-related events in patients with metastatic or castrate-resistant prostate cancer and unlike bisphosphonates, it can also reduce the risk of vertebral fractures in men receiving ADT for non-metastatic prostate cancer. Toremifene, a selective estrogen receptor inhibitor, has dual beneficial effects on ADT-related osteoporosis and metabolic dysfunction. Metformin coupled with lifestyle modification is also a well-tolerated treatment for metabolic changes during ADT. While producing similar oncological outcomes, intermittent ADT is associated with higher quality of life in patients under ADT by improving bone health, less metabolic and hematologic complications, and fewer hot flashes and sexual dysfunction events. PMID:25045284

  11. Safety and long term efficacy of porfimer sodium photodynamic therapy in locally advanced biliary tract carcinoma

    PubMed Central

    Pereira, Stephen P; Aithal, Guruprasad P; Ragunath, Krish; Devlin, John; Owen, Faye; Meadows, Helen

    2012-01-01

    Background In patients with unresectable cholangiocarcinoma, photodynamic therapy (PDT) with porfimer sodium promotes biliary drainage and may improve survival and quality of life. Aim To prospectively evaluate the safety and efficacy of PDT in patients with locally advanced biliary tract carcinoma. Methods Eligible patients had unresectable, histologically confirmed disease, a Karnofsky performance status of ≥30% and life expectancy >12 weeks. Patients received 2mg/kg i.v. of porfimer sodium, followed by endobiliary laser activation and stent replacement 48 hrs later. Patients were assessed clinically and radiologically before treatment and on day 28, and followed up thereafter at three-monthly intervals until death. Results 36 patients were entered over an 18 months period: 14 males, 22 females, with a median age of 65 (30-79) yr and performance status of 80 (50-100). PDT was technically successful in all cases and was generally well tolerated; there was no grade 4 toxicity and no treatment-associated mortality. The median survival was 12 (1-84) months. Conclusions Porfimer sodium PDT can be delivered safely to patients with biliary tract cancer and is suitable for testing in phase III studies (UKCRN ID 1218). PMID:23200007

  12. Early Breast Cancer in the Elderly: Characteristics, Therapy, and Long-Term Outcome.

    PubMed

    Gal, Omer; Ishai, Yael; Sulkes, Aaron; Shochat, Tzipora; Yerushalmi, Rinat

    2017-09-27

    The number of older adults diagnosed with breast cancer is increasing. However, data on breast cancer characteristics, treatment, and survival in elderly women are sparse. The database of a tertiary cancer center was searched for all women aged ≥65 years who were diagnosed with early breast cancer in 2004-2007. Patients were divided into 2 age groups: 65-75 years and >75 years. Data on tumor, treatment, and outcome parameters were compared. The cohort included 390 patients. The older group underwent more mastectomies but less axillary surgery or adjuvant systemic therapy. Median overall survival (OS) was 9.5 years in the older group and not reached in the younger group; the 8-year disease-free survival rates were 85 and 88%, respectively (p = 0.27). Both age and tumor subtype had an effect on OS and recurrence rates (p < 0.001 for OS; p = 0.16 for recurrence). The worst outcome was noted in women aged >75 years with triple-negative (TN) disease. The treatment approach was different between both age groups, despite similar tumor characteristics. TN subtype presented as the most aggressive disease in both age groups. Physicians should be alert to these findings and select treatment on a case-by-case basis. © 2017 S. Karger AG, Basel.

  13. "Panic attacks" in Parkinson's disease. A long-term complication of levodopa therapy.

    PubMed

    Vázquez, A; Jiménez-Jiménez, F J; García-Ruiz, P; García-Urra, D

    1993-01-01

    A series of 31 Parkinson's disease (PD) patients suffering from panic attacks (PA), late in the evolution of their disease, was analyzed from a group of 131 levodopa-treated PD patients. We found that many of motor, sensory, and vegetative symptoms, previously described as complicating phenomena in PD, constituted some of the symptoms of panic disorders. Comparing PA series with the series of PD patients who did not complain of PA, we discovered a clear-cut relationship of PA with the presence of standing/gait troubles (p < 0.001), depression (p < 0.001), and dyskinesias/fluctuations (p < 0.001). The patients of the PA series also presented a more precocious age of PD onset, were put on levodopa therapy earlier, and needed to be treated with higher doses of levodopa than the patients without PA. Finally, we hypothesize that PA could be considered to be a sort of abstinence syndrome from levodopa, because they appears mostly (90.3%) in the OFF phase of fluctuations, and are relieved administering new doses of levodopa or dopaminergic agonists. Nevertheless, we suggest PA are not directly related to the pharmacological properties of levodopa, but to alterations of the noradrenergic systems in the CNS.

  14. Gene therapy for Wiskott-Aldrich syndrome--long-term efficacy and genotoxicity.

    PubMed

    Braun, Christian Jörg; Boztug, Kaan; Paruzynski, Anna; Witzel, Maximilian; Schwarzer, Adrian; Rothe, Michael; Modlich, Ute; Beier, Rita; Göhring, Gudrun; Steinemann, Doris; Fronza, Raffaele; Ball, Claudia Regina; Haemmerle, Reinhard; Naundorf, Sonja; Kühlcke, Klaus; Rose, Martina; Fraser, Chris; Mathias, Liesl; Ferrari, Rudolf; Abboud, Miguel R; Al-Herz, Waleed; Kondratenko, Irina; Maródi, László; Glimm, Hanno; Schlegelberger, Brigitte; Schambach, Axel; Albert, Michael Heinrich; Schmidt, Manfred; von Kalle, Christof; Klein, Christoph

    2014-03-12

    Wiskott-Aldrich syndrome (WAS) is characterized by microthrombocytopenia, immunodeficiency, autoimmunity, and susceptibility to malignancies. In our hematopoietic stem cell gene therapy (GT) trial using a γ-retroviral vector, 9 of 10 patients showed sustained engraftment and correction of WAS protein (WASP) expression in lymphoid and myeloid cells and platelets. GT resulted in partial or complete resolution of immunodeficiency, autoimmunity, and bleeding diathesis. Analysis of retroviral insertion sites revealed >140,000 unambiguous integration sites and a polyclonal pattern of hematopoiesis in all patients early after GT. Seven patients developed acute leukemia [one acute myeloid leukemia (AML), four T cell acute lymphoblastic leukemia (T-ALL), and two primary T-ALL with secondary AML associated with a dominant clone with vector integration at the LMO2 (six T-ALL), MDS1 (two AML), or MN1 (one AML) locus]. Cytogenetic analysis revealed additional genetic alterations such as chromosomal translocations. This study shows that hematopoietic stem cell GT for WAS is feasible and effective, but the use of γ-retroviral vectors is associated with a substantial risk of leukemogenesis.

  15. Tamoxifen as the first targeted long-term adjuvant therapy for breast cancer.

    PubMed

    Jordan, V Craig

    2014-06-01

    Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine has continued to surprise us, perform, and save lives for the past 40 years. Unlike any other medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinoma in situ, and male breast cancer and pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that 'longer was going to be better' when tamoxifen was being considered as an adjuvant therapy. This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation with Nature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society.

  16. Long-term pioglitazone therapy improves arterial stiffness in patients with type 2 diabetes mellitus.

    PubMed

    Harashima, Keiichiro; Hayashi, Junichi; Miwa, Takashi; Tsunoda, Tooru

    2009-06-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, not only improves insulin resistance and glycemic control, but may also have additional beneficial vascular effects in patients with type 2 diabetes mellitus. We investigated whether pioglitazone had an influence on arterial stiffness, which is an independent predictor of cardiovascular events, in 204 patients with type 2 diabetes mellitus. A prospective, nonrandomized, open-label trial was performed that involved 41 patients treated with pioglitazone, 46 patients receiving sulfonylureas, 67 patients on insulin, and 50 patients on diet/exercise only. The follow-up period was 56 +/- 3 months. Arterial stiffness was evaluated by using the arterial stiffness index (ASI), which was based on analysis of the pulse wave amplitude pattern obtained during automated blood pressure measurement in the upper limb. The 4 groups had a similar baseline ASI, which was greater than the reference range in each group. Although antidiabetic therapies improved hemoglobin A(1c) and low-density lipoprotein cholesterol, ASI only decreased significantly in the pioglitazone group. Thus, pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement. These findings may have important clinical implications in the use of pioglitazone in patients with type 2 diabetes mellitus.

  17. Plasma diazepam and desmethyldiazepam concentrations during long-term diazepam therapy.

    PubMed Central

    Greenblatt, D J; Laughren, T P; Allen, M D; Harmatz, J S; Shader, R I

    1981-01-01

    1 Factors influencing steady-state plasma concentrations of diazepam (DZ) and its major metabolite desmethyldiazepam (DMDZ) were assessed in 110 male Veterans Administration outpatient clinic patients (mean age 53 years). 2 Patients reportedly had taken DZ for 1 to 14 years (mean duration 5.1 years) at a mean daily dose of 20 mg (range 2 to 55 mg). 3 Steady-state plasma concentrations of DZ (mean 329 ng/ml) and DMDZ (mean 389 ng/ml) were highly correlated (r = 0.80), with a mean DMDZ/DZ ratio of 1.26. 4 Weight-corrected daily dose were significantly correlated with plasma level of DZ (r = 0.32), DMDZ (r = 0.38) and the sum of DZ plus DMDZ (r = 0.37), but explained a small fraction of individual variation. 5 Duration of therapy, smoking habits, alcohol consumption, and number of other drugs coingested were not significantly related to plasma level. PMID:6783055

  18. Redevelopment of essential hypertension after cessation of long term therapy; preliminary findings.

    PubMed

    Jennings, G; Korner, P; Esler, M; Restall, R

    1984-01-01

    We have previously found that the vascular hypertrophy that accounts for the maintenance of a substantial fraction of the elevation of the total peripheral resistance index (TPRI) in essential hypertension can be almost completely reversed by one years antihypertensive treatment (1). On ceasing treatment, blood pressure returns rapidly to pretreatment values suggesting that the original cause of the hypertension is still present. In the present study, 7 patients stopped a standard regimen for 10 weeks after at least 2 years of normotension. In the first week, standing and lying blood pressure increased related to rise in supine cardiac index and TPRI. Thereafter standing pressures, supine systolic blood pressure and cardiac index (CI) increased further, but supine diastolic blood pressure and TPRI did not alter. Changes in measurements of resting sympathetic activity, plasma volume or renin-angiotensin did not account for these observations. The return of hypertension after stopping effective therapy has some features previously described in borderline hypertension, particularly increasing systolic blood pressure, CI and postural blood pressure responses. Some of the changes may reflect the relative preponderance of cardiac and vascular amplifiers.

  19. Surgical treatment of bilateral femoral stress fractures related with long-term alendronate therapy.

    PubMed

    Kanatlı, Ulunay; Ataoğlu, M Baybars; Özer, Mustafa; Topçu, H Nevzat; Çetinkaya, Mehmet

    2017-04-01

    A 67-year-old female patient admitted to our outpatient clinic suffering from pain in both thighs for one year without any history of trauma. Patient was receiving alendronate therapy for five years. Physical examination revealed pain increasing with weight-bearing in both thighs with full range of hip and knee movements. Radiographs showed an area of thickened cortex of middle femoral diaphysis in both femurs, but no fracture. Bone scan showed a single area of increased uptake of radioisotope. These images were compatible with stress fractures of both femurs. Dual-energy X-ray absorptiometry revealed a T-score of -3.2 for the lumbar spine and -3.5 for the hip. Alendronate treatment was ceased. Calcium and vitamin D treatment were started. Patient was performed prophylactic surgical stabilization by titanium elastic nails in May 2009. On first day after the surgery, unsupported mobilization and weight-bearing activities were started. Upon persistence of pain on left thigh, plate fixation was performed for the nonunion in June 2012. Patient is now pain-free and able to walk with full weight-bearing without any complications.

  20. Cognitive-behavioral therapy for obsessive–compulsive disorder: access to treatment, prediction of long-term outcome with neuroimaging

    PubMed Central

    O’Neill, Joseph; Feusner, Jamie D

    2015-01-01

    This article reviews issues related to a major challenge to the field for obsessive–compulsive disorder (OCD): improving access to cognitive-behavioral therapy (CBT). Patient-related barriers to access include the stigma of OCD and reluctance to take on the demands of CBT. Patient-external factors include the shortage of trained CBT therapists and the high costs of CBT. The second half of the review focuses on one partial, yet plausible aid to improve access – prediction of long-term response to CBT, particularly using neuroimaging methods. Recent pilot data are presented revealing a potential for pretreatment resting-state functional magnetic resonance imaging and magnetic resonance spectroscopy of the brain to forecast OCD symptom severity up to 1 year after completing CBT. PMID:26229514

  1. Meditation with yoga, group therapy with hypnosis, and psychoeducation for long-term depressed mood: a randomized pilot trial.

    PubMed

    Butler, Lisa D; Waelde, Lynn C; Hastings, T Andrew; Chen, Xin-Hua; Symons, Barbara; Marshall, Jonathan; Kaufman, Adam; Nagy, Thomas F; Blasey, Christine M; Seibert, Elizabeth O; Spiegel, David

    2008-07-01

    This randomized pilot study investigated the effects of meditation with yoga (and psychoeducation) versus group therapy with hypnosis (and psychoeducation) versus psychoeducation alone on diagnostic status and symptom levels among 46 individuals with long-term depressive disorders. Results indicate that significantly more meditation group participants experienced a remission than did controls at 9-month follow-up. Eight hypnosis group participants also experienced a remission, but the difference from controls was not statistically significant. Three control participants, but no meditation or hypnosis participants, developed a new depressive episode during the study, though this difference did not reach statistical significance in any case. Although all groups reported some reduction in symptom levels, they did not differ significantly in that outcome. Overall, these results suggest that these two interventions show promise for treating low- to moderate-level depression.

  2. Long-term outcomes of ethanol injection therapy for locally recurrent papillary thyroid cancer.

    PubMed

    Kim, Soo Young; Kim, Seok-Mo; Chang, Hojin; Kim, Bup-Woo; Lim, Chi Young; Lee, Yong Sang; Chang, Hang-Seok; Park, Cheong Soo

    2017-06-29

    The standard treatment regimen for locally recurrent lesions is total thyroidectomy, or complete removal of the recurrent thyroid lesion within the thyroid bed. However, reoperation increases the risk of complications and patients have to undergo general anesthesia. Percutaneous ethanol injection therapy represents a far less invasive procedure without general anesthesia and with lower risk of complications. Thirty-four patients who received PEIT at Yonsei University Medical Center between October 2002 and August 2009 for recurrent cervical nodal metastases of differentiated papillary thyroid cancer were included in this retrospective study. During a minimum follow-up of 60 months, treatment outcomes were determined by measuring the lesion size prior to the first injection and 3 months after the last injection. A total of 46 recurrent lesions were detected in 34 patients. Five patients underwent surgery and PEIT was administered to the remaining 19 and 22 lesions in the central compartment and lateral neck lymph nodes, respectively. Size increases were observed in seven (17.1%) lesions, whereas no changes in size and decreases were detected in 10 (24.4%) and 24 (58.5%) lesions. Patients with increased lymph nodes were significantly older (65.3 ± 14.4 vs. 48.2 ± 16.3 years; p = 0.02) and had smaller sizes (9.3 ± 1.0 vs. 12.3 ± 6.4 mm; p = 0.012). Although reoperation remains the first-line treatment for recurrent thyroid cancer, PEIT may be considered as a treatment option in selected patients with lesions larger than 1 cm who are ineligible for surgery or have refused reoperation.

  3. Effect of long-term vigabatrin therapy on selected neurotransmitter concentrations in cerebrospinal fluid.

    PubMed

    Ben-Menachem, E; Persson, L I; Mumford, J; Haegele, K D; Huebert, N

    1991-01-01

    Ten patients, suffering from drug-resistant complex partial seizures were treated for a period of up to 3 years with vigabatrin (Sabril). Vigabatrin is a novel antiepileptic agent, whose action is based on the inhibition of gamma-aminobutyric acid (GABA) aminotransferase, the enzyme responsible for the catabolism of the neurotransmitter GABA. Samples of lumbar cerebrospinal fluid were obtained from the patients prior to commencing vigabatrin therapy, and thereafter at 6 months, 1 year, 2 years, and up to 3 years following the initiation of vigabatrin treatment. The influence of vigabatrin on the cerebrospinal fluid concentrations of free and total GABA, homocarnosine, homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol, as well as of the drug itself, was assessed. All patients demonstrated a clinical response to vigabatrin, and the drug was well tolerated over the entire observation period. Mean (+/- SD) reduction of seizure frequency was 65% +/- 23% (range, 26% to 100%) when comparing the end of the treatment period to the previgabatrin baseline. The cerebrospinal fluid concentrations of both free and total GABA and of the dipeptide homocarnosine showed approximately 2- to 5-fold increases over baseline values, with free GABA and homocarnosine being the more sensitive variables. Cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were not altered in a significant manner over the observation period. These findings support the concept that the effects of vigabatrin are restricted to an effect on GABA catabolism and do not extend to the neurotransmitters dopamine and norepinephrine. Clinical efficacy and elevation of GABA and homocarnosine concentration were sustained over the period of observation.

