Need For Long-term Treatment Research Articles

Review of safety and efficacy of approved systemic psoriasis therapies.

Psoriasis is a chronic inflammatory disease which affects nearly 3% of the adult US population. Due to the chronic nature of the disease and need for long-term treatment, psoriasis is associated with substantial disease burden and negative impact on patients' quality of life. In the past, systemic agents such as methotrexate, cyclosporine, and acitretin have been the mainstay treatment for moderate to severe psoriasis. Multiple new molecular targets have been recently identified, and novel biologic therapies directed at these targets have been approved leading to a paradigm shift in psoriasis management. However, despite the availability of several treatment options and continued introduction of highly efficacious biologics, undertreatment of psoriasis patients remains a huge problem. This can be largely attributed to several causes including high cost of biologics, lack of experience, and reluctance of practitioners to initiate or switch to systemic treatment regimens in moderate to severe psoriasis patients. In this article, we aim to provide a concise review of mechanism, safety, and efficacy of the approved systemic treatments for psoriasis.

Potential role of zinc in the visceromegaly regression and recovery of hematological parameters during treatment of visceral leishmaniasis in children from an endemic area.

ABSTRACTLeishmaniasis is a disease complex with various clinical symptoms caused by different species of parasites of the genus Leishmania. The visceral form of the disease, characterized by severe symptoms is fatal, if not treated. The high toxicity of current antileishmanial drugs and the need for long-term treatment make the therapy complicated, especially in a large number of infected children. Hence, the search for new therapies must be intensified. Oral administration of the trace element zinc has been considered in alternative treatments against different clinical forms of leishmaniasis. This study revealed that the administration of zinc in children with visceral leishmaniasis, during treatment with amphotericin B or glucantime, accelerates the regression of the spleen enlargement without interfering with the recovery of hematological parameters.

Pharmacokinetic evaluation of the aripiprazole (once-monthly) injection for the treatment of bipolar disorder

ABSTRACTIntroduction: Bipolar disorder is a severe, chronic psychiatric disorder with a need for long-term treatment. Patient nonadherence is frequent and poses a major problem in maintenance therapy. Aripiprazole once-monthly long-acting injectable (AOM LAI) is a recently US Food and Drug Administration-approved treatment option for maintenance therapy that could be of great value.Areas covered: This paper reviews the pharmacokinetic, efficacy and safety data for AOM LAI in bipolar disorder.Expert opinion: AOM LAI is a safe and efficacious treatment option in the maintenance therapy of bipolar I disorder. However, further research is still needed to determine the position of AOM LAI relative to other available treatment options.

Transition to adult care for Aboriginal children with rheumatic fever: a review informed by a focussed ethnography in northern Australia.

Aboriginal children in northern Australia have high rates of rheumatic fever and rheumatic heart disease, which are chronic conditions because of the need for long-term treatment and monitoring. This article critically reviews the literature on transition to adult care for children with chronic conditions and considers applicability to the care of these children. The review was merged with findings from a focussed ethnography conducted in four remote Aboriginal communities with young people who have these conditions. Transition care aims to support adolescents on a healthcare trajectory to facilitate best long-term health and personal outcomes. Characteristics of the two medical conditions, the children and their local health services in northern Australia were generalised and merged with principles from the transition care literature, including policies governing transition clinics in urban locations. In this setting, the challenge is to transition Aboriginal children safely through to adulthood without rheumatic heart damage rather than to a separate health service on reaching adulthood. Recommended tailoring of transition care involves engaging and valuing local navigators who can address language and cultural barriers to provide a sustainable alternative to transition coordinators in mainstream programs. This has potential to improve care without further burdening overstretched clinical resources.

In Vitro Antileishmanial Activity of a Black Morel, Morchella importuna (Ascomycetes).

