Long-term Clinical Experience Research Articles

Monotherapy with lanreotide depot for acromegaly: long-term clinical experience in a pituitary center.

Long-acting somatostatin analogs are one of the main classes of medical therapy used for acromegaly and most patients require ongoing treatment. Few studies have evaluated the long-term efficacy and safety of lanreotide depot beyond 2years. The goal of this study was to provide a long-term longitudinal assessment of efficacy and safety of lanreotide depot in lanreotide responders compared to a surgically cured control group. In this retrospective longitudinal case-control study, patients with acromegaly receiving lanreotide depot monotherapy continuously for at least 24months (N=24) and surgically cured patients (N=39) were compared. Serum IGF-1, pituitary MRIs, lanreotide dose, co-morbidities and adverse effects were assessed longitudinally. In the lanreotide group, IGF-1 remained normal and unchanged over 6years; comparable to the surgery only group. There was no difference in prevalence of normal IGF-1 between the lanreotide and surgery only groups at 6months (100 vs. 97%), 6years (89 vs. 90%) and at last follow-up (96 vs. 92%). Tumor size remained stable (79%) or decreased (21%) in the lanreotide group. In the surgery only group, tumor size remained unchanged in all patients. Hemoglobin A1C did not differ between lanreotide and surgery only groups (baseline 5.8 vs. 6.1%; last follow-up 6.0 vs. 5.7%). Two (8%) of the lanreotide and none of the surgery only group developed new diabetes mellitus. Lanreotide depot maintains normalization of IGF-1 in 89% of responders after 6years, comparable to surgically cured controls, and controlled tumor size in all without significant adverse effects.

Why perimenopausal women should consider to use a levonorgestrel intrauterine system

Objective: The use of a levonorgestrel intrauterine system (LNG-IUS) is useful in preventing pregnancy and for the treatment of menstrual disturbances. A smooth or symptom-free transition to and through menopause is possible when LNG-IUS is combined with estrogen therapy. Unfortunately the majority of physicians are generally unaware of this usefulness combined hormonal therapy in the pre-, peri- and postmenopausal women.Design and method: Based on long-term clinical experience with LNG-IUS in the form of Femilis®, 104 women where followed from the premenopause through the menopausal transition into the postmenopause. These perimenopausal women received supplemental 17 β-estradiol by gel or patch, or orally as estradiol valerate. Patients received one or two separate Femilis insertions at 5 year intervals. Main outcome measures included acceptability and continued use of the combined regimen for the treatment of climacteric symptoms and for prevention of cardiovascular disease, osteoporosis and other adverse effects caused by estrogen deprivation.Results: The average age at insertion was 48 years (range 28–58) and the total duration of use was 137 months (range 80–161). The Femilis LNG-IUS was well tolerated as the number of removals for LNG-IUS-related reasons was low. The LNG-IUS was well retained in the uterine cavity as no expulsions were observed. Seven women were lost to follow-up. Eighty-six women (82%) opted for replacement of an LNG-IUS at expiry after 5 years and continued with the estrogen therapy.Conclusion: Intrauterine progestogen delivery for endometrial suppression in combination with estrogen therapy in the symptomatic perimenopausal women is highly practical as it combines the benefits of prevention of endometrial proliferation and treatment of menorrhagia and hyperplasia, if present. In addition, the contraceptive effect of locally administered LNG is highly desirable as many perimenopausal women run considerable risk of unintended pregnancy. For these reasons, the author views this regimen as one of the most effective, safest and best accepted route resulting in high patient compliance. It is important to convey this message to general practitioners as well as women.

Fingolimod in the treatment of relapsing-remitting multiple sclerosis: long-term experience and an update on the clinical evidence.

Since the approval in 2010 of fingolimod 0.5 mg (Gilenya; Novartis Pharma AG, Basel, Switzerland) in the USA as an oral therapy for relapsing forms of multiple sclerosis, long-term clinical experience with this therapy has been increasing. This review provides a summary of the cumulative dataset from clinical trials and their extensions, plus postmarketing studies that contribute to characterizing the efficacy and safety profile of fingolimod in patients with relapsing forms of multiple sclerosis. Data from the controlled, phase III, pivotal studies [FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis), FREEDOMS II and TRANSFORMS (Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis)] in relapsing-remitting multiple sclerosis have shown that fingolimod has a robust effect on clinical and magnetic resonance imaging outcomes. The respective study extensions show that effects on annualized relapse rates are sustained with continued fingolimod treatment. Consistent, significant reductions in magnetic resonance imaging lesion counts and brain volume loss have also been sustained with long-term treatment. The safety profile of fingolimod is also examined, particularly in light of its long-term use. A summary of the adverse events of interest that are associated with fingolimod treatment and associated label guidelines are also considered, which include cardiac effects following first-dose administration, infections, lymphopenia, macular edema and pregnancy. Historic hurdles to the prescription of fingolimod and how these challenges are being met are also discussed.