  4. Long-term treatment with cinacalcet and conventional therapy reduces parathyroid hyperplasia in severe secondary hyperparathyroidism

    PubMed Central

    Meola, Mario; Petrucci, Ilaria; Barsotti, Giuliano

    2009-01-01

    Background. The effect of cinacalcet on the structural pattern of hyperplastic parathyroid glands was evaluated, using high-resolution colour Doppler (CD) sonography, in haemodialysis patients with severe, inadequately controlled, secondary hyperparathyroidism (sHPT). Methods. Nine patients (6 males, 3 females; mean age ± SD, 55.5 ± 12.6 years) received cinacalcet, with adaptation of existing concomitant therapies. Biochemical parameters and the morphology and vascular pattern of hyperplastic parathyroid glands were measured at baseline and every 6 months thereafter, for a follow-up period of 24–30 months. Results. At baseline, 28 hyperplastic glands were identified. Cinacalcet led to a reduction in glandular volume during the course of the study: 68% in glands with a baseline volume <500 mm3 and 54% in glands with a baseline volume ≥500 mm3. The mean volume ± SD of glands <500 mm3 changed significantly from the baseline (233 ± 115 mm3) to the end of follow-up (102 ± 132 mm3, P = 0.007). Levels of mean serum phosphorus, calcium and calcium–phosphorus product decreased, but not significantly, whereas there were significant decreases in mean parathyroid hormone ± SD levels (1196 ± 381 pg/ml versus 256 ± 160 pg/ml; P < 0.0001) and alkaline phosphatase ± SD levels (428 ± 294 versus 223 ± 88 IU/l; P = 0.04), accompanied by an improvement in a subjective clinical score. Conclusions. Cinacalcet, in combination with conventional treatments, led to an improvement in biochemical and clinical parameters of sHPT and reduced glandular volume in patients with severe sHPT. Volume reduction was more evident in smaller glands. Longer term, larger, randomized clinical trials are needed to confirm these preliminary findings and to further define a more systematic approach in the treatment of sHPT. PMID:19181759

  5. Best Practices for Intrathecal Baclofen Therapy: Dosing and Long-Term Management.

    PubMed

    Boster, Aaron L; Adair, Roy L; Gooch, Judith L; Nelson, Mary Elizabeth S; Toomer, Andrea; Urquidez, Joe; Saulino, Michael

    2016-08-01

    Intrathecal baclofen (ITB) therapy aims to reduce spasticity and provide functional control. An expert panel consulted on best practices. Pump fill and drug delivery can be started intraoperatively, with monitoring for at least eight hours. Initiate with the 500 mcg/mL concentration. The starting daily dose should be twice the effective bolus screening dose, or the screening dose if the patient had a prolonged response (greater than eight hours) or negative reactions. Oral antispasmodics can be weaned, one drug at a time beginning with oral baclofen after ITB begins. Assessment should occur within 24 hours of a dose change. For adults, daily dose increases may be 5% to 15% once every 24 hours for cerebral-origin spasticity and 10% to 30% once every 24 hours for spinal-origin spasticity. Daily dose increases can be 5% to 15% once every 24 hours for children. Inpatients should be assessed at least every 24 hours and receive rehabilitation. Step dosing can be used for outpatients who cannot return daily. Dosing options include simple continuous dosing, variable 24-hour flex dosing, or regularly scheduled boluses. Patients/caregivers should understand the care plan, responsibilities, and possible side-effects. Low-reservoir alarm dates and refill schedules should be written down, along with emergency contact information. A higher concentration at refill can extend refill intervals, and a bridge bolus must be programmed. Time changes may affect flex dosing. Pump replacement should be scheduled at least three months in advance. ITB dosing is multistep and individualized. © 2016 International Neuromodulation Society.

  6. Motexafin lutetium-photodynamic therapy of prostate cancer: Short and long term effects on PSA

    PubMed Central

    Patel, Hiral; Mick, Rosemarie; Finlay, Jarod; Zhu, Timothy C.; Rickter, Elizabeth; Cengel, Keith A.; Malkowicz, S. Bruce; Hahn, Stephen M.; Busch, Theresa M.

    2009-01-01

    Purpose: The time course of serum PSA response to photodynamic therapy (PDT) of prostate cancer was measured. Experimental Design: Seventeen patients were treated in a Phase I trial of motexafin lutetium-PDT. PDT dose was calculated in each patient as the product of the ex vivo-measured pre-PDT photosensitizer level and the in situ-measured light dose. Serum PSA level was measured within two months prior to PDT (baseline), and at day 1; weeks 1-3; months 1, 2 and 3; months 4-6 and months 7-11 after PDT. Results: At 24h after PDT, serum PSA increased by 98±36% (mean ± SE) relative to baseline levels (p=0.007). When patients were dichotomized based on median PDT dose, those who received high PDT dose demonstrated a 119±52% increase in PSA compared to a 54±27% increase in patients treated at low PDT dose. Patients treated with high vs. low PDT dose demonstrated a median biochemical delay of 82 vs. 43 days (p=0.024), with biochemical delay defined as the length of time between PDT and a nonreversible increase in PSA to a value ≥baseline. Conclusions: Results show PDT to induce large, transient increases in serum PSA levels. Patients who experienced high PDT dose demonstrated greater short-term increase in PSA and a significantly more durable PSA response (biochemical delay). These data strongly promote the need for individualized delivery of PDT dose and assessment of treatment effect in PDT of prostate cancer. Information gained from such patient-specific measurements could facilitate the introduction of multiple PDT sessions in patients who would benefit. PMID:18676760

  7. Long term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma

    PubMed Central

    Trzil, Julie E; Masseau, Isabelle; Webb, Tracy L; Chang, Chee-hoon; Dodam, John R; Cohn, Leah A; Liu, Hong; Quimby, Jessica M; Dow, Steven W; Reinero, Carol R

    2014-01-01

    the effect was not sustained at month 12. Further study of MSC therapy including repeated MSC administration is warranted to assess impact on remodeling in chronic asthma. PMID:25220646

  8. Association of apical rocking with long-term major adverse cardiac events in patients undergoing cardiac resynchronization therapy.

    PubMed

    Ghani, Abdul; Delnoy, Peter Paul H M; Ottervanger, Jan Paul; Ramdat Misier, Anand R; Smit, Jaap Jan J; Adiyaman, Ahmet; Elvan, Arif

    2016-02-01

    Correctly identifying patients who will benefit from cardiac resynchronization therapy (CRT) is still challenging. 'Apical rocking' is observed in asynchronously contracting ventricles and is associated with echocardiographic response to CRT. The association of apical rocking and long-term clinical outcome is however unknown at present. We assessed the predictive value of left ventricular (LV) apical rocking on a long-term clinical outcome in patients treated with CRT. Consecutive heart failure patients treated with primary indication for CRT-D between 2005 and 2009 were included in a prospective registry. Echocardiography was performed prior to CRT to assess apical rocking, defined as motion of the LV apical myocardium perpendicular to the LV long axis. Major adverse cardiac event (MACE) was defined as combined end point of cardiac death and/or heart failure hospitalization and/or appropriate therapy (ATP and/or ICD shocks). All echocardiograms were assessed by independent cardiologists, blinded for clinical data. Multivariable analyses were performed to adjust for potential confounders. Two hundred and ninety-five patients with echocardiography prior to implantation were included in the final analyses. Apical rocking was present in 45% of the study patients. Apical rocking was significantly more common in younger patients, females, patients with sinus rhythm, non-ischaemic cardiomyopathy, and in patients with LBBB and wider QRS duration. During a mean clinical follow-up of 5.2 ± 1.6 years, 92 (31%) patients reached the end point of the study (MACE). Patients with MACE had shorter QRS duration, had more ischaemic cardiomyopathy, and were more often on Amiodarone. In univariate analyses, MACE was associated with shorter QRS duration, ischaemic aetiology, and the absence of apical rocking. After multivariable analyses, apical rocking was associated with less MACE (hazards ratio, HR 0.44, 95% confidence interval, CI 0.25-0.77). Apical rocking is an independent

  9. Experiences of a long-term randomized controlled prevention trial in a maiden environment: Estonian Postmenopausal Hormone Therapy trial

    PubMed Central

    Hovi, Sirpa-Liisa; Veerus, Piret; Rahu, Mati; Hemminki, Elina

    2008-01-01

    Background Preventive drugs require long-term trials to show their effectiveness or harms and often a lot of changes occur during post-marketing studies. The purpose of this article is to describe the research process in a long-term randomized controlled trial and discuss the impact and consequences of changes in the research environment. Methods The Estonian Postmenopausal Hormone Therapy trial (EPHT), originally planned to continue for five years, was planned in co-operation with the Women's International Study of Long-Duration Oestrogen after Menopause (WISDOM) in the UK. In addition to health outcomes, EPHT was specifically designed to study the impact of postmenopausal hormone therapy (HT) on health services utilization. Results After EPHT recruited in 1999–2001 the Women's Health Initiative (WHI) in the USA decided to stop the estrogen-progestin trial after a mean of 5.2 years in July 2002 because of increased risk of breast cancer and later in 2004 the estrogen-only trial because HT increased the risk of stroke, decreased the risk of hip fracture, and did not affect coronary heart disease incidence. WISDOM was halted in autumn 2002. These decisions had a major influence on EPHT. Conclusion Changes in Estonian society challenged EPHT to find a balance between the needs of achieving responses to the trial aims with a limited budget and simultaneously maintaining the safety of trial participants. Flexibility was the main key for success. Rapid changes are not limited only to transiting societies but are true also in developed countries and the risk must be included in planning all long-term trials. The role of ethical and data monitoring committees in situations with emerging new data from other studies needs specification. Longer funding for preventive trials and more flexibility in budgeting are mandatory. Who should prove the effectiveness of an (old) drug for a new preventive indication? In preventive drug trials companies may donate drugs but they take a

  10. Long-Term Effects of Two Formats of Cognitive Behavioral Therapy for Insomnia Comorbid with Breast Cancer.

    PubMed

    Savard, Josée; Ivers, Hans; Savard, Marie-Hélène; Morin, Charles M

    2016-04-01

    The goal of this randomized controlled trial, conducted in breast cancer patients, was to assess the long-term efficacy of a video-based cognitive behavioral therapy for insomnia (VCBT-I), as compared to a professionally administered intervention (PCBT-I) and to a no-treatment group (CTL). An earlier report revealed that, at posttreatment, VCBT-I patients showed significantly greater sleep improvements than CTL, but that PCBT-I produced superior effects than VCBT-I on some sleep and secondary outcomes. In this report, long-term effects are compared. Two hundred forty-two women with breast cancer and with insomnia symptoms or using hypnotic medications participated to this three-arm randomized controlled trial: (1) PCBT-I (n = 81); (2) VCBT-I (n = 80); or (3) no treatment (CTL; n = 81) group. PCBT-I was composed of six weekly, individual sessions of approximately 50 min, whereas VCBT-I comprised a 60-min animated video and six booklets. Study measures (sleep and secondary variables) were administered at pretreatment and posttreatment, and at a 3-, 6-, and 12-mo follow-up. Treatment gains were well sustained at follow-up in both PCBT-I and VCBT-I. As at posttreatment, the remission rate of insomnia at follow-up was greater in PCBT-I than in VCBT-I, which was greater than in CTL. Although face-to-face therapy remains the optimal format to efficaciously administer CBT for insomnia in cancer patients, a minimal intervention, such as the video-based intervention tested in this study, produces significant and sustainable treatment effects. ClinicalTrials.gov identifier NCT00674830. © 2016 Associated Professional Sleep Societies, LLC.

  11. Long-Term Follow-Up of Cyclophosphamide Compared with Azathioprine for Initial Maintenance Therapy in ANCA-Associated Vasculitis

    PubMed Central

    Faurschou, Mikkel; Berden, Annelies; Flossmann, Oliver; Bajema, Ingeborg; Hoglund, Peter; Smith, Rona; Szpirt, Wladimir; Westman, Kerstin; Pusey, Charles D.; Jayne, David R.W.

    2014-01-01

    Background and objectives Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis. This study comprised patients undergoing long-term follow-up who were randomly allocated to azathioprine after 3–6 months or after 12 months of cyclophosphamide treatment. Design, setting, participants, & measurements Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible. At the time of diagnosis, participants were randomly allocated to convert to azathioprine after 3–6 months (the azathioprine group) or after 12 months of cyclophosphamide (the cyclophosphamide group). Patients who did not achieve a remission within 6 months were excluded. This study assessed relapses, ESRD, and death during long-term follow-up. Results Patients were allocated to the azathioprine group (n=71) and the cyclophosphamide group (n=73). Of these patients, 63 (43.8%) developed a relapse, 35 (24.3%) developed a renal relapse, 13 (9.0%) developed ESRD, and 21 (14.6%) died. Although there were worse outcomes in the azathioprine group, none were statistically significant. The subdistribution hazard ratio [sHR] for relapse was 1.63 (95% confidence interval [95% CI], 0.99 to 2.71), the composite of relapse or death hazard ratio [HR] was 1.59 (95% CI, 1.00 to 2.54), the ESRD sHR was 1.71 (95% CI, 0.56 to 5.19), and the death HR was 0.75 (95% CI, 0.32 to 1.79). Conclusions It remains uncertain whether converting to azathioprine after 3–6 months of induction cyclophosphamide therapy is as effective as converting after 12 months. Outcomes are still poor for this group of patients and further research is required to determine the optimal timing of maintenance therapy. PMID:24970876

  12. Long-term gene therapy with thrombospondin 2 inhibits TGF-β activation, inflammation and angiogenesis in chronic allograft nephropathy.

    PubMed

    Daniel, Christoph; Vogelbacher, Regina; Stief, Andrea; Grigo, Christina; Hugo, Christian

    2013-01-01

    We recently identified Thrombospondin-2 (TSP-2) as a regulator of matrix remodelling and inflammation in experimental kidney disease by using TSP-2 null mice and successfully proved TSP-2 overexpression as a therapeutic concept in a short term glomerulonephritis model in the rat. In this current study, we investigated if long-term TSP-2 overexpression is also capable to ameliorate the progression of chronic kidney disease in the setting of the chronic allograft nephropathy F344-Lewis model in the rat. Two weeks after renal transplantation, two rat thigh muscles were transfected once only with either a TSP-2 overexpressing plasmid (n = 8) or a luciferase-expressing plasmid as control (n = 8). Rats were monitored for renal function, histological changes and gene expression in the graft for up to 30 weeks after transplantation. Unexpectedly, only in the TSP-2 treated group 2 rats died before the end of the experiment and renal function tended to be worsened in the TSP-2 group compared to the luciferase-treated controls. In addition, glomerular sclerosis and tubular interstitial injury as well as cortical fibronectin deposition was significantly increased in the TSP-2 treated kidneys despite reduced TGF-β activation and marked anti-inflammatory (macrophages, T-cells and B-cells) effects in this group. Long-term TSP-2 therapy impaired repair of renal endothelium, as demonstrated by significant higher glomerular and peritubular endothelial rarefaction and reduced endothelial cell proliferation in the transplanted kidneys from TSP-2 treated rats compared to controls. This TSP-2 effect was associated with decreased levels of renal VEGF but not VEGF1 receptor. In conclusion, despite its anti-inflammatory and TGF-β activation blocking effects, TSP-2 gene therapy did not ameliorate but rather worsened experimental chronic allograft nephropathy most likely via its anti-angiogenic properties on the renal microvasculature.

  13. Long-term functional and morphologic retinal changes after ranibizumab and photodynamic therapy in myopic choroidal neovascularization.

    PubMed

    Parravano, Mariacristina; Ricci, Federico; Oddone, Francesco; Missiroli, Filippo; De Felici, Cecilia; Varano, Monica

    2014-10-01

    To assess and compare the long-term functional and anatomical outcomes in eyes with myopic choroidal neovascularization (CNV) treated with intravitreal injections of ranibizumab or with photodynamic therapy (PDT). Eighty-five eyes of 85 consecutive patients with myopic CNV and treated with either PDT (43/85) or ranibizumab 0.5 mg (42/85) and at least 24 months of follow-up were collected. Data from the best-corrected visual acuity, optical coherence tomography, and fluorescein angiography were compared between the groups. Differences in the regression pattern of myopic CNV and the rate of chorioretinal atrophy development were also compared between the groups. The effect of treatment over time on best-corrected visual acuity and the central retinal thickness was significantly greater in the ranibizumab group (P = 0.0012 and P < 0.0002, respectively), with eyes treated with ranibizumab showing a significant central retinal thickness decrease since the first visit and maintained until 24 months. The proportion of patients showing a complete closure of CNV was similar between the groups (93% [39 of 42 eyes in the ranibizumab group] vs. 88% [38 of 43 eyes in the PDT group], P = 0.48). Both treatments were associated with an increase of chorioretinal atrophy size, which was greater in the PDT-treated eyes (P = 0.016). Ranibizumab therapy showed a greater long-term efficacy compared with PDT in myopic CNV eyes, with a fewer proportion of eyes developing an increase of lesion and chorioretinal atrophy size.