We studied the anti-Leishmania activity of a fractionated extract from the mushroom Morchella importuna in an in vitro system. Leishmaniasis is an important infectious disease caused by a range of Leishmania species, which are multihost protozoa parasites transmitted to humans by the sand fly and infecting macrophages. Leishmaniasis is an increasing worldwide health problem, including in the Mediterranean basin. Current chemotherapy treatments are limited by their toxic effects, the need for long-term treatment, and the increasing development of resistance by the parasite cells. Thus, alternative therapies are being considered, including herbal and mushroom products. We studied the effect of extracts from M. importuna on L. tropica promastigote cell proliferation and survival, and on their toxicity against human macrophages. The aqueous mushroom extract was compared with 3 successive extracted fractions: an 80% ethanol fraction, a water-soluble polysaccharide fraction, and a polyphenolic fraction. All 4 extracts showed anti-Leishmania activity; the aqueous extract was most active. The inhibition activity was dose dependent in killing Leishmania. No cell recovery was recorded after exposure to the mushroom extract. Microscopic observation showed morphological changes and the loss of flagella on the parasites. No cytotoxic activity was recorded against human macrophages at the same extract concentrations. The findings suggest the potential use of extracts of an edible Morchella mushroom against the Leishmania parasite in humans.

Advancing alcohol research and treatment: contentions and debates about treatment intensity, goals and outcomes in the 1970s and 1980s.

This narrative exploration of alcohol treatment research focuses on key contentions and advances in alcohol treatment during the critical 1970s and 1980s. Papers and books which signal some of the major debates and advances in alcohol treatment research were selected from the 1970s and 1980s. The selection process was based on significant debate during this period, and included those that influenced the field in general and this author in particular. This was a period where challenges to traditional models and concepts, and the perceived universal need for long-term treatment, were accompanied by contention but also advances in research and treatment approaches. The debates and advances resonate today. These include the recognition that: intensive and long-term treatment is not always required; for dependent drinkers, relapse is a common treatment outcome meriting specific treatment approaches to prevent and reduce this risk; controlled drinking is a treatment option, especially for younger and less dependent drinkers; and an important contributor to enduring change is access to, and realization of, improvements in the quality of life. Pioneering research and publications in the 1970s and 1980s, sometimes conducted and produced in contentious contexts, influenced significantly conceptualizations of alcohol-related problems, and laid the foundations for treatment hypotheses and research, improving access to a broader range of evidence-based treatment. These underpinning works influenced the development of stepped-up care from brief to intensive interventions, relapse prevention and treatment options not limited to abstinence, and they identified the need to include a stronger focus on quality of life.

Ocular Involvement in Sarcoidosis.

AbstractOcular involvement in sarcoidosis occurs in ∼40% and the eye is the presenting organ in roughly 20%. The course of ocular disease does not necessarily parallel that of systemic disease. Uveitis is the most common presentation and shows mainly a chronic course; anterior uveitis is associated with better visual prognosis than posterior localization. Painful bilateral anterior granulomatous uveitis most commonly occurs in black patients at younger age, while painless posterior bilateral involvement with peripheral multifocal choroiditis is commonly seen in elderly white females. Patients with posterior uveitis develop often ocular complications and central nervous system involvement. Vitritis, segmental periphlebitis, choroidal granulomas, and peripheral multifocal chorioretinitis are often seen clinical features. Optic nerve involvement is uncommon, but if present, results often in poor visual outcome. Lacrimal gland and conjunctival involvement are also common and present clinically as dry eyes or remain asymptomatic with good visual prognosis. Sarcoidosis-associated uveitis is mostly managed by local treatment with steroid drops or periocular and intraocular steroid injections or with novel intraocular corticosteroid implants. Patients with sight-threatening disease or optic nerve involvement need systemic therapy. Systemic therapy is based on a step-up regimen where corticosteroids are used in the initial phase of the disease and if long-term treatment is required, steroid-sparing immunomodulatory drugs are implemented such as methotrexate or biological agents. Despite the mainly chronic course, need for long-term treatment, and frequent ocular surgeries in the majority of patients, the visual outcome of sarcoidosis-associated uveitis is fairly good if therapy has started on time.

