Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study.

PubMed

Findling, Robert L; Johnson, Jacqueline L; McClellan, Jon; Frazier, Jean A; Vitiello, Benedetto; Hamer, Robert M; Lieberman, Jeffrey A; Ritz, Louise; McNamara, Nora K; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

2010-06-01

To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. Of the 116 youths randomized in the acute trial, 54 entered maintenance treatment (molindone, n = 20; olanzapine, n = 13; risperidone, n = 21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (n = 15), inadequate efficacy (n = 14), or study nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. Only 12% of youths with early-onset schizophrenia spectrum disorders continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for early-onset schizophrenia spectrum disorders. Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Early treatment of posterior crossbite - a randomised clinical trial

PubMed Central

2013-01-01

Background The aim of this randomised clinical trial was to assess the effect of early orthodontic treatment in contrast to normal growth effects for functional unilateral posterior crossbite in the late deciduous and early mixed dentition by means of three-dimensional digital model analysis. Methods This randomised clinical trial was assessed to analyse the orthodontic treatment effects for patients with functional unilateral posterior crossbite in the late deciduous and early mixed dentition using a two-step procedure: initial maxillary expansion followed by a U-bow activator therapy. In the treatment group 31 patients and in the control group 35 patients with a mean age of 7.3 years (SD 2.1) were monitored. The time between the initial assessment (T1) and the follow-up (T2) was one year. The orthodontic analysis was done by a three-dimensional digital model analysis. Using the ‘Digimodel’ software, the orthodontic measurements in the maxilla and mandible and for the midline deviation, the overjet and overbite were recorded. Results Significant differences between the control and the therapy group at T2 were detected for the anterior, median and posterior transversal dimensions of the maxilla, the palatal depth, the palatal base arch length, the maxillary arch length and inclination, the midline deviation, the overjet and the overbite. Conclusions Orthodontic treatment of a functional unilateral posterior crossbite with a bonded maxillary expansion device followed by U-bow activator therapy in the late deciduous and early mixed dentition is an effective therapeutic method, as evidenced by the results of this RCT. It leads to three-dimensional therapeutically induced maxillary growth effects. Dental occlusion is significantly improved, and the prognosis for normal craniofacial growth is enhanced. Trial registration Registration trial DRKS00003497 on DRKS PMID:23339736

Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost-effectiveness analysis.

PubMed

Finckh, Axel; Bansback, Nick; Marra, Carlo A; Anis, Aslam H; Michaud, Kaleb; Lubin, Stanley; White, Marc; Sizto, Sonia; Liang, Matthew H

2009-11-03

Long-term control or remission of rheumatoid arthritis (RA) may be possible with very early treatment. However, no optimal first therapeutic strategy has been determined. To assess the potential cost-effectiveness of major therapeutic strategies for very early RA. Decision analytic model with probabilistic sensitivity analyses. Published data, the National Data Bank for Rheumatic Diseases, and actual 2007 hospital costs. U.S. adults with very early RA (symptom duration early DMARD therapy with methotrexate; and early therapy with biologics and methotrexate. Cost per quality-adjusted life-year (QALY) gained. By reducing the progression of joint erosions and subsequent functional disability, both early intervention strategies increase quality-adjusted life more than the pyramid strategy and save long-term costs. When the cost of very early intervention is factored in, the cost-effectiveness ratio of the early DMARD strategy is $4849 per QALY (95% CI, $0 to $16 354 per QALY) compared with the pyramid strategy, whereas the benefits gained through the early biologic strategy come at a substantial incremental cost. The early DMARD strategy maximizes the effectiveness of early DMARDs and reserves the use of biologics for patients with more treatment-resistant disease of longer duration, for which the incremental benefit of biologics is greater. The early biologic strategy becomes more cost-effective if drug prices are reduced, risk for death is permanently lowered through biologic therapy, patients experience drug-free remission, responders can be selected before therapy initiation, or effective alternative antirheumatic agents are available for

Effect of chiropractic treatment on primary or early secondary prevention: a systematic review with a pedagogic approach.

PubMed

Goncalves, Guillaume; Le Scanff, Christine; Leboeuf-Yde, Charlotte

2018-01-01

The chiropractic vitalistic approach to the concept of 'subluxation' as a cause of disease lacks both biological plausibility and possibly proof of validity. Nonetheless, some chiropractors purport to prevent disease in general through the use of chiropractic care. Evidence of its effect is needed to be allowed to continue this practice. The objective of this systematic review was therefore to investigate if there is any evidence that spinal manipulations/chiropractic care can be used in primary prevention (PP) and/or early secondary prevention in diseases other than musculoskeletal conditions. We searched PubMed, Embase, Index to Chiropractic Literature , and some specialized chiropractic journals, from inception to October 2017, using terms including: "chiropractic", "subluxation", "wellness", "prevention", "spinal manipulation", "mortality". Included were English language articles that indicated that they studied the clinical preventive effec t of or benefit from manipulative therapy/chiropractic treatment in relation to PP and/or early treatment of physical diseases/morbidity in general, other than musculoskeletal disorders. Also, population studies were eligible. Checklists were designed in relation to the description of the reviewed articles and some basic quality criteria. Outcomes of studies were related to their methodological quality, disregarding results from those unable to answer the research questions on effect of treatment. Of the 13.099 titles scrutinized, 13 articles were included (eight clinical studies and five population studies). These studies dealt with various disorders of public health importance such as diastolic blood pressure, blood test immunological markers, and mortality. Only two clinical studies could be used for data synthesis. None showed any effect of spinal manipulation/chiropractic treatment. We found no evidence in the literature of an effect of chiropractic treatment in the scope of PP or early secondary prevention for

Clozapine Titration for People in Early Psychosis: A Chart Review and Treatment Guideline.

PubMed

Ballon, Jacob S; Ashfaq, Hera; Noordsy, Douglas L

2018-06-01

The use of clozapine, particularly in young people, is often limited by early treatment-emergent adverse effects including drowsiness and lethargy. Concerns about adverse effects, medication adherence, and the need for blood monitoring often impede the use of clozapine in this population, leading to repeated trials of less effective medications. Current clozapine dosing recommendations are based on people further in the course of their illness and thus reflect different responsiveness and sensitivities to antipsychotic medication. As such, there is a need for evidence-based guidelines for titration and dosing of clozapine among people in early psychosis. We performed a chart review of 14 people treated with clozapine within our early psychosis team. Data regarding dose titration, response, time to discontinuation, symptom severity, weight gain, and other adverse effects were gathered at clozapine initiation, 3 months, and last available visit on clozapine. People treated with slow titration within their first year of psychosis onset achieved sustained response at very low maintenance doses (mean dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow titration with longer duration of illness (mean dose = 350 mg/d, mean duration of treatment = 68 weeks) or standard dose titration in early psychosis (mean dose = 112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects in all groups were weight gain and sedation, with the groups requiring higher mean doses reporting a broader range of adverse effects. There was no apparent difference in the clinical global impression for severity or improvement between the slow titration and standard titration groups in people with early psychosis. These observations are synthesized into a proposed treatment guideline for use of clozapine among people in early psychosis. We describe development of a slow titration approach to initiating clozapine among people in early psychosis. This

Comparison of Doxycycline and Benzathine Penicillin G for the Treatment of Early Syphilis.

PubMed

Xiao, Hailu; Liu, Dianchang; Li, Zhen; Zheng, Rongtao; Li, Zhongwei; Hou, Jianling; Zhang, Shengjia; Chu, Tongsheng; Tian, Hongqing; Zhang, Furen

2017-07-01

Doxycycline is the preferred recommended second-line treatment for the treatment of early syphilis. Recent reports showed a declining efficacy trend of doxycycline in treatment of early syphilis. The aim of our study was to assess the serological response to the treatment for early syphilis with doxycycline compared with benzathine penicillin G and evaluate whether doxycycline is still an effective agent for the treatment of early syphilis. A record-based retrospective study was conducted. Patients were diagnosed with early syphilis in an sexually transmitted disease (STD) clinic from January 1, 2008 to December 31, 2014. They were treated with a single dose of benzathine penicillin G 2.4MU or oral doxycycline 100 mg twice daily for 14 days. Pearson's chi-squared test was used for data analysis. 601 cases were included in the final study sample: 105 (17.5%) patients received a 14-day course of doxycycline (doxycycline group), and 496 (82.5%) patients received single-dose benzathine penicillin G (BPG group). The serological responses at 6 months and 12 months after treatment were compared. No statistically significant differences were found between the two groups at 6 months (69.52% vs. 75.00%, P=0.245), and at 12 months (92.38% vs. 96.17%, P=0.115). Doxycycline is still an effective agent for the treatment of early syphilis.

Effects of site preparation treatments on early growth and survival of planted longleaf pine (Pinus palustris Mill.) seedlings in North Carolina

Treesearch

Benjamin O. Knapp; G. Geoff Wang; Joan L. Walker; Susan Cohen

2006-01-01

We tested the effects of eight site preparation treatments on early growth and survival of container-grown longleaf pine (Pinus palustris Mill.) seedlings. Treatments included an untreated check, six combinations of two initial vegetation control treatments (chopping or herbicide) with three planting site conditions (flat [no additional treatment],...

Functional Recovery in Major Depressive Disorder: Focus on Early Optimized Treatment.

PubMed

Habert, Jeffrey; Katzman, Martin A; Oluboka, Oloruntoba J; McIntyre, Roger S; McIntosh, Diane; MacQueen, Glenda M; Khullar, Atul; Milev, Roumen V; Kjernisted, Kevin D; Chokka, Pratap R; Kennedy, Sidney H

2016-09-01

This article presents the case that a more rapid, individualized approach to treating major depressive disorder (MDD) may increase the likelihood of achieving full symptomatic and functional recovery for individual patients and that studies show it is possible to make earlier decisions about appropriateness of treatment in order to rapidly optimize that treatment. A PubMed search was conducted using terms including major depressive disorder, early improvement, predictor, duration of untreated illness, and function. English-language articles published before September 2015 were included. Additional studies were found within identified research articles and reviews. Thirty antidepressant studies reporting predictor criteria and outcome measures are included in this review. Studies were reviewed to extract definitions of predictors, outcome measures, and results of the predictor analysis. Results were summarized separately for studies reporting effects of early improvement, baseline characteristics, and duration of untreated depression. Shorter duration of the current depressive episode and duration of untreated depression are associated with better symptomatic and functional outcomes in MDD. Early improvement of depressive symptoms predicts positive symptomatic outcomes (response and remission), and early functional improvement predicts an increased likelihood of functional remission. The approach to treatment of depression that exhibits the greatest potential for achieving full symptomatic and functional recovery is early optimized treatment: early diagnosis followed by rapid individualized treatment. Monitoring symptoms and function early in treatment is crucial to ensuring that patients do not remain on ineffective or poorly tolerated treatment, which may delay recovery and heighten the risk of residual functional deficits. © Copyright 2016 Physicians Postgraduate Press, Inc.

Nanomedicine for Early Disease Detection and Treatment

DTIC Science & Technology

2013-09-01

AD_________________ Award Number: W81XWH-11-1-0442 TITLE: Nanomedicine for early disease ...been developed to report and cure diseases . ESNM is prepared with multiple layers of polyelectrolytes, sequentially assembled on an inert gold...molecular characteristics of the patient and his/her specific diseased tissues with the treatment. In order to maximize therapeutic effects and

Early Identification and Treatment of Antisocial Behavior.

PubMed

Frick, Paul J

2016-10-01

Severe and persistent antisocial behavior is a prevalent, serious, and costly mental health problem. Individuals who are most likely to show persistent antisocial behavior through adolescence and into adulthood often show patterns of severe and varied conduct problems early in childhood. Treatments that intervene early in the development of these problems are most effective and least costly. Furthermore, there appear to be several common causal pathways that differ in their genetic, emotional, cognitive, and contextual characteristics. These pathways are differentiated by the level of callous-unemotional traits displayed by the individual. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment Moderators and Predictors of Outcome in the Treatment of Early Age Mania (TEAM) Study

ERIC Educational Resources Information Center

Vitiello, Benedetto; Riddle, Mark A.; Yenokyan, Gayane; Axelson, David A.; Wagner, Karen D.; Joshi, Paramjit; Walkup, John T.; Luby, Joan; Birmaher, Boris; Ryan, Neal D.; Emslie, Graham; Robb, Adelaide; Tillman, Rebecca

2012-01-01

Objective: Both the diagnosis and treatment of bipolar disorder in youth remain the subject of debate. In the Treatment of Early Age Mania (TEAM) study, risperidone was more effective than lithium or divalproex in children diagnosed with bipolar mania and highly comorbid with attention-deficit/hyperactivity disorder (ADHD). We searched for…

Early-onset scoliosis: current treatment.

PubMed

Cunin, V

2015-02-01

Early-onset scoliosis, which appears before the age of 10, can be due to congenital vertebral anomalies, neuromuscular diseases, scoliosis-associated syndromes, or idiopathic causes. It can have serious consequences for lung development and significantly reduce the life expectancy compared to adolescent scoliosis. Extended posterior fusion must be avoided to prevent the crankshaft phenomenon, uneven growth of the trunk and especially restrictive lung disease. Conservative (non-surgical) treatment is used first. If this fails, fusionless surgery can be performed to delay the final fusion procedure until the patient is older. The gold standard delaying surgical treatment is the implantation of growing rods as described by Moe and colleagues in the mid-1980s. These rods, which are lengthened during short surgical procedures at regular intervals, curb the scoliosis progression until the patient reaches an age where fusion can be performed. Knowledge of this technique and its complications has led to several mechanical improvements being made, namely use of rods that can be distracted magnetically on an outpatient basis, without the need for anesthesia. Devices based on the same principle have been designed that preferentially attach to the ribs to specifically address chest wall and spine dysplasia. The second category of surgical devices consists of rods used to guide spinal growth that do not require repeated surgical procedures. The third type of fusionless surgical treatment involves slowing the growth of the scoliosis convexity to help reduce the Cobb angle. The indications are constantly changing. Improvements in surgical techniques and greater surgeon experience may help to reduce the number of complications and make this lengthy treatment acceptable to patients and their family. Long-term effects of surgery on the Cobb angle have not been compared to those involving conservative "delaying" treatments. Because the latter has fewer complications associated with

Retrospective 25-year follow-up of treatment outcomes in angle Class III patients : Early versus late treatment.

PubMed

Wendl, B; Muchitsch, A P; Winsauer, H; Walter, A; Droschl, H; Jakse, N; Wendl, M; Wendl, T

2017-05-01

To assess early versus late treatment of Class III syndrome for skeletal and dental differences. Thirty-eight Class III patients treated with a chincup were retrospectively analyzed. Baseline data were obtained by reviewing pretreatment (T0) anamnestic records, cephalograms, and casts. The cases were assigned to an early or a late treatment group based on age at T0 (up to 9 years or older than 9 years but before the pubertal growth spurt). Both groups were further compared based on posttreatment data (T1) and long-term follow-up data collected approximately 25 years after treatment (T2). Early treatment was successful in 74% and late treatment in 67% of cases. More failures were noted among male patients. The late treatment group was characterized post therapeutically by significantly more pronounced skeletal parameters of jaw size relative to normal Class I values; in addition, a greater skeletal discrepancy between maxilla and mandible, higher values for mandibular length, Cond-Pog, ramus height, overjet, anterior posterior dysplasia indicator (APDI), lower anterior face height, and gonial angle were measured at T1. The angle between the AB line and mandibular plane was found to be larger at T0, T1, and T2, as well as more pronounced camouflage positions of the lower anterior teeth at T0. The early treatment group was found to exhibit greater amounts of negative overjet at T0 but more effective correction at T1. Early treatment of Class III syndrome resulted in greater skeletal changes with less dental compensation.

[Short-term curative effects of Tantalum rod treatment in early avascular necrosis].

PubMed

Ye, Fu-Sheng; Ni, Zhe-Ji; Chu, Xiao-Bing; He, Bang-Jian; Li, Ju; Tong, Pei-Jian

2013-08-01

To explore the recent clinical curative effect of Tantalum rod in treating the early avascular necrosis. From January 2008 to November 2008, the 25 patients (39 hips) with early avascular necrosis accepted tantalum rod placement and included 9 males (11 hips) and 16 females (28 hips) with an average age of 37 years old ranging from 18 to 74 years old. Four patients (6 hips) caused by Alcoholic, 6 patients (8 hips) by hormone, 2 cases (2 hips) by traumatic, 13 cases (23 hips) by idiopathic. Steinberg preoperative stage involved 7 hips in period I, 24 hips in period II, 8 hips in period III. Curative effect analysis included preoperative and postoperative Harris score, radiographic changes and hip replacement for follow-up to accept the end of the femoral head survival rate. All patients were followed up for 6 to 47 months (averaged 37.4 months). All 12 hips imaging appeard progress,including tantalum rod exit in 1 hip, hip hemiarthroplasty collapse in 3 hips, the area increased to avascular necrosis in 8 hips. Six hips accepted total hip replacement, including imaging progress in 5 hips (41.7%, 5/12), no imaging progress in 1 hip (3.7%,1/27). All hips' Kaplan-Meier survival curves showed 6-month survival rate was (97.4 +/- 2.5)% after tantalum stick insertion, 1-year survival rate was (94.7 +/- 3.6), and 2-year survival rate was (88.6 +/- 5.4)%, 3-year survival rate was (72.5 +/- 11.2). It is effective for treatment of avascular necrosis of femoral head in Steinberg I and II by Tantalum rod, and it can effectively relieve femoral head replacement time.

Early complications in bariatric surgery: incidence, diagnosis and treatment.

PubMed

Santo, Marco Aurelio; Pajecki, Denis; Riccioppo, Daniel; Cleva, Roberto; Kawamoto, Flavio; Cecconello, Ivan

2013-01-01

Bariatric surgery has proven to be the most effective method of treating severe obesity. Nevertheless, the acceptance of bariatric surgery is still questioned. The surgical complications observed in the early postoperative period following surgeries performed to treat severe obesity are similar to those associated with other major surgeries of the gastrointestinal tract. However, given the more frequent occurrence of medical comorbidities, these patients require special attention in the early postoperative follow-up. Early diagnosis and appropriate treatment of these complications are directly associated with a greater probability of control. The medical records of 538 morbidly obese patients who underwent surgical treatment (Roux-en-Y gastric bypass surgery) were reviewed. Ninety-three (17.2%) patients were male and 445 (82.8%) were female. The ages of the patients ranged from 18 to 70 years (average = 46), and their body mass indices ranged from 34.6 to 77 kg/m2. Early complications occurred in 9.6% and were distributed as follows: 2.6% presented bleeding, intestinal obstruction occurred in 1.1%, peritoneal infections occurred in 3.2%, and 2.2% developed abdominal wall infections that required hospitalization. Three (0.5%) patients experienced pulmonary thromboembolism. The mortality rate was 0,55%. The incidence of early complications was low. The diagnosis of these complications was mostly clinical, based on the presence of signs and symptoms. The value of the clinical signs and early treatment, specially in cases of sepsis, were essential to the favorable surgical outcome. The mortality was mainly related to thromboembolism and advanced age, over 65 years.

Early intensive rehabilitation after oral cancer treatment.

PubMed

Bschorer, Maximilian; Schneider, Daniel; Hennig, Matthias; Frank, Bernd; Schön, Gerhard; Heiland, Max; Bschorer, Reinhard

2018-06-01

The treatment of oral cancer requires an effective rehabilitation strategy such as an early intensive rehabilitation (EIR) program. The medical records and data of 41 patients who participated in an EIR program and 20 control group patients were analyzed. These patients all underwent surgical resection of the primary tumor followed by microsurgical reconstruction using free flaps. The length of stay (LOS) at the acute care hospital was compared between the two groups. Four indexes were used to evaluate the effectiveness of the EIR program. EIR patients stayed an average of 11.6 fewer days at the acute care hospital. All indexes showed significant improvements (p < 0.001). The Barthel Index (BI) and the Early Intensive Rehabilitation Barthel Index (EIR-BI) improved by 36.0 and 103.6 points, respectively. At discharge, the Bogenhausener Dysphagia Score (BODS) had improved to a score of 11.0 compared to the 13.9 at admission. EIR patients had a Work Ability Index (WAI) score of 25.7. Length of stay at the acute care hospital can be reduced using early intensive rehabilitation if patients are transferred to an intensive rehabilitation clinic early. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Deep brain stimulation effects in dystonia: time course of electrophysiological changes in early treatment.

PubMed

Ruge, Diane; Tisch, Stephen; Hariz, Marwan I; Zrinzo, Ludvic; Bhatia, Kailash P; Quinn, Niall P; Jahanshahi, Marjan; Limousin, Patricia; Rothwell, John C

2011-08-15

Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A) -ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia. Copyright © 2011 Movement Disorder Society.

Cost-effectiveness analysis of early versus non-early intervention in acute migraine based on evidence from the 'Act when Mild' study.

PubMed

Slof, John

2012-05-01

In spite of the important progress made in the abortive treatment of acute migraine episodes since the introduction of triptans, reduction of pain and associated symptoms is in many cases still not as effective nor as fast as would be desirable. Recent research pays more attention to the timing of the treatment, and taking triptans early in the course of an attack when pain is still mild has been found more efficacious than the usual strategy of waiting for the attack to develop to a higher pain intensity level. To investigate the cost effectiveness of early versus non-early intervention with almotriptan in acute migraine. An economic evaluation was conducted from the perspectives of French society and the French public health system based on patient-level data collected in the AwM (Act when Mild) study, a placebo-controlled trial that compared the response to early and non-early treatment of acute migraine with almotriptan. Incremental cost-effectiveness ratios (ICERs) were determined in terms of QALYs, migraine hours and productive time lost. Costs were expressed in Euros (year 2010 values). Bootstrapping was used to derive cost-effectiveness acceptability curves. Early treatment has shown to lead to shorter attack duration, less productive time lost, better quality of life, and is, with 92% probability, overall cost saving from a societal point of view. In terms of drug costs only, however, non-early treatment is less expensive. From the public health system perspective, the (bootstrap) mean ICER of early treatment amounts to €0.38 per migraine hour avoided, €1.29 per hour of productive time lost avoided, and €14,296 per QALY gained. Considering willingness-to-pay values of approximately €1 to avoid an hour of migraine, €10 to avoid the loss of a productive hour, or €30,000 to gain one QALY, the approximate probability that early treatment is cost effective is 90%, 90% and 70%, respectively. These results remain robust in different scenarios for the

Artificially regenerating longleaf pine on wet sites: preliminary analysis of effects of site preparation treatments on early survival and growth

Treesearch

Benjamin O. Knapp; G. Geoff Wang; Joan L. Walker

2010-01-01

Our study, conducted over two years on poorly drained, sandy sites in Onslow County, NC, compared the effects of eight common site preparation treatments on early survival and growth of planted longleaf pine seedlings. Through two growing seasons, we found survival to be similar across all treatments (p = 0.8806), but root collar diameter was greatest with combinations...

Endoscopic methods in the treatment of early-stage esophageal cancer

PubMed Central

2014-01-01

Most patients with early esophageal cancer restricted to the mucosa may be offered endoscopic therapy, which is similarly effective, less invasive and less expensive than esophagectomy. Selection of appropriate relevant treatment and therapy methods should be performed at a specialized center with adequate facilities. The selection of an endoscopic treatment method for high-grade dysplasia and early-stage esophageal adenocarcinoma requires that tumor infiltration is restricted to the mucosa and that there is no neighboring lymph node metastasis. In squamous cell carcinoma, this treatment method is accepted in cases of tumors invading only up to the lamina propria of mucosa (m2). Tumors treated with the endoscopic method should be well or moderately differentiated and should not invade lymphatic or blood vessels. When selecting endoscopic treatments for these lesions, a combination of endoscopic resection and endoscopic ablation methods should be considered. PMID:25097676

Effects of Early Training and Nicotine Treatment on the Performance of Male NMRI Mice in the Water Maze

PubMed Central

Vicens, Paloma; Carrasco, M. Carmen; Redolat, Rosa

2003-01-01

This research aimed to evaluate the effect of nicotine treatment and prior training on a spatial learning task in differently aged NMRI male mice. In a longitudinal study, mice were randomly assigned to one of 14 experimental groups receiving different combinations of chronically injected nicotine (0.35 mg/kg) administered for 10 days (5 days before and during 5 days acquisition of task) or control treatments and training in the water maze at different ages. The mice displayed shorter escape latencies when evaluated at 6 and 10 months than when tested in this task at 2 months for the first time, demonstrating that early training preserves performance in the water maze up to 8 months after the initial experience. Nicotine treatment did not significantly change performance in the water maze at any age tested. Early practice in a spatial reference memory task appears to have lasting consequences and can potentially contribute to preventing some age-related spatial learning deficits. PMID:15152984

A review of evidence-based early intervention for behavioural problems in children with autism spectrum disorder: the core components of effective programs, child-focused interventions and comprehensive treatment models.

PubMed

Tonge, Bruce J; Bull, Kerry; Brereton, Avril; Wilson, Rebecca

2014-03-01

This article reviews recent evidence and other earlier relevant articles regarding early intervention studies for children with autism spectrum disorder (ASD). There is a well-established body of empirical evidence for the effectiveness of Early Intensive Behavioural Intervention (EIBI) with young children with ASD. The importance of parent skills training, education and positive behaviour support is also a key factor in influencing outcomes. Drug treatment is of short-term benefit for disruptive behaviour but long-term outcome and metabolic side-effects have not been studied. Few studies have measured the long-term value and effectiveness of early intervention treatments, and currently there are no articles published on effects into adulthood of such treatments. Such research would indicate whether early intervention results in reduced reliance on health services into adulthood.

A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus.

PubMed

Kluckow, Martin; Jeffery, Michele; Gill, Andy; Evans, Nick

2014-03-01

Failure of closure of the patent ductus arteriosus (PDA) may be associated with harm. Early cardiac ultrasound-targeted treatment of a large PDA may result in a reduction in adverse outcomes and need for later PDA closure with no increase in adverse effects. Multicentre, double-blind, placebo-controlled randomised trial. Three neonatal intensive care units in Australia. Eligible infants born <29 weeks were screened for a large PDA and received indomethacin or placebo before age 12 h. Death or abnormal cranial ultrasound. The trial ceased enrolment early due to lack of availability of indomethacin. 164 eligible infants were screened before 12 h; of the 92 infants with a large PDA, 44 were randomised to indomethacin and 48 to placebo. There was no difference in the main outcome between groups. Infants receiving early indomethacin had significantly less early pulmonary haemorrhage (PH) (2% vs 21%), a trend towards less periventricular/intraventricular haemorrhage (PIVH) (4.5% vs 12.5%) and were less likely to receive later open-label treatment for a PDA (20% vs 40%). The 72 non-randomised infants with a small PDA were at low risk of pulmonary haemorrhage and had an 80% spontaneous PDA closure rate. Early cardiac ultrasound-targeted treatment of a large PDA is feasible and safe, resulted in a reduction in early pulmonary haemorrhage and later medical treatment but had no effect on the primary outcome of death or abnormal cranial ultrasound. Australian New Zealand Clinical Trials Registry (ACTRN12608000295347).