In Vivo Safety of Aqueous Leaf Extract of Lippia javanica in Mice Models

Rural dwellers in Kenya often resort to herbal remedy and dietary control in the treatment of several diseases including diabetes mellitus (DM), hypertension, cancer and cardiac diseases. The therapeutic applications of such plants has largely rested upon their long-term clinical experience, however, their safety profiles has not been well evaluated. The present study aimed at determining the in vivo toxic effects of orally and intraperitoneally administering Lippia javanica leaf extract at dosage levels of 450 mg/kgbwt, 670 mg/kgbwt and 1000 mg/kgbwt daily for 28 days on the body and organ weights, hematological indices and biochemical parameters in normal male swiss white albino mice. During this period, the mice were allowed free access to mice pellets and water ad libitum and observed for signs of general illness, change in behavior and mortality. Phytochemical composition was assessed using standard procedures. The oral and intraperitoneal administration of 450 mg/kgbwt, 670 mg/kgbwt and1000 mg/kg body weight of the extract decreased the body weight gain and altered the organ to body weight percentage of the brain, kidney, liver, heart, testes and lungs. Oral and intraperitoneal administration of the same doses caused a change in levels of RBC, WBC, Hb, PCV, PLT, MPV, MCV, MCH, MCHC, neutrophils, lymphocytes, eosinophils, basophils, monocytes and biochemical parameters: AST, ALP, ALT, GGT, CK, α-AMYL, LDH, T-BIL, D-BIL, I-BIL, TG, TC, LDL-C, HDL-C, BUN, UA, Urea and Creatinine. The extracts contained alkaloids, sterols, terpenoids, flavonoids, tannins and saponins.

CURRENT DIAGNOSTIC BRONCHOSCOPY FOR EARLY CENTRAL LUNG CANCER (Review of literature)

The article tells about the evolution in the development of endoscopic diagnostic methods for early central lung cancer, from rigid bronchoscopes to modern high-resolution video endoscopes. The current multimodal diagnostic methods are described, including the recent data on the use of confocal laser endomicroscopy and endocytoscopy which allow to detect lesions caused by intramucosal cancer in the tracheobronchial tree as well as to study the cellular-level morphology in vivo. Long-term clinical experience of the P.A. Herzen Moscow Oncology Research Institute in the diagnosis of central lung cancer is presented.

ПОГЛЯД НА ТРАВМУ В КОНТЕКСТІ ПИТАННЯ ПРО ПЕРЕДУМОВИ ПОЯВИ ПСИХІЧНИХ НАСЛІДКІВ СУСПІЛЬНИХ КРИЗ

The paper presents an overview of the problem of psychic trauma within the study of the issue concerning the prerequisites for the emergence of psychical effects of public crises. It is emphasized in the paper that the realities of our present time in the world society are characterized with a high density of crisis states and processes. It is shown in the paper that the question of the emergence of the negative psychical effects of public crises practically is not raised as a scientific problem. Based on the analysis of the forms, manifestations, dynamics and specifics of public crisis phenomena, as well as on the examination of the peculiarities of the psychical response to the crisis phenomena, the author presents an analysis of psychical conditions under which public crisis factors become pathogenic and cause person’s negative psychical processes and states. The elaborate study of long-term clinical experience of psychoanalysts and theoretical analysis of psychoanalytic papers testify that the subject’s traumatization is not predetermined by the principle of linear determinism (when the past affects the present), but on the contrary, the experience of the past can be updated as a traumatic one in the light of present events. In other words, the event of the past can get the traumatic significance through the sense of the event of the present.

Duration of anti-resorptive therapy for osteoporosis.

Osteoporotic fractures are common, and available medications reduce fracture risk by up to half. However, because the most commonly used drugs, bisphosphonates, have side effects that may be related to duration of therapy and because long-term efficacy has not been established, the optimal length of treatment has not been determined. Based on two long-term studies and extensive clinical experience, a plan is provided to treat patients at risk for 5 years with re-assessment every 2 years thereafter. Assessment tools are limited, but for each individual, the potential risks and benefits of continuing, discontinuing, re-instituting, or changing therapy can be estimated.