Human Tuberculosis. III. Current and Prospective Approaches in Anti-Tubercular Therapy

Ineffectively treated tuberculosis (TB) is associated with substantial morbidity and mortality. Cure of TB patients is hampered by the development of multidrug resistance in M. tuberculosis and the need of long-term treatment. The diarylquinoline derivative bedaquiline was approved in December 2012 under the accelerated-approval regulations of FDA as part of a combination therapy for treating adults with pulmonary MDR-TB for whom effective cures are not otherwise available. The bicyclic nitroimidazoles delamanid and its companion pretomanid inhibit mycolic acid synthesis via an unknown mechanism. In November 2013, delamanid received conditional approval by the European Medicines Agency for MDR-TB treatment. Use of both drugs, however, is limited owing to toxicity issues. If the aim to reduce treatment duration is pursued in order to limit costs and improve patient adherence, it is mandatory to demonstrate their noninferiority with fewer months of therapy. In three phase III clinical trials the efficacy of the most recent fluoroquinolones, gatifloxacin and moxifloxacin, has been investigated in a four-month treatment regimen of drug-susceptible TB. In all three studies, after two months the culture conversion rates of observed sputum indicated that fluoroquinolone-based therapies were likely to be superior. However, this feature did not reliably predict sterilizing activity or a risk of relapse. In other words, the shortened treatments were not noninferior to standard treatments. To counteract mycobacterial survival strategies and reduce the timelength of treatment with anti-TB drugs, other novel and powerful agents, as well as tuberculosis vaccines, are under intense clinical investigation for safety and efficacy assessment.

Impact of Provoking Risk Factors on the Prognosis of Cerebral Venous Thrombosis in Korean Patients.

Background and PurposeLittle is known about the relationships between provoking risk factors, prognosis, and optimal duration of anticoagulation in patients with cerebral venous thrombosis (CVT), especially in Asians. We aimed to investigate whether the prognosis and required duration of anticoagulation in CVT patients differ according to the provoking risk factors.MethodsProspectively recorded data from a tertiary medical center in South Korea were retrospectively reviewed. CVTs were categorized into three groups: unprovoked, those with possibly resolved provoking factors (PR), and those with persistent provoking factors (PP). The baseline characteristics, treatment, and prognosis of patients in these three groups were analyzed.ResultsFrom 2000 to 2015, 61 patients presented with CVT: 19 (31.1%) unprovoked, 11 (18.0%) with PR, and 31 (50.9%) with PP. The patients in our cohort had a slight female predominance and lower frequency of oral contraceptive use compared to Western cohorts. Median follow-up and duration of anticoagulation were 35 and 8 months, respectively. Despite the similarities in baseline characteristics, deaths (n=3; P=0.256) and recurrences (n=7; P=0.020) were observed only in the PP group. The median intervals to death and recurrence were 9 and 13 months, respectively. Death was associated with underlying disease activity, not with CVT progression. Recurrences in the PP group were associated with lack of anticoagulation (P=0.012).ConclusionsAlthough the prognosis of CVT is generally benign in Koreans, recurrence and death were observed in patients with persistent risk factors, suggesting their need for long-term treatment with anticoagulants.

Factors of esophageal atresia treatment outcome in newborns operated on at Department of Pediatric Surgery, Split University Hospital, during the 1991-2014 period

Objectives and background: Esophageal atresia is an anomaly that stands out from other anomalies in view of emergency, exact work, delicate postoperative treatment and the need for long-term treatment and control. With this anomaly, other anomalies often associate, particularly heart anomalies. Clinical examination and radiologic diagnosis are the basis for making the right diagnosis. Early recognition of this anomaly is of great importance, primarily due to the fact that this is a life-threatening anomaly whose early diagnosis and surgery reduces complications and improves the outcome. The aim of this study was to determine the epidemiological, demographic and clinical characteristics of patients operated for esophageal atresia and compare them to other relevant studies. Patients and methods: In the period from January 1991 to September 2014 the medical history of 46 patients treated for esophageal atresia were retrospectively reviewed. Data was collected from protocols of the Department for Pediatric Surgery, the Department of Neonatology and ICU Split University Hospital archives and the history of the disease. Each subject was analyzed by the following parameters: date of birth, sex, weight at birth, surgery, type of anomaly, survival, early and late complications. Results: Esophageal atresia was more frequent with female respondents (60%). The most common type of esophageal atresia according to the Vogts classification was the type 3B (92 %). Overall mortality was 35%, noting that the mortality before the introduction of the Intensive Care Unit was 80%, and after the introduction only 14%. Pneumonia was the most common early complication, while the most common late complications were dysphagia (35%) and anastomotic stricture (12%). Cardiovascular anomalies were the most common congenital malformations and account for 45% of all associated anomalies, and they are presented in 30% of the children with esophageal atresia. Conclusions: Early recognition of this anomaly is of great importance, primarily due to the fact that this is a life - threatening anomaly whose early diagnosis and surgery reduces complications and improve the outcome. For child survival a multidisciplinary approach and recognition of associated anomalies is necessary. In addition to early diagnosis and the surgery intensive postoperative care is crucial for survival.