  14. Long-term stability of combined rapid palatal expansion-lip bumper therapy followed by full fixed appliances.

    PubMed

    Ferris, Tyler; Alexander, R G; Boley, Jimmy; Buschang, Peter H

    2005-09-01

    The purpose of this study was to evaluate the long-term postretention stability of rapid palatal expansion-lip bumper therapy followed by full fixed appliances. The sample included 20 treated patients (11 women and 9 men) who were recalled to obtain postretention records. The subjects were out of retention for a minimum of 4 years and an average of 7.9 years. They had begun treatment in the late mixed dentition at a mean age of 11.1 with considerable incisor crowding but, on average, no tooth size-arch length discrepancies. Pretreatment, posttreatment (mean age, 13.6 years), and postretention (mean age, 24.3 years) models were digitized, and the computed measurements were compared with untreated reference data. The majority of treatment increases in maxillary and mandibular arch dimensions were statistically significant (P < .05) and greater than expected for untreated controls. Although many measurements decreased postretention, net gains were maintained for 21 of the 30 measurements evaluated. The notable exception was arch perimeter, which decreased to less than pretreatment values. Postretention incisor irregularity increased 0.5 +/- 1.2 mm in the maxillary arch and 1.1 +/- 1.5 mm in the mandibular arch. Based on the good long-term stability observed in this study, we concluded that use of rapid palatal expansion-lip bumper expansion therapy in the late mixed dentition followed by full fixed appliances is an effective form of treatment for patients with up to moderate tooth size-arch length discrepancies.

  15. Long-Term Gene Therapy with Thrombospondin 2 Inhibits TGF-β Activation, Inflammation and Angiogenesis in Chronic Allograft Nephropathy

    PubMed Central

    Daniel, Christoph; Vogelbacher, Regina; Stief, Andrea; Grigo, Christina; Hugo, Christian

    2013-01-01

    We recently identified Thrombospondin-2 (TSP-2) as a regulator of matrix remodelling and inflammation in experimental kidney disease by using TSP-2 null mice and successfully proved TSP-2 overexpression as a therapeutic concept in a short term glomerulonephritis model in the rat. In this current study, we investigated if long-term TSP-2 overexpression is also capable to ameliorate the progression of chronic kidney disease in the setting of the chronic allograft nephropathy F344-Lewis model in the rat. Two weeks after renal transplantation, two rat thigh muscles were transfected once only with either a TSP-2 overexpressing plasmid (n = 8) or a luciferase-expressing plasmid as control (n = 8). Rats were monitored for renal function, histological changes and gene expression in the graft for up to 30 weeks after transplantation. Unexpectedly, only in the TSP-2 treated group 2 rats died before the end of the experiment and renal function tended to be worsened in the TSP-2 group compared to the luciferase-treated controls. In addition, glomerular sclerosis and tubular interstitial injury as well as cortical fibronectin deposition was significantly increased in the TSP-2 treated kidneys despite reduced TGF-β activation and marked anti-inflammatory (macrophages, T-cells and B-cells) effects in this group. Long-term TSP-2 therapy impaired repair of renal endothelium, as demonstrated by significant higher glomerular and peritubular endothelial rarefaction and reduced endothelial cell proliferation in the transplanted kidneys from TSP-2 treated rats compared to controls. This TSP-2 effect was associated with decreased levels of renal VEGF but not VEGF1 receptor. In conclusion, despite its anti-inflammatory and TGF-β activation blocking effects, TSP-2 gene therapy did not ameliorate but rather worsened experimental chronic allograft nephropathy most likely via its anti-angiogenic properties on the renal microvasculature. PMID:24376766

  16. A Short-Term Biological Indicator for Long-Term Kidney Damage after Radionuclide Therapy in Mice

    PubMed Central

    Pellegrini, Giovanni; Siwowska, Klaudia; Haller, Stephanie; Antoine, Daniel J.; Schibli, Roger; Kipar, Anja; Müller, Cristina

    2017-01-01

    Folate receptor (FR)-targeted radionuclide therapy using folate radioconjugates is of interest due to the expression of the FR in a variety of tumor types. The high renal accumulation of radiofolates presents, however, a risk of radionephropathy. A potential option to address this challenge would be to use radioprotectants, such as amifostine. Methods for early detection of kidney damage that—in this case—cannot be predicted based on dose estimations, would facilitate the development of novel therapies. The aim of this study was, therefore, to assess potentially changing levels of plasma and urine biomarkers and to determine DNA damage at an early stage after radiofolate application. The identification of an early indicator for renal damage in mice would be useful since histological changes become apparent only several months after treatment. Mice were injected with different quantities of 177Lu-folate (10 MBq, 20 MBq and 30 MBq), resulting in mean absorbed kidney doses of ~23 Gy, ~46 Gy and ~69 Gy, respectively, followed by euthanasia two weeks (>85% of the mean renal radiation dose absorbed) or three months later. Whereas all investigated biomarkers remained unchanged, the number of γ-H2AX-positive nuclei in the renal cortex showed an evident dose-dependent increase as compared to control values two weeks after treatment. Comparison with the extent of kidney injury determined by histological changes five to eight months after administration of the same 177Lu-folate activities suggested that the quantitative assessment of double-strand breaks can be used as a biological indicator for long-term radiation effects in the kidneys. This method may, thus, enable faster assessment of radiopharmaceuticals and protective measures by preventing logistically challenging long-term investigations to detect kidney damage. PMID:28635637

  17. Online Training in Mind-Body Therapies: Different Doses, Long-term Outcomes.

    PubMed

    Kemper, Kathi J; Rao, Nisha; Gascon, Gregg; Mahan, John D

    2017-01-01

    There is a high rate of burnout among health professionals, driving diverse attempts to promote resilience and well-being to counter this trend. The purpose of this project was to assess the dose-response relationship between the number of hours of online mind-body skills training for health professionals and relevant outcomes a year later. Among 1438 registrants for online training (including up to 12 hours of training on mind-body practices) between December 2013 and November 2015, we analyzed responses from the first 10% who responded to an anonymous online survey between December 1, 2015 and February 1, 2016. Questions included the type and frequency of mind-body practice in the past 30 days and whether the online training had any impact on personal life or professional practice. Standardized measures were used to assess stress, mindfulness, confidence in providing compassionate care, and burnout. The 149 respondents represented a variety of ages and health professions; 55% completed one or more mind-body training modules an average of 14 months previously. Most (78%) engaged in one or more mind-body practices in the 30 days before the survey; 79% reported changes in self-care and 71% reported changes in the care of others as a result of participating. Increasing number of hours of training were significantly associated with practicing mind-body skills more frequently; increasing practice frequency was associated with less stress and burnout, which were associated with missing less work. Greater practice frequency was also associated with improvements in stress, mindfulness, and resilience, which were associated with increased confidence in providing compassionate care. Online training in mind-body therapies is associated with changes in self-reported behavior one year later; increasing doses of training are associated with more frequent practice which is associated with less stress, burnout, and missing work, and higher levels of mindfulness, resilience, and

  18. Long-term dosimetric stability of multiple TomoTherapy delivery systems.

    PubMed

    Smilowitz, Jennifer B; Dunkerley, David; Hill, Patrick M; Yadav, Poonam; Geurts, Mark W

    2017-05-01

    The dosimetric stability of six TomoTherapy units was analyzed to investigate changes in performance over time and with system upgrades. Energy and output were tracked using monitor chamber signal, onboard megavoltage computed tomography (MVCT) detector profile, and external ion chamber measurements. The systems (and monitoring periods) include three Hi-Art (67, 61, and 65 mos.), two TomoHDA (31 and 26 mos.), and one Radixact unit (11 mos.), representing approximately 10 years of clinical use. The four newest systems use the Dose Control Stability (DCS) system and Fixed Target Linear Accelerator (linac) (FTL). The output stability is reported as deviation from reference monitor chamber signal for all systems and/or from an external chamber signal. The energy stability was monitored using relative (center versus off-axis) MVCT detector signal (beam profile) and/or the ratio of chamber measurements at 2 depths. The clinical TomoHDA data were used to benchmark the Radixact stability, which has the same FTL but runs at a higher dose rate. The output based on monitor chamber data of all systems is very stable. The standard deviation of daily output on the non-DCS systems was 0.94-1.52%. As expected, the DCS systems had improved standard deviation: 0.004-0.06%. The beam energy was also very stable for all units. The standard deviation in profile flatness was 0.23-0.62% for rotating target systems and 0.04-0.09% for FTL. Ion chamber output and PDD ratios supported these results. The output stability on the Radixact system during extended treatment delivery (20, 30, and 40 min) was comparable to a clinical TomoHDA system. For each system, results are consistent between different measurement tools and techniques, proving not only the dosimetric stability, but also these quality parameters can be confirmed with various metrics. The replacement history over extended time periods of the major dosimetric components of the different delivery systems (target, linac, and magnetron

  19. Can long-term alopecia occur after appropriate pulsed-dye laser therapy in hair-bearing sites? Pediatric dermatologists weigh in.

    PubMed

    Feldstein, Stephanie; Totri, Christine R; Friedlander, Sheila F

    2015-03-01

    The risk of long-term alopecia after pulsed-dye laser (PDL) therapy is unknown. To identify how many practitioners treat hair-bearing sites with PDL and how commonly long-term alopecia occurs, the authors queried pediatric dermatologists about their experiences using this modality. A survey was designed to evaluate the frequency of and factors contributing to long-term alopecia after PDL treatment of port-wine stains (PWS). "Long-term" was defined as no sign of hair regrowth after several years of nontreatment. The survey was administered to attendees at the 2014 Society for Pediatric Dermatology biannual meeting. Sixty-four pediatric dermatologists completed the survey, 50 of whom had experience using PDL. Of these physicians, 86% have used PDL to treat PWS of the eyebrow and 80% have treated PWS of the scalp. Over one-quarter of respondents (25.5%) using PDL on hair-bearing areas had at least 1 of their patients develop long-term alopecia after PDL treatment. The incidence of long-term alopecia after PDL treatment in the surveyed population was 1.5% to 2.6%. The occurrence of long-term alopecia at hair-bearing sites after treatment with PDL may be greater than previously thought. Because the majority of physicians using PDL treat hair-bearing areas, prospective studies are needed to more accurately determine the risk of long-term alopecia and the factors that contribute to it.

  20. Outcome of Long-Term Bisphosphonate Therapy in McCune-Albright Syndrome and Polyostotic Fibrous Dysplasia.

    PubMed

    Majoor, Bas Cj; Appelman-Dijkstra, Natasha M; Fiocco, Martha; van de Sande, Michiel Aj; Dijkstra, Pd Sander; Hamdy, Neveen At

    2017-02-01

    McCune-Albright syndrome (MAS) is a rare bone disorder characterized by fibrous dysplasia (FD), endocrinopathies, and café-au-lait patches. FD patients have been shown to respond favorably to treatment with bisphosphonates, but data are scarce in the more severe polyostotic form (PFD), including MAS, and factors determining treatment outcome are not known, particularly in the long-term. We evaluated the biochemical (bone turnover markers [BTMs]) and clinical (pain reduction) outcome of bisphosphonate therapy in 11 patients with MAS and 30 patients with PFD: median duration of treatment 6 years (range, 2 to 25 years). Prognostic factors for treatment outcome were identified in both groups. Patients with MAS were younger at diagnosis (p = 0.001), all had precocious puberty, and four (36%) had additional growth hormone (GH) excess associated with severe craniofacial FD. Extent of skeletal disease was more severe in MAS compared to PFD. MAS patients had higher serum alkaline phosphatase (ALP) concentrations (p = 0.005), higher skeletal burden scores (p < 0.001), and more fractures (p = 0.021). MAS patients had also higher levels of FGF-23 (p = 0.008) and higher prevalence of hypophosphatemia (p = 0.013). Twenty-four of 30 PFD patients (80%) demonstrated a complete clinical and biochemical response within a year of starting treatment (p = 0.015), compared to only four of 11 MAS patients (36%). There were no nonresponders. In the whole group, FGF-23, total ALP, P1NP, and CTX positively correlated with skeletal burden scores (all p ≤ 0.001), which was the only significant risk factor for an incomplete response to bisphosphonate therapy (p < 0.01). Our data suggest a beneficial and safe outcome of long-term bisphosphonate therapy in the majority of patients with PFD, although response to therapy was limited by the higher skeletal disease burden in MAS patients. In the PFD/MAS population studied, the only identified prognostic factor

  1. Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay.

    PubMed

    Auricchio, Angelo; Stellbrink, Christoph; Sack, Stefan; Block, Michael; Vogt, Jürgen; Bakker, Patricia; Huth, Christof; Schöndube, Friedrich; Wolfhard, Ulrich; Böcker, Dirk; Krahnefeld, Olaf; Kirkels, Hans

    2002-06-19

    We sought to compare the short- and long-term clinical effects of atrial synchronous pre-excitation of one (univentricular) or both ventricles (biventricular), that provide cardiac resynchronization therapy (CRT). In patients with heart failure (HF) who have a ventricular conduction delay, CRT improves systolic hemodynamic function. The clinical benefit of CRT is still being investigated. Forty-one patients were randomized to four weeks of first treatment with biventricular or univentricular stimulation, followed by four weeks without treatment, and then four weeks of a second treatment with the opposite stimulation. The best CRT stimulation was continued for nine months. Cardiac resynchronization therapy was optimized by hemodynamic testing at implantation. The primary end points were exercise capacity measures. Data were analyzed by two-way repeated-measures analysis of variance. The left ventricle was selected for univentricular pacing in 36 patients. The clinical effects of univentricular and biventricular CRT were not significantly different. The results of each method were pooled to assess sequential treatment effects. Oxygen uptake during bicycle exercise increased from 9.48 to 10.4 ml/kg/min at the anaerobic threshold (p = 0.03) and from 12.5 to 14.3 ml/kg/min at peak exercise (p < 0.001) with the first treatment, and from 10.0 to 10.7 ml/kg/min at the anaerobic threshold (p = 0.2) and from 13.4 to 15.2 ml/kg/min at peak exercise (p = 0.002) with the second treatment. The 6-min walk distance increased from 342 m at baseline to 386 m after the first treatment (p < 0.001) and to 416 m after the second treatment (p = 0.03). All improvements persisted after 12 months of therapy. Cardiac resynchronization therapy produces a long-term improvement in the clinical symptoms of patients with HF who have a ventricular conduction delay. The differences between optimized biventricular and univentricular therapy appear to be small for short-term treatment.

  2. Associations between physical therapy and long-term outcomes for individuals with lumbar spinal stenosis in the SPORT study.

    PubMed

    Fritz, Julie M; Lurie, Jon D; Zhao, Wenyan; Whitman, Julie M; Delitto, Anthony; Brennan, Gerard P; Weinstein, James N

    2014-08-01

    A period of nonsurgical management is advocated before surgical treatment for most patients with lumbar spinal stenosis. Currently, little evidence is available to define optimal nonsurgical management. Physical therapy is often used, however its use and effectiveness relative to other nonsurgical strategies has not been adequately explored. Describe the use of physical therapy and other nonsurgical interventions by patients with lumbar spinal stenosis and examine the relationship between physical therapy and long-term prognosis. Secondary analysis of the Spine Patient Outcomes Research Trial (SPORT) combining data from randomized and observational studies. Thirteen spine clinics in 11 states in the United States. Patients with lumbar spinal stenosis receiving nonsurgical management including those who did or did not receive physical therapy within 6 weeks of enrollment. Primary outcome measures included crossover to surgery, the bodily pain and physical function scales changes from the Survey Short Form 36 (SF-36), and the modified Oswestry Disability Index. Secondary outcome measures were patient satisfaction and the Sciatica Bothersomeness Index. Baseline characteristics and rates of crossover to surgery were compared between patients who did or did not receive physical therapy. Baseline factors predictive of receiving physical therapy were examined with logistic regression. Mixed effects models were used to compare outcomes between groups at 3 and 6 months and 1 year after enrollment adjusted for baseline severity and patient characteristics. Physical therapy was used in the first 6 weeks by 90 of 244 patients (37%) and was predicted by the absence of radiating pain and being single instead of married. Physical therapy was associated with a reduced likelihood of crossover to surgery after 1 year (21% vs. 33%, p=.045), and greater reductions on the Short Form 36 physical functioning scale after 6 months (mean difference=6.0, 95% confidence interval: 0

  3. The Associations Between Physical Therapy and Long-Term Outcomes for Individuals with Lumbar Spinal Stenosis in the SPORT study

    PubMed Central

    Fritz, Julie M.; Lurie, Jon D.; Zhao, Wenyan; Whitman, Julie M.; Delitto, Anthony; Brennan, Gerard P.; Weinstein, James N.