Early surgical treatment of retinal hemangioblastomas.

PubMed

van Overdam, Koen A; Missotten, Tom; Kilic, Emine; Spielberg, Leigh H

2017-02-01

To evaluate the clinical course after early surgical treatment with excision of retinal hemangioblastomas (RHs) before development of major complications. Interventional case series of four eyes (four patients) with a peripheral RH that had not yet been treated by laser or cryotherapy prior to surgery. All eyes underwent 23-gauge vitrectomy with lesion excision. One patient underwent ligation of the feeder vessel prior to lesion excision. Best-corrected visual acuity and clinical course were assessed during a follow-up period of at least 4 years. Four patients (mean age 27.3 years; range 19-32) were included, of whom two had von Hippel-Lindau syndrome. Visual acuity improved in three patients (mean 4.8 lines; range 3-10) and remained stable at 0.0 logMAR in one patient. There were no intraoperative complications. Postoperative complications included transient mild vitreous haemorrhage (n = 2), and local epiretinal membrane formation at the excision location (n = 1). At 4 years postoperatively, there were no long-term complications. There was one case of a new lesion, which was effectively treated with laser. Vitrectomy with RH excision seems to be an effective approach for larger RHs and could be considered an early treatment option in selected cases. Postoperative complications were limited in scope of this case series. Important points to consider during vitrectomy are effective closure of feeder and draining vessels as well as complete removal of posterior hyaloid and epiretinal membranes in order to avoid postoperative vitreous haemorrhage and proliferative vitreoretinopathy. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Distress Tolerance Treatment for Early-Lapse Smokers

PubMed Central

Brown, Richard A.; Palm, Kathleen M.; Strong, David R.; Lejuez, Carl W.; Kahler, Christopher W.; Zvolensky, Michael J.; Hayes, Steven C.; Wilson, Kelly G.; Gifford, Elizabeth V.

2008-01-01

A significant percentage of individuals attempting smoking cessation lapse within a matter of days, and very few are able to recover to achieve long-term abstinence. This observation suggests that many smokers may have quit-attempt histories characterized exclusively by early lapses to smoking following quit attempts. Recent negative-reinforcement conceptualizations of early lapse to smoking suggest that individuals' reactions to withdrawal and inability to tolerate the experience of these symptoms, rather than withdrawal severity itself, may represent an important treatment target in the development of new behavioral interventions for this subpopulation of smokers. This article presents the theoretical rationale and describes a novel, multicomponent distress-tolerance treatment for early-lapse smokers that incorporates behavioral and pharmacological elements of standard smoking-cessation treatment, whereas drawing distress-tolerance elements from exposure-based and Acceptance and Commitment Therapy–based treatment approaches. Preliminary data from a pilot study (N = 16) are presented, and clinical implications are discussed. PMID:18391050

Effects of an 18-week exercise programme started early during breast cancer treatment: a randomised controlled trial.

PubMed

Travier, Noémie; Velthuis, Miranda J; Steins Bisschop, Charlotte N; van den Buijs, Bram; Monninkhof, Evelyn M; Backx, Frank; Los, Maartje; Erdkamp, Frans; Bloemendal, Haiko J; Rodenhuis, Carla; de Roos, Marnix A J; Verhaar, Marlies; ten Bokkel Huinink, Daan; van der Wall, Elsken; Peeters, Petra H M; May, Anne M

2015-06-08

Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue. This multi-centre controlled trial randomly assigned 204 breast cancer patients to usual care (n = 102) or supervised aerobic and resistance exercise (n = 102). By design, all patients received chemotherapy between baseline and 18 weeks. Fatigue (i.e., primary outcome at 18 weeks), quality of life, anxiety, depression, and physical fitness were measured at 18 and 36 weeks. Intention-to-treat mixed linear model analyses showed that physical fatigue increased significantly less during cancer treatment in the intervention group compared to control (mean between-group differences at 18 weeks: -1.3; 95 % CI -2.5 to -0.1; effect size -0.30). Results for general fatigue were comparable but did not reach statistical significance (-1.0, 95%CI -2.1; 0.1; effect size -0.23). At 18 weeks, submaximal cardiorespiratory fitness and several muscle strength tests (leg extension and flexion) were significantly higher in the intervention group compared to control, whereas peak oxygen uptake did not differ between groups. At 36 weeks these differences were no longer statistically significant. Quality of life outcomes favoured the exercise group but were not significantly different between groups. A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength. Exercise early during treatment of breast cancer can be recommended. At 36 weeks, these effects were no longer statistically significant. This might have been caused by the control participants' high physical

Early effect of fractional CO2 laser treatment in Post-menopausal women with vaginal atrophy.

PubMed

Eder, Scott Evan

2018-03-31

Fractional CO 2 lasers have been shown to provide improvement of vulvovaginal atrophy (VVA). The aim of the current study was to assess the early effect of a fractional CO 2 laser system in treating postmenopausal women with clinical symptoms of VVA. 28 healthy post-menopausal women (mean age 60.1 ± 5.55 years) with VVA-related symptoms were treated with fractional CO 2 laser 3 times, in 4-week intervals. At each study visit, VHIS score and VVA symptom severity were recorded. Sexual function was assessed with the Female Sexual Function Index (FSFI). One month following the first laser treatment, the mean VHIS score was significantly improved (13.89 ± 4.25 vs. baseline 11.93 ± 3.82; p < 0.05), and improved further at 3 and 6 months following all three laser treatments (16.43 ± 4.20 and 17.46 ± 4.07, respectively). Almost all VVA symptoms were significantly improved at one month following the first treatment. A further significant improvement in VVA symptoms was noted at 3 and 6 months following the third laser treatment. Following treatments, the FSFI score increased significantly (22.36 ± 10.40 vs. baseline 13.78 ± 7.70; p < 0.05), and remained significantly higher than baseline at the 3- and 6-month follow-up visits. CO 2 laser therapy for post-menopausal women can be considered an effective therapeutic option providing relief of symptoms already noted after one laser treatment.

The Impact of Early Substance Use Disorder Treatment Response on Treatment Outcomes Among Pregnant Women With Primary Opioid Use.

PubMed

Tuten, Michelle; Fitzsimons, Heather; Hochheimer, Martin; Jones, Hendree E; Chisolm, Margaret S

2018-03-13

This study examined the impact of early patient response on treatment utilization and substance use among pregnant participants enrolled in substance use disorder (SUD) treatment. Treatment responders (TRs) and treatment nonresponders (TNRs) were compared on pretreatment and treatment measures. Regression models predicted treatment utilization and substance use. TR participants attended more treatment and had lower rates of substance use relative to TNR participants. Regression models for treatment utilization and substance use were significant. Maternal estimated gestational age (EGA) and baseline cocaine use were negatively associated with treatment attendance. Medication-assisted treatment, early treatment response, and baseline SUD treatment were positively associated with treatment attendance. Maternal EGA was negatively associated with counseling attendance; early treatment response was positively associated with counseling attendance. Predictors of any substance use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline cocaine use. The single predictor of any substance use at 2 months was early treatment nonresponse. Predictors of opioid use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline SUD treatment. Predictors of opioid use at 2 months were early treatment nonresponse, and baseline cocaine and marijuana use. Predictors of cocaine use at 1 month were early treatment nonresponse, baseline cocaine use, and baseline SUD treatment. Predictors of cocaine use at 2 months were early treatment nonresponse and baseline cocaine use. Early treatment response predicts more favorable maternal treatment utilization and substance use outcomes. Treatment providers should implement interventions to maximize patient early response to treatment.

Cognitive function in early clinical phase huntington disease after rivastigmine treatment.

PubMed

Sešok, Sanja; Bolle, Nika; Kobal, Jan; Bucik, Valentin; Vodušek, David B

2014-09-01

In Huntington disease (HD) patients receiving rivastigmine treatment improvement of behavioral symptoms and of cognitive function (assessed with screening diagnostic instruments) has been reported. The aim of the present study was to verify such improvement in cognitive function by cognitive function assessment with a detailed neuropsychological battery covering all relevant cognitive systems expected to be impaired in early phase HD. Eighteen (18) HD patients entered the study and were randomly allocated to the rivastigmine and placebo group. All subjects underwent neuropsychological assessment at baseline. Follow-up neuropsychological assessment was applied after 6 months of rivastigmine or placebo treatment. Eighteen (18) healthy controls entered the study to control for practice effect and underwent neuropsychological assessment at baseline and after 6 months, without treatment. The neuropsychological battery consisted of assessment tools that are sensitive to cognitive impairment seen in early phase HD: CTMT, SDMT, Stroop (attention and information control), RFFT, TOL, Verbal fluency (executive functioning), CVLT-II, RCFT (learning and memory). Effect of rivastigmine and possible effect of practice was assessed using the mixed ANOVA model. No statistically significant effect of rivastigmine treatment on cognitive function in HD patients was detected. There was no evidence for practice or placebo effect. Detailed neuropsychological assessment did not confirm previously reported effect of rivastigmine treatment on cognitive function in HD patients. The limitations of our study are, in particular, small sample size and the lack of a single measure of relevant cognitive functioning in HD patients. Instead of focusing solely on statistical significance, a clinical relevance study is proposed to clarify the issue of rivastigmine effects in HD.

Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm.

PubMed

Giovannoni, Gavin

2018-06-01

The treatment of multiple sclerosis is evolving rapidly with 11 classes of disease-modifying therapies (DMTs). This article provides an overview of a new classification system for DMTs and treatment paradigm for using these DMTs effectively and safely. A summary of research into the use of more active approaches to early and effective treatment of multiple sclerosis with defined treatment targets of no evident disease activity (NEDA). New insights are discussed that is allowing the field to begin to tackle more advanced multiple sclerosis, including people with multiple sclerosis using wheelchairs. However, the need to modify expectations of what can be achieved in more advanced multiple sclerosis are discussed; in particular, the focus on neuronal systems with reserve capacity, for example, upper limb, bulbar and visual function. The review describes a new more active way of managing multiple sclerosis and concludes with a call to action in solving the problem of slow adoption of innovations and the global problem of untreated, or undertreated, multiple sclerosis.

Changes in the Vaginal Microenvironment with Metronidazole Treatment for Bacterial Vaginosis in Early Pregnancy

PubMed Central

Balkus, Jennifer; Agnew, Kathy; Lawler, Richard; Hitti, Jane

2009-01-01

Abstract Objective Bacterial vaginosis (BV) is associated with preterm delivery, but there is little evidence that treatment improves pregnancy outcomes. We examined whether oral or vaginal metronidazole treatment for BV in early pregnancy was more effective in restoring the normal vaginal environment. Methods This was a randomized controlled trial comparing oral and intravaginal metronidazole for treatment of BV in early pregnancy (<20 weeks). Vaginal samples collected at baseline and 4 weeks after treatment were evaluated using gram stain, culture, colorimetric detection of sialidase, and immunoassay for measurement of proinflammatory cytokines interleukins-1β, -6, -8 (IL-1β, IL-6, IL-8) and secretory leukocyte protease inhibitor (SLPI). We compared the effect of treatment between groups (using chi-square and t test) and within individuals (McNemar's test). Results Of 126 subjects, 108 (86%) completed follow-up (55 oral, 53 intravaginal). Of the study population, 34% achieved therapeutic cure, and this was not different between treatment groups. BV-associated bacteria were significantly reduced in both groups, but few subjects regained colonization with protective lactobacilli. Among women who achieved therapeutic cure, the level of IL-1β dropped significantly (p < 0.001) and SLPI increased (p = 0.003). More women in the vaginal treatment group had undetectable sialidase after treatment (p = 0.013). Conclusions Treatment with oral or intravaginal metronidazole in early pregnancy reduced colonization with BV-associated bacteria but was not effective in achieving therapeutic cure or in restoring healthy vaginal lactobacilli. PMID:19951217

Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion

PubMed Central

Ma, Jing; Zhang, Jing; Hou, Wei Wei; Wu, Xiao Hua; Liao, Ru Jia; Chen, Ying; Wang, Zhe; Zhang, Xiang Nan; Zhang, Li San; Zhou, Yu Dong; Chen, Zhong; Hu, Wei Wei

2015-01-01

Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0–3), but not the late stage after rUCCAO (day 4–32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD. PMID:26174710

Methodological approach to determine minor, considerable, and major treatment effects in the early benefit assessment of new drugs

PubMed Central

Wieseler, Beate; Kaiser, Thomas; Thomas, Stefanie; Bender, Ralf; Windeler, Jürgen; Lange, Stefan

2016-01-01

At the beginning of 2011, the early benefit assessment of new drugs was introduced in Germany with the Act on the Reform of the Market for Medicinal Products (AMNOG). The Federal Joint Committee (G‐BA) generally commissions the Institute for Quality and Efficiency in Health Care (IQWiG) with this type of assessment, which examines whether a new drug shows an added benefit (a positive patient‐relevant treatment effect) over the current standard therapy. IQWiG is required to assess the extent of added benefit on the basis of a dossier submitted by the pharmaceutical company responsible. In this context, IQWiG was faced with the task of developing a transparent and plausible approach for operationalizing how to determine the extent of added benefit. In the case of an added benefit, the law specifies three main extent categories (minor, considerable, major). To restrict value judgements to a minimum in the first stage of the assessment process, an explicit and abstract operationalization was needed. The present paper is limited to the situation of binary data (analysis of 2 × 2 tables), using the relative risk as an effect measure. For the treatment effect to be classified as a minor, considerable, or major added benefit, the methodological approach stipulates that the (two‐sided) 95% confidence interval of the effect must exceed a specified distance to the zero effect. In summary, we assume that our approach provides a robust, transparent, and thus predictable foundation to determine minor, considerable, and major treatment effects on binary outcomes in the early benefit assessment of new drugs in Germany. After a decision on the added benefit of a new drug by G‐BA, the classification of added benefit is used to inform pricing negotiations between the umbrella organization of statutory health insurance and the pharmaceutical companies. PMID:26134089

Current developments in the treatment of early-stage classical Hodgkin lymphoma.

PubMed

Borchmann, Sven; von Tresckow, Bastian; Engert, Andreas

2016-09-01

After presenting the current treatment recommendations for early-stage Hodgkin lymphoma, we give an overview on recently published clinical trials in this setting. Furthermore, the potential influence of current trials on the treatment of early-stage Hodgkin lymphoma and integration of newly emerging drugs into treatment protocols will be discussed. Trials attempting treatment de-escalation and omission of radiotherapy on the basis of early interim PET-scans have been disappointing so far, but results of some large trials employing this strategy are still awaited. In contrast, a more defensive strategy of starting treatment with less aggressive doxorubicine, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy and intensifying treatment in early interim PET-positive patients has shown encouraging results. New drugs such as brentuximab vedotin and immune checkpoint inhibitors have shown promising results in relapsed and refractory Hodgkin lymphoma. Clinical trials of brentuximab vedotin in early-stage Hodgkin lymphoma have been initiated. Additionally, biomarker-based treatment de-escalation might be a possible route for future improvements. The challenge for future clinical research in early-stage Hodgkin lymphoma is to continue to cure the majority of patients with first-line treatment while reducing long-term toxicity. New strategies to achieve that goal are currently being developed and will further refine treatment of early-stage Hodgkin lymphoma.

Callous-unemotional traits and early life stress predict treatment effects on stress and sex hormone functioning in incarcerated male adolescents.

PubMed

Johnson, Megan; Vitacco, Michael J; Shirtcliff, Elizabeth A

2018-03-01

The stress response system is highly plastic, and hormone rhythms may "adaptively calibrate" in response to treatment. This investigation assessed whether stress and sex hormone diurnal rhythms changed over the course of behavioral treatment, and whether callous-unemotional (CU) traits and history of early adversity affected treatment results on diurnal hormone functioning in a sample of 28 incarcerated adolescent males. It was hypothesized that the treatment would have beneficial effects, such that healthier diurnal rhythms would emerge post-treatment. Diurnal cortisol, testosterone, and dehydroepiandrosterone (DHEA) were sampled two weeks after admission to the correctional/treatment facility, and again approximately four months later. Positive treatment effects were detected for the whole sample, such that testosterone dampened across treatment. CU traits predicted a non-optimal hormone response to treatment, potentially indicating biological preparedness to respond to acts of social dominance and aggression. The interaction between CU traits and adversity predicted a promising and sensitized response to treatment including increased cortisol and a steeper testosterone drop across treatment. Results suggest that stress and sex hormones are highly receptive to treatment during this window of development.

Impact of early treatment programs on HIV epidemics: An immunity-based mathematical model.

PubMed

Rahman, S M Ashrafur; Vaidya, Naveen K; Zou, Xingfu

2016-10-01

While studies on pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) have demonstrated substantial advantages in controlling HIV transmission, the overall benefits of the programs with early initiation of antiretroviral therapy (ART) have not been fully understood and are still on debate. Here, we develop an immunity-based (CD4+ T cell count based) mathematical model to study the impacts of early treatment programs on HIV epidemics and the overall community-level immunity. The model is parametrized using the HIV prevalence data from South Africa and fully analyzed for stability of equilibria and infection persistence criteria. Using our model, we evaluate the effects of early treatment on the new infection transmission, disease death, basic reproduction number, HIV prevalence, and the community-level immunity. Our model predicts that the programs with early treatments significantly reduce the new infection transmission and increase the community-level immunity, but the treatments alone may not be enough to eliminate HIV epidemics. These findings, including the community-level immunity, might provide helpful information for proper implementation of HIV treatment programs. Copyright © 2016 Elsevier Inc. All rights reserved.

Early, but not late, treatment with human umbilical cord blood-derived mesenchymal stem cells attenuates cisplatin nephrotoxicity through immunomodulation.

PubMed

Park, Ji Hyeon; Jang, Hye Ryoun; Kim, Do Hee; Kwon, Ghee Young; Lee, Jung Eun; Huh, Wooseong; Choi, Soo Jin; Oh, Wonil; Oh, Ha Young; Kim, Yoon-Goo

2017-10-01

Preemptive treatment with mesenchymal stem cells (MSCs) can attenuate cisplatin-induced acute kidney injury (AKI). However, it is uncertain whether MSC treatment after the development of renal dysfunction prevents AKI progression or if MSC immunomodulatory properties contribute to MSC therapy. In this study, human umbilical cord blood (hUCB)-derived MSCs were used to compare the effects and mechanisms of early and late MSC therapy in a murine model. After cisplatin injection into C57BL/6 mice, hUCB-MSCs were administered on day 1 (early treatment) or day 3 (late treatment). With early treatment, cisplatin nephrotoxicity was attenuated as evidenced by decreased blood urea nitrogen (BUN) and reduced apoptosis and tubular injury scores on day 3 Early treatment resulted in downregulation of intrarenal monocyte chemotactic protein-1 and IL-6 expression and upregulation of IL-10 and VEGF expression. Flow cytometric analysis showed similar populations of infiltrated immune cells in both groups; however, regulatory T-cell (Treg) infiltration was 2.5-fold higher in the early treatment group. The role of Tregs was confirmed by the blunted effect of early treatment on renal injury after Treg depletion. In contrast, late treatment (at a time when BUN levels were 2-fold higher than baseline levels) showed no renoprotective effects on day 6 Neither the populations of intrarenal infiltrating immune cells (including Tregs) nor cytokine expression levels were affected by late treatment. Our results suggest that early MSC treatment attenuates renal injury by Treg induction and immunomodulation, whereas a late treatment (i.e., after the development of renal dysfunction) does not prevent AKI progression or alter the intrarenal inflammatory micromilieu. Copyright © 2017 the American Physiological Society.

Treatment strategies in the acute therapy of migraine: stratified care and early intervention.

PubMed

D'Amico, D; Moschiano, F; Usai, S; Bussone, G

2006-05-01

Various treatment strategies have been proposed to help clinicians provide the most effective acute treatment for migraine patients. Stratified care is based on the concept that the most appropriate initial treatment can be prescribed after evaluation of each patient's headache characteristics. The results of a large multicentre trial showed that when patients were stratified according to disability grade, clinical outcomes were significantly better than with step-care approaches. Prospective studies have shown that treating migraines with triptans when pain is mild (early intervention) considerably increases success rates for endpoints (pain-free at 2 h, sustained pain-free state) for which triptans had relatively poor efficacy in pivotal trials, and which contribute most to patient satisfaction. Stratified care and early treatment are also cost-effective. However these strategies are not suitable for all patients. Stratified care may be rendered difficult by medication contraindications and changes in attack characteristics over time. Early triptan intervention carries a risk of medication overuse and might not be indicated in patients with lack of pain progression. Successful implementation of both strategies requires that physicians are well informed, and that they elicit an exhaustive headache history from each patient.

Contemporary treatment principles for early rheumatoid arthritis: a consensus statement.

PubMed

Kiely, Patrick D W; Brown, Andrew K; Edwards, Christopher J; O'Reilly, David T; Ostör, Andrew J K; Quinn, Mark; Taggart, Allister; Taylor, Peter C; Wakefield, Richard J; Conaghan, Philip G

2009-07-01

RA has a substantial impact on both patients and healthcare systems. Our objective is to advance the understanding of modern management principles in light of recent evidence concerning the condition's diagnosis and treatment. A group of practicing UK rheumatologists formulated contemporary management principles and clinical practice recommendations concerning both diagnosis and treatment. Areas of clinical uncertainty were documented, leading to research recommendations. A fundamental concept governing treatment of RA is minimization of cumulative inflammation, referred to as the inflammation-time area under the curve (AUC). To achieve this, four core principles of management were identified: (i) detect and refer patients early, even if the diagnosis is uncertain: patients should be referred at the first suspicion of persistent inflammatory polyarthritis and rheumatology departments should provide rapid access to a diagnostic and prognostic service; (ii) treat RA immediately: optimizing outcomes with conventional DMARDs and biologics requires that effective treatment be started early-ideally within 3 months of symptom onset; (iii) tight control of inflammation in RA improves outcome: frequent assessments and an objective protocol should be used to make treatment changes that maintain low-disease activity/remission at an agreed target; (iv) consider the risk-benefit ratio and tailor treatment to each patient: differing patient, disease and drug characteristics require long-term monitoring of risks and benefits with adaptations of treatments to suit individual circumstances. These principles focus on effective control of the inflammatory process in RA, but optimal uptake may require changes in service provision to accommodate appropriate care pathways.

Photoacoustic Imaging of Cancer Treatment Response: Early Detection of Therapeutic Effect from Thermosensitive Liposomes

PubMed Central

Wirtzfeld, Lauren A.; Undzys, Elijus; Li, Shyh-Dar; Kolios, Michael C.

2016-01-01

Imaging methods capable of indicating the potential for success of an individualized treatment course, during or immediately following the treatment, could improve therapeutic outcomes. Temperature Sensitive Liposomes (TSLs) provide an effective way to deliver chemotherapeutics to a localized tumoral area heated to mild-hyperthermia (HT). The high drug levels reached in the tumor vasculature lead to increased tumor regression via the cascade of events during and immediately following treatment. For a TSL carrying doxorubicin (DOX) these include the rapid and intense exposure of endothelial cells to high drug concentrations, hemorrhage, blood coagulation and vascular shutdown. In this study, ultrasound-guided photoacoustic imaging was used to probe the changes to tumors following treatment with the TSL, HaT-DOX (Heat activated cytoToxic). Levels of oxygen saturation (sO2) were studied in a longitudinal manner, from 30 min pre-treatment to 7 days post-treatment. The efficacious treatments of HT-HaT-DOX were shown to induce a significant drop in sO2 (>10%) as early as 30 min post-treatment that led to tumor regression (in 90% of cases); HT-Saline and non-efficacious HT-HaT-DOX (10% of cases) treatments did not show any significant change in sO2 at these timepoints. The changes in sO2 were further corroborated with histological data, using the vascular and perfusion markers CD31 and FITC-lectin. These results allowed us to further surmise a plausible mechanism of the cellular events taking place in the TSL treated tumor regions over the first 24 hours post-treatment. The potential for using photoacoustic imaging to measure tumor sO2 as a surrogate prognostic marker for predicting therapeutic outcome with a TSL treatment is demonstrated. PMID:27788199

Quantifying the bias in the estimated treatment effect in randomized trials having interim analyses and a rule for early stopping for futility.

PubMed

Walter, S D; Han, H; Briel, M; Guyatt, G H

2017-04-30

In this paper, we consider the potential bias in the estimated treatment effect obtained from clinical trials, the protocols of which include the possibility of interim analyses and an early termination of the study for reasons of futility. In particular, by considering the conditional power at an interim analysis, we derive analytic expressions for various parameters of interest: (i) the underestimation or overestimation of the treatment effect in studies that stop for futility; (ii) the impact of the interim analyses on the estimation of treatment effect in studies that are completed, i.e. that do not stop for futility; (iii) the overall estimation bias in the estimated treatment effect in a single study with such a stopping rule; and (iv) the probability of stopping at an interim analysis. We evaluate these general expressions numerically for typical trial scenarios. Results show that the parameters of interest depend on a number of factors, including the true underlying treatment effect, the difference that the trial is designed to detect, the study power, the number of planned interim analyses and what assumption is made about future data to be observed after an interim analysis. Because the probability of stopping early is small for many practical situations, the overall bias is often small, but a more serious issue is the potential for substantial underestimation of the treatment effect in studies that actually stop for futility. We also consider these ideas using data from an illustrative trial that did stop for futility at an interim analysis. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Intestinal microbiota composition after antibiotic treatment in early life: the INCA study.

PubMed

Rutten, N B M M; Rijkers, G T; Meijssen, C B; Crijns, C E; Oudshoorn, J H; van der Ent, C K; Vlieger, A M

2015-12-09

The acquisition and development of infant gut microbiota can be influenced by numerous factors, of which early antibiotic treatment is an important one. However, studies on the effects of antibiotic treatment in early life on clinical outcomes and establishment and development of the gut microbiota of term infants are limited. Disturbed microbiota composition is hypothesized to be an underlying mechanism of an aberrant development of the immune system. This study aims to investigate the potential clinical and microbial consequences of empiric antibiotic use in early life. 450 term born infants, of whom 150 are exposed to antibiotic treatment in early life and 300 are not (control group), are included in this observational cohort study with a one-year follow-up. Clinical outcomes, including coughing, wheezing, fever >38 °C, runny nose, glue ear, rash, diarrhea and >3 crying hours a day, are recorded daily by parents and examined by previously defined doctor's diagnosis. A blood sample is taken at closure to investigate the infant's vaccination response and sensitization for food and inhalant allergens. Fecal samples are obtained at eight time points during the first year of life. Potential differences in microbial profiles of infants treated with antibiotics versus healthy controls will be determined by use of 16S-23S rRNA gene analysis (IS-pro). Microbiota composition will be described by means of abundance, diversity and (dis)similarity. Diversity is calculated using the Shannon index. Dissimilarities between samples are calculated as the cosine distance between each pair of samples and analyzed with principal coordinate analysis. Clinical variables and possible associations are assessed by appropriate statistics. Both clinical quantitative and qualitative microbial effects of antibiotic treatment in early life may be demonstrated. These findings can be important, since there is evidence that manipulation of the infant microbiota by using pre- or probiotics can

Effective treatment of haemorrhoids: early complication and late results after 150 consecutive stapled haemorrhoidectomies.