Abstract WP225: Prognosis of Cerebral Venous Thrombosis and Provoking Risk Factors

Background and hypothesis: Little is known about the relationships between the presence/type of provoking risk factors and the prognosis and optimal duration of anticoagulation in patients with cerebral vein and dural sinus thrombosis (CVT). We aimed to analyze data of treatment and long-term prognosis in patients with CVT classified by the presence and type of provoking risk factors. Methods: Prospectively recorded data of a tertiary medical center were retrospectively reviewed. Patients with CVT were categorized into three groups by risk factors: unprovoked, those with possibly resolved provoking factors (PR), and those with persistent provoking factors (PP). The baseline characteristics, treatment, and prognosis of these three groups were analyzed. Results: From 2000 to 2015, 61 patients were registered for CVT, 19 (31.1%) with unprovoked, 11 (18.0%) with PR, and 31 (50.9%) with PP. Median follow-up and duration of anticoagulation were 35 and 8 months, respectively. The PR group consisted of patients with causative drugs or arteriovenous fistula successfully treated. Despite the similarities in baseline characteristics of the three groups, deaths (n=3; P = 0.256) and recurrences (n=7; P = 0.020) were observed only in the PP group. The median interval to death and recurrence were 9 and 13 months, respectively. Death was associated with underlying disease activity, not with CVT progression. Recurrences were associated with lack of initial administration of anticoagulation (P = 0.028); of the seven patients with recurrence, five (71.4%) did not receive anticoagulation at the second event. Conclusions: Although the prognosis of CVT is generally benign, recurrence and death were observed in the patients with persistent risk factors, suggesting their need for long-term treatment with anticoagulants.

P99 Renal and bone safety of tenofovir alafenamide vs tenofovir disoproxil fumarate

<h3>Background</h3> Off-target renal and bone side effects may occur with tenofovir disoproxil fumarate (TDF) use. Compared with TDF, tenofovir alafenamide (TAF) results in significantly reduced plasma tenofovir (TFV) and may have less renal and bone toxicity. <h3>Methods</h3> Treatment naïve HIV-1+ adults were randomised 1:1 to a single tablet regimen of E/C/F/TAF or E/C/F/TDF once daily in two double blind studies. Assessments for all subjects included measures of glomerular and proximal renal tubular function, and bone mineral density (BMD). Four pre-specified secondary safety endpoints were tested: serum creatinine, treatment-emergent proteinuria, spine and hip BMD. Week 48 off-target side effects data are described. <h3>Results</h3> 1,733 subjects were randomised and treated. Plasma TFV was &gt;90% lower (mean AUC_tau 297 vs. 3,410 ng·hr/mL) in the E/C/F/TAF arm, compared to the E/C/F/TDF arm. Serum creatinine (mean change: +0.08 vs +0.11 mg/dL, p &lt; 0.001), quantified proteinuria (UPCR, median % change; -3 vs +20, p &lt; 0.001), and fractional excretion of phosphate (median % change; +0.9 vs +1.7), all favoured E/C/F/TAF. There were no cases of proximal tubulopathy in either arm. Mean% decrease in BMD was significantly less in the E/C/F/TAF arm for both lumbar spine (−1.30 vs −2.86, p &lt; 0.001) and total hip (−0.66 vs −2.95, p &lt; 0.001). <h3>Conclusions</h3> Through 48 weeks, subjects receiving E/C/F/TAF had significantly better outcomes related to renal and bone health than those treated with E/C/F/TDF;. These data demonstrate important safety benefits of TAF relative to TDF, especially given the ageing of the HIV population and the need for long-term treatment.

Treatment of Onychomycosis - a Clinical Study.