    2013-01-01

    Background/Context A period of non-surgical management is advocated prior to surgical treatment for most patients with lumbar spinal stenosis. Currently, little evidence is available to define optimal non-surgical management. Physical therapy is often used, however its use and effectiveness relative to other non-surgical strategies has not been adequately explored. Purpose Describe the utilization of physical therapy and other non-surgical interventions by patients with lumbar spinal stenosis and examine the relationship between physical therapy and long-term prognosis. Study Design Secondary analysis of the Spine Patient Outcomes Research Trial (SPORT) combining data from randomized and observational studies. Setting 13 spine clinics in 11 states in the United States. Patient Sample Patients with lumbar spinal stenosis receiving non-surgical management including those who did or did not receive physical therapy within 6 weeks of enrollment. Outcome Measures Primary outcome measures included cross-over to surgery, the bodily pain and physical function scales changes from the Survey Short Form 36 (SF-36), and the modified Oswestry Disability Index. Secondary outcome measures were patient satisfaction and the Sciatica Bothersomeness Index. Methods Baseline characteristics and rates of cross-over to surgery were compared between patients who did or did not receive physical therapy. Baseline factors predictive of receiving physical therapy were examined with logistic regression. Mixed effects models were used to compare outcomes between groups at 3 and 6 months, and 1 year after enrollment adjusted for baseline severity and patient characteristics. Results Physical therapy was used in the first 6 weeks by 90 of 244 patients (37%) and was predicted by the absence of radiating pain and being single instead of married. Physical therapy was associated with a reduced likelihood of cross-over to surgery after 1 year (21% vs 33%, p=0.045), and greater reductions on the SF-36

  4. Insulin therapy for management of type 2 diabetes mellitus: strategies for initiation and long-term patient adherence.

    PubMed

    Barag, Steven H

    2011-07-01

    Effective glycemic control is essential to minimize the long-term complications of type 2 diabetes mellitus (T2DM). However, it is well documented that many patients spend prolonged periods outside of the optimal glycemic range. The use of insulin is important to effectively control the disease process in patients with T2DM. Even so, resistance to insulin use among patients and healthcare providers often limits initiation and intensification of insulin therapy. With the increasing prevalence of T2DM across all socioeconomic strata, an expanded viewpoint of early and sustained insulin use is crucial to enhance glycemic control in patients. To manage the effects of T2DM on cardiovascular disease in the aging population, physicians can promote insulin therapy as an affordable and effective treatment option. The author reviews beliefs and myths about the use of insulin in the management of T2DM and discusses strategies to overcome barriers to initiation of insulin therapy in the primary care setting.

  5. Long-term maintenance therapy using rituximab-induced continuous B-cell depletion in patients with ANCA vasculitis.

    PubMed

    Pendergraft, William F; Cortazar, Frank B; Wenger, Julia; Murphy, Andrew P; Rhee, Eugene P; Laliberte, Karen A; Niles, John L

    2014-04-01

    Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission. A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined. In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase-ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS] = 0) was achieved in all patients. Major relapse (BVAS ≥ 3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population. This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted.

  6. Long-term monitoring of insulin sensitivity in growth hormone-deficient adults on substitutive recombinant human growth hormone therapy.

    PubMed

    Giavoli, Claudia; Porretti, Silvia; Ronchi, Cristina L; Cappiello, Vincenzo; Ferrante, Emanuele; Orsi, Emanuela; Arosio, Maura; Beck-Peccoz, Paolo

    2004-06-01

    Since the effects of recombinant human growth hormone (rhGH) replacement therapy on glucose metabolism are still a matter of debate, the aim of the present study was to evaluate the impact of long-term rhGH treatment on insulin sensitivity. Simple indices of insulin resistance (IR) and insulin sensitivity (IS), based on fasting glucose and insulin, such as the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin check index (QUICKI), were used to estimate the degree of IR and IS in 20 normoglycemic patients (11 men and 9 women; mean age, 44 +/- 14 years) with severe adult-onset GH deficiency (GHD). Measurements were determined at baseline and after 1 and 5 years of continuous rhGH therapy. Basal values were compared to those obtained in 20 healthy sex- and age-matched controls. Starting rhGH dose ranged from 3 to 8 microg/kg/d in keeping with sex and age, then doses were titrated according to insulin-like growth factor-I (IGF-I) levels. At baseline all patients had low IGF-I levels (10 +/- 5.4 nmol/L), high body mas index (BMI; 27.5 +/- 4 kg/m(2)), and elevated body fat percentage (BF%; 31.8 +/- 9.6). Fasting glucose and insulin levels, as well as HOMA-IR and QUICKI, did not differ significantly from those recorded in the control group. After 1 year of rhGH replacement therapy, normalization in IGF-I levels and a significant reduction in BF% were observed (P <.001), and these effects were maintained after 5 years of treatment. Fasting glucose increased from 79 +/- 10 to 87 +/- 13, and 87 +/- 12 mg/dL (P <.05) after 1 and 5 years of therapy, respectively. Fasting insulin significantly increased after 1 year, without further modifications in the long-term follow-up. HOMA-IR significantly increased from 2.1 +/- 1.7 to 2.5 +/- 1.7 (P <.05) after 1 year, then decreased to 2.3 +/- 1.5 (P = not significant [NS] v basal) after 5 years. A specular decrease in QUICKI from 0.37 +/- 0.05 to 0.34 +/- 0.03 (P <.01) occurred after 1 year, with

  7. Clinicopathologic features and long-term outcome of patients with medullary breast carcinoma managed with breast-conserving therapy (BCT)

    SciTech Connect

    Ha Vu-Nishino; Tavassoli, Fattaneh A.; Ahrens, Willam A.; Haffty, Bruce G. . E-mail: hafftybg@umdnj.edu

    2005-07-15

    Purpose: The purpose of this study is to compare the clinical characteristics and outcome of medullary carcinoma to infiltrating ductal carcinoma of the breast in a large cohort of conservatively managed patients with long-term follow-up. Methods and Materials: Chart records of patients with invasive breast cancer managed with breast-conserving therapy (BCT) at the therapeutic radiology facilities of Yale University School of Medicine before 2001 were reviewed. Forty-six cases (1971-2001) were identified with medullary histology; 1,444 patients with infiltrating ductal carcinoma served as a control group. Results: The medullary cohort presented at a younger age with a higher percentage of patients in the 35 years or younger age group (26.1% vs. 6.6%, p < 0.00001). Twelve patients with medullary histology underwent genetic screening, and 6 patients were identified with deleterious mutations. This group showed greater association with BRCA1/2 mutations compared with screened patients in the control group (50.0% vs. 15.8%, p 0.0035). The medullary cohort was also significantly associated with greater T stage and tumor size (37.0% vs. 17.2% T2, mean size 3.2 vs. 2.5 cm, p 0.00097) as well as negative ER (84.9% vs. 37.6%, p < 0.00001) and PR (87.5% vs. 48.1%, p = 0.00001) status. As of February 2003, median follow-up times for the medullary and control groups were 13.9 and 14.0 years, respectively. Although breast relapse-free rates were not significantly different (76.7% vs. 85.2%), 10-year distant relapse-free survival in the medullary cohort was significantly better than in the control group (94.9% vs. 77.5%, p = 0.028). Conclusions: Despite poor clinicopathologic features, patients with medullary histology demonstrate favorable long-term distant relapse-free survival. Local control rates of patients with medullary and infiltrating ductal carcinoma are comparable. These findings suggest that patients diagnosed with medullary carcinoma are appropriate candidates for

  8. Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications

    PubMed Central

    2014-01-01

    Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on long-term complications and associated conditions, the course of Gaucher disease was modelled. The cohort consisted of all diagnosed GD patients in the Netherlands. Mutually exclusive disease states were defined as ‘asymptomatic’, ‘signs/symptoms’, ‘recovery’, ‘splenectomy’, ‘bone complication’, ‘multiple complications’ and ‘malignancy’. A natural history (NH) cohort was delineated based upon historical data on Dutch patients before ERT was available. Cumulative incidence curves were composed for progression from each disease state to the next. Two scenarios were applied for the ERT cohort: time to complications was calculated from A. start of ERT; B. entering the previous disease state. Median time for the development of signs and/or symptoms was 30.1 years (N = 73). In the NH cohort (N = 42), 9% had developed a bone complication after 10 years in the signs/symptoms phase, while 21% had undergone a splenectomy. In the ERT cohort (N = 29 (A), N = 28 (B)), 12% (A) or 4% (B) had developed a bone complication after 10 years in this phase and no patient was splenectomized. No patients in the NH cohort recovered, compared to 50% in the ERT cohort after 3.6 years (N = 28 (A)) or 22.4 years (N = 27 (B)) of treatment. Median time from a first to a second complication was 11 years in the NH cohort (N = 31), whereas 16 respectively 14 percent had developed a second complication after 10 years in the ERT cohort (N = 17, scenario A/B). Fourteen percent (scenario A/B) developed an associated malignancy after 10 years in the phase ‘multiple complications’ (N = 23). Associated malignancies occurred almost exclusively in advanced disease stages, therefore it

  9. Do Autotransplanted Teeth Require Elective Root Canal Therapy? A Long-Term Follow-Up Case Series.

    PubMed

    Murtadha, Linda; Kwok, Jerry

    2017-09-01

    To determine the long-term survival and outcomes of 252 autotransplanted teeth with a novel root canal therapy (RCT) and follow-up protocol and to establish whether elective RCT after autotransplantation is routinely required for teeth with complete root formation. A retrospective analysis of 209 patients 10 to 58 years old, with a total of 252 autotransplants was carried out with a minimum observational period of 1 year and a maximum period of 29 years. Patients were reviewed at specified intervals. Only the teeth showing any radiographic or clinical signs of internal resorption (IR), external resorption (ER), or pulpal necrosis underwent RCT. A failure was considered the loss or extraction of the autotransplanted tooth. Ten of the 252 autotransplants constituted failures, with 249, 190, 155, 97, 70, and 35 teeth surviving at 1, 2, 3, 5, 7, and 10 years, respectively; the remainder were lost to follow-up. Eighteen percent of teeth (n = 46) showed radiographic signs of IR, ER, and apical pathology (AP). Most cases of ER were observed by 3 years (18 of 28 teeth) and then at 5 to -8 years. Only 3 teeth showed signs of IR, which were observed within 5 years. Most cases of AP were observed within the first year (8 of 15 teeth) and then at 3 to 6 years. Five teeth showed signs of pulp obliteration or sclerosis and did not require RCT, with a maximum period of 16 years after identification of sclerosis. Retrospective analysis of the data showed that 184 autotransplanted teeth had complete root formation and 68 had incomplete root formation at the time of autotransplantation. Of the teeth that were followed for at least 5 years, 59.3% had complete root formation with no signs of pathology and required no RCT. Despite the limitation of this long-term study of patients lost to follow-up, the results suggest that, with close monitoring, some autotransplanted teeth with complete root formation that do not undergo RCT could have the potential for revascularization

  10. Comparative evaluation of long-term monotherapies & combination therapies in patients with chronic hepatitis B: A pilot study

    PubMed Central

    Srivastava, Manjita; Singh, Neha; Dixit, Vinod Kumar; Nath, Gopal; Jain, Ashok Kumar

    2016-01-01

    Background & objectives: Reduction of viraemia in patients with chronic hepatitis B virus (HBV) infection using nucleoside/nucleotide analogues reduces fatal liver disease-related events, but development of resistance in virus presents serious clinical challenge. Therefore, comparative evaluation of prolonged antiviral monotherapy and combination therapies was prospectively studied to assess their influence on viral suppression, rapidity of response, development of drug resistance and surfacing mutants in chronic liver disease (CLD) patients. Methods: A total of 158 (62eAg-ve) chronic hepatitis B patients were prospectively studied for 24 months. Final analysis was performed on patients treated with lamivudine (LAM, n = 28), adefovirdipivoxil (ADV, n = 24), tenofovir disoproxil fumarate (TDF, n = 26), entecavir (ETV, n = 25), LAM + ADV (n = 28) and LAM + TDF (n = 27). Quantitative hepatitis B virus DNA was detected using real-time polymerase chain reaction. Multiple comparisons among drugs and genotypic mutations were analyzed. Results: Progressive biochemical and virological response were noted with all the regimens at 24 months except LAM and ADV which were associated with viral breakthrough (VBT) in 46.4 and 25 per cent, respectively. Mutations: rtM204V (39.3%), M204V+L180M (10.7%) while rtA181V (8.1%) and rtN236T (8.3%) were observed with LAM and ADV regimen, respectively. LAM + ADV combination therapy revealed VBT in seven per cent of the cases without mutations whereas TDF, ETV and LAM + TDF therapies neither showed VBT nor mutations. Interpretation & conclusions: LAM was the least potent drug among all therapeutic options followed by ADV. TDF and ETV were genetically stable antivirals with a strong efficacy. Among newer combination therapies, LAM + TDF revealed more efficacy in virological remission and acted as a profound genetic barrier on long term. Hence, newer generation molecules (TDF, ETV) and effective combination therapy should be a certain choice

  11. Recovery of menstruation after long-term chemotherapy and endocrine therapy in pre-menopausal patients with breast cancer.

    PubMed

    Sakurai, Kenichi; Enomoto, Katsuhisa; Amano, Sadao

    2011-04-01

    A luteinizing hormone-releasing hormone (LH-RH) agonist and tamoxifen (TAM) are used in hormonal therapy following pre- and post-operative chemotherapy in pre-menopausal advanced breast cancer patients who are positive for hormone receptors. However, it remains to be clarified how often patients recover menstruation after long-term LH-RH agonist plus TAM therapy. In this study, the incidence of menstruation recovery after therapy was examined. The subjects included 125 pre-menopausal patients with breast cancer who were positive for hormone receptors and had undergone surgery at our institution. They were treated with four cycles of the CEF regimen and four cycles of docetaxel (Doc) before surgery as adjuvant chemotherapy. Thereafter, they were treated with an LH-RH agonist plus TAM for 24 months and followed to determine menstruation recovery. Menstruation resumed in 24 cases (19.2%) after the last LH-RH agonist treatment session. It took 7.3 ± 2.8 months for the patients to recover menstruation. The rate of menstruation recovery was 42.1% in patients aged 40 or younger and 9.2% in those aged 41 or older; the difference was significant. The period until menstruation recovery tended to be longer in older patients at the end of treatment. The menstruation recovery rate after therapy was higher in younger women. However, since ovarian function may be lost even in younger patients, the potential consequences of this therapy should be fully explained beforehand to patients who may wish to become pregnant.

  12. Continuing Risk of Ipsilateral Breast Relapse After Breast-Conserving Therapy at Long-Term Follow-up

    SciTech Connect

    Kreike, Bas; Hart, Augustinus A.M.; Velde, Tony van de; Borger, Jacques; Peterse, Hans; Rutgers, Emiel; Bartelink, Harry; Vijver, Marc J. van de

    2008-07-15

    Purpose: Currently, the local treatment of most patients with early invasive breast cancer consists of breast-conserving therapy (BCT). We have previously reported on the risk factors for ipsilateral breast relapse (IBR) in 1,026 patients treated with BCT after a median follow-up of 5.5 years. In the present study, we evaluated the IBR incidence and the risk factors for IBR after prolonged follow-up. Methods and Materials: We updated the disease outcome for all 1,026 patients using the clinical information collected from the medical registration of The Netherlands Cancer Institute and performed step-wise proportional hazard Cox regression analysis to identify the risk factors associated with an increased risk of IBR after BCT at long-term follow-up. Results: After a median follow-up of 13.3 years, 114 patients had developed an IBR as the first event. The IBR rate was 9.3% and 13.8%, respectively, at 10 and 15 years. Also, the increase in IBR was continuous without reaching a plateau, even after 15 years. Univariate analysis showed that involved surgical resection margins, young age, vascular invasion, and the presence and quantity of an in situ component are risk factors for IBR. Multivariate analysis showed that tumor-positive surgical resection margins (hazard ratio, 2.9; 95% confidence interval, 1.7-5.2, p = 0.0002) or the presence of vascular invasion (hazard ratio, 2.0; 95% confidence interval, 1.2-3.2, p = 0.004) is the major independent risk factor for IBR. Conclusions: The data from long-term follow-up showed a constant increase in IBR among patients treated by BCT, even after 15 years, without reaching a plateau. Involved surgical resection margins and vascular invasion were the most important risk factors for IBR.