PubMed

Bove, Aldo; Bongarzoni, Giuseppe; Palone, Gino; Chiarini, Stella; Calisesi, Enrico Maria; Corbellini, Luciano

2009-01-01

Haemorrhoidectomy according to Longo potentially reduces post-operative pain and allows an early return to work. The aim of this study was to evaluate the efficacy of the technique, the early and especially late complications, and recurrences, in 150 patients. Between January 2005 and December 2006, we performed 150 consecutive haemorrhoidectomies with the Longo technique: 82 for third degree haemorrhoids and 68 for fourth degree haemorrhoids. The mean age of patients was 42 years. Every patient had a pre-operative proctoscopy and endoscopy KIT PPH01 (Ethicon Endo Surgery) was used. We evaluated the length of the operation, the post-operative pain, the early and late complications, and the recurrence of the disease. The mean follow up was 52 months (range 36-72). There was no mortality. The mean length of the operation was 25 minutes with a range of 15 to 45 minutes. Pain, evaluated using the V.A.S. scale, was very light in 114 patients (V.A.S. 2,1) and light in 36 (V.A.S. 3.2). Only 11 (7.5%) patients took painkillers, on demand, for a week after discharge from hospital and 2 patients (1,3%) for more than one month. Early complications (6.6%) were: 5 bleeding (2 after seven days), 4 acute urinary retentions, 1 external haemorrhoid thrombosis and 1 haematoma of the rectus wall. Mean Hospital stay was 2.1 days. Late complications (10%) were: 5 "faecal urgency" which disappeared after six months, 6 moderate asymptomatic strictures, and 4 persistent skin tags. There were 8 recurrences (5.1%), 2 for haemorrhoids of grade 3 e 6 for haemorrhoids of grade 4. All the recurrences appeared within the first 24 months. The stapled procedure according to Longo is an effective treatment for haemorrhoids. The results for postoperative pain and early return to work are very good. However, special care for haemostasis is essential in order to avoid bleeding. An effective surgical technique prevents late complications, but results after long term follow up show a not insignificant

Neratinib for the treatment of HER2-positive early stage breast cancer.

PubMed

Echavarria, Isabel; López-Tarruella, Sara; Márquez-Rodas, Iván; Jerez, Yolanda; Martin, Miguel

2017-08-01

Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer. Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting. Management of neratinib-induced toxicity, future perspectives for the drug, and ongoing trials are also discussed in this review. Expert commentary: Neratinib is emerging as a promising oral drug for the treatment of HER2-positive breast cancer. Although FDA and EMA approval is derived from the extended adjuvant treatment, this setting may not be the ideal scenario to obtain the beneficial effects of neratinib. Confirmatory data in the neoadjuvant setting and subgroup analysis from the ExTENET trial might bring some light into the best setting for neratinib therapy. Data from confirmatory trials in the metastatic setting are also required.

Effective Treatment for Rapid Improvement of Both Disease Activity and Self-Reported Physical Activity in Early Rheumatoid Arthritis.

PubMed

Konijn, Nicole P C; van Tuyl, Lilian H D; Boers, Maarten; den Uyl, Debby; Ter Wee, Marieke M; Kerstens, Pit; Voskuyl, Alexandre E; Nurmohamed, Michael; van Schaardenburg, Dirkjan; Lems, Willem F

2016-02-01

To investigate the longitudinal relationship between disease activity and self-reported physical activity (PA) in patients with early rheumatoid arthritis during the first year of treatment with combination therapy. PA was measured with the Short Questionnaire to Assess Health-Enhancing Physical Activity at baseline, 13 weeks, 26 weeks, and 52 weeks after start of treatment in the context of the Combinatietherapie Bij Reumatoïde Artritis-Light trial. The reported PA classified patients as meeting or not meeting the World Health Organization (WHO) PA guideline (cutoff: 150 minutes of moderate-to-intense activity per week). Other measurements included the Disease Activity Score (DAS). Since both treatment arms showed equal treatment effect, these were analyzed as 1 group with simple before-after analyses and generalized estimating equations (GEE). In these analyses, 140 patients (86% of the trial population, 66% women, mean age 52 years) with complete data were included. At entry, 69% of the patients met the WHO PA guideline, increasing to 90% at week 13, and remaining stable at 89% after 1 year (P < 0.001). Mean DAS improved from 4.0 to 1.8 during the first year of treatment (P < 0.001). In GEE analyses, DAS decreases were significantly associated with PA increases (P = 0.008). Patients with clinically relevant responses (expressed as DAS remission, European League Against Rheumatism good response or American College of Rheumatology criteria for 70% improvement response) showed higher PA levels compared to nonresponders, regardless of the definition of response, for both the WHO and Dutch PA guideline. Early rheumatoid arthritis patients using combination therapy improved both disease activity and PA, a beneficial effect persisting for at least 1 year. © 2016, American College of Rheumatology.

Treatment of Early Onset Schizophrenia: Recent Trends, Challenges and Future Considerations

PubMed Central

Vyas, Nora S.; Gogtay, Nitin

2012-01-01

Early onset schizophrenia (onset before adulthood) is a rare, severe, and chronic form of schizophrenia. The clinical presentation of schizophrenia at this unusually early age of onset has been associated with premorbid developmental abnormalities, poor response to neuroleptic treatment, greater admission rates, and poor prognosis. This is a brief, condensed review of current treatment strategies for the early onset population highlighting the need for novel treatment strategies for these generally treatment-refractory cases. Based on the current literature, second-generation antipsychotics remain the mainstay of treatment, although current medications provide suboptimal response at best. Based on the adult literature, combining antipsychotic treatment with psychotherapeutic intervention may be a more comprehensive treatment strategy. Indeed, early detection, identification of relevant biomarkers, coupled with advancing knowledge of the neurochemical and neuroanatomic pathways may help design informed and novel treatment strategies. PMID:22485097

Walking ability as a measure of treatment effect in early rheumatoid arthritis.

PubMed

Hamilton, J; Brydson, G; Fraser, S; Grant, M

2001-04-01

To assess the clinical usefulness of a prototype walkmat system in patients with early rheumatoid arthritis (RA). Twenty-four subjects with early RA and symptomatic forefoot disease requiring therapy with second-line drugs were recruited. Each subject underwent clinical assessment together with gait analysis on the contact sensitive walkmat system and Kistler forceplate before and after six months of treatment with second-line drugs. Two subjects were lost to follow-up. There was the expected improvement in disease activity in response to therapy. Significant differences were also demonstrated in defined gait parameters that indicated improved weight-bearing and enhanced forefoot propulsion. Medical therapy improved walking ability in patients with RA and the walkmat system provided a useful adjunct to existing outcome measures in the assessment of lower limb function.

Methodological approach to determine minor, considerable, and major treatment effects in the early benefit assessment of new drugs.

PubMed

Skipka, Guido; Wieseler, Beate; Kaiser, Thomas; Thomas, Stefanie; Bender, Ralf; Windeler, Jürgen; Lange, Stefan

2016-01-01

At the beginning of 2011, the early benefit assessment of new drugs was introduced in Germany with the Act on the Reform of the Market for Medicinal Products (AMNOG). The Federal Joint Committee (G-BA) generally commissions the Institute for Quality and Efficiency in Health Care (IQWiG) with this type of assessment, which examines whether a new drug shows an added benefit (a positive patient-relevant treatment effect) over the current standard therapy. IQWiG is required to assess the extent of added benefit on the basis of a dossier submitted by the pharmaceutical company responsible. In this context, IQWiG was faced with the task of developing a transparent and plausible approach for operationalizing how to determine the extent of added benefit. In the case of an added benefit, the law specifies three main extent categories (minor, considerable, major). To restrict value judgements to a minimum in the first stage of the assessment process, an explicit and abstract operationalization was needed. The present paper is limited to the situation of binary data (analysis of 2 × 2 tables), using the relative risk as an effect measure. For the treatment effect to be classified as a minor, considerable, or major added benefit, the methodological approach stipulates that the (two-sided) 95% confidence interval of the effect must exceed a specified distance to the zero effect. In summary, we assume that our approach provides a robust, transparent, and thus predictable foundation to determine minor, considerable, and major treatment effects on binary outcomes in the early benefit assessment of new drugs in Germany. After a decision on the added benefit of a new drug by G-BA, the classification of added benefit is used to inform pricing negotiations between the umbrella organization of statutory health insurance and the pharmaceutical companies. © 2015 The Authors. Biometrical Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Kidney Disease: Early Detection and Treatment

MedlinePlus

... Bar Home Current Issue Past Issues Special Section Kidney Disease: Early Detection and Treatment Past Issues / Winter ... called a "urine albumin-to-creatinine ratio." Treating Kidney Disease Kidney disease is usually a progressive disease, ...

Effects of Early Writing Intervention Delivered within a Data-Based Instruction Framework

ERIC Educational Resources Information Center

Jung, Pyung-Gang; McMaster, Kristen L.; delMas, Robert C.

2017-01-01

We examined effects of research-based early writing intervention delivered within a data-based instruction (DBI) framework for children with intensive needs. We randomly assigned 46 students with and without disabilities in Grades 1 to 3 within classrooms to either treatment or control. Treatment students received research-based early writing…

Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

PubMed

Dorhout Mees, Sanne M; Algra, Ale; Wong, George K C; Poon, Wai S; Bradford, Celia M; Saver, Jeffrey L; Starkman, Sidney; Rinkel, Gabriel J E; van den Bergh, Walter M; van Kooten, F; Dirven, C M; van Gijn, J; Vermeulen, M; Rinkel, G J E; Boet, R; Chan, M T V; Gin, T; Ng, S C P; Zee, B C Y; Al-Shahi Salman, R; Boiten, J; Kuijsten, H; Lavados, P M; van Oostenbrugge, R J; Vandertop, W P; Finfer, S; O'Connor, A; Yarad, E; Firth, R; McCallister, R; Harrington, T; Steinfort, B; Faulder, K; Assaad, N; Morgan, M; Starkman, S; Eckstein, M; Stratton, S J; Pratt, F D; Hamilton, S; Conwit, R; Liebeskind, D S; Sung, G; Kramer, I; Moreau, G; Goldweber, R; Sanossian, N

2015-11-01

Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH. © 2015 American Heart Association, Inc.

Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum Study (TEOSS)

PubMed Central

Findling, Robert L; Johnson, Jacqueline L; McClellan, Jon; Frazier, Jean A; Vitiello, Benedetto; Hamer, Robert M; Lieberman, Jeffrey A; Ritz, Louise; McNamara, Nora K; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

2010-01-01

OBJECTIVE To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders (EOSS). METHOD Patients (age 8–19 years) who had improved during an 8-week, randomized double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed following defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. RESULTS Of the 116 youth randomized in the acute trial, 54 entered maintenance treatment (molindone, N=20; olanzapine, N=13; risperidone, N=21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (N=15), inadequate efficacy (N=14), or study non-adherence (N=8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom reduction or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. CONCLUSIONS Only 12 % of youth with EOSS continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for EOSS. PMID:20494268

Is early benign prostatic hyperplasia (BPH) treatment worthwhile?

PubMed

Presicce, Fabrizio; De Nunzio, Cosimo; Tubaro, Andrea

2017-08-01

The medical armamentaria for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) have been extensively implemented over the past decade. Nevertheless, the timeliest moment for a possible treatment has not been fully established. A systematic literature search in January 1996 until June 2016 was performed to answer the following question: in men with LUTS due to BPH, does early treatment result in better outcome? An ad hoc Population/patient Intervention/indicator Comparator/control Outcome (PICO) was developed.The Medline, PubMed and Scopus databases were searched. Each article title and abstract were reviewed for relevance and appropriateness with regard to the topic of this review. Overtime, the introduction of novel medications and the implementation of surgical techniques have significantly improved the treatment outcomes and markedly reduced the rate of BPH surgery. Early treatments in patients at risk of disease progression may result in better clinical outcomes than a delayed approach. However, the evidence to support early intervention remains weak and criteria to identify the patient phenotype that could best benefit from immediate treatment remain ill-defined.On the contrary, the patients who ultimately undergo surgery following prolonged pharmacological treatment present with larger prostates, older age and comorbidities. At the same time, the technological progress has partly compensated this critical scenario, and commonly, a nonpejorative trend has been recorded in perioperative complications. The ideal moment to begin a treatment in LUTS/BPH patients is still uncertain, and surprisingly, rare good quality studies are available on this topic.

Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population

PubMed Central

Chahal, Harinder S.; Marseille, Elliot A.; Tice, Jeffrey A.; Pearson, Steve D.; Ollendorf, Daniel A.; Fox, Rena K.; Kahn, James G.

2016-01-01

IMPORTANCE Novel treatments for hepatitis C virus (HCV) infection are highly efficacious but costly. Thus, many insurers cover therapy only in advanced fibrosis stages. The added health benefits and costs of early treatment are unknown. OBJECTIVE To assess the cost-effectiveness of (1) treating all patients with HCV vs only those with advanced fibrosis and (2) treating each stage of fibrosis. DESIGN, SETTING, AND PARTICIPANTS This study used a decision-analytic model for the treatment of HCV genotype 1. The model used a lifetime horizon and societal perspective and was representative of all US patients with HCV genotype 1 who had not received previous treatment. Comparisons in the model included antiviral treatment of all fibrosis stages (METAVIR [Meta-analysis of Histological Data in Virial Hepatitis] stages F0 [no fibrosis] to F4 [cirrhosis]) vs treatment of stages F3 (numerous septa without cirrhosis) and F4 only and by specific fibrosis stage. Data were collected from March 1 to September 1, 2014, and analyzed from September 1, 2014, to June 30, 2015. INTERVENTIONS Six HCV therapy options (particularly combined sofosbuvir and ledipasvir therapy) or no treatment. MAIN OUTCOMES AND MEASURES Cost and health outcomes were measured using total medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), calculated as the difference in costs between strategies divided by the difference in QALYs. RESULTS We simulated 1000 individuals, but present the results normalized to a single HCV-infected person. In the base-case analysis, among patients receiving 8 or 12 weeks of sofosbuvir-ledipasvir treatment, treating all fibrosis stages compared with treating stages F3 and F4 adds 0.73 QALYs and $28 899, for an ICER of $39 475 per QALY gained. Treating at stage F2 (portal fibrosis with rare septa) costs $19 833 per QALY gained vs waiting until stage F3; treating at stage F1 (portal fibrosis without septa), $81 165 per QALY gained

Early orthodontic treatment for Class III malocclusion: A systematic review and meta-analysis.

PubMed

Woon, See Choong; Thiruvenkatachari, Badri

2017-01-01

Class III malocclusion affects between 5% and 15% of our population. The 2 most common dilemmas surrounding Class III treatment are the timing of treatment and the type of appliance. A number of appliances have been used to correct a Class III skeletal discrepancy, but there is little evidence available on their effectiveness in the long term. Similarly, early treatment of Class III malocclusion has been practiced with increasing interest. However, there has been no solid evidence on the benefits in the long term. The aim of this systematic review was to evaluate the effectiveness of orthodontic/orthopedic methods used in the early treatment of Class III malocclusion in the short and long terms. Several sources were used to identify all relevant studies independently of language. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase (Ovid), and MEDLINE (Ovid) were searched to June 2016. The selection criteria included randomized controlled trials (RCTs) and prospective controlled clinical trials (CCTs) of children between the ages of 7 and 12 years on early treatment with any type of orthodontic/orthopedic appliance compared with another appliance to correct Class III malocclusion or with an untreated control group. The primary outcome measure was correction of reverse overjet, and the secondary outcomes included skeletal changes, soft tissue changes, quality of life, patient compliance, adverse effect, Peer Assessment Rating score, and treatment time. The search results were screened for inclusion, and the data extracted by 2 independent authors. The data were analyzed using software (version 5.1, Review Manager; The Nordic Cochrane Centre, The Cochrane Collaboration; Copenhagen, Denmark). The mean differences with 95% confidence intervals were expressed for the continuous data. Random effects were carried out with high levels of clinical or statistical heterogeneity and fixed affects when the heterogeneity was low

Treatment of early-stage Hodgkin lymphoma.

PubMed

Engert, Andreas; Raemaekers, John

2016-07-01

Hodgkin lymphoma (HL) has become one of the best curable malignancies today. This is particularly true for patients with early-stage disease. Today, most patients in this risk group are treated with a combination of chemotherapy followed by small-field radiotherapy. More recent clinical trials such as the German Hodgkin Study Group (GHSG) HD10 study demonstrated, that even two cycles of ABVD followed by 20 Gy involved-field radiation therapy (IF-RT) are sufficient and result in more than 90% of patients being cured. The current treatment for early unfavorable patients is either four cycles of ABVD plus 30 Gy IF-RT or two cycles of BEACOPPbaseline followed by two cycles of ABVD plus IF-RT. Here, the European Organization for Research and Treatment of Cancer (EORTC) demonstrated that in positron emission tomography (PET)-positive patients after two cycles of ABVD, treatment switched to two cycles of BEACOPPbaseline plus radiotherapy results in significantly improved outcomes. Other aspects including attempts to further reduce intensity of treatment will be discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

[Cost-effectiveness analysis of sofosbuvir, peginterferon and ribavirin in patients with chronic hepatitis C: Early treatment in the initial stage of fibrosis vs. delayed treatment in advanced fibrosis].

PubMed

Buti, María; Domínguez-Hernández, Raquel; Oyagüez, Itziar; Casado, Miguel Ángel

2016-01-01

Cost-effectiveness analysis of sofosbuvir combined with peginterferon alpha-2a and ribavirin (SOF/Peg-IFN/RBV) in early versus advanced fibrosis in previously untreated patients with chronic hepatitis C genotype 1 (CHC-GT1), from the perspective of the Spanish National Health System (NHS). A Markov model was developed to compare lifetime costs and outcomes (life years gained [LYGs] and quality-adjusted life years [QALYs]) of 2 treatment strategies: SOF/Peg-IFN/RBV administered during early fibrosis (mild-moderate fibrosis; F2-F3) or advanced fibrosis (cirrhosis; F4). Efficacy (sustained virologic response), annual transition probabilities, disease management costs and utilities were obtained from the literature. Costs and outcomes were discounted annually at 3%. Direct costs were considered, expressed in Euros (€, 2014). Probabilistic sensitivity analysis (PSA) was also performed. SOF/Peg-IFN/RBV therapy at F2-F3 was more effective (19.12 LYGs and 14.14 QALYs) compared to F4. In a cohort of 1,000 patients, SOF/Peg-IFN/RBV prevented 66 cases of decompensated cirrhosis, 60 hepatocellular carcinomas and 4 liver transplantations compared with therapy in advanced fibrosis. The total lifetime cost of early therapy (€43,263) was less than the cost of treatment in the advanced stage (€49,018). Early therapy was a dominant strategy, more effective and less costly in all simulations. In the PSA analysis, administration of SOF/PEG-IFN/RBV at F2-F3 was dominant in all simulations. Starting SOF/Peg-IFN/RBV therapy at F2-F3, compared with therapy at F4, reduced the incidence of liver disease complications and was associated with cost savings for the Spanish NHS in CHC-GT1 patients. Copyright © 2016 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Clarifying uncertainty regarding detection and treatment of early-stage prostate cancer.

PubMed

Wilt, Timothy J

2002-02-01

Detection and treatment of prostate cancer can theoretically identify and cure a potentially disabling and deadly disease. However, controversy exists primarily because of the absence of randomized controlled trials (RCTs) documenting that these strategies improve survival and quality of life. In the absence of definitive information from RCTs, patients seek information and recommendations from many sources. Physicians have an opportunity to help patients and their families sort through the vast array of conflicting and confusing information. Rather then recommending for or against routine prostate-specific antigen (PSA) testing, physicians should provide men who are interested in prostate cancer testing, 50 years of age and older, and have a life expectancy of at least 10 to 15 years, with balanced information about the potential benefits and established harms of screening, diagnosis, and treatment. Validated informational materials can effectively and efficiently promote shared decision making. For early prostate cancer detection, the minimum information should include: the likelihood that prostate cancer will be diagnosed, possibilities of false-positive and false-negative results, anxiety associated with a positive test, and uncertainty regarding whether screening reduces the risk for death from prostate cancer. For men with localized prostate cancer, acceptable treatment options include radical prostatectomy, radiation therapy, cryotherapy, early androgen-suppression therapy, and watchful waiting. These are all considered acceptable options because data do not provide clear-cut evidence for the superiority of any 1 treatment. The only RCT comparing surgery to watchful waiting, though of relatively small size and conducted before PSA testing, showed no difference in survival after 23 years of follow-up. Watchful waiting does not remove prostate cancer, may miss an opportunity to cure or delay disease progression, and may lead to increased patient anxiety

Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

PubMed Central

Nobel, Yael R.; Cox, Laura M.; Kirigin, Francis F.; Bokulich, Nicholas A.; Yamanishi, Shingo; Teitler, Isabel; Chung, Jennifer; Sohn, Jiho; Barber, Cecily M.; Goldfarb, David S.; Raju, Kartik; Abubucker, Sahar; Zhou, Yanjiao; Ruiz, Victoria E.; Li, Huilin; Mitreva, Makedonka; Alekseyenko, Alexander V.; Weinstock, George M.; Sodergren, Erica; Blaser, Martin J.

2015-01-01

Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment. PMID:26123276

Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment.

PubMed

Nobel, Yael R; Cox, Laura M; Kirigin, Francis F; Bokulich, Nicholas A; Yamanishi, Shingo; Teitler, Isabel; Chung, Jennifer; Sohn, Jiho; Barber, Cecily M; Goldfarb, David S; Raju, Kartik; Abubucker, Sahar; Zhou, Yanjiao; Ruiz, Victoria E; Li, Huilin; Mitreva, Makedonka; Alekseyenko, Alexander V; Weinstock, George M; Sodergren, Erica; Blaser, Martin J

2015-06-30

Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

Early versus Deferred Treatment for Smoldering Multiple Myeloma: A Meta-Analysis of Randomized, Controlled Trials

PubMed Central

Tompkins, Van S.; Gao, Lu; Wu, Xiaosong; Tao, Yi; Hu, Xiaojing; Hou, Jun; Han, Ying; Xu, Hongwei; Zhan, Fenghuang; Shi, Jumei

2014-01-01

Purpose Whether patients with smoldering multiple myeloma (SMM) needed to receive early interventional treatment remains controversial. Herein, we conducted a meta-analysis comparing the efficacy and safety of early treatment over deferred treatment for patients with SMM. Methods MEDLINE and Cochrane Library were searched to May 2014 for randomized controlled trials (RCTs) that assessed the effect of early treatment over deferred treatment. Primary outcome measure was mortality, and secondary outcome measures were progression, response rate, and adverse events. Results Overall, 5 trials including 449 patients were identified. There was a markedly reduced risk of disease progression with early treatment (Odds Ratio [OR] = 0.13, 95% confidence interval [CI] = 0.07 to 0.24). There were no significant differences in mortality and response rate (OR = 0.85, 95% CI = 0.45 to 1.60, and OR = 0.63, 95% CI = 0.32 to 1.23, respectively). More patients in the early treatment arm experienced gastrointestinal toxicities (OR = 10.02, 95%CI = 4.32 to 23.23), constipation (OR = 8.58, 95%CI = 3.20 to 23.00) and fatigue or asthenia (OR = 2.72, 95%CI = 1.30 to 5.67). No significant differences were seen with the development of acute leukemia (OR = 2.80, 95%CI = 0.42 to 18.81), hematologic cancer (OR = 2.07, 95%CI = 0.43 to 10.01), second primary tumors (OR = 3.45, 95%CI = 0.81 to 14.68), nor vertebral compression (OR = 0.18, 95%CI = 0.02 to 1.59). Conclusions Early treatment delayed disease progression but increased the risk of gastrointestinal toxicities, constipation and fatigue or asthenia. The differences on vertebral compression, acute leukemia, hematological cancer and second primary tumors were not statistically significant. Based on the current evidence, early treatment didn’t significantly affect mortality and response rate. However, further much larger trials were needed to provide more evidence

Ponderosa pine needle length: an early indicator of release treatment effectiveness

Treesearch

Philip M. McDonald; Carl N. Skinner; Gary O. Fiddler

1992-01-01

Growth responses of ponderosa pine seedlings range from fast to slow after release and often demonstrate the effectiveness of the prescribed treatments. Although several morphological parameters have have identified as being sensitive to competition, no link to future growth and treatment effectiveness has been made. Shrubs and grasses in four 1- to 3-year-old...

Treatment decisions and the impact of adverse events before and during extended endocrine therapy in postmenopausal early breast cancer.

PubMed

Blok, Erik J; Kroep, Judith R; Meershoek-Klein Kranenbarg, Elma; Duijm-de Carpentier, Marjolijn; Putter, Hein; Liefers, Gerrit-Jan; Nortier, Johan W R; Rutgers, Emiel J Th; Seynaeve, Caroline M; van de Velde, Cornelis J H

2018-05-01

Extended endocrine therapy beyond 5 years for postmenopausal breast cancer has been studied within multiple phase III trials. Treatment compliance in these trials is generally poor. In this analysis, we aimed to determine factors that were associated with participation in the phase III Investigation on the Duration of Extended Adjuvant Letrozole (IDEAL) trial and with early treatment discontinuation, and how this influenced survival outcome. In the IDEAL trial, postmenopausal patients were randomised between 2.5 or 5 years of extended letrozole, after completing 5 years of endocrine therapy for hormone receptor-positive early breast cancer. A subgroup of this population participated earlier in the Tamoxifen Exemestane Adjuvant Multinational trial (5 years of exemestane or 2.5 years of tamoxifen followed by exemestane as primary adjuvant therapy) in which we explored which factors were determinative for enrolment in the IDEAL study. In the IDEAL cohort, we evaluated which factors predicted for early treatment discontinuation and the effect of early treatment discontinuation on disease-free survival (DFS). Nodal status, younger age and adjuvant chemotherapy were significantly associated with higher enrolment in the IDEAL trial. In the IDEAL cohort, adverse events (AEs), the type of primary endocrine therapy and the interval between primary and extended therapy were associated with early treatment discontinuation. Among the reported AEs, depressive feelings (56%) were most frequently associated with early treatment discontinuation. Early treatment discontinuation was not associated with worse DFS (hazard ratio [HR] = 1.02, 95% confidence interval = 0.76-1.37). In this analysis, we found that risk factors were most strongly associated enrolment in the IDEAL trial. In contrast, patient experiences were the most significant factors leading to early treatment discontinuation, with no effect on DFS. Copyright © 2018 Elsevier Ltd. All rights reserved.