1222 Long-term clinical experiences of patients (pts) with non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) or metastatic melanoma (MEL): A SEER-Medicare analysis

1222 Long-term clinical experiences of patients (pts) with non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) or metastatic melanoma (MEL): A SEER-Medicare analysis

Long-term clinical and real-world experience with pirfenidone in the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible, progressively destructive lung disease that culminates in respiratory failure and death. Randomised controlled trials have demonstrated that treatment of IPF patients with pirfenidone reduces lung function decline, improves progression-free survival and significantly reduces the risk of all-cause mortality at 1 year. Pirfenidone has been shown to have a favourable safety profile and was generally well tolerated over the long term in clinical trials and real-world experience. However, side-effect management is critical to help some patients remain on treatment over the long term. The primary treatment-related adverse events associated with pirfenidone therapy are gastrointestinal upset, rash and photosensitivity. Gastrointestinal events may be mitigated by ensuring that pirfenidone is taken with food, while skin symptoms may be reduced by avoiding sun exposure and frequent use of sunblock. Educating patients about the potential for these adverse events to occur and providing instructions prior to treatment to avoid adverse drug reactions are an important means of ensuring patients may derive the important benefits provided by long-term treatment with pirfenidone.

Gastrointestinal cancer: nonliver proton therapy for gastrointestinal cancers.

Multimodality therapy for gastrointestinal (GI) cancers carries considerable risk for toxicity; even single-modality radiation therapy in this population carries with it a daunting side effect profile. Supportive care can certainly mitigate some of the morbidity, but there remain numerous associated acute and late complications that can compromise the therapy and ultimately the outcome. Gastrointestinal cancers inherently occur amid visceral organs that are particularly sensitive to radiotherapy, creating a very narrow therapeutic window for aggressive cell kill with minimal normal tissue damage. Radiation therapy is a critical component of locoregional control, but its use has historically been limited by toxicity concerns, both real and perceived. Fundamental to this is the fact that long-term clinical experience with radiation in GI cancers derives almost entirely from 2-dimensional radiation (plain x-ray-based planning) and subsequently 3-dimensional conformal radiation. The recent use of intensity-modulated photon-based techniques is not well represented in most of the landmark chemoradiation trials. Furthermore, the elusive search for efficacious but tolerable local therapy in GI malignancies raises the possibility that proton radiotherapy's physical and dosimetric differences relative to conventional therapy may make it better suited to the challenge. In many sites, local recurrences after chemoradiation pose a particular challenge, and reirradiation in these sites may be done successfully with proton radiotherapy.

Buerger's disease in the northeast of Iran: Epidemiology and clinical features.

The aim of this study is to present our long-term clinical experience in describing a clinical picture of Buerger's disease in our region. In a retrospective study, files of 225 patients who were admitted to the hospital with diagnosis of thromboangiitis obliterans in a 10 year period from 2000 to 2010 were reviewed. All data including demographic, signs and symptoms, history of previous illness, history of smoking, medications, laboratory tests, angiography, and details of surgical operation were obtained. A total of 222 (98.7%) and 3 (1.3%) of patients were male and female, respectively. Average age of hospitalized patients was 40.7 ± 8.5 (20-62) years. A total of 200 patients (88.9%) were active cigarette smokers while 168 (74.7%) of them were opium addicts. The most prevalent symptoms were chronic ulcers (80%) and claudication (63.6%). Minor and major amputation was required in 113 (50.2%) and 41 (18.4%) patients, respectively. Amputation was carried out on the lower limb (80%), upper limb (4.1%), or on both (15.1%). Also, four patients underwent revascularization through surgical bypass procedures. The diagnosis and treatment of Buerger's Disease is still a challenge in those communities where the disease is endemic. Therefore, identifying the natural course of the disease can play a pivotal role in the diagnosis and treatment of these patients.

Long-term clinical experience with helical tomotherapy for head and neck cancer

Objective The objective of this study is to review a long-term single-institutional experience with helical tomotherapy (HT) for the radiotherapeutic management of head and neck cancer.