  13. Rape-related symptoms in adolescents: short- and long-term outcome after cognitive behavior group therapy

    PubMed Central

    Bicanic, Iva; de Roos, Carlijn; van Wesel, Floryt; Sinnema, Gerben; van de Putte, Elise

    2014-01-01

    Background Efficacy studies on treatment in adolescent victims of single rape are lacking, even though sexual victimization is most likely to occur during adolescence and despite the fact that adolescents are at risk to develop subsequent posttraumatic stress disorder. Aim The aim of this prospective observational study was to evaluate the short- and long-term outcomes of a nine-session cognitive behavior group therapy (STEPS), including a parallel six-session parents’ group on rape-related symptomatology in female adolescents (13–18 years). STEPS includes psychoeducation, exposure in sensu as well as in vivo, cognitive restructuring, and relapse prevention. Methods Fifty-five female adolescents with mental health problems due to single rape, but without prior sexual trauma, received STEPS while their parents participated in a support group. Subjects were assessed on posttraumatic stress (PTS) and comorbid symptoms using self-report questionnaires prior to and directly after treatment, and at 6 and 12 months follow-up. Results Repeated measures analysis showed a significant and large decrease in symptoms of PTS, anxiety, depression, anger, dissociation, sexual concerns, and behavior problems directly after treatment, which maintained at 12 months follow-up. Time since trauma did not influence the results. Dropout during STEPS was 1.8%. Conclusions The results potentially suggest that the positive treatment outcomes at short- and long-term may be caused by STEPS. The encouraging findings need confirmation in future controlled studies on the effectiveness of STEPS because it may be possible that the treatment works especially well for more chronic symptoms, while the less chronic part of the sample showed considerable improvement on its own. PMID:24936285

  14. Ribozyme rescue of photoreceptor cells in P23H transgenic rats: long-term survival and late-stage therapy.

    PubMed

    LaVail, M M; Yasumura, D; Matthes, M T; Drenser, K A; Flannery, J G; Lewin, A S; Hauswirth, W W

    2000-10-10

    Ribozyme-directed cleavage of mutant mRNAs appears to be a potentially effective therapeutic measure for dominantly inherited diseases. We previously demonstrated that two ribozymes targeted to the P23H mutation in rhodopsin slow photoreceptor degeneration in transgenic rats for up to 3 months of age when injected before significant degeneration at postnatal day (P) 15. We now have explored whether ribozyme rescue persists at older ages, and whether ribozymes are effective when injected later in the degeneration after significant photoreceptor cell loss. Recombinant adeno-associated virus (rAAV) vectors incorporating a proximal bovine rod opsin promoter were used to transfer either hairpin or hammerhead ribozyme genes to photoreceptors. For the study of long-term survival, rAAV was administered by subretinal injection at P15, and the rats were allowed to live up to 8 months of age. For the study of late-stage gene transfer, rAAV was administered at P30 or P45, when 40-45% of the photoreceptors already had degenerated. Eyes were examined functionally by the electroretinogram and structurally by morphometric analysis. When injected at P15, expression of either ribozyme markedly slowed the rate of photoreceptor degeneration for at least 8 months and resulted in significantly greater electroretinogram amplitudes at least up to P180. When injected at P30 or P45, virtually the same number of photoreceptors survived at P130 as when injected at P15. Ribozyme rescue appears to be a potentially effective, long-term therapy for autosomal dominant retinal degeneration and is highly effective even when the gene transfer is done after significant photoreceptor cell loss.

  15. Self-Reported Long-Term Benefits of Mindfulness-Based Cognitive Therapy in Patients with Bipolar Disorder.

    PubMed

    Weber, Béatrice; Sala, Loretta; Gex-Fabry, Marianne; Docteur, Aurélie; Gorwood, Philip; Cordera, Paolo; Bondolfi, Guido; Jermann, Françoise; Aubry, Jean-Michel; Mirabel-Sarron, Christine

    2017-07-01

    This study focused on patients with bipolar disorder (BD), several years after their participation in mindfulness-based cognitive therapy (MBCT). It aimed at documenting sustained mindfulness practice, perceived long-term benefit from the program, and changes regarded as direct consequences of the intervention. This cross-sectional survey took place at least 2 years after MBCT for 70.4% of participants. It was conducted in two specialized outpatient units for BDs that are part of the Geneva University Hospitals (Switzerland) and the Sainte-Anne Hospital in Paris (France). Eligibility criteria were a diagnosis of BD according to DSM-IV and participation in at least four MBCT sessions. Response rate was 66.4%. The final sample included 71 outpatients (71.8% bipolar I, 28.2% bipolar II). A questionnaire retrospectively assessed patient-perceived change, benefit from MBCT, and current mindfulness practice. Proportions of respondents who practiced mindfulness at least once a week were 54.9% for formal practice (body scan, sitting meditation, mindful walking, or movements) and 57.7% for informal practice (mindful daily activities). Perceived benefit for the prevention of relapse was moderate, but patients acknowledged long-lasting effects and persistent changes in their way of life. Formal mindfulness practice at least once a week tended to be associated with increased long-lasting effects (p = 0.052), whereas regular informal practice and mindful breathing were significantly associated with persistent changes in daily life (p = 0.038) and better prevention of depressive relapse (p = 0.035), respectively. The most frequently reported positive change was increased awareness of being able to improve one's health. Despite methodological limitations, this survey allowed documenting mindfulness practice and perceived sustained benefit from MBCT in patients with BD. Participants particularly valued increased awareness that they can influence their own health. Both

  16. Nonrandomized Intervention Study of Naloxone Coprescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain.

    PubMed

    Coffin, Phillip O; Behar, Emily; Rowe, Christopher; Santos, Glenn-Milo; Coffa, Diana; Bald, Matthew; Vittinghoff, Eric

    2016-08-16

    Unintentional overdose involving opioid analgesics is a leading cause of injury-related death in the United States. To evaluate the feasibility and effect of implementing naloxone prescription to patients prescribed opioids for chronic pain. 2-year nonrandomized intervention study. 6 safety-net primary care clinics in San Francisco, California. 1985 adults receiving long-term opioid therapy for pain. Providers and clinic staff were trained and supported in naloxone prescribing. Outcomes were proportion of patients prescribed naloxone, opioid-related emergency department (ED) visits, and prescribed opioid dose based on chart review. 38.2% of 1985 patients receiving long-term opioids were prescribed naloxone. Patients prescribed higher doses of opioids and with an opioid-related ED visit in the past 12 months were independently more likely to be prescribed naloxone. Patients who received a naloxone prescription had 47% fewer opioid-related ED visits per month in the 6 months after receipt of the prescription (incidence rate ratio [IRR], 0.53 [95% CI, 0.34 to 0.83]; P = 0.005) and 63% fewer visits after 1 year (IRR, 0.37 [CI, 0.22 to 0.64]; P < 0.001) compared with patients who did not receive naloxone. There was no net change over time in opioid dose among those who received naloxone and those who did not (IRR, 1.03 [CI, 0.91 to 1.27]; P = 0.61). Results are observational and may not be generalizable beyond safety-net settings. Naloxone can be coprescribed to primary care patients prescribed opioids for pain. When advised to offer naloxone to all patients receiving opioids, providers may prioritize those with established risk factors. Providing naloxone in primary care settings may have ancillary benefits, such as reducing opioid-related adverse events. National Institutes of Health.

  17. Long-Term γ-Hydroxybutyric Acid (GHB) and Disulfiram Combination Therapy in GHB Treatment-Resistant Chronic Alcoholics

    PubMed Central

    Maremmani, Angelo Giovanni Icro; Pani, Pier Paolo; Rovai, Luca; Pacini, Matteo; Dell’Osso, Liliana; Maremmani, Icro

    2011-01-01

    Leading Italian studies support the use of γ-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30–40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of ‘antagonist’ effect by using the ‘psychological threat’ of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its ‘non-blockade’ effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis. PMID:21845160

  18. Bone mineral density, microarchitectural and mechanical alterations of osteoporotic rat bone under long-term whole-body vibration therapy.

    PubMed

    Xie, Pengfei; Tang, Zhurong; Qing, Fangzhu; Chen, Xuening; Zhu, Xiangdong; Fan, Yujiang; Yang, Xiao; Zhang, Xingdong

    2016-01-01

    Low-magnitude, high-frequency whole body vibration (WBV) is receiving increasing interest as a non-pharmacological anti-osteoporosis approach. However, the long-term effect of WBV therapy is seldom studied. In this study, the efficacy of 16-week WBV (0.3g, 30 Hz) on bone mineral density (BMD), microarchitectural parameters and mechanical properties of ovariectomized rat femur were examined by in vivo peripheral quantitative computed tomography (pQCT), ex vivo micro-computed tomography (µCT), dynamic mechanical analysis (DMA) and fracture test. To the best of our knowledge, 16 weeks of WBV administration (20 min/day) is currently the longest duration on rodent. The longitudinal BMD change showed that positive effect of WBV on ovariectomized rat femoral neck diminished with prolonged administration duration. In addition, 16-week of WBV treatment was found to cause significantly reduction in the mean BMD, trabecular BMD (Tb.BMD), trabecular bone volume ration (BV/TV), trabecular number (Tb.N) and maximum load in femoral neck of ovariectomized rat. Metaphyseal Tb.BMD and BV/TV were also significantly decreased in WBV treated ovariectomized group than non-treated controls. Whole-femur DMA was demonstrated as a sensitive tool in distinguishing osteoporotic femur from healthy aged-matched controls, in terms of decreased storage modulus (E') and loss factor (tan δ). However, E' and tan δ are not enhanced by 16-week WBV treatment. Together, these findings indicate that administration duration played an important role in the effect of WBV. 16-week WBV may exacerbate trabecular bone loss in ovariectomized rat femur, especially in trabecular-rich femoral neck region. An optimal WBV protocol including administration duration should be established prior to long-term clinical practice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Long-Term Outcomes of Fractionated Stereotactic Radiation Therapy for Pituitary Adenomas at the BC Cancer Agency

    SciTech Connect

    Kim, Julian O.; Ma, Roy; Akagami, Ryojo; McKenzie, Michael; Johnson, Michelle; Gete, Ermias; Nichol, Alan

    2013-11-01

    Purpose: To assess the long-term disease control and toxicity outcomes of fractionated stereotactic radiation therapy (FSRT) in patients with pituitary adenomas treated at the BC Cancer Agency. Methods and Materials: To ensure a minimum of 5 years of clinical follow-up, this study identified a cohort of 76 patients treated consecutively with FSRT between 1998 and 2007 for pituitary adenomas: 71% (54/76) had nonfunctioning and 29% (22/76) had functioning adenomas (15 adrenocorticotrophic hormone-secreting, 5 growth hormone-secreting, and 2 prolactin-secreting). Surgery was used before FSRT in 96% (73/76) of patients. A median isocenter dose of 50.4 Gy was delivered in 28 fractions, with 100% of the planning target volume covered by the 90% isodose. Patients were followed up clinically by endocrinologists, ophthalmologists, and radiation oncologists. Serial magnetic resonance imaging was used to assess tumor response. Results: With a median follow-up time of 6.8 years (range, 0.6 - 13.1 years), the 7-year progression-free survival was 97.1% and disease-specific survival was 100%. Of the 2 patients with tumor progression, both had disease control after salvage surgery. Of the 22 patients with functioning adenomas, 50% (11/22) had complete and 9% (2/22) had partial responses after FSRT. Of the patients with normal pituitary function at baseline, 48% (14/29) experienced 1 or more hormone deficiencies after FSRT. Although 79% (60/76) of optic chiasms were at least partially within the planning target volumes, no patient experienced radiation-induced optic neuropathy. No patient experienced radionecrosis. No secondary malignancy occurred during follow-up. Conclusion: In this study of long-term follow-up of patients treated for pituitary adenomas, FSRT was safe and effective.

  20. Long-term γ-hydroxybutyric acid (GHB) and disulfiram combination therapy in GHB treatment-resistant chronic alcoholics.

    PubMed

    Maremmani, Angelo Giovanni Icro; Pani, Pier Paolo; Rovai, Luca; Pacini, Matteo; Dell'Osso, Liliana; Maremmani, Icro

    2011-07-01

    Leading Italian studies support the use of γ-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30-40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of 'antagonist' effect by using the 'psychological threat' of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its 'non-blockade' effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.

  1. Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder.

    PubMed

    Sayer, Gregory R; McGough, James J; Levitt, Jennifer; Cowen, Jennifer; Sturm, Alexandra; Castelo, Edward; McCracken, James T

    2016-12-01

    This study examines cardiovascular (CV) effects of guanfacine immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and their combination (COMB) during acute and long-term treatment of youth with attention-deficit/hyperactivity disorder. Two hundred seven participants aged 7-14 years enrolled in an 8-week double-blind randomized trial of GUAN-IR (1-3 milligrams (mg)/day), DMPH (5-20 mg/day), or COMB with fixed-flexible dosing and titrated to optimal behavioral response. Heart rate, systolic blood pressure (BP), diastolic BP, and electrocardiograms were assessed at baseline, end of blinded optimization, and over a 1-year open-label maintenance phase. During acute titration, GUAN-IR decreased heart rate, systolic BP, and diastolic BP; DMPH increased heart rate, systolic BP, diastolic BP, and corrected QT (QTc) interval; COMB increased diastolic BP, but had no effects on heart rate, systolic BP, or QTc. During maintenance, GUAN-IR-associated decreases in heart rate and DMPH-associated increases in systolic BP returned to baseline values. Other variables across the three groups remained unchanged from the end of blinded titration. There were no discontinuations due to CV adverse events. GUAN-IR, DMPH, and COMB were well tolerated and safe. Expected changes in CV parameters during acute titration were seen in GUAN-IR and DMPH groups, with COMB values falling intermediately between the two other treatment groups. No serious CV events occurred in any participant. GUAN-IR- and DMPH-associated CV changes generally returned to baseline with sustained therapy. These data suggest that COMB treatment might attenuate long-term CV effects of GUAN-IR and stimulant monotherapy, possibly reducing risk of the small but statistically significant changes associated with either single treatment. Clinicaltrials.gov Identifier: NCT00429273.

  2. Inverse Relationship of Blood Pressure to Long-Term Outcomes and Benefit of Cardiac Resynchronization Therapy in Patients With Mild Heart Failure: A Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy Long-Term Follow-Up Substudy.

    PubMed

    Biton, Yitschak; Moss, Arthur J; Kutyifa, Valentina; Mathias, Andrew; Sherazi, Saadia; Zareba, Wojciech; McNitt, Scott; Polonsky, Bronislava; Barsheshet, Alon; Brown, Mary W; Goldenberg, Ilan

    2015-09-01

    Previous studies have shown that low blood pressure is associated with increased mortality and heart failure (HF) in patients with left ventricular dysfunction. Cardiac resynchronization therapy (CRT) was shown to increase systolic blood pressure (SBP). Therefore, we hypothesized that treatment with CRT would provide incremental benefit in patients with lower SBP values. The independent contribution of SBP to outcome was analyzed in 1267 patients with left bundle brunch block enrolled in Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). SBP was assessed as continuous measures and further categorized into approximate quintiles. The risk of long-term HF or death and CRT with defibrillator versus implantable cardioverter defibrillator benefit was assessed in multivariate Cox proportional hazards regression models. Multivariate analysis showed that in the implantable cardioverter defibrillator arm, each 10-mm Hg decrement of SBP was independently associated with a significant 21% (P<0.001) increased risk for HF or death, and patients with lower quintile SBP (<110 mm Hg) experienced a corresponding >2-fold risk-increase. CRT with defibrillator provided the greatest HF or mortality risk reduction in patients with SBP<110 mm Hg hazard ratio of 0.34, P<0.001, when compared with hazard ratio of 0.52, P<0.001, in those with 110>SBP≥136 mm Hg and hazard ratio of 0.94, P=0.808, with SBP>136 mm Hg (P for trend=0.001). In patients with mild HF, prolonged QRS, and left bundle brunch block, low SBP is related to higher risk of mortality or HF with implantable cardioverter defibrillator therapy alone. Treatment with CRT is associated with incremental clinical benefits in patients with lower baseline SBP values. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271. © 2015 American Heart Association, Inc.

  3. Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

    SciTech Connect

    Fujita, Tetsuo; Teh, Bin S.; Mai, W.-Y.; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

    2006-05-01

    Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR{sup +}CD8{sup +} T cells were increased at all timepoints up to 8 months. The mean percentages of DR{sup +}CD4{sup +} T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer.

  4. Protein Kinase C β: a New Target Therapy to Prevent the Long-Term Atypical Antipsychotic-Induced Weight Gain.

    PubMed

    Rimessi, Alessandro; Pavan, Chiara; Ioannidi, Elli; Nigro, Federica; Morganti, Claudia; Brugnoli, Alberto; Longo, Francesco; Gardin, Chiara; Ferroni, Letizia; Morari, Michele; Vindigni, Vincenzo; Zavan, Barbara; Pinton, Paolo

    2017-02-15

    Antipsychotic drugs are currently used in clinical practice for a variety of mental disorders. Among them, clozapine is the most effective medication for treatment-resistant schizophrenia and is most helpful in controlling aggression and the suicidal behavior in schizophrenia and schizoaffective disorder. Although clozapine is associated with a low likelihood of extrapyramidal symptoms and other neurological side effects, it is well known for the weight gain and metabolic side effects, which expose the patient to a greater risk of cardiovascular disorders and premature death, as well as psychosocial issues, leading to non-adherence to therapy. The mechanisms underlying these iatrogenic metabolic disorders are still controversial. We have therefore investigated the in vivo effects of the selective PKCβ inhibitor, ruboxistaurin (LY-333531), in a preclinical model of long-term clozapine-induced weight gain. Cell biology, biochemistry, and behavioral tests have been performed in wild-type and PKCβ knockout mice to investigate the contribution of endogenous PKCβ and its pharmacological inhibition to the psychomotor effects of clozapine. Finally, we also shed light on a novel aspect of the mechanism underlying the clozapine-induced weight gain, demonstrating that the clozapine-dependent PKCβ activation promotes the inhibition of the lipid droplet-selective autophagy process. This paves the way to new therapeutic approaches to this serious complication of clozapine therapy.Neuropsychopharmacology advance online publication, 15 February 2017; doi:10.1038/npp.2017.20.

  5. Progressive cutaneous Cryptococcosis complicated with meningitis in a myasthenia gravis patient on long-term immunosuppressive therapy - a case report.