Potential role of immunoablation and hematopoietic cell transplantation in the treatment of early diabetes type 1.

PubMed

Snarski, Emilian; Milczarczyk, Alicja; Franek, Edward; Jedrzejczak, Wieslaw

2010-01-01

Immunoablation with autologous hematopoietic cell transplantation has shown some effectiveness in the treatment of autoimmune diseases as diverse as aplastic anemia, systemic lupus erythematosus, multiple sclerosis and Crohn's disease. It has been recently shown that this treatment might prevent or delay development of diabetes type 1. The majority of more than 30 patients with early diabetes type 1 who underwent immunoablation and hematopoietic cell transplantation in various centers in the world achieved durable remission of diabetes and independence of exogenous insulin. This review summarizes advantages and risks of this treatment of early diabetes type 1.

Neurocognitive outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders study.

PubMed

Frazier, Jean A; Giuliano, Anthony J; Johnson, Jacqueline L; Yakutis, Lauren; Youngstrom, Eric A; Breiger, David; Sikich, Linmarie; Findling, Robert L; McClellan, Jon; Hamer, Robert M; Vitiello, Benedetto; Lieberman, Jeffrey A; Hooper, Stephen R

2012-05-01

To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site, randomized, double-blind clinical trial comparing molindone, olanzapine, and risperidone. The primary outcomes were overall group change from baseline in neurocognitive composite and six domain scores after 8 weeks and continued treatment up to 52 weeks. Age and sex were included as covariates in all analyses. Of 116 TEOSS participants, 77 (66%) had post-baseline neurocognitive data. No significant differences emerged in the neurocognitive outcomes of the three medication groups. Therefore, the three treatment groups were combined into one group to assess overall neurocognitive outcomes. Significant modest improvements were observed in the composite score and in three of six domain scores in the acute phase, and in four of six domain scores in the combined acute and maintenance phases. Partial correlation analyses revealed very few relationships among Positive and Negative Syndrome Scale (PANSS) baseline or change scores and neurocognition change scores. Antipsychotic intervention in youth with early-onset schizophrenia spectrum disorders (EOSS) led to modest improvement in measures of neurocognitive function. The changes in cognition were largely unrelated to baseline symptoms or symptom change. Small treatment effect sizes, easily accounted for by practice effects, highlight the critical need for the development of more efficacious interventions for the enduring neurocognitive deficits seen in EOSS. Clinical trial registry information-Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS); http://www.clinicaltrials.gov; NCT00053703. Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published

Rostral anterior cingulate cortex activity and early symptom improvement during treatment for major depressive disorder

PubMed Central

Korb, Alexander S.; Hunter, Aimee M.; Cook, Ian A.; Leuchter, Andrew F.

2011-01-01

In treatment trials for Major Depressive Disorder (MDD), early symptom improvement is predictive of eventual clinical response. Clinical response may also be predicted by elevated pretreatment theta (4-7 Hz) current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC). We investigated the relationship between pretreatment EEG and early improvement in predicting clinical outcome in 72 MDD subjects across three placebo-controlled treatment trials. Subjects were randomized to receive fluoxetine, venlafaxine, or placebo. Theta current density in the rACC and mOFC was computed with Low-Resolution Brain Electromagnetic Tomography (LORETA). An ANCOVA, examining week 8 Hamilton Depression Rating Scale (HamD) percent change, showed a significant effect of week-2-HamD-percent-change, and a significant three-way interaction of week-2-HamD-percent-change × Treatment × rACC. Medication subjects with robust early improvement showed almost no relationship between rACC theta current density and final clinical outcome. However, in subjects with little early improvement, rACC activity showed a strong relationship with clinical outcome. The model examining mOFC showed a trend in the three-way interaction. A combination of pretreatment rACC activity and early symptom improvement may be useful for predicting treatment response. PMID:21546222

Early and late arrhythmogenic effects of doxorubicin.

PubMed

Kilickap, Saadettin; Barista, Ibrahim; Akgul, Ebru; Aytemir, Kudret; Aksoy, Sercan; Tekuzman, Gulten

2007-03-01

To determine the incidence of early and late arrhythmogenic effects of doxorubicin-containing chemotherapy regimens. A prospective study including 29 patients who were treated with doxorubicin-containing regimens. Cardiac evaluation was based on 24-hour electrocardiographic monitorization (Holter), which was performed during the first cycle of doxorubicin-containing regimens, as well as after the last cycle of chemotherapy. The mean age of the patients was 45.8 +/- 15.1 (range 18-69). Holter records obtained during the first cycle of treatment revealed varying arrhythmias in 19 patients (65.5%) and in 18 (62.1%) patients after completion of therapy. One patient presented with syncope and both Mobitz Type 2 atrioventricular block and complete atrioventricular block were demonstrated. The patient subsequently underwent permanent pacemaker implantation. Doxorubicin may result in arrhythmias both in early and late periods of treatment. These arrhythmias are rarely life threatening.

Molecular Profiling of Glatiramer Acetate Early Treatment Effects in Multiple Sclerosis

PubMed Central

Achiron, Anat; Feldman, Anna; Gurevich, Michael

2009-01-01

Background: Glatiramer acetate (GA, Copaxone®) has beneficial effects on the clinical course of relapsing-remitting multiple sclerosis (RRMS). However, the exact molecular mechanisms of GA effects are only partially understood. Objective: To characterized GA molecular effects in RRMS patients within 3 months of treatment by microarray profiling of peripheral blood mononuclear cells (PBMC). Methods: Gene-expression profiles were determined in RRMS patients before and at 3 months after initiation of GA treatment using Affimetrix (U133A-2) microarrays containing 14,500 well-characterized human genes. Most informative genes (MIGs) of GA-induced biological convergent pathways operating in RRMS were constructed using gene functional annotation, enrichment analysis and pathway reconstruction bioinformatic softwares. Verification at the mRNA and protein level was performed by qRT-PCR and FACS. Results: GA induced a specific gene expression molecular signature that included altered expression of 480 genes within 3 months of treatment; 262 genes were up-regulated, and 218 genes were down-regulated. The main convergent mechanisms of GA effects were related to antigen-activated apoptosis, inflammation, adhesion, and MHC class-I antigen presentation. Conclusions: Our findings demonstrate that GA treatment induces alternations of immunomodulatory gene expression patterns that are important for suppression of disease activity already at three months of treatment and can be used as molecular markers of GA activity. PMID:19893201

Risk factors for early treatment discontinuation in patients with obsessive-compulsive disorder

PubMed Central

Diniz, Juliana Belo; Malavazzi, Dante Marino; Fossaluza, Victor; Belotto-Silva, Cristina; Borcato, Sonia; Pimentel, Izabel; Miguel, Euripedes Constantino; Shavitt, Roseli Gedanke

2011-01-01

INTRODUCTION: In obsessive-compulsive disorder, early treatment discontinuation can hamper the effectiveness of first-line treatments. OBJECTIVE: This study aimed to investigate the clinical correlates of early treatment discontinuation among obsessive-compulsive disorder patients. METHODS: A group of patients who stopped taking selective serotonin reuptake inhibitors (SSRIs) or stopped participating in cognitive behavioral therapy before completion of the first twelve weeks (total n = 41; n = 16 for cognitive behavioral therapy and n = 25 for SSRIs) were compared with a paired sample of compliant patients (n = 41). Demographic and clinical characteristics were obtained at baseline using structured clinical interviews. Chi-square and Mann-Whitney tests were used when indicated. Variables presenting a p value <0.15 for the difference between groups were selected for inclusion in a logistic regression analysis that used an interaction model with treatment dropout as the response variable. RESULTS: Agoraphobia was only present in one (2.4%) patient who completed the twelve-week therapy, whereas it was present in six (15.0%) patients who dropped out (p = 0.044). Social phobia was present in eight (19.5%) patients who completed the twelve-week therapy and eighteen (45%) patients who dropped out (p = 0.014). Generalized anxiety disorder was present in eight (19.5%) patients who completed the twelve-week therapy and twenty (50%) dropouts (p = 0.004), and somatization disorder was not present in any of the patients who completed the twelve-week therapy; however, it was present in six (15%) dropouts (p = 0.010). According to the logistic regression model, treatment modality (p = 0.05), agoraphobia, the Brown Assessment of Beliefs Scale scores (p = 0.03) and the Beck Anxiety Inventory (p = 0.02) scores were significantly associated with the probability of treatment discontinuation irrespective of interactions with other variables

Orofacial hereditary haemorrhagic telangiectasia: high power diode laser in early and advanced lesion treatment

NASA Astrophysics Data System (ADS)

Tempesta, Angela; Franco, Simonetta; Miccoli, Simona; Suppressa, Patrizia; De Falco, Vincenzo; Crincoli, Vito; Lacaita, Mariagrazia; Giuliani, Michele; Favia, Gianfranco

2014-01-01

Hereditary Haemorrhagic Telangiectasia (HHT) is a muco-cutaneous inherited disease. Symptoms are epistaxis, visceral arterio-venous malformations, multiple muco-cutaneous telangiectasia with the risk of number increasing enlargement, bleeding, and super-infection. The aim of this work is to show the dual Diode Laser efficacy in preventive treatment of Early Lesions (EL < 2mm) and therapeutic treatment of Advanced Lesions (AL < 2mm). 21 patients affected by HHT with 822 muco-cutaneous telangiectatic nodules have been treated in several sessions with local anaesthesia and cooling of treated sites. EL preventive treatment consists of single Laser impulse (fibre 320) in ultrapulsed mode (2 mm single point spot). AL therapeutic treatment consists of repeated Laser impulses in pulsed mode (on 200ms / off 400ms). According to the results, Diode Laser used in pulsed and ultra-pulsed mode is very effective as noninvasive treatment both in early and advanced oral and perioral telangiectasia.

Integrated Specialized Early-Course Psychosis Treatment Services - University Psychiatric Hospital Vrapce Model.

PubMed

Ostojić, DraŽenka; Čulo, Ilaria; Silić, Ante; Kos, Suzana; Savić, Aleksandar

2018-06-01

First episode of psychosis presents a critical period in terms of numerous associated risks, but also possibilities for effective therapeutic interventions. There is a continued focus on early interventions in prodromal states and early course of frank psychosis, aimed at ensuring faster remission, reducing relapses, achieving better long-term functioning, and preventing adverse outcomes linked to untreated psychosis and chronic psychotic disorders. A number of different specialized treatment models and services exist trying to close knowledge gaps and provide clinical interventions to first-episode psychosis (FEP) patients, but there is still no generally accepted standard of care informing our every-day practice. FEP and early-course psychosis specialized treatment model developed in 2004 in University Psychiatric Hospital Vrapce rests on integration of care across different organization units and clinical presentation acuity levels and patient needs (intensive care, FEP inpatient unit, FEP outpatient services including day hospital). Such integration of FEP services allows for flexible entry point on multiple levels, earlier structuring of therapeutic alliance for those requiring inpatient care, reduction of risks associated with FEP, quicker formation of long-term treatment plans, reduction of delay in accessing specialized services, and a more coordinated diagnostic process and recruitment of FEP patient population. Detailed evaluations of outcomes and comparisons with different treatment models are necessary in order to assess strengths and weaknesses of each specific model and inform modifications to current practice models.

Psychosocial Acute Treatment in Early-Episode Schizophrenia Disorders

ERIC Educational Resources Information Center

Bola, John R.

2006-01-01

Objective: This article reviews evidence on the treatment of early episode schizophrenia spectrum disorders that contradicts, in some cases, the American Psychiatric Association's generic recommendation of antipsychotic medication treatment for at least a year. Method: Evidence on lack of diagnostic validity, absence of demonstrated long-term…

[Therapeutic effect of early applying hydrotherapy with Chinese drugs on children hypoxic ischemic encephalopathy].

PubMed

Ma, Yun-Zhi; Zhai, Hong-Yin; Su, Chun-Ya

2009-02-01

To observe the therapeutic effect of hydrotherapy with Chinese drugs (HT-C) in early intervention on children hypoxic ischemic encephalopathy (HIE). HIE children were assigned to the treatment group and the control group, 50 in each, at random depending on the willingness of patients' parents. Both groups received the conventional functional training, according to the "0 -3-year-old early intervention outline", but for the treatment group, HT-C was applied additionally. Indexes for quality of sleep, gross motor function, severity of spasm and intellectual development were observed and compared before and after treatment to assess the therapeutic effects. Therapeutic effect in the treatment group was better than that in the control group in all the indexes observed, showing statistical significance (all P <0.05). Early intervention of HT-C could improve clinical symptom, promote the functional recovery and intellectual development in children HIE, and also could reduce or prevent the sequelae occurrence of the nervous system in them.

Client Attachment Status and Changes in Therapeutic Alliance Early in Treatment.

PubMed

Siefert, Caleb J; Hilsenroth, Mark J

2015-01-01

Several studies have examined associations between client attachment status and therapeutic alliance. Most, however, measure alliance at a single time point only. This study is among the first to examine how client attachment relates to changes in the therapeutic alliance early in treatment. Forty-six outpatients from a university-based community clinic participated. Attachment status was assessed with the Relationship Questionnaire (Bartholomew & Horowitz, 1991) prior to beginning treatment. Participants rated therapeutic alliance after an evaluation feedback session and again early in psychotherapy. Fearful insecurity was associated with declines in therapeutic alliance, while attachment security was associated with increasing client-therapist bonds. Although unrelated to global alliance, preoccupied insecurity was associated with greater confident collaboration at both time points and declines in idealized relationship from the evaluation to the early therapy time point. Results are discussed in light of prior theoretical formulations and previous research. Limitations of the study are reviewed, implications for clinical practice are noted, and suggestions for future research are made. Assessing client attachment status can provide clinicians with information that helps them identify clients at risk for difficulties establishing a therapeutic alliance. Clients high in attachment security are more likely to develop strong bonds with therapists during the early portion of treatment. Clients high in fearful insecurity are at risk for developing weaker alliances early in treatment. Such clients appear more likely to experience declines in client-therapist bond, goal-task agreement and overall alliance early in the treatment process. Clients high in preoccupied insecurity may enter therapy with great confidence in the therapist and willing to engage in therapy but report more conflicts with therapists in the early phase of treatment. Copyright © 2014 John Wiley

Early pregnancy failure: factors affecting successful medical treatment.

PubMed

Odeh, Marwan; Tendler, Rene; Kais, Mohamad; Maximovsky, Olga; Ophir, Ella; Bornstein, Jacob

2010-06-01

The results of medical treatment for early pregnancy failure are conflicting. To determine whether gestational sac volume measurement as well as other variables can predict the success rate of medical treatment for early pregnancy failure. The study group comprised 81 women diagnosed with missed abortion or anembryonic pregnancy who consented to medical treatment. Demographic data were collected and beta-human chorionic gonadotropin level was documented. Crown-rump length and the sac volume were measured using transvaginal ultrasound. TVU was performed 12-24 hours after intravaginal administration of 800 micro g misoprostol. If the thickness of the uterine cavity was less than 30 mm, the women were discharged. If the sac was still intact or the thickness of the uterine cavity exceeded 30 mm, they were offered an additional dosage of intravaginal misoprostol or surgical uterine evacuation. Medical treatment successfully terminated 32 pregnancies (39.5%), 30 after one dose of misoprostol and 2 after two doses (group A); 49 underwent surgical evacuation (group B), 47 following one dose of misoprostol and 2 following two doses. There were no significant differences between the groups in age and gestational week. Gestational sac volume did not differ between groups A and B (10.03 and 11.98 ml respectively, P = 0.283). Parity (0.87 and 1.43, P = 0.015), previous pregnancies (2.38 and 2.88, P = 0.037), and betahCG concentration (6961 and 28,748 mlU, P = 0.013) differed significantly between the groups. Gestational sac volume is not a predictor of successful medical treatment for early pregnancy failure. Previous pregnancies and deliveries and higher betahCG concentration negatively affect the success rate of medical treatment.

Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

PubMed

Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

2015-03-01

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

EARLY COMPLICATIONS IN THE ORTHOPEDIC TREATMENT OF BONE METASTASES.

PubMed

Teixeira, Luiz Eduardo Moreira; Miranda, Ricardo Horta; Ghedini, Daniel Ferreira; Aguilar, Rafael Bazílio; Novais, Eduardo Nilo Vasconcelos; de Abreu E Silva, Guilherme Moreira; Araújo, Ivana Duval; de Andrade, Marco Antônio Percope

2009-01-01

To assess the early complications in the orthopedic treatment of metastatic bone lesions and the factors associated with these complications. There were assessed, retrospectively, 64 patients that underwent surgical treatment for bone metastases, analyzing the complications that occurred in the pre-operative and early post- operative period and associating them with the tumor origin, type of procedure done, the need of blood reposition before the surgery, the need of new surgical procedures and the mortality due to the complications. Early complications in the treatment were observed in 17 (26.6%) patients, of which six (35.2%) ended up dying due to these complications. Regarding the type, 15 (23.8%) cases were due to surgical complications, four (6.3%) clinical and three (4.7%) patients showed clinical and surgical complications. There was no significant difference in the frequency of complications or mortality when assessed the type of reconstruction or affected region. The tumors with a renal origin needed more blood reposition and showed a bigger frequency of complications. The complications occurred in 26.6%. The complications are not related to the kind of treatment performed or to the region affected. The renal origin tumors showed a higher risk of hemorrhage.

Instrumental relating and treatment decision making among older women with early-stage breast cancer.

PubMed

Pieters, Huibrie C; Heilemann, Marysue V; Maliski, Sally; Dornig, Katrina; Mentes, Jan

2012-01-01

To understand how women aged 70 years and older who had recently undergone treatment for early-stage breast cancer experienced treatment decision making. Qualitative, descriptive study guided by grounded theory. PARTICIPANTS' houses and apartments in southern California. 18 women, aged 70-94 years, who completed treatment for primary, early-stage breast cancer 3-15 months prior (X = 8.5 months). Twenty-eight semistructured personal interviews that lasted, on average, 104 minutes. Data were collected and analyzed using constructivist grounded theory. Gero-oncology perspective of treatment decision making. A major finding was that the power of relating spontaneously was used as a vehicle to connect with others. That process, which the authors called "instrumental relating," was grounded in a foundation of mutual caring for themselves and others. Within that mutual caring, the women participated in three ways of relating to share in treatment decision making: obtaining information, interpreting healthcare providers, and determining the trustworthiness of their providers. Those ways of relating were effortlessly and simultaneously employed. The women used their expert abilities of relating to get the factual and emotional information that they needed. That information supported what the women perceived to be decisions that were shared and effective. The findings are the first evidence of the importance of relating as a key factor in decision making from the personal perspective of older women with early-stage breast cancer. This work serves as a springboard for future clinical interventions and research opportunities to individualize communication and enhance effective decision making for older patients who wish to participate in their cancer care.

Health economics evaluation of a gastric cancer early detection and treatment program in China.

PubMed

Li, Dan; Yuan, Yuan; Sun, Li-Ping; Fang, Xue; Zhou, Bao-Sen

2014-01-01

To use health economics methodology to assess the screening program on gastric cancer in Zhuanghe, China, so as to provide the basis for health decision on expanding the program of early detection and treatment. The expense of an early detection and treatment program for gastric cancer in patients found by screening, and also costs of traditional treatment in a hospital of Zhuanghe were assessed. Three major techniques of medical economics, namely cost-effective analysis (CEA), cost-benefit analysis (CBA) and cost-utility analysis (CUA), were used to assess the screening program. RESULTS from CEA showed that investing every 25, 235 Yuan on screening program in Zhuanghe area, one gastric cancer patient could be saved. Data from CUA showed that it was cost 1, 370 Yuan per QALY saved. RESULTS from CBA showed that: the total cost was 1,945,206 Yuan with a benefit as 8,669,709 Yuan and an CBR of 4.46. The early detection and treatment program of gastric cancer appears economic and society-beneficial. We suggest that it should be carry out in more high risk areas for gastric cancer.

Oculomotor and Neuropsychological Effects of Antipsychotic Treatment for Schizophrenia

PubMed Central

Hill, S. Kristian; Reilly, James L.; Harris, Margret S. H.; Khine, Tin; Sweeney, John A.

2008-01-01

Cognitive enhancement has become an important target for drug therapies in schizophrenia. Treatment development in this area requires assessment approaches that are sensitive to procognitive effects of antipsychotic and adjunctive treatments. Ideally, new treatments will have translational characteristics for parallel human and animal research. Previous studies of antipsychotic effects on cognition have relied primarily on paper-and-pencil neuropsychological testing. No study has directly compared neurophysiological biomarkers and neuropsychological testing as strategies for assessing cognitive effects of antipsychotic treatment early in the course of schizophrenia. Antipsychotic-naive patients with schizophrenia were tested before treatment with risperidone and again 6 weeks later. Matched healthy participants were tested over a similar time period. Test-retest reliability, effect sizes of within-subject change, and multivariate/univariate analysis of variance were used to compare 3 neurophysiological tests (visually guided saccade, memory-guided saccade, and antisaccade) with neuropsychological tests covering 4 cognitive domains (executive function, attention, memory, and manual motor function). While both measurement approaches showed robust neurocognitive impairments in patients prior to risperidone treatment, oculomotor biomarkers were more sensitive to treatment-related effects on neurocognitive function than traditional neuropsychological measures. Further, unlike the pattern of modest generalized cognitive improvement suggested by neuropsychological measures, the oculomotor findings revealed a mixed pattern of beneficial and adverse treatment-related effects. These findings warrant further investigation regarding the utility of neurophysiological biomarkers for assessing cognitive outcomes of antipsychotic treatment in clinical trials and in early-phase drug development. PMID:17932088

[Treatment of early onset scoliosis : How far can we go?].

PubMed

Studer, D; Hasler, C C; Schulze, A

2015-11-01

Recently, inconsistent definitions of early onset scoliosis (EOS) and a wide variety of treatment options have been observed. To clearly define the term EOS, to depict non-operative and operative treatment options, and to present the limitations of the boundaries of these techniques. Review of the literature, including conference presentations and expert opinions, in addition to personal experiences. Early onset scoliosis (EOS) refers to spine deformity that is present before 10 years of age, regardless of etiology. All existing operative treatment options share a high risk of complications. Therefore, non-operative treatment should act as a time-buying approach to postpone surgery. Awareness of treatment options and their specific indications, in addition to respecting each patient's individual needs and feasibilities, are crucial for the optimal outcome.

Polymeric composite devices for localized treatment of early-stage breast cancer

PubMed Central

Kan-Dapaah, Kwabena; Soboyejo, Wole

2017-01-01

For early-stage breast cancers mastectomy is an aggressive form of treatment. Therefore, there is a need for new treatment strategies that can enhance the use of lumpectomy by eliminating residual cancer cells with limited side effects to reduce local recurrence. Although, various radiotherapy-based methods have been developed, residual cells are found in 20–55% of the time at the first operation. Furthermore, some current treatment methods result in poor cosmesis. For the last decade, the authors have been exploring the use of polymeric composite materials in single and multi-modal implantable biomedical devices for post-operative treatment of breast cancer. In this paper, the concept and working principles of the devices, as well as selected results from experimental and numerical investigations, are presented. The results show the potential of the biomedical implants for cancer treatment. PMID:28245288

Early treatment using fractional CO2 laser before skin suture during scar revision surgery in Asians.

PubMed

Du, Feiya; Yu, Yusheng; Zhou, Zhiqin; Wang, Liujia; Zheng, Shusen

2018-04-01

Fractional CO 2 laser is one of the most effective treatment options used to resurface scars. However, most previous studies have been performed on mature scars at least 2 months after surgery. Recent studies have emphasized the importance of early treatment to reduce scar formation. In the present study, we described our experience with fractional CO 2 laser intervention before skin suture during scar revision surgery in Asians, and found the treatment was safe and effective.

EARLY COMPLICATIONS IN THE ORTHOPEDIC TREATMENT OF BONE METASTASES

PubMed Central

Teixeira, Luiz Eduardo Moreira; Miranda, Ricardo Horta; Ghedini, Daniel Ferreira; Aguilar, Rafael Bazílio; Novais, Eduardo Nilo Vasconcelos; de Abreu e Silva, Guilherme Moreira; Araújo, Ivana Duval; de Andrade, Marco Antônio Percope

2015-01-01

Objective: To assess the early complications in the orthopedic treatment of metastatic bone lesions and the factors associated with these complications. Method: There were assessed, retrospectively, 64 patients that underwent surgical treatment for bone metastases, analyzing the complications that occurred in the pre-operative and early post- operative period and associating them with the tumor origin, type of procedure done, the need of blood reposition before the surgery, the need of new surgical procedures and the mortality due to the complications. Results: Early complications in the treatment were observed in 17 (26.6%) patients, of which six (35.2%) ended up dying due to these complications. Regarding the type, 15 (23.8%) cases were due to surgical complications, four (6.3%) clinical and three (4.7%) patients showed clinical and surgical complications. There was no significant difference in the frequency of complications or mortality when assessed the type of reconstruction or affected region. The tumors with a renal origin needed more blood reposition and showed a bigger frequency of complications. Conclusion: The complications occurred in 26.6%. The complications are not related to the kind of treatment performed or to the region affected. The renal origin tumors showed a higher risk of hemorrhage. PMID:27077063

Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study.