Introduction:Onychomycosis is a fungal infection of the nail unit. Anatomical and physiological characteristics of the nail apparatus impose the need for long-term treatment to achieve complete cure.Goal:The main goal of this project is to study the effectiveness of several treatment protocols for onychomycosis based on Scoring Clinical Index for Onychomycosis (SCIO).Material and methods:The study included 133 patients with onychomycosis, diagnosed by KOH microscopy and culture. Based on disease severity, patients were grouped into groups with SCIO values: 6-9, and 12-16. These groups were randomly subdivided to 5 subgroups according to the given treatment protocols: fluconazole 150 mg 1x weekly, itraconazole continual therapy, itraconazole pulse therapy, terbinafine 250 mg/d, and terbinafine + ciclopirox 8% lacquer, respectively. The cure rate was evaluated at the end of 48 week.Results:The obtained cure rates according to the above mentioned protocols were: 92.30%, 81.81%, 83.33%, 90.90%, and 100%, respectively for groups of patients with SCIO values 6 – 9. Within patients with SCIO values 12-16, were achieved cure rates as follows: 78.57%, 78.57%, 75%, 80%, and 86.66%.Conclusions:There was no statistically significant difference in cure rate between five treatment protocols applied in this study. In patients with high SCIO values is expected a decrease in cure rate.

Nutraceutical potential of Aerva lanata (L.) Juss. ex Schult ameliorates secondary complications in streptozotocin-induced diabetic rats

Nutraceuticals provide health benefits beyond their basic nutrition by modulating a number of biochemical pathways. They are derived from natural products and have gained recognition worldwide as an adjuvant or therapy in the treatment of metabolic disorders such as diabetes. Although the regulation of blood glucose with drugs and insulin greatly reduces the incidence of secondary complications, the need for long-term treatment raises issues of tolerance and affordability. Therefore, the aim of the present study is to explore the nutraceutical potential of Aerva lanata, a herb widely used for its culinary and therapeutic potential in streptozotocin (STZ)-induced diabetic rats. Treatment with 70% ethanolic extract (ALE) at 500 mg per kg b.w per day for 21 days significantly improved the fasting blood glucose (120.33 ± 1.99 mg dL(-1)), insulin level (9.81 ± 0.38 mU L(-1)), HbA1c (7.3 ± 0.36%) and glycogen content in the liver (35.33 ± 1.38 mg g(-1) protein) and muscle (7.67 ± 0.11 mg g(-1) protein) compared to diabetic controls. The extract also showed a significant decrease in blood glucose by 47.29% towards the end of 2 h in oral glucose tolerance test on Day 21. Its therapeutic potential could be partly attributable to the presence of flavonoids, tannins and terpenes (alpha amyrin, betulin and beta sitosterol) along with micronutrients such as potassium, magnesium, calcium and zinc. Hence, we suggest the suitability of Aerva lanata as a nutraceutical for diabetic patients.

Providing free treatment for severe mental disorders in China.

Providing free treatment for severe mental disorders in China.

Targeting EGFR and sonic hedgehog pathways for locally advanced eyelid and periocular carcinomas.

For patients with metastatic or locally advanced eyelid and periocular carcinoma not amenable to surgical excision, targeted therapies have shown efficacy with better tolerability compared to cytotoxic chemotherapy. Overexpression of epithelial growth factor receptor was found in squamous cell carcinomas. Vismodegib targets the mutation in the hedgehog pathway identified in basal cell carcinoma and basal cell nevus syndrome. Targeted therapies provide a novel and potentially effective treatment alternative for patients with eyelid carcinoma not amendable for surgery, including those with metastatic, locally advanced disease, advanced age, and significant comorbidities. High cost, need for long-term treatment, and toxicity are relative limitations.