    PubMed

    Huong, Nguyen Thi Cam; Altibi, Ahmed M A; Hoa, Nguyen My; Tuan, Le Anh; Salman, Samar; Morsy, Sara; Lien, Nguyen Thi Bich; Truong, Nguyen Thanh; Mai, Nguyen Thi Hoang; Hoa, Pham Thi Le; Thang, Nguyen Ba; Trung, Van The

    2017-04-26

    Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus neoformans and most remarkably manifests in HIV-infected individuals, especially in the settings of very low CD4 count. Development of cryptococcosis in HIV-uninfected individuals is exceedingly rare and usually signifies a marked immunodeficiency. Cryptococcosis in association with myasthenia gravis or thymoma has been previously documented in only very few cases in the literature. We reported a complicated case of severe cutaneous cryptococcosis in a 39-year-old Vietnamese male patient with myasthenia gravis on long-term immunosuppressive therapy. The patient presented with a five month history of recurrent and progressive skin lesions that later on progressed into cryptococcal meningitis. Through this case, we aimed to emphasize the importance of including cutaneous cryptococcosis in the differential diagnosis of cutaneous lesions in patients on chronic immunosuppressive therapy. The cutaneous manifestations of cryptococcosis can be the first clue for a disseminated disease, which makes early recognition crucial and life-saving.

  6. Sustained remission after long-term biological therapy in patients with large vessel vasculitis: an analysis of ten cases.

    PubMed

    Vinicki, Juan P; García-Vicuña, Rosario; Arredondo, Miguel; López-Bote, Juan P; García-Vadillo, Jesús A; Castañeda, Santos; Álvaro-Gracia, José M

    To describe the results obtained in clinical practice with the use of biological therapy (BT) in patients diagnosed with Takayasu arteritis (TA) and giant cell arteritis (GCA). Retrospective single center study of TA/GCA patients who received BT (infliximab [IFX], etanercept [ETN] and tocilizumab [TCZ]). In TA, active disease was defined according to a previous National Institutes of Health study. In GCA, active disease was defined with a modified criteria and clinical manifestations secondary to temporal artery involvement or polymyalgia rheumatica symptoms. Clinical data and outcomes are reported using descriptive statistics. Five patients with TA and 5 with GCA were included. The main reason for starting BT was lack of response to prior therapy and/or ≥2 relapses during GC tapering. Five patients started IFX, four TCZ and 1 ETN. Remission was observed before 6 months in all cases. Only one patient had a relapse during long-term follow-up and the overall GC daily dose was reduced by 70%. Two AEs were considered attributable to IFX and one to TCZ. A favorable and sustained response to BT was observed in our patients with TA and GCA. Thus, BT might be considered as an alternative in patients with large vessel arteritis refractory to conventional treatment or with GC related comorbidities. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  7. Long-term follow-up study of compensated low-dose /sup 131/I therapy for Graves' disease

    SciTech Connect

    Sridama, V.; McCormick, M.; Kaplan, E.L.; Fauchet, R.; DeGroot, L.J.

    1984-08-16

    We treated 187 patients who had Graves' disease with low-dose radioactive iodide (/sup 131/I), using a protocol that included a compensation for thyroid size. The incidence of early hypothyroidism (12 per cent) was acceptably low in the first year after /sup 131/I treatment, but we found a cumulative high incidence (up to 76 per cent) at the end of the 11th year. In contrast, the incidence of permanent hypothyroidism was relatively stable in 166 surgically treated patients, increasing from 19 to 27 per cent at the end of 11 years. Among 122 medically treated patients, only 40 per cent entered remission, and hypothyroidism developed in 2 per cent during the same period of follow-up. The long-term incidence of hypothyroidism in our patients treated with low-dose /sup 131/I therapy was much higher than that found in earlier studies using a comparable dose. Our study suggests that it will be difficult to modify therapy with /sup 131/I alone to produce both early control of thyrotoxicosis and a low incidence of hypothyroidism.

  8. Discordance between genotypic resistance and pseudovirus phenotypic resistance in AIDS patients after long-term antiretroviral therapy and virological failure.

    PubMed

    Yang, Jing; Geng, Wenqing; Zhang, Min; Han, Xiaoxu; Shang, Hong

    2014-10-01

    Sixteen original recombinant pseudoviruses were generated by cloning the reverse transcriptase and protease genes of human immunodeficiency virus (HIV)-1 from patients into a plasmid vector (pNL4-3-ΔE-EGFP). By site-directed mutagenesis two restriction endonuclease sites, ApaI and AgeI, were inserted into pNL4-3-ΔE-EGFP. Phenotypic susceptibility of recombinant pseudoviruses to five different classes of antiretroviral drugs was determined using a luciferase reporter assay system. The results were subjected to comparative analyses to detect genotype-phenotype associations. Among 16 strains tested, 12 strains had a discordant genotype-phenotype resistance pattern to at least one drug. In five strains resistance to two, in two strains to three, and in one strain resistance to four drugs was detected. HIV resistance genotyping could predict the phenotype for nevirapine and azidothymidine. For lamivudine, 2'-3'-didehydro-2'-3'dideoxythymidine and didanosine, phenotypic resistance testing was necessary. The study showed that in patients who experienced long-term highly active antiretroviral therapy and virological failure, there is some discordance between genotypic and phenotypic HIV drug resistance. To address the issue of limited resources in China, genotypic and phenotypic resistance testing should be done for different drugs in order to guide clinical therapy more effectively.

  9. Pregnancy outcomes in HIV-infected women receiving long-term isoniazid prophylaxis for tuberculosis and antiretroviral therapy.

    PubMed

    Taylor, Allan W; Mosimaneotsile, Barudi; Mathebula, Unami; Mathoma, Anikie; Moathlodi, Ritah; Theebetsile, Irene; Samandari, Taraz

    2013-01-01

    While 6- to 12-month courses of isoniazid for tuberculosis prevention are considered safe in pregnant women, the effects of longer-term isoniazid prophylaxis or isoniazid in combination with antiretroviral therapy (ART) are not established in human-immunodeficiency-virus-(HIV-) infected women who experience pregnancy during the course of therapy. Nested study of pregnancy outcomes among HIV-infected women participating in a placebo-controlled, TB-prevention trial using 36 months daily isoniazid. Pregnancy outcomes were collected by interview and record review. Among 196 pregnant women, 103 (52.6%) were exposed to isoniazid during pregnancy; all were exposed to antiretroviral drugs. Prior to pregnancy they had received a median of 341 days (range 1-1095) of isoniazid. We observed no isoniazid-associated hepatitis or other severe isoniazid-associated adverse events in the 103 women. Pregnancy outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital abnormality. In a multivariable model, neither isoniazid nor ART exposure during pregnancy was significantly associated with adverse pregnancy outcome (adjusted odds ratios 0.6, 95% CI: 0.3-1.1 and 1.8, 95% CI 0.9-3.6, resp.). Long-term isoniazid prophylaxis was not associated with adverse pregnancy outcomes, such as preterm delivery, even in the context of ART exposure.

  10. Pregnancy Outcomes in HIV-Infected Women Receiving Long-Term Isoniazid Prophylaxis for Tuberculosis and Antiretroviral Therapy

    PubMed Central

    Taylor, Allan W.; Mosimaneotsile, Barudi; Mathebula, Unami; Mathoma, Anikie; Moathlodi, Ritah; Theebetsile, Irene; Samandari, Taraz

    2013-01-01

    Objective. While 6- to 12-month courses of isoniazid for tuberculosis prevention are considered safe in pregnant women, the effects of longer-term isoniazid prophylaxis or isoniazid in combination with antiretroviral therapy (ART) are not established in human-immunodeficiency-virus-(HIV-) infected women who experience pregnancy during the course of therapy. Design. Nested study of pregnancy outcomes among HIV-infected women participating in a placebo-controlled, TB-prevention trial using 36 months daily isoniazid. Pregnancy outcomes were collected by interview and record review. Results. Among 196 pregnant women, 103 (52.6%) were exposed to isoniazid during pregnancy; all were exposed to antiretroviral drugs. Prior to pregnancy they had received a median of 341 days (range 1–1095) of isoniazid. We observed no isoniazid-associated hepatitis or other severe isoniazid-associated adverse events in the 103 women. Pregnancy outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital abnormality. In a multivariable model, neither isoniazid nor ART exposure during pregnancy was significantly associated with adverse pregnancy outcome (adjusted odds ratios 0.6, 95% CI: 0.3–1.1 and 1.8, 95% CI 0.9–3.6, resp.). Conclusions. Long-term isoniazid prophylaxis was not associated with adverse pregnancy outcomes, such as preterm delivery, even in the context of ART exposure. PMID:23533318

  11. Long-term effects of growth hormone replacement therapy on thyroid function in adults with growth hormone deficiency.

    PubMed

    Losa, Marco; Scavini, Marina; Gatti, Elisa; Rossini, Alessandro; Madaschi, Sara; Formenti, Ilaria; Caumo, Andrea; Stidley, Christine A; Lanzi, Roberto

    2008-12-01

    Clinical studies on the effect of growth hormone (GH) on thyroid function in patients with GH deficiency are contradictory. Further, the majority of published observations are limited to the first 6-12 months of GH replacement therapy. The aim of our study was to estimate the incidence of clinically relevant hypothyroidism in a cohort of patients with adult GH deficiency (AGHD) during long-term therapy with recombinant human GH (rhGH). The study was designed as a retrospective collection of data on thyroid function in 49 AGHD patients of whom 44 (90%) had multiple hormone deficiency. Thirty-seven patients (76%) were on stable levothyroxine (LT4) replacement therapy (HYPO), and 12 (24%) were euthyroid (EUT). Therapy with rhGH was started at a dose of 3.5 microg/kg body weight and adjusted according to insulin-like growth factor-I (IGF-I) levels. At baseline, 6 months, 12 months, and yearly thereafter we measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, and IGF-I. Study outcome was fT4 level below the normal range (9 pmol/L), irrespectively of fT3 or thyroid-stimulating hormone levels. During a follow-up of 115 patient-years, mean fT4 level decreased significantly, although remaining within the normal range (p = 0.0242; month 48 vs. baseline). The largest decrease was between baseline and month 6, when fT4 decreased of 1.43 pmol/L (95% confidence interval, 0.33-2.53) per 1 unit (microg/kg body weight) increase in rhGH dose. The incidence of hypothyroidism was 1.2 (HYPO group) and 6.7 (EUT group) events per 100 patient-years. We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs.

  12. Surgical Experience and Long-term Results of Baroreflex Activation Therapy for Heart Failure With Reduced Ejection Fraction.

    PubMed

    Weaver, Fred A; Abraham, William T; Little, William C; Butter, Christian; Ducharme, Anique; Halbach, Marcel; Klug, Didier; Lovett, Eric G; Madershahian, Navid; Müller-Ehmsen, Jochen; Schafer, Jill E; Senni, Michele; Swarup, Vijay; Wachter, Rolf; Zile, Michael R

    2016-01-01

    The purpose of this publication is to describe the intraoperative experience along with long-term safety and efficacy of the second-generation baroreflex activation therapy (BAT) system in patients with heart failure (HF) and reduced ejection fraction HF (HFrEF). In a randomized trial of New York Heart Association Class III HFrEF, 140 patients were assigned 1:1 to receive BAT plus medical therapy or medical therapy alone. Procedural information along with safety and efficacy data were collected and analyzed over 12 months. Within the cohort of 71 patients randomized to BAT, implant procedure time decreased with experience, from 106 ± 37 minutes on the first case to 83 ± 32 minutes on the third case. The rate of freedom from system- and procedure-related complications was 86% through 12 months, with the percentage of days alive without a complication related to system, procedure, or underlying cardiovascular condition identical to the control group. The complications that did occur were generally mild and short-lived. Overall, 12 months therapeutic benefit from BAT was consistent with previously reported efficacy through 6 months: there was a significant and sustained beneficial treatment effect on New York Heart Association functional Class, quality of life, 6-minute hall walk distance, plasma N-terminal pro-brain natriuretic peptide, and systolic blood pressure. This was true for the full trial cohort and a predefined subset not receiving cardiac resynchronization therapy. There is a rapid learning curve for the specialized procedures entailed in a BAT system implant. BAT system implantation is safe with the therapeutic benefits of BAT in patients with HFrEF being substantial and maintained for at least 1 year.

  13. The Modern Role of Radiation Therapy in Treating Advanced-Stage Retinoblastoma: Long-Term Outcomes and Racial Differences

    SciTech Connect

    Orman, Amber; Koru-Sengul, Tulay; Miao, Feng; Markoe, Arnold; Panoff, Joseph E.

    2014-12-01

    Purpose/Objective(s): To evaluate the effects of various patient characteristics and radiation therapy treatment variables on outcomes in advanced-stage retinoblastoma. Methods and Materials: This was a retrospective review of 41 eyes of 30 patients treated with external beam radiation therapy between June 1, 1992, and March 31, 2012, with a median follow-up time of 133 months (11 years). Outcome measures included overall survival, progression-free survival, local control, eye preservation rate, and toxicity. Results: Over 90% of the eyes were stage V. Definitive external beam radiation therapy (EBRT) was delivered in 43.9% of eyes, adjuvant EBRT in 22% of eyes, and second-line/salvage EBRT in 34.1% of eyes. A relative lens sparing (RLS) technique was used in 68.3% of eyes and modified lens sparing (MLS) in 24.4% of eyes. Three eyes were treated with other techniques. Doses ≥45 Gy were used in 68.3% of eyes. Chemotherapy was a component of treatment in 53.7% of eyes. The 10-year overall survival was 87.7%, progression-free survival was 80.5%, and local control was 87.8%. White patients had significantly better overall survival than did African-American patients in univariate analysis (hazard ratio 0.09; 95% confidence interval 0.01-0.84; P=.035). Toxicity was seen in 68.3% of eyes, including 24.3% with isolated acute dermatitis. Conclusions: External beam radiation therapy continues to be an effective treatment modality for advanced retinoblastoma, achieving excellent long-term local control and survival with low rates of treatment-related toxicity and secondary malignancy.

  14. Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti-inflammatory effect.

    PubMed

    Nelson, David R; Tu, Zhengkun; Soldevila-Pico, Consuelo; Abdelmalek, Manal; Zhu, Haizhen; Xu, Yi Ling; Cabrera, Roniel; Liu, Chen; Davis, Gary L

    2003-10-01

    An imbalance in Th1 and Th2 cytokine production is implicated in disease progression of HCV. Our aim was to determine the effect of IL-10 administration in patients with HCV-related liver disease. Thirty patients with advanced fibrosis who had failed antiviral therapy were enrolled in a 12-month treatment regimen with SQ IL-10 given daily or thrice weekly. Liver biopsies were performed before and after therapy. Serum and PBMC were collected for HCV RNA, ALT, and functional T-cell analysis. IL-10 led to significant improvement in serum ALT (mean ALT: day 0 = 142 +/- 17 vs. month 12 = 75 +/- 10; P <.05). Hepatic inflammation score decreased by at least 2 in 13 of 28 patients (mean decrease from 4.6 +/- 0.3 to 3.7 +/- 0.3, P <.05) and 11 of 28 showed a reduction in fibrosis score (mean change from 5.0 +/- 0.2 to 4.5 +/- 0.3, P <.05). Serum HCV RNA levels increased by 0.5 log during therapy (mean HCV RNA day 0: 12.3 +/- 3.0 Meq/mL; 12 months: 38 Meq/mL; P <.05) and returned to baseline at the end of follow-up (11.0 +/- 2.4 Meq/mL). Five patients developed viral loads of greater than 120 Meq/mL and two of these developed an acute flare in serum ALT. IL-10 caused a decrease in the number of HCV-specific CD4+ and CD8+ IFN-gamma secreting T cells and alterations in PBMC cytokine production towards a Th2 dominant profile. These changes parallel the improvement in ALT and rise in HCV RNA. In conclusion, long-term rIL-10 therapy appears to decrease disease activity, but also leads to increased HCV viral burden via alterations in immunologic viral surveillance.

  15. Outcome of Long-term Maintenance Steroid Therapy Cessation in Patients With Autoimmune Pancreatitis: A Prospective Study.

    PubMed

    Hirano, Kenji; Tada, Minoru; Isayama, Hiroyuki; Sasahira, Naoki; Umefune, Gyotane; Akiyama, Dai; Watanabe, Takeo; Saito, Tomotaka; Takagi, Kaoru; Takahara, Naminatsu; Hamada, Tsuyoshi; Mizuno, Suguru; Miyabayashi, Koji; Mohri, Dai; Kogure, Hirofumi; Yamamoto, Natsuyo; Nakai, Yousuke; Arizumi, Toshihiko; Toda, Nobuo; Koike, Kazuhiko

    2016-04-01

    To predict the duration of steroid maintenance therapy required to achieve good prognosis in patients with autoimmune pancreatitis. The study sample comprised 21 patients with autoimmune pancreatitis who met the following criteria: (1) they received steroid therapy (ST) for at least 3 years without clinical relapse; and (2) immunoglobulin (Ig) G<1600 mg/dL was observed in the past year with a prednisolone maintenance dose ≤5 mg. All patients could be diagnosed with international consensus diagnostic criteria. Patients were prospectively followed up after tapering and cessation of steroids. Clinical relapse was defined as the need to resume ST. Serological relapse was defined as having an IgG level of >1600 mg/dL. During the 43-month (range, 19 to 48 mo) follow-up period, clinical relapse occurred in 10 patients: pancreatic lesion in 4; coronary lesion in 2; submandibular lesion in 1; both pulmonary and renal lesions in 1; pulmonary, retroperitoneal, and submandibular lesions in 1; and bronchial asthma in 1. Serological relapse was observed in 12 patients. Although clinical and serological relapse occurred concomitantly in 3 patients, serological relapse preceded clinical relapse in 4 patients. Five patients experienced serological relapse alone, and no clinical or serological relapse occurred in 6 patients. According to Cox proportional hazard analysis, the duration of ST before tapering was a significant predictive parameter (hazard ratio, 0.969/month; 95% confidence interval, 0.940-0.998; P=0.038). ST cessation resulted in a high rate of clinical relapses, even in patients with long-term maintenance therapy. Therefore, it appears desirable to continue steroid maintenance therapy for a period >3 years to prevent relapse.