PubMed

McGready, R; Lee, S J; Wiladphaingern, J; Ashley, E A; Rijken, M J; Boel, M; Simpson, J A; Paw, M K; Pimanpanarak, M; Mu, Oh; Singhasivanon, P; White, N J; Nosten, F H

2012-05-01

The effects of malaria and its treatment in the first trimester of pregnancy remain an area of concern. We aimed to assess the outcome of malaria-exposed and malaria-unexposed first-trimester pregnancies of women from the Thai-Burmese border and compare outcomes after chloroquine-based, quinine-based, or artemisinin-based treatments. We analysed all antenatal records of women in the first trimester of pregnancy attending Shoklo Malaria Research Unit antenatal clinics from May 12, 1986, to Oct 31, 2010. Women without malaria in pregnancy were compared with those who had a single episode of malaria in the first trimester. The association between malaria and miscarriage was estimated using multivariable logistic regression. Of 48,426 pregnant women, 17,613 (36%) met the inclusion criteria: 16,668 (95%) had no malaria during the pregnancy and 945 (5%) had a single episode in the first trimester. The odds of miscarriage increased in women with asymptomatic malaria (adjusted odds ratio 2·70, 95% CI 2·04-3·59) and symptomatic malaria (3·99, 3·10-5·13), and were similar for Plasmodium falciparum and Plasmodium vivax. Other risk factors for miscarriage included smoking, maternal age, previous miscarriage, and non-malaria febrile illness. In women with malaria, additional risk factors for miscarriage included severe or hyperparasitaemic malaria (adjusted odds ratio 3·63, 95% CI 1·15-11·46) and parasitaemia (1·49, 1·25-1·78 for each ten-fold increase in parasitaemia). Higher gestational age at the time of infection was protective (adjusted odds ratio 0·86, 95% CI 0·81-0·91). The risk of miscarriage was similar for women treated with chloroquine (92 [26%] of 354), quinine (95 [27%) of 355), or artesunate (20 [31%] of 64; p=0·71). Adverse effects related to antimalarial treatment were not observed. A single episode of falciparum or vivax malaria in the first trimester of pregnancy can cause miscarriage. No additional toxic effects associated with artesunate

Final visual acuity results in the early treatment for retinopathy of prematurity study.

PubMed

Good, William V; Hardy, Robert J; Dobson, Velma; Palmer, Earl A; Phelps, Dale L; Tung, Betty; Redford, Maryann

2010-06-01

To compare visual acuity at 6 years of age in eyes that received early treatment for high-risk prethreshold retinopathy of prematurity (ROP) with conventionally managed eyes. Infants with symmetrical, high-risk prethreshold ROP (n = 317) had one eye randomized to earlier treatment at high-risk prethreshold disease and the other eye managed conventionally, treated if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to either early treatment or conventional management. The main outcome measure was ETDRS visual acuity measured at 6 years of age by masked testers. Retinal structure was assessed as a secondary outcome. Analysis of all subjects with high-risk prethreshold ROP showed no statistically significant benefit for early treatment (24.3% vs 28.6% [corrected] unfavorable outcome; P = .15). Analysis of 6-year visual acuity results according to the Type 1 and 2 clinical algorithm showed a benefit for Type 1 eyes (25.1% vs 32.8%; P = .02) treated early but not Type 2 eyes (23.6% vs 19.4%; P = .37). Early-treated eyes showed a significantly better structural outcome compared with conventionally managed eyes (8.9% vs 15.2% unfavorable outcome; P < .001), with no greater risk of ocular complications. Early treatment for Type 1 high-risk prethreshold eyes improved visual acuity outcomes at 6 years of age. Early treatment for Type 2 high-risk prethreshold eyes did not. Application to Clinical Practice Type 1 eyes, not Type 2 eyes, should be treated early. These results are particularly important considering that 52% of Type 2 high-risk prethreshold eyes underwent regression of ROP without requiring treatment. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

Treatment of early-stage prostate cancer among rural and urban patients.

PubMed

Baldwin, Laura-Mae; Andrilla, C Holly A; Porter, Michael P; Rosenblatt, Roger A; Patel, Shilpen; Doescher, Mark P

2013-08-15

Geographic barriers and limited availability of cancer specialists may influence early prostate cancer treatment options for rural men. This study compares receipt of different early prostate cancer treatments between rural and urban patients. Using 2004-2006 SEER Limited-Use Data, 51,982 early prostate cancer patients were identified (T1c, T2a, T2b, T2c, T2NOS; no metastases) who were most likely to benefit from definitive treatment (< 75 years old, Gleason score < 8, PSA ≤ 20). Definitive treatment included radical prostatectomy, daily external beam radiation for 5 to 8 weeks, brachytherapy, or combination external beam radiation/brachytherapy. Adjusted definitive treatment rates were calculated by rural-urban residence overall, and for different sociodemographic and cancer characteristics, and different states based on logistic regression analyses, using general estimating equation methods to account for clustering by county. Adjusted definitive treatment rates were lower for rural (83.7%) than urban (87.1%) patients with early-stage prostate cancer (P ≤ .01). Rural men were more likely than urban men to receive non-definitive surgical treatment and no initial treatment. The lowest definitive treatment rates were among rural subgroups: 70 to 74 years (73.9%), African Americans (75.6%), American Indians/Alaska Natives (77.8%), single/separated/divorced (76.8%), living in New Mexico (69.3%), and living in counties with persistent poverty (79.6%). Between 2004 and 2006, this adjusted analysis found that men who were living in rural areas were less likely to receive definitive treatment for their early-stage prostate cancer than those living in urban areas. Certain rural patient groups with prostate cancer need particular attention to ensure their access to appropriate treatment. Rural providers, rural health care systems, and cancer advocacy and support organizations should ensure resources are in place so that the most vulnerable rural groups (men

Controlling fear: Jordanian women's perceptions of the diagnosis and surgical treatment of early-stage breast cancer.

PubMed

Obeidat, Rana F; Dickerson, Suzanne S; Homish, Gregory G; Alqaissi, Nesreen M; Lally, Robin M

2013-01-01

Despite the fact that breast cancer is the most prevalent cancer among Jordanian women, practically nothing is known about their perceptions of early-stage breast cancer and surgical treatment. The objective of this study was to gain understanding of the diagnosis and surgical treatment experience of Jordanian women with a diagnosis of early-stage breast cancer. An interpretive phenomenological approach was used for this study. A purposive sample of 28 Jordanian women who were surgically treated for early-stage breast cancer within 6 months of the interview was recruited. Data were collected using individual interviews and analyzed using Heideggerian hermeneutical methodology. Fear had a profound effect on Jordanian women's stories of diagnosis and surgical treatment of early-stage breast cancer. Women's experience with breast cancer and its treatment was shaped by their preexisting fear of breast cancer, the disparity in the quality of care at various healthcare institutions, and sociodemographic factors (eg, education, age). Early after the diagnosis, fear was very strong, and women lost perspective of the fact that this disease was treatable and potentially curable. To control their fears, women unconditionally trusted God, the healthcare system, surgeons, family, friends, and/or neighbors and often accepted treatment offered by their surgeons without questioning. Jordanian healthcare providers have a responsibility to listen to their patients, explore meanings they ascribe to their illness, and provide women with proper education and the support necessary to help them cope with their illness.

Financial analysis of early stand treatments in southwest Oregon.

Treesearch

Helge Eng; K. Norman Johnson; Roger D. Fight

1990-01-01

Management guidelines for economically efficient early stand treatments were developed by identifying treatments that would maximize financial returns over the rotation for coast Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. menziesii) in southwest Oregon. Short rotations and low stand densities (trees per acre) gave...

Effects of early whole-body vibration treatment on knee neuromuscular function and postural control after anterior cruciate ligament reconstruction: A randomized controlled trial.

PubMed

Pistone, Eugenio Maria; Laudani, Luca; Camillieri, Gianluca; Di Cagno, Alessandra; Tomassi, Gabriele; Macaluso, Andrea; Giombini, Arrigo

2016-11-11

To assess the effects of adding a whole-body vibration protocol at optimal frequency (WBV-OF) to a traditional rehabilitation programme (TRP) early after anterior cruciate ligament reconstruction, on maximal strength and balance, in comparison with a traditional rehabilitation programme. A total of 34 anterior cruciate ligament reconstructed patients with hamstring-tendon graft underwent either 4 weeks of WBV-OF training in addition to a traditional rehabilitation programme, or a traditional rehabilitation programme only, starting from the first month after surgery. Patients were assessed for maximal voluntary isometric strength during both knee extension and flexion and for balance on a force platform before, 1 month after treatment and at 3-month follow-up. Strength symmetry of the knee flexor muscles improved in WBV-OF+TRP patients more than in TRP patients 1 month after treatment (mean 66% (standard deviation (SD) 15) vs 58% SD 13), and also at the 3-month follow-up (mean 77% (SD 15) vs 64% (SD 15)), with no differences in balance improvements between the groups. Adding 4-weeks of WBV-OF to a traditional rehabilitation programme 1 month after surgery is effective in improving muscle strength of the knee flexor muscles. This early intervention may be incorporated into current rehabilitation to facilitate early strength recovery of anterior cruciate ligament reconstructed patients.

Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep

PubMed Central

Meng, Wenbin; Shang, Hongkai; Li, Shaofu; Sloboda, Deborah M.; Ehrlich, Loreen; Lange, Karolin; Xu, Huaisheng; Henrich, Wolfgang; Dudenhausen, Joachim W.; Plagemann, Andreas; Newnham, John P.; Challis, John R. G.

2015-01-01

Glucocorticoid treatment given in late pregnancy in sheep resulted in altered placental development and function. An imbalance of placental survival and apoptotic factors resulting in an increased rate of apoptosis may be involved. We have now investigated the effects of dexamethasone (DEX) in early pregnancy on binucleate cells (BNCs), placental apoptosis, and fetal sex as a determinant of these responses. Pregnant ewes carrying singleton fetuses (n = 105) were randomized to control (n = 56, 2 mL saline/ewe) or DEX treatment (n = 49, intramuscular injections of 0.14 mg/kg ewe weight per 12 hours over 48 hours) at 40 to 41 days of gestation (dG). Placentomes were collected at 50, 100, 125, and 140 dG. At 100 dG, DEX in females reduced BNC numbers, placental antiapoptotic (proliferating cell nuclear antigen), and increased proapoptotic factors (Bax, p53), associated with a temporarily decrease in fetal growth. At 125 dG, BNC numbers and apoptotic markers were restored to normal. In males, ovine placental lactogen-protein levels after DEX were increased at 50 dG, but at 100 and 140 dG significantly decreased compared to controls. In contrast to females, these changes were independent of altered BNC numbers or apoptotic markers. Early DEX was associated with sex-specific, transient alterations in BNC numbers, which may contribute to changes in placental and fetal development. Furthermore, in females, altered placental apoptosis markers may be involved. PMID:25063551

Clinically relevant characteristics associated with early treatment drug use versus abstinence.

PubMed

Cochran, Gerald; Stitzer, Maxine; Nunes, Edward V; Hu, Mei-Chen; Campbell, Aimee

2014-04-04

This study describes early treatment drug use status and associated clinical characteristics in a diverse sample of patients entering outpatient substance abuse psychosocial counseling treatment. The goal is to more fully characterize those entering treatment with and without active use of their primary drug in order to better understand associated treatment needs and resilience factors. We examined baseline data from a NIDA Clinical Trials Network (CTN) study (Web-delivery of Treatment for Substance Use) with an all-comers sample of patients (N = 494) entering 10 outpatient treatment centers. Patients were categorized according to self-identified primary drug of abuse (alcohol, cocaine/stimulants, opioids, marijuana) and by baseline drug use status (positive/negative) based on urine testing or self-reports of recent use (alcohol). Characteristics were examined by primary drug and early use status. Classified as drug-negative were 84%, 76%, 62%, and 33% of primary opioid, stimulant, alcohol, and marijuana users; respectively. Drug-positive versus -negative patients did not differ on demographics or rates of substance abuse/dependence diagnoses. However, those negative for active use had better physical and mental health profiles, were less likely to be using a secondary drug, and were more likely to be attending 12-step self-help meetings. Early treatment drug abstinence is common among substance users entering outpatient psychosocial counseling programs, regardless of primary abused drug. Abstinence (by negative UA) is associated with better health and mental health profiles, less secondary drug use, and more days of 12-step attendance. These data highlight differential treatment needs and resiliencies associated with early treatment drug use status. NCT01104805.

Trastuzumab in early stage breast cancer: a cost-effectiveness analysis for Belgium.

PubMed

Neyt, Mattias; Huybrechts, Michel; Hulstaert, Frank; Vrijens, France; Ramaekers, Dirk

2008-08-01

Although trastuzumab is traditionally used in metastatic breast cancer treatment, studies reported on the efficacy and safety of trastuzumab in adjuvant setting for the treatment of early stage breast cancer in HER2+ tumors. We estimated the cost-effectiveness and budget impact of reimbursing trastuzumab in this indication from a payer's perspective. We constructed a health economic model. Long-term consequences of preventing patients to progress to metastatic breast cancer and side effects such as congestive heart failure were taken into account. Uncertainty was handled applying probabilistic modeling and through probabilistic sensitivity analyses. In the HERA scenario, applying an arbitrary threshold of euro30000 per life-year gained, early stage breast cancer treatment with trastuzumab is cost-effective for 9 out of 15 analyzed subgroups (according to age and stage). In contrast, treatment according to the FinHer scenario is cost-effective in 14 subgroups. Furthermore, the FinHer regimen is most of the times cost saving with an average incremental cost of euro668, euro-1045, and euro-6869 for respectively stages I, II and III breast cancer patients whereas the HERA regimen is never cost saving due to the higher initial treatment costs. The model shows better cost-effectiveness for the 9-week initial treatment (FinHer) compared to no trastuzumab treatment than for the 1-year post-chemotherapy treatment (HERA). Both from a medical and an economic point of view, the 9-week initial treatment regimen with trastuzumab shows promising results and justifies the initiation of a large comparative trial with a 1-year regimen.

Power analysis to detect treatment effects in longitudinal clinical trials for Alzheimer's disease.

PubMed

Huang, Zhiyue; Muniz-Terrera, Graciela; Tom, Brian D M

2017-09-01

Assessing cognitive and functional changes at the early stage of Alzheimer's disease (AD) and detecting treatment effects in clinical trials for early AD are challenging. Under the assumption that transformed versions of the Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale tests'/components' scores are from a multivariate linear mixed-effects model, we calculated the sample sizes required to detect treatment effects on the annual rates of change in these three components in clinical trials for participants with mild cognitive impairment. Our results suggest that a large number of participants would be required to detect a clinically meaningful treatment effect in a population with preclinical or prodromal Alzheimer's disease. We found that the transformed Mini-Mental State Examination is more sensitive for detecting treatment effects in early AD than the transformed Clinical Dementia Rating Scale-Sum of Boxes and Alzheimer's Disease Assessment Scale-Cognitive Subscale. The use of optimal weights to construct powerful test statistics or sensitive composite scores/endpoints can reduce the required sample sizes needed for clinical trials. Consideration of the multivariate/joint distribution of components' scores rather than the distribution of a single composite score when designing clinical trials can lead to an increase in power and reduced sample sizes for detecting treatment effects in clinical trials for early AD.

Cost-effectiveness of screening and treatment for bacterial vaginosis in early pregnancy among women at low risk for preterm birth.

PubMed

Kekki, Minnamaija; Kurki, Tapio; Kotomäki, Teija; Sintonen, Harri; Paavonen, Jorma

2004-01-01

Bacterial vaginosis (BV) is an important risk factor for preterm birth. BV is detected in 10-30% of pregnant women and is often asymptomatic. Treatment of BV during pregnancy seems to reduce the risk of preterm delivery among high-risk women. We performed a cost-effectiveness analysis of screening and treatment for BV in early pregnancy among asymptomatic women at low risk for preterm delivery. A decision tree was built with two arms. For the screening (and treatment) arm the probabilities were derived from our earlier randomized trial on screening and treatment for BV, consisting of BV-positive women treated with intravaginal clindamycin cream or placebo and also of BV-negative pregnant women. The probabilities of outcomes among these women were collected from antenatal clinic records and hospital records, and for the no-screening arm mainly from the Finnish Perinatal Statistics. The outcomes considered were preterm delivery, mode of delivery, peripartum infections and postpartum complications. The unit costs associated with these outcomes were mainly based on disease-related groups (DRGs). No-screening was compared with two screening programs (one with clindamycin, the other with metronidazole treatment) and subjected to sensitivity analyses. There was no significant difference between screening and no-screening strategies in the costs and in the rate of preterm deliveries but the screening strategy produced significantly fewer peripartum infections and postpartum complications. Sensitivity analyses suggested that the screening strategy may become cost-saving if the rate of preterm deliveries exceeds 3%. Screening and treatment for BV in early pregnancy may not reduce costs compared to no-screening in a population at low risk for preterm birth but would produce, at the same cost, more health benefits in terms of fewer peripartum infections and postpartum complications. However, it may be cost-saving if the rate of preterm deliveries is higher than 3%.

HIV Infection: Transmission, Effects on Early Development, and Interventions.

ERIC Educational Resources Information Center

Lowenthal, Barbara

1997-01-01

Describes the modes of transmission of HIV and the course of the disease in infants and toddlers. Information is provided on its effects on early development, medical screening and treatments, therapies, psychosocial assistance, and interventions, including nutritional therapy, occupational and physical therapies, and speech and language therapy.…

Early postnatal treatment with clomipramine induces female sexual behavior and estrous cycle impairment.

PubMed

Molina-Jiménez, Tania; Limón-Morales, Ofelia; Bonilla-Jaime, Herlinda

2018-03-01

Administration of clomipramine (CMI), a tricyclic antidepressant, in early stages of development in rats, is considered an animal model for the study of depression. This pharmacological manipulation has induced behavioral and physiological alterations, i.e., less pleasure-seeking behaviors, despair, hyperactivity, cognitive dysfunction, alterations in neurotransmitter systems and in HPA axis. These abnormalities in adult male rats are similar to the symptoms observed in major depressive disorders. One of the main pleasure-seeking behaviors affected in male rats treated with CMI is sexual behavior. However, to date, no effects of early postnatal CMI treatment have been reported on female reproductive cyclicity and sexual behavior. Therefore, we explored CMI administration in early life (8-21 PN) on the estrous cycle and sexual behavior of adult female rats. Compared to the rats in the early postnatal saline treatment (CTRL group), the CMI rats had fewer estrous cycles, fewer days in the estrous stage, and longer cycles during a 20-day period of vaginal cytology analysis. On the behavioral test, the CMI rats displayed fewer proceptive behaviors (hopping, darting) and had lower lordosis quotients. Also, they usually failed to display lordosis and only rarely manifested marginal or normal lordosis. In contrast, the CTRL rats tended to display normal lordosis. These results suggest that early postnatal CMI treatment caused long-term disruptions of the estrous cycle and female sexual behavior, perhaps by alteration in the hypothalamic-pituitary-gonadal (HPG) axes and in neuronal circuits involved in the regulation of the performance and motivational of sexual behavior as the noradrenergic and serotonergic systems. Copyright © 2018 Elsevier Inc. All rights reserved.

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

ERIC Educational Resources Information Center

McClellan, Jon; Sikich, Linmarie; Findling, Robert L.; Frazier, Jean A.; Vitiello, Benedetto; Hlastala, Stefanie A.; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E.; Ritz, Louise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

2007-01-01

Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early…

Glutaric aciduria type 1--importance of early diagnosis and treatment.

PubMed

Afroze, Bushra; Yunus, Zabedah Mohammad

2014-05-01

Glutaric aciduria type 1 is a rare inherited organic academia. Untreated patients characteristically develop dystonia secondary to striatal injury during early childhood, which results in high morbidity and mortality. In patients diagnosed during neonatal period, striatal injury can be prevented by metabolic treatment including low lysine diet, carnitine supplementation and aggressive emergency treatment during acute episode of inter current illnesses. However, after the onset of neurological damage initiation of treatment is generally not effective. Therefore; glutaric aciduria type 1 is included in newborn screening panel for inherited metabolic diseases in many countries. We describe two children in a family with glutaric aciduria type 1 and their different long term outcomes. The first child was diagnosed late leading to severe neurological damage. The second child was diagnosed in the neonatal period as a result of selective high-risk screening and was treated appropriately giving a normal growth.

Early diagnosis and treatment of ankylosing spondylitis in Africa and the Middle East.

PubMed

Rachid, Bahiri; El Zorkany, Bassel; Youseif, Ehab; Tikly, Mohammed

2012-11-01

Ankylosing spondylitis (AS) is the prototype for spondyloarthritis primarily affecting young men. Geographic and ethnic variations exist in the prevalence and severity of AS and relate to the wide disparity in the frequency of human leukocyte antigen (HLA)-B27, a major genetic risk factor. The strength of the disease association with HLA-B27 is lower in most Arab populations (25-75 %) than in Western European populations (>90 %), and there is no association in sub-Saharan Africa, where the prevalence of HLA-B27 is <1 %. Other epidemiologic differences between European and African populations are the apparent later age at presentation in sub-Saharan Africa, and the high rate of spondyloarthropathies associated with human immunodeficiency virus infection. Diagnosis of AS is often delayed 8-10 years; potential reasons for the delay in Africa and the Middle East include low awareness among physicians and patients, the requirement for radiographic evidence of sacroiliitis for diagnosis, and limited access to magnetic resonance imaging in some countries. Treatment should be initiated early to prevent or reduce skeletal deformity and physical disability. Nonsteroidal anti-inflammatory drugs are effective first-line treatment and anti-tumor necrosis factor-α drugs are indicated for patients who have an inadequate response to first-line therapy. In Africa and the Middle East, such treatments may be precluded either by cost or contraindicated because of the high prevalence of latent tuberculosis infection. Research is sorely needed to develop cost-effective tools to diagnose AS early as well as effective, inexpensive, and safe treatments for these developing regions.

Early surgical suction and washout for treatment of cytotoxic drug extravasations.

PubMed

Vandeweyer, E; Deraemaecker, R

2000-02-01

This case report is presented to assess safety and efficiency of early suction and saline washout of extravasated cytotoxic drugs. Through multiple small skin incisions, the area of extravasation is first suctioned and subsequently extensively washed out with saline. Incisions are left open and the arm is elevated for 24 hours. A complete healing was obtained in five days without any skin or soft tissue loss. No additional treatment was needed. Early referral and surgical treatment by suction and washout is a safe and reliable treatment protocol for major cytotoxic drug extravasation injuries.

Neurocognitive Outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study

PubMed Central

Frazier, Jean A.; Giuliano, Anthony J.; Johnson, Jacqueline L.; Yakutis, Lauren; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.; Hooper, Stephen R.

2012-01-01

Objective To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Method Neurocognitive functioning of youth (ages 8–19 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site randomized, double-blind clinical trial comparing molindone, olanzapine or risperidone. The primary outcomes were overall group change from baseline in neurocognitive composite and six domain scores after 8 weeks and continued treatment up to 52 weeks. Age and sex were included as covariates in all analyses. Results Seventy-seven of 116 TEOSS participants (66%) had post-baseline neurocognitive data. No significant differences emerged in the neurocognitive outcomes of the three medication groups. Therefore, the three treatment groups were combined into one group to assess overall neurocognitive outcomes. Significant modest improvements were observed in the composite score and in three of six domain scores in the acute phase, and in four of six domain scores in the combined acute and maintenance phases. Partial correlation analyses revealed very few relationships among Positive and Negative Syndrome Scale (PANSS) baseline or change scores and neurocognition change scores. Conclusions Antipsychotic intervention in youth with early-onset schizophrenia spectrum disorders (EOSS) led to modest improvement in measures of neurocognitive function. The changes in cognition were largely unrelated to baseline symptoms or symptom change. Small treatment effect sizes, easily accounted for by practice effects, highlight the critical need for the development of more efficacious interventions for the enduring neurocognitive deficits seen in EOSS. PMID:22525956

Early versus delayed hormonal treatment in locally advanced or asymptomatic metastatic prostatic cancer patient dilemma.

PubMed

Prezioso, Domenico; Iacono, Fabrizio; Romeo, Giuseppe; Ruffo, Antonio; Russo, Nicola; Illiano, Ester

2014-06-01

The objective of this work is to compare the effectiveness of hormonal treatment (luteinizing hormone-releasing hormone agonists and/or antiandrogens) as an early or as a deferred intervention for patients with locally advanced prostate cancer (LAPC) and/or asymptomatic metastasis. Systematic review of trials published in 1950-2007. Sources included MEDLINE and bibliographies of retrieved articles. Eligible trials included adults with a history of LAPC who are not suitable for curative local treatment of prostate cancer. We retrieved 22 articles for detailed review, of which 8 met inclusion criteria. The Veterans Administration Cooperative Urological Research Group suggested that delaying hormonal therapy did not compromise overall survival and that many of the patients died of causes other than prostate cancer. In European Organisation for Research and Treatment of Cancer (EORTC) 30846 trial, the median survival for delayed endocrine treatment was 6.1 year, and for immediate treatment 7.6 year, the HR for survival on delayed versus immediate treatment was 1.23 (95 % CI 0.88-1.71), indicating a 23 % nonsignificant trend in favour of early treatment. In EORTC 30891, the immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival. The protocol SAKK 08/88 showed the lack of any major advantage of immediate compared with deferred hormonal treatment regarding quality of life or overall survival. The early intervention with hormonal treatment for patients with LAPC provides important reductions in all-cause mortality, prostate cancer-specific mortality, overall progression, and distant progression compared with deferring their use until standard care has failed to halt the disease.

Controversies in the diagnosis and treatment of early cutaneous melanoma

PubMed Central

Orzan, OA; Șandru, A; Jecan, CR

2015-01-01

Cutaneous melanoma (CM) is a disease with an unpredictable evolution mainly due to its high metastatic ability. The steadily increasing incidence and the poor outcome in advanced stages made this cancer an interesting field for many research groups. Given that CM is a curable disease in early stages, efforts have been made to detect it as soon as possible, which led to the diversification and refining of diagnosis methods and therapies. But, as the data from trials have been published, doubts about the indications and efficacy of established treatments have arisen. In fact, there is probably no single aspect of early CM that has not given birth to controversy. This article intends to present the current disputes regarding the early detection, diagnosis, treatment and postoperative follow-up of patients with localized CM. After analyzing both pros and cons, several conclusions were drawn, that reflect our experience in managing patients with early CM. PMID:25866567

Safe and effective treatment of early suprahepatic inferior vena caval outflow compromise following orthotopic liver transplantation using percutaneous transluminal angioplasty and stent placement.

PubMed

Tasse, Jordan; Borge, Marc; Pierce, Kenneth; Brems, John

2011-01-01

To describe the safety and efficacy of percutaneous transluminal angioplasty and stent placement in patients presenting with suprahepatic inferior vena cava (IVC) outflow compromise in the early postoperative period following orthotopic liver transplantation. Between October 2002 and April 2009, 3 patients presented with IVC outflow compromise in the first 2 months following orthotopic liver transplantation. All 3 underwent percutaneous transluminal angioplasty and stent placement without complication and showed significant clinical improvement at short and intermediate term follow-up. Percutaneous transluminal angioplasty and Gianturco stent placement is a safe and effective treatment for IVC outflow compromise in the early postoperative period following orthotopic liver transplantation.