Explanatory models of hypertension among Nigerian patients at a University Teaching Hospital

Objective. To elicit the explanatory models (EM) of hypertension among patients in a hospital-based primary care practice in Nigeria. Design. Semi-structured in-depth individual interviews and focus groups were conducted with 62 hypertensive patients. Interviews and focus groups were audiotaped and transcribed verbatim. Data analysis was guided by phenomenology and content analysis using qualitative research software ATLAS.ti 5.0. Results. Patients expressed four categories of EM of hypertension: (1) perceptions of hypertension, (2) consequences, (3) effect on daily life, and (4) perception of treatment. Focus group discussions and individual interviews yielded a wide range of insights into the social and cultural factors influencing patients' beliefs and health behavior. Participants were aware of the risks of hypertension. There was disagreement between participants' own understanding of the serious nature of hypertension, the need for long-term treatment, and the desire to take long-term medication. Participants acknowledged the use of traditional medicine (e.g. teas and herbs) and healers. Different themes emerged for men versus women such that women often focused on family issues while men tended to discuss external stressors stemming from work as a cause of hypertension. Men were concerned with frequent urination, decreased libido, and erectile dysfunction. Conclusion. Knowledge gained will inform development of patient-centered treatment plans and targeted behavioral and educational interventions.

Salivary 17-hydroxyprogesterone (17-OHP) and androstenedionein monitoring efficacy of treatment among Indonesian Congenital Adrenal Hyperplasia Patients

Objective. Early diagnosis of congenital adrenal hyperplasia (CAH) and the need for long term treatment are of great concern to the medical community. The aim of this study was to evaluate the effectiveness of glucocorticoid treatment-monitoring based on salivary 17-hydroxyprogesterone (17-OHP) and androstenedione measurements in CAH patients in Semarang, Indonesia in comparison to patients treated in Rotterdam, the Netherlands. Methodology. 25 out of 43 patients with CAH from Semarang, Indonesia were included in the study. For comparison, twenty CAH patients from the Sophia Children’s Hospital/ Erasmus Medical Center Rotterdam, the Netherlands were included. The effects of treatment were monitored by estimations of the steroids 17-OHP and androstenedione in saliva. Auxology and bone age determination were recorded. Result. 17-OHP and androstenedione levels were high in a substantial number of Indonesian patients under treatment but decreased after adjustment of dosage and timing. The steroid concentrations obtained after adjustment were similar to those found under comparable circumstances in patients in Rotterdam. Conclusion. Optimal treatment of CAH patients in Semarang Indonesia can be reached by introducing hydrocortisone treatment and adjusting dosage and timing on the basis of salivary steroid monitoring. However, in Indonesia the management of these patients is still constrained by the lack of diagnostic and therapeutic means.

PERSIST: Physician&amp;#39;s Evaluation of Restasis&amp;reg; Satisfaction in Second Trial of topical cyclosporine ophthalmic emulsion 0.05% for dry eye: a retrospective review

BackgroundChronic dry eye disease often requires long-term therapy. Tear film alterations in the setting of dry eye may include reduced tear volume as well as an increase in inflammatory cytokines and osmolarity. Topical cyclosporine ophthalmic emulsion 0.05% (Restasis®; Allergan Inc, Irvine, CA) is indicated to increase tear production in patients with dry eye and reduced tear production presumed to be due to ocular inflammation. This study was designed to evaluate the efficacy of a second trial of topical cyclosporine in patients with dry eye who were previously considered treatment failures.Materials and methodsThis multicenter (three cornea practices) retrospective chart review evaluated clinical outcomes in patients with dry eye who received a second trial of cyclosporine after a prior treatment failure, defined as prior discontinuation of topical cyclosporine after less than 12 weeks.ResultsThirty-five patients, most of whom were female (71.4%) and Caucasian (62.9%), were identified. Prior discontinuation was most commonly due to burning/stinging (60%). The median duration of second treatment was 10 months (range 1 week to 45 months). Physician education was provided in the second trial in 97.1% of cases. At initiation of the second trial of cyclosporine, 10 (28.6%) patients received courses of topical corticosteroids. Physicians reported on a questionnaire that 80% of patients achieved clinical benefit with a second trial of cyclosporine.ConclusionA repeat trial with topical cyclosporine can achieve clinical success. Direct patient education via the physician and staff may be key to success. Proper patient education may overcome adherence issues, particularly with respect to the need for long-term treatment of chronic dry eye. This study has the usual limitations associated with a retrospective chart review, and future prospective studies are warranted.

Abstract PL01-03: The landscape of cancer prevention: Personalized approach in lung cancer

Abstract PL01-03: The landscape of cancer prevention: Personalized approach in lung cancer