  16. Protective Effect of Long-Term CPAP Therapy on Cognitive Performance in Elderly Patients with Severe OSA: The PROOF Study

    PubMed Central

    Crawford-Achour, Emilie; Dauphinot, Virginie; Saint Martin, Magali; Tardy, Magali; Gonthier, Régis; Barthelemy, Jean Claude; Roche, Frédéric

    2015-01-01

    Objective: Obstructive sleep apnea syndrome (OSA) leads to a deterioration in cognitive functions, with regard to memory and executive functions. However, few studies have investigated the impact of treatment on these cognitive functions in elderly subjects. Methods: The study was conducted in a large cohort of subjects aged 65 years or older (the PROOF cohort). Subjects were not diagnosed or treated for OSA. Subjects underwent a polygraphic recording. Cognitive performance was assessed in all OSA subjects at baseline and 10 years later, whether or not they were receiving continuous positive airway pressure (CPAP) therapy. Results: A group of 126 patients were analyzed. Only 26% of them were treated, with therapy initiated at the discretion of the primary care physician. Among treated subjects, self-reported compliance with therapy was good (> 6 h/night on average), and 66% of them reported an improvement in their quality of life. Patients receiving CPAP treatment had a higher apneahypopnea index (p = 0.006), a higher oxygen desaturation index (p < 0.001), and experienced more pronounced daytime repercussions (p = 0.004). These patients showed a statistically significant improvement in mental agility (similarities test; p < 0.0001) and memory performance (Grober and Buschke delayed free recall; p = 0.02). Conclusion: CPAP treatment is associated with the maintenance of memory performance over time. Citation: Crawford-Achour E, Dauphinot V, Saint Martin M, Tardy M, Gonthier R, Barthelemy JC, Roche F. Protective effect of long-term CPAP therapy on cognitive performance in elderly patients with severe OSA: the PROOF study. J Clin Sleep Med 2015;11(5):519–524. PMID:25700873

  17. Endocrine function and bone disease during long-term chelation therapy with deferasirox in patients with β-thalassemia major.

    PubMed

    Casale, Maddalena; Citarella, Serena; Filosa, Aldo; De Michele, Elisa; Palmieri, Francesco; Ragozzino, Alfonso; Amendola, Giovanni; Pugliese, Umberto; Tartaglione, Immacolata; Della Rocca, Filomena; Cinque, Patrizia; Nobili, Bruno; Perrotta, Silverio

    2014-12-01

    Iron overload in β-thalassemia major (TM) typically results in iron-induced cardiomyopathy, liver disease, and endocrine complications. We examined the incidence and progression of endocrine disorders (hypothyroidism, diabetes, hypoparathyroidism, hypogonadism), growth and pubertal delay, and bone metabolism disease during long-term deferasirox chelation therapy in a real clinical practice setting. We report a multicenter retrospective cohort study of 86 transfusion-dependent patients with TM treated with once daily deferasirox for a median duration of 6.5 years, up to 10 years. No deaths or new cases of hypothyroidism or diabetes occurred. The incidence of new endocrine complications was 7% (P = 0.338, for change of prevalence from baseline to end of study) and included hypogonadism (n = 5) and hypoparathyroidism (n = 1). Among patients with hypothyroidism or diabetes at baseline, no significant change in thyroid parameters or insulin requirements were observed, respectively. Mean lumbar spine bone mineral density increased significantly (P < 0.001) and the number of patients with lumbar spine osteoporosis significantly decreased (P = 0.022) irrespective of bisphosphonate therapy, hormonal replacement therapy, and calcium or vitamin D supplementation. There were no significant differences in the number of pediatric patients below the 5th centile for height between baseline and study completion. Six pregnancies occurred successfully, and four of them were spontaneous without ovarian stimulation. This is the first study evaluating endocrine function during the newest oral chelation therapy with deferasirox. A low rate of new endocrine disorders and a stabilization of those pre-exisisting was observed in a real clinical practice setting.

  18. Physical factors affecting chloroquine binding to melanin.

    PubMed

    Schroeder, R L; Pendleton, P; Gerber, J P

    2015-10-01

    Chloroquine is an antimalarial drug but is also prescribed for conditions such as rheumatoid arthritis. Long-term users risk toxic side effects, including retinopathy, thought to be caused by chloroquine accumulation on ocular melanin. Although the binding potential of chloroquine to melanin has been investigated previously, our study is the first to demonstrate clear links between chloroquine adsorption by melanin and system factors including temperature, pH, melanin type, and particle size. In the current work, two Sepia melanins were compared with bovine eye as a representative mammalian melanin. Increasing the surface anionic character due to a pH change from 4.7 to 7.4 increased each melanin's affinity for chloroquine. Although the chloroquine isotherms exhibited an apparently strong interaction with each melanin, isosteric heat analysis indicated a competitive interaction. Buffer solution cations competed effectively at low surface coverage; chloroquine adsorption occurs via buffer cation displacement and is promoted by temperature-influenced secondary structure swelling.

  19. Lipoprotein(a) and coronary atheroma progression rates during long-term high-intensity statin therapy: Insights from SATURN.

    PubMed

    Puri, Rishi; Ballantyne, Christie M; Hoogeveen, Ron C; Shao, Mingyuan; Barter, Philip; Libby, Peter; Chapman, M John; Erbel, Raimund; Arsenault, Benoit J; Raichlen, Joel S; Nissen, Steven E; Nicholls, Stephen J

    2017-08-01

    Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle that associates with major adverse cardiovascular events (MACE). We examined relationships between Lp(a) measurements and changes in coronary atheroma volume following long-term maximally-intensive statin therapy in coronary artery disease patients. Study of coronary atheroma by intravascular ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. Baseline and follow-up Lp(a) levels were measured in 915 of the 1039 SATURN participants, and were correlated with changes in percent atheroma volume (ΔPAV). Mean age was 57.7 ± 8.6 years, 74% were men, 96% were Caucasian, with statin use prior to study enrolment occurring in 59.3% of participants. Baseline [median (IQR)] LDL-cholesterol (LDL-C) and measured Lp(a) levels (mg/dL) were 114 (99, 137) and 17.4 (7.6, 52.9) respectively; follow-up measures were 60 (47, 77), and 16.5 (6.7, 57.7) (change from baseline: p < 0.001, p = 0.31 respectively). At baseline, there were 676 patients with Lp(a) levels <50 mg/dL [median Lp(a) of 10.9 mg/dL], and 239 patients with Lp(a) levels ≥ 50 mg/dL [median Lp(a) of 83.2 mg/dL]. Quartiles of baseline and follow-up Lp(a) did not associate with ΔPAV. Irrespective of the achieved LDL-C ( 50 mg/dL. In coronary artery disease patients prescribed long-term maximally intensive statin therapy with low on-treatment LDL-C levels, measured Lp(a) levels (predominantly below the 50 mg/dL threshold) do not associate with coronary atheroma progression. Alternative biomarkers may

  20. Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease.

    PubMed

    Lindahl, Bertil; Baron, Tomasz; Erlinge, David; Hadziosmanovic, Nermin; Nordenskjöld, Anna; Gard, Anton; Jernberg, Tomas

    2017-04-18

    Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 5% to 10% of all patients with myocardial infarction. Clinical trials of secondary prevention treatment in MINOCA patients are lacking. Therefore, the aim of this study was to examine the associations between treatment with statins, renin-angiotensin system blockers, β-blockers, dual antiplatelet therapy, and long-term cardiovascular events. This is an observational study of MINOCA patients recorded in the SWEDEHEART registry (the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapy) between July 2003 and June 2013 and followed until December 2013 for outcome events in the Swedish Cause of Death Register and National Patient Register. Of 199 162 myocardial infarction admissions, 9466 consecutive unique patients with MINOCA were identified. Among those, the 9136 patients surviving the first 30 days after discharge constituted the study population. Mean age was 65.3 years, and 61% were women. No patient was lost to follow-up. A stratified propensity score analysis was performed to match treated and untreated groups. The association between treatment and outcome was estimated by comparing between treated and untreated groups by using Cox proportional hazards models. The exposures were treatment at discharge with statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and dual antiplatelet therapy. The primary end point was major adverse cardiac events defined as all-cause mortality, hospitalization for myocardial infarction, ischemic stroke, and heart failure. At discharge, 84.5%, 64.1%, 83.4%, and 66.4% of the patients were on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and dual antiplatelet therapy, respectively. During the follow-up of a mean of 4.1 years, 2183 (23.9%) patients experienced a major adverse cardiac event

  1. Long-term rescue of cone photoreceptor degeneration in retinitis pigmentosa 2 (RP2)-knockout mice by gene replacement therapy.

    PubMed

    Mookherjee, Suddhasil; Hiriyanna, Suja; Kaneshiro, Kayleigh; Li, Linjing; Li, Yichao; Li, Wei; Qian, Haohua; Li, Tiansen; Khanna, Hemant; Colosi, Peter; Swaroop, Anand; Wu, Zhijian

    2015-11-15

    Retinal neurodegenerative diseases are especially attractive targets for gene replacement therapy, which appears to be clinically effective for several monogenic diseases. X-linked forms of retinitis pigmentosa (XLRP) are relatively severe blinding disorders, resulting from progressive photoreceptor dysfunction primarily caused by mutations in RPGR or RP2 gene. With a goal to develop gene therapy for the XLRP-RP2 disease, we first performed detailed characterization of the Rp2-knockout (Rp2-KO) mice and observed early-onset cone dysfunction, which was followed by progressive cone degeneration, mimicking cone vision impairment in XLRP patients. The mice also exhibited distinct and significantly delayed falling phase of photopic b-wave of electroretinogram (ERG). Concurrently, we generated a self-complementary adeno-associated viral (AAV) vector carrying human RP2-coding sequence and demonstrated its ability to mediate stable RP2 protein expression in mouse photoreceptors. A long-term efficacy study was then conducted in Rp2-KO mice following AAV-RP2 vector administration. Preservation of cone function was achieved with a wide dose range over 18-month duration, as evidenced by photopic ERG and optomotor tests. The slower b-wave kinetics was also completely restored. Morphologically, the treatment preserved cone viability, corrected mis-trafficking of M-cone opsin and restored cone PDE6 expression. The therapeutic effect was achieved even in mice that received treatment at an advanced disease stage. The highest AAV-RP2 dose group demonstrated retinal toxicity, highlighting the importance of careful vector dosing in designing future human trials. The wide range of effective dose, a broad treatment window and long-lasting therapeutic effects should make the RP2 gene therapy attractive for clinical development. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Long-term efficacy of B cell depletion therapy on lung and skin involvement in diffuse systemic sclerosis.

    PubMed

    Bosello, Silvia L; De Luca, Giacomo; Rucco, Manuela; Berardi, Giorgia; Falcione, Matteo; Danza, Francesco Maria; Pirronti, Tommaso; Ferraccioli, Gianfranco

    2015-02-01

    To assess the long-term efficacy and safety of single and multiple courses of rituximab therapy in systemic sclerosis (SSc) patients with and without lung disease. A total of 20 SSc patients with a diffuse disease were treated with rituximab. At baseline and during follow-up the lung involvement was evaluated with pulmonary function tests (FVC and DLCO) and with lung high-resolution computed tomography (HRCT). The skin score, activity, and severity indices improved significantly after 12 months and at final follow-up compared to baseline. After 12 months, there was a significant increase of FVC and TLC compared to baseline (p = 0.024 and p = 0.005, respectively), while the mean DLCO value remained stable. Considering the last available follow-up in six patients with restrictive lung disease at baseline, two patients (33.3%) experienced an increase of more than 10% of FVC, one patient had a decrease of FVC >10%, while in three patients FVC remained stable (50%). After the mean follow-up of 48.5 ± 20.4 months, among the patients with normal lung parameters at baseline, FVC remained stable in 12 (85.7%) and in one patient (14.3%) it increased by more than 10%. At the final follow-up, the alveolar and interstitial HRCT scores remained stable in more than 80% of patients, both in patients with and without restrictive lung disease at baseline. Anti-CD20 B cell depletion therapy is effective on skin involvement but seems also to preserve the pulmonary function, as supported by a stable or improved FVC and stable interstitial score, suggesting a possible role of rituximab as a modifying therapy overall in early diffuse SSc. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study

    PubMed Central

    Lind, H; Waldenström, A-C; Dunberger, G; al-Abany, M; Alevronta, E; Johansson, K-A; Olsson, C; Nyberg, T; Wilderäng, U; Steineck, G; Åvall-Lundqvist, E

    2011-01-01

    Background: We surveyed the occurrence of physical symptoms among long-term gynaecological cancer survivors after pelvic radiation therapy, and compared with population-based control women. Methods: We identified a cohort of 789 eligible gynaecological cancer survivors treated with pelvic radiation therapy alone or combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478 women was randomly sampled from the Swedish Population Registry. Data were collected through a study-specific validated postal questionnaire with 351 questions concerning gastrointestinal and urinary tract function, lymph oedema, pelvic bones and sexuality. Clinical characteristics and treatment details were retrieved from medical records. Results: Participation rate was 78% for gynaecological cancer survivors and 72% for control women. Median follow-up time after treatment was 74 months. Cancer survivors reported a higher occurrence of symptoms from all organs studied. The highest age-adjusted relative risk (RR) was found for emptying of all stools into clothing without forewarning (RR 12.7), defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR 4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR 3.6). Survivors treated with radiation therapy alone showed in general higher rates of symptoms. Conclusion: Gynaecological cancer survivors previously treated with pelvic radiation report a higher occurrence of symptoms from the urinary and gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic pain compared with non-irradiated control women. Health-care providers need to actively ask patients about specific symptoms in order to provide proper diagnostic investigations and management. PMID:21847122

  4. Long-term rescue of cone photoreceptor degeneration in retinitis pigmentosa 2 (RP2)-knockout mice by gene replacement therapy

    PubMed Central

    Mookherjee, Suddhasil; Hiriyanna, Suja; Kaneshiro, Kayleigh; Li, Linjing; Li, Yichao; Li, Wei; Qian, Haohua; Li, Tiansen; Khanna, Hemant; Colosi, Peter; Swaroop, Anand; Wu, Zhijian

    2015-01-01

    Retinal neurodegenerative diseases are especially attractive targets for gene replacement therapy, which appears to be clinically effective for several monogenic diseases. X-linked forms of retinitis pigmentosa (XLRP) are relatively severe blinding disorders, resulting from progressive photoreceptor dysfunction primarily caused by mutations in RPGR or RP2 gene. With a goal to develop gene therapy for the XLRP-RP2 disease, we first performed detailed characterization of the Rp2-knockout (Rp2-KO) mice and observed early-onset cone dysfunction, which was followed by progressive cone degeneration, mimicking cone vision impairment in XLRP patients. The mice also exhibited distinct and significantly delayed falling phase of photopic b-wave of electroretinogram (ERG). Concurrently, we generated a self-complementary adeno-associated viral (AAV) vector carrying human RP2-coding sequence and demonstrated its ability to mediate stable RP2 protein expression in mouse photoreceptors. A long-term efficacy study was then conducted in Rp2-KO mice following AAV-RP2 vector administration. Preservation of cone function was achieved with a wide dose range over 18-month duration, as evidenced by photopic ERG and optomotor tests. The slower b-wave kinetics was also completely restored. Morphologically, the treatment preserved cone viability, corrected mis-trafficking of M-cone opsin and restored cone PDE6 expression. The therapeutic effect was achieved even in mice that received treatment at an advanced disease stage. The highest AAV-RP2 dose group demonstrated retinal toxicity, highlighting the importance of careful vector dosing in designing future human trials. The wide range of effective dose, a broad treatment window and long-lasting therapeutic effects should make the RP2 gene therapy attractive for clinical development. PMID:26358772

  5. Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

    PubMed Central

    Pendergraft, William F.; Cortazar, Frank B.; Wenger, Julia; Murphy, Andrew P.; Rhee, Eugene P.; Laliberte, Karen A.; Niles, John L.

    2014-01-01

    Background and objectives Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission. Design, setting, participants, & measurements A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined. Results In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase–ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS]=0) was achieved in all patients. Major relapse (BVAS≥3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population. Conclusion This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted. PMID:24626432

  6. A comparison of short- and long-term intravenous antibiotic therapy in the postoperative management of adult osteomyelitis.