Regulation Theory and Affect Regulation Psychotherapy: A Clinical Primer

This article offers an essay on the influence of advances in developmental neuroscience and neuropsychoanalysis for our understanding of the interpersonal neurobiological change mechanisms embedded in the mother–infant and client–therapist relationship. Regulation theory and affect regulation therapy are reviewed, along with attachment, affect regulation, and the development of the right brain. Right-brain communications within the therapeutic alliance are described, leading to the conclusion that the right brain is dominant in psychotherapy. Changes in not only the client’s but also the clinician’s brain over long-term clinical experiences are discussed.

Clinical performance of a sutureless aortic bioprosthesis: Five-year results of the 3f Enable long-term follow-up study

Sutureless valves are designed to facilitate surgical implantation, including less-invasive techniques in aortic valve replacement, by maintaining surgical precision of implantation compared with transcatheter techniques. Long-term clinical experience with sutureless valves is lacking. We report the 5-year follow-up results of an international, prospective, multicenter study evaluating the clinical performance and safety of the 3f Enable valve (Medtronic Inc, Minneapolis, Minn). Between March 2007 and December 2009, 141 patients (54 male; mean age, 76.1±5.7 years) undergoing aortic valve replacement with the 3f Enable valve were enrolled in 10 European sites. The mean follow-up was 2.76 years (range, 2 days to 5.1 years; total, 388.7 patient-years). Echocardiographic valvular hemodynamic and morphologic analyses were performed by an independent core laboratory. The mean systolic gradient was 10.4±4.4 mm Hg at discharge and 7.7±4.1 mm Hg at 5 years. The mean effective orifice area was 1.7±0.5 cm2 at discharge and 1.6±0.2 cm2 at 5 years. Freedom from all-cause and valve-related mortality was 87.6%±2.9% and 96.8%±1.6% at 1 year (113 patients at risk) and 77.0%±7.5% and 93.8%±4.8% at 5 years (24 patients at risk), respectively. Six patients underwent reoperation (4 because of major paravalvular leakage and 2 because of endocarditis). Freedom from reoperation was 95.4%±1.9% at 1 year and 95.4%±6.1% at 5 years. No structural valve deterioration occurred during the follow-up period. The sutureless 3f Enable valve represents a safe and effective treatment for aortic valve stenosis, providing an excellent hemodynamic profile. This study represents the longest follow-up study for a sutureless bioprosthesis. Sutureless valves may become an option for all patients with indicated biological aortic valve replacement.

Long‐term clinical experience with amplatzer ductal occluder II for closure of the persistent arterial duct in children

To describe the long-term clinical experience and follow-up with the Amplatzer Ductal Occluder II (ADO II) in children. All patients undergoing attempted transcatheter closure of patent arterial duct (PDA) with the ADO II were included. Data collected included demographic, clinical, and echocardiographic parameters. From March 2008 until March 2013, 62 patients with a median age of 1.2 years (range 0.43-11.1 years) and median weight of 9 kg (range 4.7-31.4 kg) underwent the procedure. The median measurement for minimal ductal diameter was 2.7 mm (range 1.3-5 mm). An ADO II was implanted in 60 patients (96.8%). Two patients had significant residual shunting following deployment of the ADO II and underwent closure with the Amplatzer ductal occluder I (ADO I) during the same procedure. In six patients, the initial ADO II was unsatisfactory, and after recapture a different size ADO II was deployed. Device embolization of the ADO II to the pulmonary artery occurred in 6.7% of patients. Of these, one underwent surgical closure and three were closed with an ADO I. Complete occlusion on echocardiography was noted prior to discharge in 87.5% of the deployed occluders and 100% at first follow-up. Five year follow-up (n = 25) revealed a 100% occlusion rate. There were three cases of persistent mild left pulmonary artery stenosis at long-term follow-up. The ADO II is effective for occlusion of PDA with variable anatomy from either arterial or venous approaches with a low profile delivery system. Stable occluder position is highly dependent on accurate device sizing, good quality imaging to visualize device configuration after deployment and operator experience.