Early treatment with metformin induces resistance against tumor growth in adult rats

PubMed Central

Trombini, Amanda B; Franco, Claudinéia CS; Miranda, Rosiane A; de Oliveira, Júlio C; Barella, Luiz F; Prates, Kelly V; de Souza, Aline A; Pavanello, Audrei; Malta, Ananda; Almeida, Douglas L; Tófolo, Laize P; Rigo, Kesia P; Ribeiro, Tatiane AS; Fabricio, Gabriel S; de Sant’Anna, Juliane R; Castro-Prado, Marialba AA; de Souza, Helenir Medri; de Morais, Hely; Mathias, Paulo CF

2015-01-01

It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer. PMID:26024008

Cost-effectiveness of hepatic resection versus percutaneous radiofrequency ablation for early hepatocellular carcinoma.

PubMed

Cucchetti, Alessandro; Piscaglia, Fabio; Cescon, Matteo; Colecchia, Antonio; Ercolani, Giorgio; Bolondi, Luigi; Pinna, Antonio D

2013-08-01

Both hepatic resection and radiofrequency ablation (RFA) are considered curative treatments for hepatocellular carcinoma (HCC), but their economic impact still remains not determined. Aim of the present study was to analyze the cost-effectiveness (CE) of these two strategies in early stage HCC (Milan criteria). As first step, a meta-analysis of the pertinent literature of the last decade was performed. Seventeen studies fulfilled the inclusion criteria: 3996 patients underwent resection and 4424 underwent RFA for early HCC. Data obtained from the meta-analysis were used to construct a Markov model. Costs were assessed from the health care provider perspective. A Monte Carlo probabilistic sensitivity analysis was used to estimate outcomes with distribution samples of 1000 patients for each treatment arm. In a 10-year perspective, for very early HCC (single nodule <2 cm) in Child-Pugh class A patients, RFA provided similar life-expectancy and quality-adjusted life-expectancy at a lower cost than resection and was the most cost-effective therapeutic strategy. For single HCCs of 3-5 cm, resection provided better life-expectancy and was more cost-effective than RFA, at a willingness-to-pay above €4200 per quality-adjusted life-year. In the presence of two or three nodules ≤3 cm, life-expectancy and quality-adjusted life-expectancy were very similar between the two treatments, but cost-effectiveness was again in favour of RFA. For very early HCC and in the presence of two or three nodules ≤3 cm, RFA is more cost-effective than resection; for single larger early stage HCCs, surgical resection remains the best strategy to adopt as a result of better survival rates at an acceptable increase in cost. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The Effectiveness of Early Intervention.

ERIC Educational Resources Information Center

Guralnick, Michael J., Ed.

This book reviews research on the effectiveness of early intervention for children with disabilities or who are at risk. Program factors for children at risk and with disabilities, the effects of early intervention on different types of disabilities, and the outcomes of early intervention are explored. Chapters include: "Second-Generation Research…

Cost-effectiveness of early compared to late inhaled nitric oxide therapy in near-term infants.

PubMed

Armstrong, Edward P; Dhanda, Rahul

2010-12-01

The purpose of this study was to determine the cost-effectiveness of early versus late inhaled nitric oxide (INO) therapy in neonates with hypoxic respiratory failure initially managed on conventional mechanical ventilation. A decision analytic model was created to compare the use of early INO compared to delayed INO for neonates receiving mechanical ventilation due to hypoxic respiratory failure. The perspective of the model was that of a hospital. Patients who did not respond to either early or delayed INO were assumed to have been treated with extracorporeal membrane oxygenation (ECMO). The effectiveness measure was defined as a neonate discharged alive without requiring ECMO therapy. A Monte Carlo simulation of 10,000 cases was conducted using first and second order probabilistic analysis. Direct medical costs that differed between early versus delayed INO treatment were estimated until time to hospital discharge. The proportion of successfully treated patients and costs were determined from the probabilistic sensitivity analysis. The mean (± SD) effectiveness rate for early INO was 0.75 (± 0.08) and 0.61 (± 0.09) for delayed INO. The mean hospital cost for early INO was $21,462 (± $2695) and $27,226 (± $3532) for delayed INO. In 87% of scenarios, early INO dominated delayed INO by being both more effective and less costly. The acceptability curve between products demonstrated that early INO had over a 90% probability of being the most cost-effective treatment across a wide range of willingness to pay values. This analysis indicated that early INO therapy was cost-effective in neonates with hypoxic respiratory failure requiring mechanical ventilation compared to delayed INO by reducing the probability of developing severe hypoxic respiratory failure. There was a 90% or higher probability that early INO was more cost-effective than delayed INO across a wide range of willingness to pay values in this analysis.

Parent perspectives on information about late effects of childhood cancer treatment and their role in initial treatment decision making.

PubMed

Greenzang, Katie A; Dauti, Angela; Mack, Jennifer W

2018-06-01

Though most childhood cancer survivors experience late effects of treatment, we know little about parent preferences for late effects information during therapy, or how parents weigh late effects when making treatment decisions. Our objective was to explore how parents of children with cancer consider late effects in initial treatment decision making and during active cancer treatment. Semistructured interviews were conducted with 12 parents of children with cancer who were actively receiving treatment at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Interviews were audio-recorded, transcribed verbatim, and qualitatively analyzed using thematic analysis. Ten of 12 parents reported that they had to decide between two or more treatment options for their child's cancer. Of those, 50% (5/10) considered late effects to be an important factor in their decision making. Most parents wanted early and detailed information about their child's risk of late effects to make treatment decisions and to feel prepared for the future. However, a few parents felt too overwhelmed to focus on late effects at diagnosis. While many recalled extensive late effects information in informed consent discussions, some parents felt these issues were minimally addressed. Parents desire detailed information about late effects to make informed treatment decisions and prepare for the future. Despite the role of late effects in treatment decision making, some parents feel that late effects are either inadequately addressed or too overwhelming to process at diagnosis. Parents may benefit from early assessment of their information needs and a return to these issues over time. © 2018 Wiley Periodicals, Inc.

Surgical treatment for apparent early stage endometrial cancer

PubMed Central

2014-01-01

Most experts would agree that the standard surgical treatment for endometrial cancer includes a hysterectomy and bilateral salpingo-oophorectomy; however, the benefit of full surgical staging with lymph node dissection in patients with apparent early stage disease remains a topic of debate. Recent prospective data and advances in laparoscopic techniques have transformed this disease into one that can be successfully managed with minimally invasive surgery. This review will discuss the current surgical management of apparent early stage endometrial cancer and some of the new techniques that are being incorporated. PMID:24596812

Update on the Treatment of Early-Stage Triple-Negative Breast Cancer.

PubMed

Sharma, Priyanka

2018-04-14

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared to other breast cancer subtypes. Currently, chemotherapy remains the main modality of treatment for early-stage TNBC, as there is no approved targeted therapy for this subtype. The biologic heterogeneity of TNBC has hindered the development and evaluation of novel agents, but recent advancements in subclassifying TNBC have paved the way for further investigation of more effective systemic therapies, including cytotoxic and targeted agents. TNBC is enriched for germline BRCA mutation and for somatic deficiencies in homologous recombination DNA repair, the so-called "BRCAness" phenotype. Together, germline BRCA mutations and BRCAness are promising biomarkers of susceptibility to DNA-damaging therapy. Various investigational approaches are consequently being investigated in early-stage TNBC, including immune checkpoint inhibitors, platinum compounds, PI3K pathway inhibitors, and androgen receptor inhibitors. Due to the biological diversity found within TNBC, patient selection based on molecular biomarkers could aid the design of early-phase clinical trials, ultimately accelerating the clinical application of effective new agents. TNBC is an aggressive breast cancer subtype, for which multiple targeted approaches will likely be required for patient outcomes to be substantially improved.

Influence of early stress on memory reconsolidation: Implications for post-traumatic stress disorder treatment

PubMed Central

Birmes, Philippe; Ferry, Barbara

2018-01-01

Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a β-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remission. However, the reason why 30% of these patients did not respond positively to propranolol treatment is still unclear. One of the major candidates as factor of treatment resistance is the patient's early-life traumatic history. To test the role of this factor, mice with pre- or postnatal stress are being tested in fear conditioning and in a new behavioral task, the "city-like", specifically designed as a mouse model of PTSD. After reactivation of the traumatic event, mice received propranolol injection to block the noradrenergic system during memory reconsolidation. Results show that, in the “city-like” test, control mice strongly avoided the shock compartment but also the compartments containing cues associated with the electric shocks. Injection of propranolol after reactivation greatly reduced the memory of the traumatic event, but this effect was not present when mice had received pre- or postnatal stress. Moreover, propranolol produced only a very weak effect in the fear conditioning test, and never changed the corticosterone level whatever the behavioral experiment. Taken together our results suggest that our new behavioural paradigm is well adapted to PTSD study in mice, and that early stress exposure may have an impact on propranolol PTSD treatment outcome. These data are critical to understanding the effect of propranolol treatment, in order to improve the therapeutic protocol currently used in humans. PMID:29352277

Influence of early stress on memory reconsolidation: Implications for post-traumatic stress disorder treatment.

PubMed

Villain, Hélène; Benkahoul, Aïcha; Birmes, Philippe; Ferry, Barbara; Roullet, Pascal

2018-01-01

Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a life-threatening event. Currently, pharmacological treatments are limited by high rates of relapse, and novel treatment approaches are needed. We have recently demonstrated that propranolol, a β-adrenergic antagonist, inhibited aversive memory reconsolidation in animals. Following this, in an open-label study 70% of patients with PTSD treated with propranolol during reactivation of traumatic memory exhibited full remission. However, the reason why 30% of these patients did not respond positively to propranolol treatment is still unclear. One of the major candidates as factor of treatment resistance is the patient's early-life traumatic history. To test the role of this factor, mice with pre- or postnatal stress are being tested in fear conditioning and in a new behavioral task, the "city-like", specifically designed as a mouse model of PTSD. After reactivation of the traumatic event, mice received propranolol injection to block the noradrenergic system during memory reconsolidation. Results show that, in the "city-like" test, control mice strongly avoided the shock compartment but also the compartments containing cues associated with the electric shocks. Injection of propranolol after reactivation greatly reduced the memory of the traumatic event, but this effect was not present when mice had received pre- or postnatal stress. Moreover, propranolol produced only a very weak effect in the fear conditioning test, and never changed the corticosterone level whatever the behavioral experiment. Taken together our results suggest that our new behavioural paradigm is well adapted to PTSD study in mice, and that early stress exposure may have an impact on propranolol PTSD treatment outcome. These data are critical to understanding the effect of propranolol treatment, in order to improve the therapeutic protocol currently used in humans.

The Relation between Trait Mindfulness and Early Maladaptive Schemas in Men Seeking Substance Use Treatment

PubMed Central

Brasfield, Hope; Anderson, Scott; Stuart, Gregory L.

2014-01-01

Recent research has examined the relation between mindfulness and substance use, demonstrating that lower trait mindfulness is associated with increased substance use, and that mindfulness-based interventions help to reduce substance use. Research has also demonstrated that early maladaptive schemas are prevalent among individuals seeking substance use treatment and that targeting early maladaptive schemas in treatment may improve outcomes. However, no known research has examined the relation between mindfulness and early maladaptive schemas despite theoretical and empirical reasons to suspect their association. Therefore, the current study examined the relation between trait mindfulness and early maladaptive schemas among adult men seeking residential substance abuse treatment (N = 82). Findings demonstrated strong negative associations between trait mindfulness and 15 of the 18 early maladaptive schemas. Moreover, men endorsing multiple early maladaptive schemas reported lower trait mindfulness than men with fewer early maladaptive schemas. The implications of these findings for future research and treatment are discussed. PMID:26085852

Endoscopic diagnosis and treatment of early esophageal squamous neoplasia

PubMed Central

Shimamura, Yuto; Ikeya, Takashi; Marcon, Norman; Mosko, Jeffrey D

2017-01-01

Esophageal cancer is one of the leading causes of cancer-related death and is associated with high morbidity and mortality. It carries a poor prognosis as more than half of patients present with advanced and unresectable disease. One contributing factor is the increased risk of lymph node metastases at early stages of disease. As such, it is essential to detect squamous cell neoplasia (SCN) at an early stage. In order to risk stratify lesions, endoscopists must be able to perform image enhanced endoscopy including magnification and Lugol’s chromoendoscopy. The assessment of both the horizontal extent and depth of any lesion is also of utmost importance prior to treatment. Endoscopic mucosal resection and submucosal dissection remain the standard of care with literature supportive their respective use. Radiofrequency ablation and other endoscopic treatments are currently available although should not be considered first line at this time. Our objective is to review the current options for the endoscopic diagnosis and treatment of esophageal SCN. PMID:28979708

[Drug treatment of early-stage (de novo and "honeymoon") Parkinson disease].

PubMed

Cesaro, P; Defebvre, L

2014-04-01

In this article, we discuss the management of motor symptoms during the early phases of Parkinson's disease, excluding that of any other clinical manifestation. We relied primarily upon recently published data and do not describe older publications relating to anticholinergic drugs or amantadine. The initial pharmacological treatment of idiopathic Parkinson's disease (IPD) is symptomatic and remains based upon dopaminergic drugs. However, the development of new drugs has broadened the range of strategic options and improved overall patient management. Announcing the diagnosis is a critical moment, as pointed out by patients' associations. Patients should be advised to maintain personal, professional, social and physical activities as long as possible. The potential benefit of early pharmacological treatment should be explained, focusing on the possible disease-modifying effect of drugs such as rasagiline. According to current guidelines, L-Dopa is preferred in patients above 65years of age, while those below 65 should be treated with dopamine agonists. Like monoamine oxidase inhibitors B (MAOI-B), synthetic dopamine agonists exhibit several advantages: easy-to-use treatment with a once-daily administration, delayed L-Dopa initiation, significant efficacy on motor symptoms (although lower than that of L-Dopa). MOAI can be prescribed in association with L-Dopa or dopamine agonists. Rasagiline also delays L-Dopa initiation, and consequently motor complications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Maximizing cost-effectiveness by adjusting treatment strategy according to glaucoma severity

PubMed Central

Guedes, Ricardo Augusto Paletta; Guedes, Vanessa Maria Paletta; Gomes, Carlos Eduardo de Mello; Chaoubah, Alfredo

2016-01-01

Abstract Background: The aim of this study is to determine the most cost-effective strategy for the treatment of primary open-angle glaucoma (POAG) in Brazil, from the payer's perspective (Brazilian Public Health System) in the setting of the Glaucoma Referral Centers. Methods: Study design was a cost-effectiveness analysis of different treatment strategies for POAG. We developed 3 Markov models (one for each glaucoma stage: early, moderate and advanced), using a hypothetical cohort of POAG patients, from the perspective of the Brazilian Public Health System (SUS) and a horizon of the average life expectancy of the Brazilian population. Different strategies were tested according to disease severity. For early glaucoma, we compared observation, laser and medications. For moderate glaucoma, medications, laser and surgery. For advanced glaucoma, medications and surgery. Main outcome measures were ICER (incremental cost-effectiveness ratio), medical direct costs and QALY (quality-adjusted life year). Results: In early glaucoma, both laser and medical treatment were cost-effective (ICERs of initial laser and initial medical treatment over observation only, were R$ 2,811.39/QALY and R$ 3,450.47/QALY). Compared to observation strategy, the two alternatives have provided significant gains in quality of life. In moderate glaucoma population, medical treatment presented the highest costs among treatment strategies. Both laser and surgery were highly cost-effective in this group. For advanced glaucoma, both tested strategies were cost-effective. Starting age had a great impact on results in all studied groups. Initiating glaucoma therapy using laser or surgery were more cost-effective, the younger the patient. Conclusion: All tested treatment strategies for glaucoma provided real gains in quality of life and were cost-effective. However, according to the disease severity, not all strategies provided the same cost-effectiveness profile. Based on our findings, there should be a

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol.

PubMed

Hodis, Howard N; Mack, Wendy J; Henderson, Victor W; Shoupe, Donna; Budoff, Matthew J; Hwang-Levine, Juliana; Li, Yanjie; Feng, Mei; Dustin, Laurie; Kono, Naoko; Stanczyk, Frank Z; Selzer, Robert H; Azen, Stanley P

2016-03-31

Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested. A total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen. After a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum. Oral estradiol

The treatment of early-morning awakening insomnia with 2 evenings of bright light.

PubMed

Lack, Leon; Wright, Helen; Kemp, Kristyn; Gibbon, Samantha

2005-05-01

To assess the effectiveness of brief bright-light therapy for the treatment of early-morning awakening insomnia. Twenty-four healthy adults with early-morning awakening insomnia were assigned to either the bright-light condition (2,500-lux white light) or the control (dim red light) condition. The circadian phase of rectal temperature and urinary melatonin rhythms were assessed with 26-hour constant routines before and after 2 evenings of light therapy. Sleep and daytime functioning were monitored using sleep diaries, activity monitors, and mood scales before light therapy and for 4 weeks during the follow-up period. While there were no significant circadian phase changes in the dim-light control group, the bright-light group had significant 2-hour phase delays of circadian temperature and melatonin rhythm. Compared to pretreatment measures, over the 4-week follow-up period, the bright-light group had a greater reduction of time awake after sleep onset, showed a trend toward waking later, and had a greater increase of total sleep time. Participants in the bright-light condition also tended to report greater reductions of negative daytime symptoms, including significantly fewer days of feeling depressed at the 4-week follow-up, as compared with the control group. Two evenings of bright-light exposure phase delayed the circadian rhythms of early-morning awakening insomniacs. It also improved diary and actigraphy sleep measures and improved some indexes of daytime functioning for up to 1 month after light exposure. The study suggests that a brief course of evening bright-light therapy can be an effective treatment for early-morning awakening insomniacs who have relatively phase advanced circadian rhythms.

Early change in coping strategies in responsive treatments for borderline personality disorder: A mediation analysis.

PubMed

Kramer, Ueli; Keller, Sabine; Caspar, Franz; de Roten, Yves; Despland, Jean-Nicolas; Kolly, Stéphane

2017-05-01

Difficulty in emotion regulation is a hallmark feature of patients with borderline personality disorder (BPD). Therefore, change in the frequency of certain patients' coping strategies-aiming at emotion regulation-are among the most promising mechanisms of change in treatments for BPD. In parallel, it was highlighted that therapist responsiveness significantly contributed to outcome across treatment approaches (Stiles, 2009). Based on a randomized controlled trial (Kramer et al., 2014), the present process-outcome mediation analysis aims at examining the patient's early change in frequency of coping strategies-in particular the decrease in behavioral forms of coping-as potential mechanism of change in responsive treatments for BPD. A total of 57 patients with BPD were included in the present analysis, out of whom 27 were randomly assigned to a 10-session psychiatric treatment and 30 to a 10-session psychiatric treatment augmented with the responsive intervention of the motive-oriented therapeutic relationship (Caspar, 2007). The 1st, 5th, and 9th session of each therapy were transcribed and analyzed using the Coping Action Pattern Rating Scale (Perry et al., 2005; 171 sessions analyzed in total), a validated observer-rated method for assessing coping strategies in the therapy process. Psychological distress was assessed using the OQ-45 at intake, after Session 5, and after Session 10. The results confirmed a responsiveness effect associated with the motive-oriented therapeutic relationship and showed a significant decrease in frequency of behavioral forms of coping, F(1, 54) = 3.09, p = .05, d = .56, which was not different between the 2 conditions. In addition, we demonstrated that the early decrease in behavioral forms of coping between Sessions 1 and 5 partially mediated the link between the group assignment and the change in psychological distress between Sessions 5 and 10. These results shed light on the centrality of therapist responsiveness in treatments for

Early improvements in anxiety, depression, and anger/hostility symptoms and response to antidepressant treatment.

PubMed

Farabaugh, Amy; Sonawalla, Shamsah; Johnson, Daniel P; Witte, Janet; Papakostas, George I; Goodness, Tracie; Clain, Alisabet; Baer, Lee; Mischoulon, David; Fava, Maurizio; Harley, Rebecca

2010-08-01

The purpose of this study was to examine whether treatment response to fluoxetine by depressed outpatients was predicted by early improvement on any of 3 subscales (Anxiety, Depression, and Anger/Hostility) of the Symptom Questionnaire (SQ). We evaluated 169 depressed outpatients (52.6% female) between ages 18 and 65 (mean age, 40.3 +/- 10.6 years) meeting DSM-IIIR criteria for major depressive disorder (MDD). All patients completed the SQ at baseline (week 0) and at weeks 2, 4, and 8 of treatment with fluoxetine 20 mg/d. We defined treatment response as a > or= 50% reduction in score on the 17-item Hamilton Rating Scale for Depression, and early improvement on 3 SQ subscales (Anxiety, Depression, and Anger/Hostility) as a >30% reduction in score by week 2. The percentage of patients with significant early improvement in anger was significantly greater than the percentage of those with early improvements in anxiety or depression. When early improvement on the Anxiety, Depression, and Anger/Hostility subscales of the SQ were assessed independently by logistic regression, all 3 subscales were predictors of response to treatment. Early improvement in anger, anxiety, and depressive symptoms may predict response to antidepressant treatment among outpatients with MDD.

Hereditary Angioedema Attacks Resolve Faster and Are Shorter after Early Icatibant Treatment

PubMed Central

Maurer, Marcus; Kaplan, Allen; Investigators, on behalf of I. O. S.

2013-01-01

Background Attacks of hereditary angioedema (HAE) are unpredictable and, if affecting the upper airway, can be lethal. Icatibant is used for physician- or patient self-administered symptomatic treatment of HAE attacks in adults. Its mode of action includes disruption of the bradykinin pathway via blockade of the bradykinin B2 receptor. Early treatment is believed to shorten attack duration and prevent severe outcomes; however, evidence to support these benefits is lacking. Objective To examine the impact of timing of icatibant administration on the duration and resolution of HAE type I and II attacks. Methods The Icatibant Outcome Survey is an international, prospective, observational study for patients treated with icatibant. Data on timings and outcomes of icatibant treatment for HAE attacks were collected between July 2009–February 2012. A mixed-model of repeated measures was performed for 426 attacks in 136 HAE type I and II patients. Results Attack duration was significantly shorter in patients treated <1 hour of attack onset compared with those treated ≥1 hour (6.1 hours versus 16.8 hours [p<0.001]). Similar significant effects were observed for <2 hours versus ≥2 hours (7.2 hours versus 20.2 hours [p<0.001]) and <5 hours versus ≥5 hours (8.0 hours versus 23.5 hours [p<0.001]). Treatment within 1 hour of attack onset also significantly reduced time to attack resolution (5.8 hours versus 8.8 hours [p<0.05]). Self-administrators were more likely to treat early and experience shorter attacks than those treated by a healthcare professional. Conclusion Early blockade of the bradykinin B2 receptor with icatibant, particularly within the first hour of attack onset, significantly reduced attack duration and time to attack resolution. PMID:23390491

Early treatment with losartan effectively ameliorates hypertension and improves vascular remodeling and function in a prehypertensive rat model.

PubMed

He, De-Hua; Lin, Jin-Xiu; Zhang, Liang-Min; Xu, Chang-Sheng; Xie, Qiang

2017-03-15

Pharmacological treatment of prehypertension may ameliorate hypertension and improve vascular structure and function. This study investigated 1) whether early treatment with either losartan or amlodipine at the onset of prehypertension can prevent hypertension and 2) whether losartan and amlodipine equally improve vascular remodeling and function in a rat model of hypertension. Stroke-prone spontaneously hypertensive (SHRSP) rats were administered losartan, amlodipine or saline for 6 or 16weeks at the onset of prehypertension. Wistar-Kyoto rats were used as a control. All groups were observed for 40weeks. Systolic blood pressure was measured using the tail-cuff method. Vascular structure and function were determined by microscopy and vascular ring contractility assays, respectively. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassays. Angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression was measured by western blot. Losartan effectively reduced progression from prehypertension to hypertension as well as vascular remodeling and improved vascular contractility in SHRSP rats. Long-term losartan (16weeks) had greater benefits than short-term (6weeks) treatment. Losartan increased Ang II and decreased Aldo levels in the serum and vessel walls of resistance vessels in a time-dependent manner. Losartan significantly decreased AT1R and increased AT2R vascular expression. Amlodipine had no effect on vascular AT1R and AT2R expression. Losartan administered at the onset of prehypertension is more effective than amlodipine in ameliorating hypertension and improving vascular remodeling and function, which is likely mediated by the renin-angiotensin-aldosterone system. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

PubMed

McClellan, Jon; Sikich, Linmarie; Findling, Robert L; Frazier, Jean A; Vitiello, Benedetto; Hlastala, Stefanie A; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E; Ritz, Louise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2007-08-01

The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

The role of early detection and treatment in malaria elimination.

PubMed

Landier, Jordi; Parker, Daniel M; Thu, Aung Myint; Carrara, Verena I; Lwin, Khin Maung; Bonnington, Craig A; Pukrittayakamee, Sasithon; Delmas, Gilles; Nosten, François H

2016-07-15

Falciparum malaria persists in hard-to-reach areas or demographic groups that are missed by conventional healthcare systems but could be reached by trained community members in a malaria post (MP). The main focus of a MP is to provide uninterrupted and rapid access to rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT) too all inhabitants of a village. RDTs allow trained community members to perform malaria diagnosis accurately and prescribe appropriate treatment, reducing as much as possible any delay between the onset of fever and treatment. Early treatment with ACT and with a low-dose of primaquine prevents further transmission from human to mosquito. A functioning MP represents an essential component of any malaria elimination strategy. Implementing large-scale, high-coverage, community-based early diagnosis and treatment through MPs requires few technological innovations but relies on a very well structured organization able to train, supervise and supply MPs, to monitor activity and to perform strict malaria surveillance.

Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors.

PubMed

Martin, Donel M; Gálvez, Verònica; Loo, Colleen K

2015-06-19

Loss of personal memories experienced prior to receiving electroconvulsive therapy is common and distressing and in some patients can persist for many months following treatment. Improved understanding of the relationships between individual patient factors, electroconvulsive therapy treatment factors, and clinical indicators measured early in the electroconvulsive therapy course may help clinicians minimize these side effects through better management of the electroconvulsive therapy treatment approach. In this study we examined the associations between the above factors for predicting retrograde autobiographical memory changes following electroconvulsive therapy. Seventy-four depressed participants with major depressive disorder were administered electroconvulsive therapy 3 times per week using either a right unilateral or bitemporal electrode placement and brief or ultrabrief pulse width. Verbal fluency and retrograde autobiographical memory (assessed using the Columbia Autobiographical Memory Interview - Short Form) were tested at baseline and after the last electroconvulsive therapy treatment. Time to reorientation was measured immediately following the third and sixth electroconvulsive therapy treatments. Results confirmed the utility of measuring time to reorientation early during the electroconvulsive therapy treatment course as a predictor of greater retrograde amnesia and the importance of assessing baseline cognitive status for identifying patients at greater risk for developing later side effects. With increased number of electroconvulsive therapy treatments, older age was associated with increased time to reorientation. Consistency of verbal fluency performance was moderately correlated with change in Columbia Autobiographical Memory Interview - Short Form scores following right unilateral electroconvulsive therapy. Electroconvulsive therapy treatment techniques associated with lesser cognitive side effects should be particularly considered for

Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors

PubMed Central

Gálvez, Verònica; Loo, Colleen K.