    PubMed

    Swiontkowski, M F; Hanel, D P; Vedder, N B; Schwappach, J R

    1999-11-01

    The current standard recommendation for antibiotic therapy in the management of chronic osteomyelitis is intravenous treatment for six weeks. We have compared this regime with short-term intravenous therapy followed by oral dosage. A total of 93 patients, with chronic osteomyelitis, underwent single-stage, aggressive surgical debridement and appropriate soft-tissue coverage. Culture-specific intravenous antibiotics were given for five to seven days, followed by oral therapy for six weeks. During surgery, the scar, including the sinus track, was excised en bloc. We used a high-speed, saline-cooled burr to remove necrotic bone, and osseous laser Doppler flowmetry to ensure that the remaining bone was viable. Infected nonunions (Cierny stage-IV osteomyelitis) were stabilised by internal fixation. In 38 patients management of dead space required antibiotic-impregnated polymethylmethacrylate beads, which were exchanged for an autogenous bone graft at six weeks. Free-tissue transfer often facilitated soft-tissue coverage. These 93 patients were compared with 22 consecutive patients treated previously who had the same surgical management, but received culture-specific intravenous antibiotics for six weeks. Of the 93 patients, 80 healed without further intervention. Of the 31 Cierny-IV lesions, 27 healed without another operation, and four fractures required additional bone grafts. No more wound drainage was needed. Treatment was successful in 91% of patients, regardless of the organism involved. There was no difference in outcome in terms of these variables when the series were compared. We conclude that the long-term administration of intravenous antibiotics is not necessary to achieve a high rate of clinical resolution of wound drainage for adult patients with chronic osteomyelitis.

  7. Current strategies for the long-term assessment, monitoring, and management of cystic fibrosis patients treated with CFTR modulator therapy.

    PubMed

    Elborn, J Stuart; Davies, Jane; Mall, Marcus A; Flume, Patrick A; Plant, Barry

    2017-01-01

    The content for this activity is based on the satellite symposium, "Current Strategies for the Long-term Assessment, Monitoring, and Management for Cystic Fibrosis Patients Treated with CFTR Modulator Therapy" that was presented at the 39th European Cystic Fibrosis Society Conference on June 10, 2016 (Online access: http://courses.elseviercme.com/ecfs2016e/619e). The emergence of novel targeted agents, that directly correct CFTR loss function alleles, has created new treatment opportunities for patients with cystic fibrosis with advanced disease. Knowledge of the role of these agents in the clinical setting is quickly evolving and will require physicians to stay acquainted with the latest data as well as evidence-based treatment guidelines in order to achieve optimized cystic fibrosis patient care. Ideally, after diagnosis, a personalized approach would be adapted and tailored to the patient through genome-informed medicine. However, due to the relative recentness of genomic-based therapeutics, physicians may have a limited knowledge base regarding these new treatment options and how to best incorporate these agents into patient management plans. Although cystic fibrosis is still largely regarded as a pediatric disease, the median survival for patients is 35years of age. Consequently, pediatric-to-adult cystic fibrosis care programs would allow suitable preparation time for this transition and develop a standardized group of self-care and management skills.

  8. Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy.

    PubMed

    von Bahr, Lena; Sundberg, Berit; Lönnies, Lena; Sander, Birgitta; Karbach, Holger; Hägglund, Hans; Ljungman, Per; Gustafsson, Britt; Karlsson, Helen; Le Blanc, Katarina; Ringdén, Olle

    2012-04-01

    Thirty-one patients treated with mesenchymal stromal cells (MSCs) for acute graft-versus-host disease (aGVHD) or hemorrhagic cystitis between 2002 and 2007 were followed to investigate predictors of outcome, immunologic effects in vivo, and long-term survival. There was no correlation between in vitro suppression by MSCs in mixed lymphocyte cultures and outcome. Soluble IL-2 receptors were measured in blood before and after MSC infusion and declined significantly during the first week after MSC infusion (P = .03). Levels of interleukin-6 and HLA-G were unaffected. Infectious complications occurred several years after recovery from aGVHD. Cytomegalovirus viral load was high, and cytomegalovirus disease was common. Among patients recovering from aGVHD, 54% died of late infections, between 4 months and 2 years after MSC treatment. No increase in leukemia relapse or graft rejection was found. Children had a better survival rate than adults (P = .005). In GVHD patients, 1-year survival was 75% in patients who received early-passage MSCs (from passages 1-2) in contrast to 21% using later passage MSCs (from passages 3-4) (P < .01). We conclude that treatment with early-passage MSCs improved survival in patients with therapy-resistant GVHD. Death from infection was common in MSC-treated patients, but there was no increase in leukemia relapse. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Plasma protein-binding parameters of prednisolone in immune disease patients receiving long-term prednisone therapy.

    PubMed

    Wagner, J G; Wexler, D; Ağabeyoğlu, I T; Bergstrom, R F; Sakmar, E; Kay, D R

    1981-04-01

    Prednisone and prednisolone bind in plasma to albumin and transcortin. In am attempt to determine whether prednisone side effects and/or type of disease correlated with prednisolone plasma protein binding, multiple plasma samples from 17 patients (three asthma, eight SLE, three RA, two PSS, one PAN) receiving long-term prednisone therapy were monitored during an interval between two prednisone doses. Prednisolone plasma protein binding was nonlinear and exhibited large intrapatient and interpatient variability. For the group, mean association constants of the prednisolone-albumin complex and the prednisolone-transcortin complex were 2.3 X 10(3) M-1 and 2.9 X 10(7) M-1, with coefficients of variation of 82% and 127%, respectively. SLE patients tended to have lower mean prednisolone association constants for albumin and transcortin than did other patients. The presence of corticosteroid side effects did not correlate with prednisolone plasma protein-binding parameters. The wide range of prednisolone free fraction noted in plasma from patients who achieved comparable total prednisolone plasma concentrations implies that administration of a uniform prednisone dose will not lead to a predictable clinical response.

  10. How can cobalamin injections be spaced in long-term therapy for inborn errors of vitamin B(12) absorption?

    PubMed

    Boina Abdallah, Amina; Ogier de Baulny, Hélène; Kozyraki, Renata; Passemard, Sandrine; Fenneteau, Odile; Lebon, Sophie; Rigal, Odile; Mesples, Bettina; Yacouben, Karima; Giraudier, Stéphane; Benoist, Jean-François; Schiff, Manuel

    2012-09-01

    Inborn errors of cobalamin (Cbl, vitamin B(12)) absorption include hereditary intrinsic factor deficiency (HIFD) and Imerslund-Gräsbeck disease (IGD). HIFD is secondary to mutations in the HIF gene while IGD is due to mutations in one of the 2 subunits of the intrinsic factor receptor that is cubilin (CUBN) or amnionless (AMN). These disorders lead to intracellular Cbl depletion which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid (MMA), and methionine depletion. The clinical presentation reflects Cbl deficiency, with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia. Mixed proteinuria, when it is present is strongly suggestive of IGD. Accurate diagnosis is always an emergency because early detection and treatment with life-long parenteral pharmacological doses of hydroxocobalamin are life saving and prevent further deterioration. However, the optimal frequency for cobalamin injections as a maintenance therapy is poorly reported. In order to evaluate the optimal maintenance schedule of cobalamin injections, we retrospectively collected clinical, biological, molecular and treatment data on 7 patients affected with congenital Cbl malabsorption. Unlike previous recommendations, we showed that a maintenance dosage of 1 mg cobalamin twice a year was enough to ensure a normal clinical status and keep the hematological and metabolic parameters in the normal range. These data suggest that patients affected with inborn errors of cobalamin absorption may be safely long-term treated with cobalamin injections every 6 months with careful follow-up of hematological and metabolic parameters. This maintenance regime is beneficial because the patients' quality of life improves.

  11. Survival outcome of radioiodine therapy in post thyroidectomy thyroid carcinoma patients: Outcome of long term follow up

    NASA Astrophysics Data System (ADS)

    Haque, F.; Nahar, N.; Sultana, S.; Nasreen, F.; Jabin, Z.; Alam, A. S. M. M.

    2016-03-01

    The overall prognosis of patients with thyroid carcinoma is excellent whenever managed following best practice guidelines. Objective: To calculate sex and age group affected by thyroid cancer; to compare between single or multiple dose of radio ablation needed after thyroidectomy and to determine the percentage of patients become disease free during their follow up. Methods: This was a retrospective study done in NINMAS, Bangladesh on 687 patients from 1984 to 2004. In all cases total or near total thyroidectomy was done before commencing radioiodine therapy. Patients TG level, neck ultrasonography, thyroid scan, whole body I131 scans, neck examination were done every six monthly/yearly. Results: Among 687 patients, female were more sufferers (68.1%) and female to male ratio was 2:1. Age group 19-40 years was mostly affected (57.8%). Most common type seen was papillary carcinoma (81.8%). After ablation 100 patients did not follow-up. Total 237 patients discontinued within 4 years. Remaining 450 patients undergone regular follow-up for 5 years and more, 394 were disease free (87.6%). Total recurrence of metastasis was 23 and 12 patients expired at different times. Conclusions: Long-term regular follow-up is necessary after radioiodine ablation to become free of disease.

  12. Long-Term Results of Photodynamic Therapy for Choroidal Neovascularization in Pediatric Patients with Best Vitelliform Macular Dystrophy.

    PubMed

    Sodi, Andrea; Murro, Vittoria; Caporossi, Orsola; Passerini, Ilaria; Bacci, Giacomo Maria; Caputo, Roberto; Menchini, Ugo

    2015-06-01

    To report long-term results of photodynamic therapy (PDT) in young patients affected by Best vitelliform macular dystrophy (VMD) complicated by choroidal neovascularization (CNV). We evaluated a group of 30 VMD patients with confirmed mutations in the BEST1 gene. Five of these patients had been diagnosed with CNV when younger than 15 years of age and three of them were treated by PDT. After the treatment they were followed for an average period of 77 months (range 62-99). In all the treated eyes visual acuity was stable during the first year of follow-up and then slowly improved even some years after the treatment. The improvement in visual acuity was associated with the development of fibrous tissue in the macula. PDT was a safe procedure in our series of pediatric patients with VMD complicated by CNV. It was followed by a CNV regression and a consequent improvement in visual acuity which continued to progress even several years after the treatment.

  13. Clinical Outcomes in Kidney Transplant Recipients Receiving Long-Term Therapy with Inhibitors of the Mammalian Target of Rapamycin

    PubMed Central

    Cortazar, F; Molnar, MZ; Isakova, T; Czira, ME; Kovesdy, CP; Roth, D; Mucsi, I; Wolf, M

    2013-01-01

    Inhibitors of the mammalian target of rapamycin (mTOR), sirolimus and everolimus, reduce the incidence of acute rejection following kidney transplantation but their impact on clinical outcomes beyond two years after transplantation is unknown. We examined risks of mortality and allograft loss in a prospective observational study of 993 prevalent kidney transplant recipients who enrolled a median of 72 months after transplantation. During a median follow-up of 37 months, 87 patients died and 102 suffered allograft loss. In the overall population, use of mTOR inhibitors at enrollment was not associated with altered risk of allograft loss, and their association with increased mortality was of borderline significance. However, history of malignancy was the strongest predictor of both mortality and therapy with an mTOR inhibitor. Among patients without a history of malignancy, use of mTOR inhibitors was associated with significantly increased risk of mortality in propensity score-adjusted (hazard ratio [HR] 2.6; 95%CI, 1.2, 5.5; P = 0.01), multivariable-adjusted (HR 3.2; 95%CI, 1.5, 6.5; P = 0.002) and one-to-one propensity score-matched analyses (HR 5.6; 95% CI 1.2, 25.7; P = 0.03). Additional studies are needed to examine the long-term safety of mTOR inhibitors in kidney transplantation, especially among recipients without a history of malignancy. PMID:22054244

  14. Long-Term Treatment with Egg Oral Immunotherapy Enhances Sustained Unresponsiveness That Persists After Cessation of Therapy

    PubMed Central

    Jones, Stacie M.; Burks, A. Wesley; Keet, Corinne; Vickery, Brian P.; Scurlock, Amy M.; Wood, Robert A.; Liu, Andrew H.; Sicherer, Scott H.; Henning, Alice K.; Lindblad, Robert W.; Dawson, Peter; Berin, Cecilia; Fleischer, David M.; Leung, Donald Y. M.; Plaut, Marshall; Sampson, Hugh A.

    2016-01-01

    Background We previously reported results of a randomized, placebo-controlled study of egg oral immunotherapy (eOIT), in which 27.5% of subjects achieved sustained unresponsiveness (SU) after 2 years. Here we report results of treatment through 4 years and long-term follow-up. Objective To evaluate the efficacy and safety of eOIT in participants treated up to 4 years. Methods Egg-allergic children (5–18 y/o) received eOIT (n=40) for up to 4 years or placebo (n=15) ≤1 year. The key outcome was the percentage of subjects achieving SU by Year 4. Safety and immunologic assessments were performed, and long-term follow-up questionnaires were administered after study conclusion (LFQ-1) and 1 year later (LFQ-2). Results Of 40 eOIT-treated subjects, 20/40 (50.0%) demonstrated SU by Year 4. For those subjects still dosing during Years 3–4, mild symptoms were present in 12/22 (54.5%) subjects. At the time of LFQ, more eOIT subjects [LFQ-1 23/34 (68%); LFQ-2 21/33 (64%)] were consuming unbaked and baked egg vs. placebos [LFQ-1 2/11(18%), p=0.006; LFQ-2 3/12 (25%), p=0.04]. Of subjects achieving SU, 18/20 (90%) completed the LFQ with 18/18 (100%) reporting consumption of all forms of egg. When compared to subjects not achieving SU, subjects achieving SU had higher IgG4 values (p=0.001) and lower egg skin prick test scores (p=0.0002) over time and a lower median baseline ratio of egg-specific IgE to total IgE (1.1% vs. 2.7%, p=0.04). Conclusions SU following egg OIT is enhanced with longer duration of therapy, and increases the likelihood of tolerating unbaked egg in the diet. PMID:26924470

  15. Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations

    PubMed Central

    Mansur, Adel H.; Pertseva, Tetyana; Kaiser, Kirsten; McIver, Tammy; Grothe, Birgit; Dissanayake, Sanjeeva

    2016-01-01

    Abstract Background: A primary goal of asthma management is the reduction of exacerbation risk. We assessed the occurrence of oral corticosteroid-requiring exacerbations (OCS exacerbations) with long-term fluticasone/formoterol therapy, and compared it with the occurrence of similar events reported with other inhaled corticosteroid/long acting β2-agonist (ICS/LABA) combinations. Methods: The occurrence of OCS exacerbations was assessed in two open-label trials of fixed-dose fluticasone/formoterol administered for between 26 to 60 weeks in adults and adolescents with asthma. The incidence of OCS exacerbations with fluticasone/formoterol was compared with those reported in three recent Cochrane meta-analyses of other ICS/LABAs. Results: The pooled incidence of OCS exacerbations with long-term fluticasone/formoterol was 2.1% (95% CI: 1.1, 3.2%, n/N = 16/752). In only two of the nineteen treatment arms summarized by Cochrane did OCS exacerbation incidence approximate that seen in the two fluticasone/formoterol trials (single-inhaler fluticasone/salmeterol [2.9%]; separate inhaler budesonide, beclometasone, or flunisolide plus formoterol [3.4%]). In Lasserson's review the pooled incidence of OCS exacerbations for single-inhaler combinations was 9.5% (95% CI: 8.4, 10.6%; n/N = 239/2516) for fluticasone/salmeterol, and 10.6% (95% CI: 9.3, 11.8%; n/N = 257/2433) for budesonide/formoterol. In Ducharme's and Chauhan's meta-analyses (primarily incorporating separate inhaler combinations [fluticasone, budesonide, beclometasone, or flunisolide plus salmeterol or formoterol]), the pooled incidences of OCS exacerbations were 16.0% (95% CI: 14.2, 17.8%, n/N = 258/1615) and 16.7% (95% CI: 14.9, 18.5, n/N = 275/1643), respectively. Conclusions: The incidence of exacerbations in two fixed-dose fluticasone/formoterol studies was low and less than in the majority of comparable published studies involving other ICS/LABA combinations. This difference could not be

  16. Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations.

    PubMed

    Papi, Alberto; Mansur, Adel H; Pertseva, Tetyana; Kaiser, Kirsten; McIver, Tammy; Grothe, Birgit; Dissanayake, Sanjeeva

    2016-08-01

    A primary goal of asthma management is the reduction of exacerbation risk. We assessed the occurrence of oral corticosteroid-requiring exacerbations (OCS exacerbations) with long-term fluticasone/formoterol therapy, and compared it with the occurrence of similar events reported with other inhaled corticosteroid/long acting β2-agonist (ICS/LABA) combinations. The occurrence of OCS exacerbations was assessed in two open-label trials of fixed-dose fluticasone/formoterol administered for between 26 to 60 weeks in adults and adolescents with asthma. The incidence of OCS exacerbations with fluticasone/formoterol was compared with those reported in three recent Cochrane meta-analyses of other ICS/LABAs. The pooled incidence of OCS exacerbations with long-term fluticasone/formoterol was 2.1% (95% CI: 1.1, 3.2%, n/N = 16/752). In only two of the nineteen treatment arms summarized by Cochrane did OCS exacerbation incidence approximate that seen in the