Long-term follow-up in patients with homozygous familial hypercholesterolemia; 13-year experience of a university hospital lipid clinic

Familiar hypercholesterolemia (FH) is a genetic disease characterized with extremely high levels of cholesterol leading to premature atherosclerosis. In homozygous individuals (HoFH) cardiovascular events could develop in childhood. In this article, long-term clinical experience with adult HoFH patients who are followed in Department of Cardiology, Ege University Faculty of Medicine is presented. Seventeen HoFH patients (11 females, 6 males) who are being followed between the years 2000-2013 were included. All data including clinical characteristics, family history, lipid levels, treatment, lipid-apheresis, cardiovascular events, complications were obtained retrospectively from patient chart records. Mean age was 31 ± 10 years at admission to our clinic. First diagnosis age was 25 ± 14. At diagnosis, mean cholesterol level was 625 ± 136 mg/dl. Admission complaints were dermatologic (41%) and ischemic symptoms (41%). A total of 3 patients (18%) were diagnosed during family screening. 65% of the patients' parents had consanguineous marriage. Xantomas was present in 59%, aortic valve pathology in 59%, and carotid artery plaques in 47%. Coronary artery disease was documented in 59%. Though all patients had indication for apheresis, 10 patients received apheresis due to high refusal rate. Age at the first apheresis was 27 ± 12 (minimum 10-maximum 42) and adherence to apheresis was 60%. With 2 years regular apheresis skin depositions were vanished, however carotid atherosclerosis and aortic pathology progressed. During the 43 ± 42 months follow-up, 4 patients died (mean age: 25 ± 5). Diagnosis is late in HoAH. Due to the delayed treatment of lipid apheresis, atherosclerosis and aortic stenosis progress in these patients. The awareness of the physicians and knowledge of the public is warranted.

The scientific basis of rasa (taste) of a substance as a tool to explore its pharmacological behavior.

Background:A rational and well-developed pharmacological basis forms the foundation of therapeutics in Ayurveda. The principles and theories of Ayurveda need to be validated in the scientific context in order to harness the millennia old knowledge. Rasa (taste) of the substance is the foremost tool in Ayurveda to assess and determine the pharmacological properties and actions of the substance. Similarity in rasa is said to signify similar structure and consequently similar pharmacological behavior. Depending on skills developed over the course of long-term clinical experience one, can register the minute variations in rasa of substances and accordingly the possible variations in pharmacological actions. Thus, rasa can be used as a scientific tool in the drug discovery process to limit and focus the target areas.Aim:To sensitize scientific community to the utility of rasa as a tool in the process of drug discovery.Materials and Methods:All relevant ancient and contemporary literature was reviewed critically to form a scientific basis of the Ayurvedic concept of rasa as a tool to identify the pharmacological behavior of a substance.Conclusion:The review finds that rasa (taste) can be used as a guide to identify potential targets in drug discovery.

Dr bhardwaj and colleagues reply.

To the Editor: Josiassen et al have written an excellent, clinically oriented letter to the editor in response to our letter.1 We agree with their pharmaceutical and clinical recommendations. Similarly, we have also observed the diurnal nature of hyponatremia in many patients. This diurnal presentation with varying sodium concentrations over time confers diagnostic and treatment concerns; one laboratory value may erroneously characterize a patient’s physiological state. The major precaution is one of close clinical monitoring with careful, continued, repeated laboratory assessments whenever treating a person with electrolyte abnormalities. This need for caution would be especially true when utilizing vaptans as a corrective measure for hyponatremia. Such a cautionary note is especially emphasized when prescribing a relatively new pharmaceutical, without long-term clinical application or experience.

RATsIONAL'NYY VYBOR FARMAKOTERAPII POSTMENOPAUZAL'NOGO OSTEOPOROZA.EFFEKTIVNOST' I BEZOPASNOST' BONVIVY: OBZOR ZA VOSEM' LET PRIMENENIYa

In this critical review, we have summarized the specific evidence on ibandronic acid (Bonviva) efficacy, tolerability, feasibility and safety acquired from randomized controlled clinical trials, meta-analyses, bridging trials, long-term extension studies, observational studies and clinical experience. We have paid special attention to reviewing the surrogate endpoints, which are routinely used in clinical practice to estimate the treatment efficacy as well as those high technology methods that are currently used in research centers to predict anti-fracture efficacy. Although the only registered indication for Bonviva in Russia is for postmenopausal osteoporosis, we have reviewed the available clinical trials on the efficacy of ibandronic acid to prevent postmenopausal osteoporosis, to treat low bone mass in males, to treat and prevent glucocorticoid induced osteoporosis and other types of secondary osteoporosis and, in particular, in patients after organ transplantation. In addition to this, we have extensively discussed the currently available data on the safety of pharmacologic treatment for osteoporosis.

The Balance Between Effective Opioid-Based Pain Management and Patient Safety: Can It Be Achieved?

The Balance Between Effective Opioid-Based Pain Management and Patient Safety: Can It Be Achieved?