2015-01-01

Background: Loss of personal memories experienced prior to receiving electroconvulsive therapy is common and distressing and in some patients can persist for many months following treatment. Improved understanding of the relationships between individual patient factors, electroconvulsive therapy treatment factors, and clinical indicators measured early in the electroconvulsive therapy course may help clinicians minimize these side effects through better management of the electroconvulsive therapy treatment approach. In this study we examined the associations between the above factors for predicting retrograde autobiographical memory changes following electroconvulsive therapy. Methods: Seventy-four depressed participants with major depressive disorder were administered electroconvulsive therapy 3 times per week using either a right unilateral or bitemporal electrode placement and brief or ultrabrief pulse width. Verbal fluency and retrograde autobiographical memory (assessed using the Columbia Autobiographical Memory Interview – Short Form) were tested at baseline and after the last electroconvulsive therapy treatment. Time to reorientation was measured immediately following the third and sixth electroconvulsive therapy treatments. Results: Results confirmed the utility of measuring time to reorientation early during the electroconvulsive therapy treatment course as a predictor of greater retrograde amnesia and the importance of assessing baseline cognitive status for identifying patients at greater risk for developing later side effects. With increased number of electroconvulsive therapy treatments, older age was associated with increased time to reorientation. Consistency of verbal fluency performance was moderately correlated with change in Columbia Autobiographical Memory Interview – Short Form scores following right unilateral electroconvulsive therapy. Conclusions: Electroconvulsive therapy treatment techniques associated with lesser cognitive side

Effectiveness of Riluzole as a pharmacotherapeutic treatment option for early cervical myelopathy: a double-blinded, placebo-controlled randomised controlled trial.

PubMed

Rajasekaran, S; Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi Mugesh; Maheswaran, Anupama; Shetty, Janardhan Yerram

2016-06-01

To evaluate the effectiveness of Riluzole as a pharmacotherapeutic treatment option for early cervical myelopathy using clinical parameters and DTI analysis. Early cervical myelopathy cases with MJOA scores ≥13, were recruited for the double-blinded, placebo-controlled randomised control trial. Thirty cases with fifteen cases each in the test and placebo group were studied. Analysis was done using diffusion tensor imaging (DTI) and clinical evaluation, pre- and post-institution of sodium channel blocker Riluzole for a period of 1 month (50 mg twice daily). Placebo group was treated with Vitamin B complex tablets. Diffusion co-efficient fractional anisotrophy (FA), apparent diffusion co-efficient (ADC), volume ratio (VR), relative anisotrophy (RA) and Eigen vectors were calculated. Outcomes analysis was based on clinical scores of MJOA, Nurick grading, SF-12, NDI, and statistical analysis of DTI datametrics. The mean MJOA score was 15.6 (13-17) with no significant change in the test and control groups. The mean ADC, FA values were 1533.36 (1238-1779) and 494.36 (364-628) and changed to 1531.57 (1312-2091) and 484.86 (294-597), respectively, in the Riluzole group. However, the changes in the values of ADC, FA, and other co-efficients including VR, RA and eigenvectors in the two groups were not statistically significant. The functional scores in the SF-12 and NDI questionnaires did not change significantly. Our study did not show a significant change in the clinical outcome and DTI Indices with the use of Riluzole as a standalone pharmacotherapeutic agent for early cervical myelopathy. More studies may be needed to confirm the usefulness of Riluzole as a treatment option for cervical myelopathy.

Effects of glucocorticoid treatment given in early or late gestation on growth and development in sheep.

PubMed

Li, S; Sloboda, D M; Moss, T J M; Nitsos, I; Polglase, G R; Doherty, D A; Newnham, J P; Challis, J R G; Braun, T

2013-04-01

Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40-42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.

Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?

PubMed Central

Burbelo, Peter D; Price, Richard W; Hagberg, Lars; Hatano, Hiroyu; Spudich, Serena; Deeks, Steven G; Gisslén, Magnus

2018-01-01

Abstract Background Despite effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) likely persists in the central nervous system (CNS) in treated individuals. We examined anti-HIV antibodies in cerebrospinal fluid (CSF) and blood as markers of persistence. Methods Human immunodeficiency virus antibodies were measured in paired CSF and serum before and after long-term treatment of chronic (n = 10) and early infection (n = 12), along with untreated early infection (n = 10). Results Treatment of chronic infection resulted in small reductions of anti-HIV antibodies in CSF and serum despite >10 years of suppressive ART. In untreated early infection, anti-HIV antibodies emerged in blood by day 30, whereas CSF antibodies reached similar levels 2 weeks later. Compared with long-term treatment of chronic infection, early ART initiation reduced CSF antibodies by 43-fold (P > .0001) and blood antibodies by 7-fold (P = .0003). Two individuals receiving pre-exposure prophylaxis and then ART early after infection failed to develop antibodies in CSF or blood, whereas CSF antibodies were markedly reduced in the Berlin patient. Conclusions To the extent that differential CSF and blood antibodies indicate HIV persistence, these data suggest a relative delay in establishment of the CNS compared with the systemic HIV reservoir that provides an opportunity for early treatment to have a greater impact on the magnitude of long-term CNS infection. PMID:29401308

Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?

PubMed

Burbelo, Peter D; Price, Richard W; Hagberg, Lars; Hatano, Hiroyu; Spudich, Serena; Deeks, Steven G; Gisslén, Magnus

2018-03-13

Despite effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) likely persists in the central nervous system (CNS) in treated individuals. We examined anti-HIV antibodies in cerebrospinal fluid (CSF) and blood as markers of persistence. Human immunodeficiency virus antibodies were measured in paired CSF and serum before and after long-term treatment of chronic (n = 10) and early infection (n = 12), along with untreated early infection (n = 10). Treatment of chronic infection resulted in small reductions of anti-HIV antibodies in CSF and serum despite >10 years of suppressive ART. In untreated early infection, anti-HIV antibodies emerged in blood by day 30, whereas CSF antibodies reached similar levels 2 weeks later. Compared with long-term treatment of chronic infection, early ART initiation reduced CSF antibodies by 43-fold (P > .0001) and blood antibodies by 7-fold (P = .0003). Two individuals receiving pre-exposure prophylaxis and then ART early after infection failed to develop antibodies in CSF or blood, whereas CSF antibodies were markedly reduced in the Berlin patient. To the extent that differential CSF and blood antibodies indicate HIV persistence, these data suggest a relative delay in establishment of the CNS compared with the systemic HIV reservoir that provides an opportunity for early treatment to have a greater impact on the magnitude of long-term CNS infection.

Increasing patient involvement in choosing treatment for early breast cancer.

PubMed

Street, R L; Voigt, B; Geyer, C; Manning, T; Swanson, G P

1995-12-01

This investigation examined factors affecting patient involvement in consultations to decide local treatment for early breast cancer and the effectiveness of two methods of preconsultation education aimed at increasing patient participation in these discussions. Sixty patients with Stage I or II breast cancer (1) were pretested on their knowledge about breast cancer treatment and optimism for the future, (2) were randomly assigned to one of two methods for preconsultation education: interactive multimedia program or brochure, (3) completed knowledge and optimism measures, (4) consulted with a medical oncologist, radiation oncologist, and general surgeon, and (5) completed self-report measures assessing their involvement in the consultations and control over decision-making. The consultations were audiorecorded and analyzed to identify behavioral indicators of patient involvement (question-asking, opinion-giving, and expressing concern) and physician utterances encouraging patient participation. College-educated patients younger than 65 years of age were more active participants in these consultations than were older, less educated patients. In addition, patients showed more involvement when they interacted with physicians who encouraged and facilitated patient participation. The method of education did not affect patient involvement although patients tended to learn more about breast cancer treatment after using the multimedia program than after reading the brochure. Although patients vary in their expressiveness, physicians may be able to increase patient participation in deciding treatment by using patient-centered behavior. Also, preconsultation education appears to be an effective clinical strategy for helping patients gain an accurate understanding of their treatment options before meeting with physicians.

Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults.

PubMed

Pfeifer, M; Verhovec, R; Zizek, B; Prezelj, J; Poredos, P; Clayton, R N

1999-02-01

Hypopituitary patients have increased mortality from vascular disease, and in these patients, early markers of atherosclerosis [increased carotid artery intima-media thickness (IMT) and reduced distensibility] are more prevalent. As GH replacement can reverse some risk factors of atherosclerosis, the present study examined the effect of GH treatment on morphological and functional changes in the carotid and brachial arteries of GH-deficient (GHD) adults. Eleven GHD hypopituitary men (24-49 yr old) were treated with recombinant human GH (0.018 U/kg BW x day) for 18 months. IMT of the common carotid artery (CCA) and the carotid bifurcation (CB), and flow-mediated endothelium-dependent dilation (EDD) of the brachial artery were measured by B mode ultrasound before and at 3, 6, 12, and 18 months of treatment, and values were compared with those in 12 age-matched control men. Serum concentrations of lipids, lipoprotein(a), insulin-like growth factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3) were also measured. In GHD men before treatment the IMTs of the CCA [mean(SD), 0.67(0.05) mm] and CB [0.75(0.04) mm] were significantly greater (P < 0.001) than those in control men [0.52(0.07) and 0.65(0.07) mm, respectively]. GH treatment normalized the IMT of the CCA by 6 months [0.53(0.04) mm] and that of the CB by 3 months [0.68(0.05) mm]. The IMT of the carotid artery (CCA and CB) was negatively correlated with serum IGF-I (r = -0.53; P < 0.0001). There was a significant improvement in flow-mediated EDD of the brachial artery at 3 months, which was sustained at 6 and 18 months of GH treatment (P < 0.05). GH treatment increased high density lipoprotein cholesterol at 3 and 6 months, but did not reduce total or low density lipoprotein cholesterol and was without effect on lipoprotein(a). There was no correlation between plasma lipids and changes in IMT or EDD of the arteries examined. In conclusion, GH treatment of hypopituitary GHD men reverses early morphological and

Current role of minimally invasive approaches in the treatment of early gastric cancer

PubMed Central

El-Sedfy, Abraham; Brar, Savtaj S; Coburn, Natalie G

2014-01-01

Despite declining incidence, gastric cancer remains one of the most common cancers worldwide. Early detection in population-based screening programs has increased the number of cases of early gastric cancer, representing approximately 50% of newly detected gastric cancer cases in Asian countries. Endoscopic mucosal resection and endoscopic submucosal dissection have become the preferred therapeutic techniques in Japan and Korea for the treatment of early gastric cancer patients with a very low risk of lymph node metastasis. Laparoscopic and robotic resections for early gastric cancer, including function-preserving resections, have propagated through advances in technology and surgeon experience. The aim of this paper is to discuss the recent advances in minimally invasive approaches in the treatment of early gastric cancer. PMID:24833843

Effects of Progress Monitoring Feedback on Early Literacy Student Achievement

ERIC Educational Resources Information Center

Lopuch, Jeremy Jon

2016-01-01

The purpose of this study was to examine the effects of diagnostic formative assessment feedback on early literacy skills. The participants were 12 first-grade general education teachers and 51 of their students who were assigned to the following treatments, diagnostic feedback and skills feedback (control) which lasted for 10 weeks. During the…

Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study.

PubMed

Sikich, Linmarie; Frazier, Jean A; McClellan, Jon; Findling, Robert L; Vitiello, Benedetto; Ritz, Louise; Ambler, Denisse; Puglia, Madeline; Maloney, Ann E; Michael, Emily; De Jong, Sandra; Slifka, Karen; Noyes, Nancy; Hlastala, Stefanie; Pierson, Leslie; McNamara, Nora K; Delporto-Bedoya, Denise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2008-11-01

Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder. This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment. In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia

Successful treatment algorithm for evaluation of early pregnancy after in vitro fertilization.

PubMed

Cookingham, Lisa Marii; Goossen, Rachel P; Sparks, Amy E T; Van Voorhis, Bradley J; Duran, Eyup Hakan

2015-10-01

To evaluate a prospectively implemented clinical algorithm for early identification of ectopic pregnancy (EP) and heterotopic pregnancy (HP) after assisted reproductive technology (ART). Analysis of prospectively collected data. Academic medical center. All ART-conceived pregnancies between January 1995 and June 2013. Early pregnancy monitoring via clinical algorithm with all pregnancies screened using human chorionic gonadotropin (hCG) levels and reported symptoms, with subsequent early ultrasound evaluation if hCG levels were abnormal or if the patient reported pain or vaginal bleeding. Algorithmic efficiency for diagnosis of EP and HP and their subsequent clinical outcomes using a binary forward stepwise logistic regression model built to determine predictors of early pregnancy failure. Of the 3,904 pregnancies included, the incidence of EP and HP was 0.77% and 0.46%, respectively. The algorithm selected 96.7% and 83.3% of pregnancies diagnosed with EP and HP, respectively, for early ultrasound evaluation, leading to earlier treatment and resolution. Logistic regression revealed that first hCG, second hCG, hCG slope, age, pain, and vaginal bleeding were all independent predictors of early pregnancy failure after ART. Our clinical algorithm for early pregnancy evaluation after ART is effective for identification and prompt intervention of EP and HP without significant over- or misdiagnosis, and avoids the potential catastrophic morbidity associated with delayed diagnosis. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Early definitive treatment rate as a quality indicator of care in acute gallstone pancreatitis.

PubMed

Green, R; Charman, S C; Palser, T

2017-11-01

Early definitive treatment (cholecystectomy or endoscopic sphincterotomy in the same admission or within 2 weeks after discharge) of gallstone disease after a biliary attack of acute pancreatitis is standard of care. This study investigated whether compliance with early definitive treatment for acute gallstone pancreatitis can be used as a care quality indicator for the condition. A retrospective cohort study was conducted using the Hospital Episode Statistics database. All emergency admissions to National Health Service hospitals in England with a first time diagnosis of acute gallstone pancreatitis in the financial years 2008, 2009 and 2010 were examined. Trends in early definitive treatment between hospital trusts were examined and patient morbidity outcomes were determined. During the study interval there were 19 510 patients with an overall rate of early definitive treatment at 34·7 (range 9·4-84·7) per cent. In the 1-year follow-up period, 4661 patients (23·9 per cent) had one or more emergency readmissions for complications related to gallstone pancreatitis. Of these, 2692 (57·8 per cent) were readmissions for acute pancreatitis; 911 (33·8 per cent) were within the first 2 weeks of discharge, with the remaining 1781 (66·2 per cent) occurring after the point at which definitive treatment should have been received. Early definitive treatment resulted in a 39 per cent reduction in readmission risk (adjusted risk ratio (RR) 0·61, 95 per cent c.i. 0·58 to 0·65). The risk was further reduced for acute pancreatitis readmissions to 54 per cent in the early definitive treatment group (adjusted RR 0·46, 0·42 to 0·51). In acute gallstone pancreatitis, compliance with recommended early definitive treatment varied considerably, with associated variation in outcomes. Compliance should be used as a quality indicator to improve care. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Structural and biomechanical characteristics after early mobilization in an Achilles tendon rupture model: operative versus nonoperative treatment.

PubMed

Krapf, Daniel; Kaipel, Martin; Majewski, Martin

2012-09-01

Acute Achilles tendon ruptures are common sports injuries; however, treatment remains a clinical challenge. Studies show a superior effect of early mobilization and full weight bearing on tendon healing and clinical outcome; however, few data exist on structural and biomechanical characteristics in the early healing phase. This study investigated the histological and biomechanical characteristics of early mobilization and full weight bearing in an Achilles tendon rupture model. Eighty rats underwent dissection of a hindpaw Achilles tendon; 40 rats were treated conservatively and 40 underwent open repair of the transected Achilles tendon by suturing. Early mobilization and full weight bearing were allowed in both groups. At 1, 2, 4, and 8 weeks after tenotomy, tensile strength, stiffness, thickness, tissue characteristics (histological analysis), and length were determined. Dissected Achilles tendons healed in all animals during full weight-bearing early mobilization. One and 2 weeks after tenotomy, rats in the operative group showed increased tensile strength and stiffness compared with the nonoperative group. Repair-site diameters were increased at 1, 2, and 8 weeks after tenotomy. Tendon length was decreased in the operative group throughout observation, whereas the nonoperative group showed increased structural characteristics on the cellular level and a more homogeneous collagen distribution. Surgical treatment of dissected rat Achilles tendons showed superior biomechanical characteristics within the first 2 weeks. Conservative treatment resulted in superior histological findings but significant lengthening of the tendon in the early healing phase (weeks 1-8). Copyright 2012, SLACK Incorporated.

A predictive model for early mortality after surgical treatment of heart valve or prosthesis infective endocarditis. The EndoSCORE.

PubMed

Di Mauro, Michele; Dato, Guglielmo Mario Actis; Barili, Fabio; Gelsomino, Sandro; Santè, Pasquale; Corte, Alessandro Della; Carrozza, Antonio; Ratta, Ester Della; Cugola, Diego; Galletti, Lorenzo; Devotini, Roger; Casabona, Riccardo; Santini, Francesco; Salsano, Antonio; Scrofani, Roberto; Antona, Carlo; Botta, Luca; Russo, Claudio; Mancuso, Samuel; Rinaldi, Mauro; De Vincentiis, Carlo; Biondi, Andrea; Beghi, Cesare; Cappabianca, Giangiuseppe; Tarzia, Vincenzo; Gerosa, Gino; De Bonis, Michele; Pozzoli, Alberto; Nicolini, Francesco; Benassi, Filippo; Rosato, Francesco; Grasso, Elena; Livi, Ugolino; Sponga, Sandro; Pacini, Davide; Di Bartolomeo, Roberto; De Martino, Andrea; Bortolotti, Uberto; Onorati, Francesco; Faggian, Giuseppe; Lorusso, Roberto; Vizzardi, Enrico; Di Giammarco, Gabriele; Marinelli, Daniele; Villa, Emmanuel; Troise, Giovanni; Picichè, Marco; Musumeci, Francesco; Paparella, Domenico; Margari, Vito; Tritto, Francesco; Damiani, Girolamo; Scrascia, Giuseppe; Zaccaria, Salvatore; Renzulli, Attilio; Serraino, Giuseppe; Mariscalco, Giovanni; Maselli, Daniele; Foschi, Massimiliano; Parolari, Alessandro; Nappi, Giannantonio

2017-08-15

The aim of this large retrospective study was to provide a logistic risk model along an additive score to predict early mortality after surgical treatment of patients with heart valve or prosthesis infective endocarditis (IE). From 2000 to 2015, 2715 patients with native valve endocarditis (NVE) or prosthesis valve endocarditis (PVE) were operated on in 26 Italian Cardiac Surgery Centers. The relationship between early mortality and covariates was evaluated with logistic mixed effect models. Fixed effects are parameters associated with the entire population or with certain repeatable levels of experimental factors, while random effects are associated with individual experimental units (centers). Early mortality was 11.0% (298/2715); At mixed effect logistic regression the following variables were found associated with early mortality: age class, female gender, LVEF, preoperative shock, COPD, creatinine value above 2mg/dl, presence of abscess, number of treated valve/prosthesis (with respect to one treated valve/prosthesis) and the isolation of Staphylococcus aureus, Fungus spp., Pseudomonas Aeruginosa and other micro-organisms, while Streptococcus spp., Enterococcus spp. and other Staphylococci did not affect early mortality, as well as no micro-organisms isolation. LVEF was found linearly associated with outcomes while non-linear association between mortality and age was tested and the best model was found with a categorization into four classes (AUC=0.851). The following study provides a logistic risk model to predict early mortality in patients with heart valve or prosthesis infective endocarditis undergoing surgical treatment, called "The EndoSCORE". Copyright © 2017. Published by Elsevier B.V.

Lidcombe Program Webcam Treatment for Early Stuttering: A Randomized Controlled Trial.

PubMed

Bridgman, Kate; Onslow, Mark; O'Brian, Susan; Jones, Mark; Block, Susan

2016-10-01

Webcam treatment is potentially useful for health care in cases of early stuttering in which clients are isolated from specialized treatment services for geographic and other reasons. The purpose of the present trial was to compare outcomes of clinic and webcam deliveries of the Lidcombe Program treatment (Packman et al., 2015) for early stuttering. The design was a parallel, open plan, noninferiority randomized controlled trial of the standard Lidcombe Program treatment and the experimental webcam Lidcombe Program treatment. Participants were 49 children aged 3 years 0 months to 5 years 11 months at the start of treatment. Primary outcomes were the percentage of syllables stuttered at 9 months postrandomization and the number of consultations to complete Stage 1 of the Lidcombe Program. There was insufficient evidence of a posttreatment difference of the percentage of syllables stuttered between the standard and webcam Lidcombe Program treatments. There was insufficient evidence of a difference between the groups for typical stuttering severity measured by parents or the reported clinical relationship with the treating speech-language pathologist. This trial confirmed the viability of the webcam Lidcombe Program intervention. It appears to be as efficacious and economically viable as the standard, clinic Lidcombe Program treatment.

Juvenile Dermatomyositis: Key Roles of Muscle Magnetic Resonance Imaging and Early Aggressive Treatment.

PubMed

Corral-Magaña, O; Bauzá-Alonso, A F; Escudero-Góngora, M M; Lacruz, L; Martín-Santiago, A

2017-09-12

Juvenile dermatomyositis is a rare systemic connective tissue disease with onset during childhood. It presents clinically with proximal muscle weakness and characteristic skin involvement. Diagnosis is based on the Bohan and Peter criteria, though many authors are now substituting biopsy with muscle magnetic resonance imaging (MRI) for both diagnosis and follow-up. Without intensive early treatment, complications such as calcinosis cutis and lipodystrophy can develop in the chronic phases of the disease. Early recognition is therefore key to management. We present a series of 5 patients who were diagnosed with Juvenile dermatomyositis on muscle MRI without undergoing muscle biopsy and who received early treatment. We draw attention to the usefulness of muscle MRI for the diagnosis of muscle involvement and to the importance of early initiation of intensive treatment to prevent complications. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

The effect on esophagus after different radiotherapy techniques for early stage Hodgkin's lymphoma.

PubMed

Jørgensen, Anni Y S; Maraldo, Maja V; Brodin, Nils Patrik; Aznar, Marianne C; Vogelius, Ivan R; Rosenschöld, Per Munck Af; Petersen, Peter M; Specht, Lena

2013-10-01

The cure rate of early stage Hodgkin's lymphoma (HL) is excellent; investigating the late effects of treatment is thus important. Esophageal toxicity is a known side effect in patients receiving radiotherapy (RT) to the mediastinum, although little is known of this in HL survivors. This study investigates the dose to the esophagus in the treatment of early stage HL using different RT techniques. Estimated risks of early esophagitis, esophageal stricture and cancer are compared between treatments. We included 46 patients ≥ 15 years with supradiaphragmatic, clinical stage I-II HL, who received chemotherapy followed by involved node RT (INRT) to 30.6 Gy at our institution. INRT was planned with three-dimensional conformal RT (3DCRT). For each patient a volumetric modulated arc therapy (VMAT), proton therapy (PT) and mantle field (MF) treatment plan was simulated. Mean, maximum and minimum dose to the esophagus were extracted from the treatment plans. Risk estimates were based on dose-response models from clinical series with long-term follow-up. Statistical analyses were performed with repeated measures ANOVA using Bonferroni corrections. Mean dose to the esophagus was 16.4, 16.4, 14.7 and 34.2 Gy (p < 0.001) with 3DCRT, VMAT, PT and MF treatment, respectively. No differences were seen in the estimated risk of developing esophagitis, stricture or cancer with 3DCRT compared to VMAT (p = 1.000, p = 1.000, p = 0.356). PT performed significantly better with the lowest risk estimates on all parameters compared to the photon treatments, except compared to 3DCRT for stricture (p = 0.066). On all parameters the modern techniques were superior to MF treatment (p < 0.001). The estimated dose to the esophagus and the corresponding estimated risks of esophageal complications are decreased significantly with highly conformal RT compared to MF treatment. The number of patients presenting with late esophageal side effects will, thus, likely be minimal in the future.

Lidcombe Program Webcam Treatment for Early Stuttering: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Bridgman, Kate; Onslow, Mark; O'Brian, Susan; Jones, Mark; Block, Susan

2016-01-01

Purpose: Webcam treatment is potentially useful for health care in cases of early stuttering in which clients are isolated from specialized treatment services for geographic and other reasons. The purpose of the present trial was to compare outcomes of clinic and webcam deliveries of the Lidcombe Program treatment (Packman et al., 2015) for early…

Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure.

PubMed

He, William J; Zhong, Chongke; Xu, Tan; Wang, Dali; Sun, Yingxian; Bu, Xiaoqing; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Zhang, Jintao; Geng, Deqin; Zhang, Jianhui; Li, Dong; Li, Yongqiu; Yuan, Xiaodong; Zhang, Yonghong; Kelly, Tanika N

2018-06-01

We studied the effect of early antihypertensive treatment on death, major disability, and vascular events among patients with acute ischemic stroke according to their baseline SBP. We randomly assigned 4071 acute ischemic stroke patients with SBP between 140 and less than 220 mmHg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A composite primary outcome of death and major disability and secondary outcomes were compared between treatment and control stratified by baseline SBP levels of less than 160, 160-179, and at least 180 mmHg. At 24 h after randomization, differences in SBP reductions were 8.8, 8.6 and 7.8 mmHg between the antihypertensive treatment and control groups among patients with baseline SBP less than 160, 160-179, and at least 180 mmHg, respectively (P < 0.001 among subgroups). At day 14 or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups among subgroups. However, there was a significant interaction between antihypertensive treatment and baseline SBP subgroups on death (P = 0.02): odds ratio (95% CI) of 2.42 (0.74-7.89) in patients with baseline SBP less than 60 mmHg and 0.34 (0.11-1.09) in those with baseline SBP at least 180 mmHg. At the 3-month follow-up, the primary and secondary clinical outcomes were not significantly different between the treatment and control groups by baseline SBP levels. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with various baseline SBP levels. Future clinical trials are warranted to test BP-lowering effects in acute ischemic stroke patients by baseline SBP levels. ClinicalTrials.gov Identifier: NCT01840072.

Painful Joints? Early Treatment for Rheumatoid Arthritis Is Key

MedlinePlus

... Print this issue Painful Joints? Early Treatment for Rheumatoid Arthritis Is Key En español Send us your comments ... type of arthritis. It’s far more common than rheumatoid arthritis. Osteoarthritis is caused by wear and tear on ...

Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis.

PubMed

Immanuel, Jincy; Simmons, David

2017-10-02

We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) RECENT FINDINGS: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24-28 weeks' gestation. A high proportion (15-70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM.

Early headgear effects on the eruption pattern of the maxillary canines.

PubMed

Silvola, Anna-Sofia; Arvonen, Päivi; Julku, Johanna; Lähdesmäki, Raija; Kantomaa, Tuomo; Pirttiniemi, Pertti

2009-05-01

To test the null hypothesis that early headgear (HG) treatment has no effect on the eruption pattern of the maxillary canines in the early mixed dentition. Sixty-eight children (40 boys and 28 girls) with a Class II tendency in occlusion and moderate crowding of the dental arches were randomized into two groups. HG treatment was initiated immediately in the first group. In the second group only minor interceptive procedures were performed during the first follow-up period of 2 years. Orthopantomograms were taken at the baseline, three times at 1-year intervals, and after growth at the age of 16. Eruption geometry was performed. The space from the maxillary first molar to the lateral incisor was measured on the dental casts. The inclination of the maxillary canine in relation to the midline appeared to be significantly more vertically oriented on the right side in the HG group 1 and 2 years after starting the HG therapy (P = .0098 and P = .0003, respectively). The inclination in relation to the lateral incisors was smaller in the HG group bilaterally after 1 year and 2 years of HG treatment, and on the right side after 3 years of treatment. The hypothesis is rejected. Early HG treatment significantly affects the inclination of the maxillary canine during eruption. The strongest influence was seen after 2 years of HG use, more prominently in the right-side canine.

Mathematical models for the early detection and treatment of colorectal cancer.

PubMed

Harper, P R; Jones, S K

2005-05-01

Colorectal cancer is a major cause of death for men and women in the Western world. When the cancer is detected through an awareness of the symptoms by a patient, typically it is at an advanced stage. It is possible to detect cancer at an early stage through screening and the marked differences in survival for early and late stages provide the incentive for the primary prevention or early detection of colorectal cancer. This paper considers mathematical models for colorectal cancer screening together with models for the treatment of patients. Illustrative results demonstrate that detailed attention to the processes involved in diseases, interventions and treatment enable us to combine data and expert knowledge from various sources. Thus a detailed operational model is a very useful tool in helping to make decisions about screening at national and local levels.

Early add-on treatment vs alternative monotherapy in patients with partial epilepsy.

PubMed

Semah, Franck; Thomas, Pierre; Coulbaut, Safia; Derambure, Philippe

2014-06-01

The aim of this study was to evaluate the impact of two different therapeutic strategies in patients with partial seizures who were intractable to the first prescribed antiepileptic drug (AED); alternative monotherapy vs early add-on treatment. We conducted an open, cluster-randomised, prospective, controlled trial in patients with persistent partial seizures, despite treatment with one AED, who were never administered any other AEDs. Neurologists were randomised to two strategies: in group A, an alternative monotherapy with a second AED was employed; in group B, add-on treatment with a second AED was employed. The primary outcome was the percentage of seizure-free patients during a two-month period after six months of treatment. The secondary outcomes were: (i) the percentage of patients achieving a 50% reduction in the number of seizures at six months; (ii) the quality of life based on the Quality Of Life In Epilepsy scale; and (iii) tolerability. A total of 143 neurologists were included and randomised, and 264 patients were evaluated. At six months, the primary outcome was 51% in group A and 45% in group B (p=0.34). The percentage of patients achieving a 50% reduction in the number of seizures at six months was 76% in group A and 84% in group B (p=0.53). The quality of life and the tolerability did not significantly differ between the two groups. Alternative monotherapy or early treatment initiation with another AED drug resulted in similar efficacy, and the side effects associated with monotherapy and combined therapies were similar, which suggests that individual susceptibility is more important than the number and burden of AEDs used.

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer.

PubMed

Keating, Gillian M

2009-08-20

Letrozole (Femara) is a third-generation, nonsteroidal aromatase inhibitor. Adjuvant therapy with letrozole is more effective than tamoxifen in postmenopausal women with hormone-responsive early breast cancer, and extended adjuvant therapy with letrozole after the completion of adjuvant tamoxifen therapy is more effective than placebo in this patient population; letrozole is generally well tolerated. Ongoing trials will help answer outstanding questions regarding the optimal duration of letrozole therapy in early breast cancer and its efficacy compared with other third-generation aromatase inhibitors such as anastrozole. In the meantime, letrozole should be considered a valuable option in the treatment of postmenopausal women with hormone-responsive early breast cancer, both as adjuvant and extended adjuvant therapy.

Cost effectiveness of outpatient treatment for febrile neutropaenia in adult cancer patients.

PubMed

Teuffel, O; Amir, E; Alibhai, S; Beyene, J; Sung, L

2011-04-26

There is uncertainty whether low-risk episodes of febrile neutropaenia (FN) in adult cancer patients are best managed in the in- or outpatient setting. A Monte Carlo cost-utility model was created to compare four treatment strategies for low-risk FN: (1) treatment in hospital with intravenous antibiotics (HospIV); (2) early discharge after 48 h in-patient observation, followed by oral outpatient treatment (EarlyDC); (3) outpatient management with IV antibiotics (HomeIV); and (4) outpatient management with oral antibiotics (HomePO). The model used a health-care payer perspective and a time horizon of one FN episode. Outcome measures were quality-adjusted FN episodes (QAFNE), costs (Canadian dollars) and incremental cost-effectiveness ratios (ICER). Parameter uncertainty was assessed with probabilistic sensitivity analyses. HomePO was cost saving ($3470 vs $4183), but less effective (0.65 QAFNE vs 0.72 QAFNE) than HomeIV. The corresponding ICER was $10,186 per QAFNE. Both EarlyDC ($6115; 0.66 QAFNE) and HospIV ($13,557; 0.62 QAFNE) were dominated strategies. At a willingness-to-pay (WTP) threshold of $4,000 per QAFNE, HomePO and HomeIV were cost effective in 54 and 38% of simulations, respectively. For adult cancer patients with an episode of low-risk FN, treatment in hospital is more expensive and less effective than outpatient strategies.

Cost effectiveness of outpatient treatment for febrile neutropaenia in adult cancer patients

PubMed Central

Teuffel, O; Amir, E; Alibhai, S; Beyene, J; Sung, L

2011-01-01

Background: There is uncertainty whether low-risk episodes of febrile neutropaenia (FN) in adult cancer patients are best managed in the in- or outpatient setting. Methods: A Monte Carlo cost–utility model was created to compare four treatment strategies for low-risk FN: (1) treatment in hospital with intravenous antibiotics (HospIV); (2) early discharge after 48 h in-patient observation, followed by oral outpatient treatment (EarlyDC); (3) outpatient management with IV antibiotics (HomeIV); and (4) outpatient management with oral antibiotics (HomePO). The model used a health-care payer perspective and a time horizon of one FN episode. Outcome measures were quality-adjusted FN episodes (QAFNE), costs (Canadian dollars) and incremental cost-effectiveness ratios (ICER). Parameter uncertainty was assessed with probabilistic sensitivity analyses. Results: HomePO was cost saving ($3470 vs $4183), but less effective (0.65 QAFNE vs 0.72 QAFNE) than HomeIV. The corresponding ICER was $10 186 per QAFNE. Both EarlyDC ($6115; 0.66 QAFNE) and HospIV ($13 557; 0.62 QAFNE) were dominated strategies. At a willingness-to-pay (WTP) threshold of $4 000 per QAFNE, HomePO and HomeIV were cost effective in 54 and 38% of simulations, respectively. Interpretation: For adult cancer patients with an episode of low-risk FN, treatment in hospital is more expensive and less effective than outpatient strategies. PMID:21468048

Intra-Abdominal Candidiasis: The Importance of Early Source Control and Antifungal Treatment

PubMed Central

Vergidis, Pascalis; Clancy, Cornelius J.; Shields, Ryan K.; Park, Seo Young; Wildfeuer, Brett N.; Simmons, Richard L.; Nguyen, M. Hong

2016-01-01

Intra-abdominal candidiasis (IAC) is poorly understood compared to candidemia. We described the clinical characteristics, microbiology, treatment and outcomes of IAC, and identified risk factors for mortality. We performed a retrospective study of adults diagnosed with IAC at our center in 2012–2013. Risk factors for mortality were evaluated using multivariable logistic regression. We identified 163 patients with IAC, compared to 161 with candidemia. Types of IAC were intra-abdominal abscesses (55%), secondary peritonitis (33%), primary peritonitis (5%), infected pancreatic necrosis (5%), and cholecystitis/cholangitis (3%). Eighty-three percent and 66% of secondary peritonitis and abscesses, respectively, stemmed from gastrointestinal (GI) tract sources. C. albicans (56%) and C. glabrata (24%) were the most common species. Bacterial co-infections and candidemia occurred in 67% and 6% of patients, respectively. Seventy-two percent of patients underwent an early source control intervention (within 5 days) and 72% received early antifungal treatment. 100-day mortality was 28%, and highest with primary (88%) or secondary (40%) peritonitis. Younger age, abscesses and early source control were independent predictors of survival. Younger age, abscesses and early antifungal treatment were independently associated with survival for IAC stemming from GI tract sources. Infectious diseases (ID) consultations were obtained in only 48% of patients. Consulted patients were significantly more likely to receive antifungal treatment. IAC is a common disease associated with heterogeneous manifestations, which result in poor outcomes. All patients should undergo source control interventions and receive antifungal treatment promptly. It is important for the ID community to become more engaged in treating IAC. PMID:27123857

EARLY Treatment with azilsartan compared to ACE-inhibitors in anti-hypertensive therapy--rationale and design of the EARLY hypertension registry.

PubMed

Gitt, Anselm K; Baumgart, Peter; Bramlage, Peter; Mahfoud, Felix; Potthoff, Sebastian A; Senges, Jochen; Schneider, Steffen; Buhck, Hartmut; Schmieder, Roland E

2013-07-02

Arterial hypertension is highly prevalent but poorly controlled. Blood pressure (BP) reduction substantially reduces cardiovascular morbidity and mortality. Recent randomized, double-blind clinical trials demonstrated that azilsartan medoxomil (AZM) is more effective in reducing BP than the ubiquitary ACE inhibitor ramipril. Therefore, we aimed to test whether these can be verified under clinical practice conditions. The "Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy" (EARLY) registry is a prospective, observational, national, multicenter registry with a follow-up of up to 12 months. It will include up to 5000 patients on AZM or ACE-inhibitor monotherapy in a ratio of 7 to 3. A subgroup of patients will undergo 24-hour BP monitoring. EARLY has two co-primary objectives: 1) Description of the safety profile of azilsartan and 2) achievement of BP targets based on recent national and international guidelines for patients treated with azilsartan in comparison to those treated with ACE-inhibitors. The most important secondary endpoints are the determination of persistence with treatment and the documentation of cardiovascular and renal events. Recruitment commenced in January 2012 and will be completed by February 2013. The data obtained will supplement previous results from randomized controlled trials to document the potential value of utilizing azilsartan medoxomil in comparison to ACE-inhibitor treatment for target BP achievement in clinical practice.

Cost-effectiveness model for prevention of early childhood caries.

PubMed

Ramos-Gomez, F J; Shepard, D S

1999-07-01

This study presents and illustrates a model that determines the cost-effectiveness of three successively more complete levels of preventive intervention (minimal, intermediate, and comprehensive) in treating dental caries in disadvantaged children up to 6 years of age. Using existing data on the costs of early childhood caries (ECC), the authors estimated the probable cost-effectiveness of each of the three preventive intervention levels by comparing treatment costs to prevention costs as applied to a typical low-income California child for five years. They found that, in general, prevention becomes cost-saving if at least 59 percent of carious lesions receive restorative treatment. Assuming an average restoration cost of $112 per surface, the model predicts cost savings of $66 to $73 in preventing a one-surface, carious lesion. Thus, all three levels of preventive intervention should be relatively cost-effective. Comprehensive intervention would provide the greatest oral health benefit; however, because more children would receive reparative care, overall program costs would rise even as per-child treatment costs decline.

Penicillin treatment for gonorrhoea in relation to early syphilis in prostitutes.

PubMed Central

Bradbeer, C S; Thin, R N; Tan, T; Thirumoorthy, T

1988-01-01

A retrospective study of prostitutes in Singapore showed that they had received less antigonorrhoeal treatment with penicillin derivatives during the three month period before early syphilis was diagnosed than in other three month periods when they had not developed syphilis. This suggests that penicillin derivatives in doses sufficient to treat gonorrhoea will abort coincidental early syphilis. PMID:3346033

Anastrozole is cost-effective vs tamoxifen as initial adjuvant therapy in early breast cancer: Canadian perspectives on the ATAC completed-treatment analysis.

PubMed

Rocchi, A; Verma, S

2006-09-01

To conduct an economic analysis comparing tamoxifen and anastrozole (Arimidex) in the adjuvant treatment of hormone receptor-positive (HR+), post-menopausal early breast cancer patients. An economic model examined typical patients (64 years of age, HR+, 64% node negative) from the Arimidex, tamoxifen alone, or in combination (ATAC) trial over a lifetime horizon. Rates of events were derived from ATAC trial results. Post-trial event rates were drawn from the literature for tamoxifen; event rates for anastrozole were modified by the relative risks observed in the ATAC trial. Resource utilization was drawn from Statistics Canada's Population Health Model for breast cancer, supplemented by an expert panel. A public health care system perspective, 2004 Canadian prices and a 5% discount rate were employed. Anastrozole-taking patients incurred additional hormonal treatment costs compared to tamoxifen-taking patients (incremental lifetime cost, 6,974 Canadian dollars per patient), partially offset by reduced downstream recurrences of breast cancer (1,143 Canadian dollars lifetime savings per patient) for a net incremental cost of 5,796 Canadian dollars per patient on anastrozole. The anastrozole-treated patients were projected to experience a 5.6% absolute risk reduction of first breast cancer recurrence and a 2.8% absolute risk reduction in breast cancer death. This corresponded to 30,000 Canadian dollars per life year gained and 28,000 Canadian dollars per quality-adjusted life year gained (95% confidence interval, 17,428 to 54,605 Canadian dollars). The results were affected by the duration and extent of anastrozole benefit under sensitivity analysis but remained cost-effective. Compared to tamoxifen, anastrozole therapy is effective and cost-effective as initial adjuvant therapy in post-menopausal, HR+ early breast cancer patients.

Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression.

PubMed

Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

2016-11-22

Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.

Pre-sowing Seed Treatments in Direct-seeded Early Rice: Consequences for Emergence, Seedling Growth and Associated Metabolic Events under Chilling Stress

NASA Astrophysics Data System (ADS)

Wang, Weiqin; Chen, Qian; Hussain, Saddam; Mei, Junhao; Dong, Huanglin; Peng, Shaobing; Huang, Jianliang; Cui, Kehui; Nie, Lixiao

2016-01-01

Double direct-seeding for double rice cropping is a simplified, labor saving, and efficient cropping system to improve multiple-crop index and total rice production in central China. However, poor crop establishment of direct-seeded early rice due to chilling stress is the main obstacle to wide spread of this system. A series of experiments were conducted to unravel the effects of pre-sowing seed treatments on emergence, seedling growth and associated metabolic events of direct-seeded early rice under chilling stress. Two seed priming treatments and two seed coating treatments were used in all the experiments. A non-treated control treatment was also maintained for comparison. In both the field and growth chamber studies, seed priming with selenium or salicylic acid significantly enhanced the emergence and seedling growth of rice compared with non-treated control. Nevertheless, such positive effects were not apparent for seed coating treatments. Better emergence and vigorous seedling growth of rice after seed priming was associated with enhanced α-amylase activity, higher soluble sugars contents, and greater respiration rate in primed rice seedlings under chilling stress. Taking together, these findings may provide new avenues for understanding and advancing priming-induced chilling tolerance in direct-seeded early rice in double rice cropping system.

Cannabinoids Reverse the Effects of Early Stress on Neurocognitive Performance in Adulthood

ERIC Educational Resources Information Center

Alteba, Shirley; Korem, Nachshon; Akirav, Irit

2016-01-01

Early life stress (ES) significantly increases predisposition to psychopathologies. Cannabinoids may cause cognitive deficits and exacerbate the effects of ES. Nevertheless, the endocannabinoid system has been suggested as a therapeutic target for the treatment of stress- and anxiety-related disorders. Here we examined whether cannabinoids…

Comparative Effectiveness of 5 Treatment Strategies for Early-Stage Non-Small Cell Lung Cancer in the Elderly

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shirvani, Shervin M.; Jiang, Jing; Chang, Joe Y.

2012-12-01

Purpose: The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, stereotactic ablative radiation therapy (SABR), and observation. Methods and Materials: Treatment strategy and covariates were determined in 10,923 patients aged {>=}66 years with stage IA-IB NSCLC. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specificmore » survival for the 5 strategies. In a second exploratory analysis, propensity-score matching was used for comparison of SABR with other options. Results: The median age was 75 years, and 29% had moderate to severe comorbidities. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In Cox regression analysis with a median follow-up time of 3.2 years, SABR was associated with the lowest risk of death within 6 months of diagnosis (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy). After 6 months, lobectomy was associated with the best overall and disease-specific survival. In the propensity-score matched analysis, survival after SABR was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is SABR). Conventional radiation and observation were associated with poor outcomes in all analyses. Conclusions: In this population-based experience, lobectomy was associated with the best long-term outcomes in fit elderly patients with early-stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy comparable with that of surgery in select

[Implementation of an early rheumatoid athritis unit for the early recognition and treatment of the disease].

PubMed

Espinoza, Francisco; Monckeberg, Gustavo; Hassi, Isabel; Queirolo, Alejandra; Chicao, Fernando; Sandoval, Ximena; Jorquera, Evelyn; Badilla, Alejandro

2018-01-01

Early recognition of rheumatoid arthritis (RA) provides clinical benefits in terms of remission induction, reduced disease progression, and eventually treatment free remission. To describe the setting of a Unit devoted exclusively to the recognition and treatment of early RA in patients referred from primary healthcare centers (PHC) in Chile. Patients were referred from nine participating PHC from 2014 through 2016. PHC physicians received a formal training to enhance criteria recognition and program adherence. Mandatory referral criteria were an age above 17 years, and arthralgia of less than 1-year duration, plus at least one of the following: morning stiffness of more than 30 minutes, swelling involving more than 3 joints for more than 1 month, a positive squeeze test or abnormal inflammatory serum markers. One hundred twenty patients aged 45 ± 12 years (90% women) were assessed at the early rheumatoid arthritis unit. Median time to referral from PHC to the Unit was 14.6 days. The median duration of symptoms for the overall sample of patients was 10.8 months. RA was identified in 43 patients (36%), with a delay between onset of symptoms and diagnosis of 8.3 months. Regarding the performance of referral criteria, the most sensitive was morning stiffness (80%, sensitivity 95% confidence intervals (CI) 64-89%) and synovitis was the most specific (specificity 83%, 95% CI 72-90%). The positive predictive value of the three clinical criteria altogether was 68.1% (95% CI 47-83%). Institution of an early RA unit was feasible within the Chilean healthcare system enabling the identification of early RA in one-third of patients.

Effects of transforming growth factor-β1 treatment on muscle regeneration and adipogenesis in glycerol-injured muscle.

PubMed

Mahdy, Mohamed A A; Warita, Katsuhiko; Hosaka, Yoshinao Z

2017-11-01

Transforming growth factor (TGF)-β1 is associated with fibrosis in many organs. Recent studies demonstrated that delivery of TGF-β1 into chemically injured muscle enhances fibrosis. In this study, we investigated the effects of exogenous TGF-β1 on muscle regeneration and adipogenesis in glycerol-injured muscle of normal mice. Tibialis anterior (TA) muscles were injured by glycerol injection. TGF-β1 was either co-injected with glycerol, as an 'early treatment' group, or injected at day 4 after glycerol, as a 'late treatment' group and the TA muscles were collected at day 7 after initial injury. Myotube density was significantly lower in the early treatment group than in the glycerol-injured group (without TGF-β1 treatment). Moreover, the Oil red O-positive area was significantly smaller in the early treatment group than in the late treatment group and glycerol-injured group. Furthermore, TGF-β1 treatment increased endomysial fibrosis and induced immunostaining of α-smooth muscle actin. The greater inhibitory effects of early TGF-β1 treatment than that of late TGF-β1 treatment during regeneration in glycerol-injured muscle suggest a more potent effect of TGF-β1 on the initial stage of muscle regeneration and adipogenesis. Combination of TGF-β1 with glycerol might be an alternative to enhance muscle fibrosis for future studies. © 2017 Japanese Society of Animal Science.

Measuring patients' perceptions of the outcomes of treatment for early prostate cancer.

PubMed

Clark, Jack A; Bokhour, Barbara G; Inui, Thomas S; Silliman, Rebecca A; Talcott, James A

2003-08-01

Compared with careful attention to the physical (eg, urinary, bowel, sexual) dysfunction that may follow treatment, little attention has been given to the behavioral, emotional, and interpersonal changes that the diagnosis of early prostate cancer and subsequent physical dysfunction may bring. To construct patient-centered measures of the outcomes of treatment for early prostate cancer. Qualitative study followed by survey of early prostate cancer patients and group of comparable patients with no history of prostate cancer. Analysis of focus groups identified relevant domains of quality of life, which were represented by Likert scale items included in survey questionnaires. Psychometric analyses of survey data defined scales evaluated with respect to internal consistency and validity. Qualitative analysis identified three domains: urinary control, sexuality, and uncertainty about the cancer and its treatment. Psychometric analysis defined 11 scales. Seven were generically relevant to most older men: urinary control (eg, embarrassment with leakage), sexual intimacy (eg, anxiety about completing intercourse), sexual confidence (eg, comfort with sexuality), marital affection (eg, emotional distance from spouse/partner), masculine self esteem (eg, feeling oneself a whole man), health worry (eg, apprehensiveness about health changes), and PSA concern (eg, closely attending to one's PSA). Four scales were specific to the treatment experience: perceived cancer control, quality of treatment decision making, regret of treatment choice, and cancer-related outlook. The scales provide definition and metrics for patient-centered research in this area. They complement measures of physical dysfunction and bring into resolution outcomes of treatment that have gone unnoticed in previous studies.

Early increase in marker of neuronal integrity with antidepressant treatment of major depression: 1H-magnetic resonance spectroscopy of N-acetyl-aspartate.

PubMed

Taylor, Matthew J; Godlewska, Beata R; Norbury, Ray; Selvaraj, Sudhakar; Near, Jamie; Cowen, Philip J

2012-11-01

Increasing interest surrounds potential neuroprotective or neurotrophic actions of antidepressants. While growing evidence points to important early clinical and neuropsychological effects of antidepressants, the time-course of any effect on neuronal integrity is unclear. This study used magnetic resonance spectroscopy to assess effects of short-term treatment with escitalopram on N-acetyl-aspartate (NAA), a marker of neuronal integrity. Thirty-nine participants with major depression were randomly assigned to receive either 10 mg escitalopram or placebo daily in a double-blind, parallel group design. On the seventh day of treatment, PRESS data were obtained from a 30×30×20 mm voxel placed in medial frontal cortex. Age and gender-matched healthy controls who received no treatment were also scanned. Levels of NAA were significantly higher in patients treated with escitalopram than in either placebo-treated patients (p<0.01) or healthy controls (p<0.01). Our findings are consistent with the proposition that antidepressant treatment in depressed patients can produce early changes in neuronal integrity.

Effectiveness of oxfendazole against early and later 4th-stage Strongylus vulgaris in ponies.

PubMed

Slocombe, J O; McCraw, B M; Pennock, P; Ducharme, N G; Baird, J D

1986-03-01

Twenty pony foals (reared worm free), 6.5 to 10 weeks of age, were inoculated with Strongylus vulgaris and allocated to 5 groups, each with 4 foals. One week after inoculation, 1 group of 4 foals was given oxfendazole (OFZ) at a dosage rate of 10 mg/kg of body weight, another group was given 2 such treatments 48 hours apart, and a 3rd group was given a placebo. All treatments were administered by stomach tube. Three weeks later, foals were euthanatized and necropsied in a test for efficacy against early 4th-stage larvae. Oxfendazole was 80% and 94.9% effective against early 4th-stage S vulgaris with 1 and 2 doses, respectively. A 4th group of 4 foals was given 2 treatments of OFZ, 48 hours apart, about 8 weeks after inoculation, and a 5th group was given a placebo. These foals were euthanatized and necropsied 5 weeks after treatment in a test for efficacy against later 4th-stage larvae. Two doses of OFZ were 96.6% effective against later 4th-stage larvae.

Early Maladaptive Schemas in a Sample of Airline Pilots seeking Residential Substance Use Treatment: An Initial Investigation

PubMed Central

Shorey, Ryan C.; Brasfield, Hope; Anderson, Scott; Stuart, Gregory L.

2014-01-01

Background Recent research has begun to examine the early maladaptive schemas of substance abusers, as it is believed that targeting these core beliefs in treatment may result in improved substance use outcomes. One special population that has received scant attention in the research literature, despite high levels of substance use, is airline pilots. Aims The current study examined the early maladaptive schemas of a sample of airline pilots (n = 64) who were seeking residential treatment for alcohol dependence and whether they differed in early maladaptive schemas from non-pilot substance abusers who were also seeking residential treatment for alcohol dependence (n = 45). Method Pre-existing medical records from patients of a residential substance abuse treatment facility were reviewed for the current study. Results Of the 18 early maladaptive schemas, results demonstrated that pilots scored higher than non-pilots on the early maladaptive schema of unrelenting standards (high internalized standards of behavior), whereas non-pilots scored higher on insufficient self-control (low frustration tolerance and self-control). Conclusions Early maladaptive schemas may be a relevant treatment target for substance abuse treatment seeking pilots and non-pilots. PMID:24701252

Interpretation Bias Modification for Youth and their Parents: A Novel Treatment for Early Adolescent Social Anxiety

PubMed Central

Reuland, Meg M.; Teachman, Bethany A.

2014-01-01

Social anxiety is the most prevalent anxiety disorder of late adolescence, yet current treatments reach only a minority of youth with the disorder. Effective and easy-to-disseminate treatments are needed. This study pilot tested the efficacy of a novel, online cognitive bias modification for interpretation (CBM-I) intervention for socially anxious youth and their parents. The CBM-I intervention targeted cognitive biases associated with early adolescents’ maladaptive beliefs regarding social situations, and with parents’ intrusive behavior, both of which have been theoretically linked with the maintenance of social anxiety in youth. To investigate the efficacy of intervening with parents and/or children, clinically diagnosed early adolescents (ages 10–15; N = 18) and their mothers were randomly assigned to one of three conditions: the first targeted early adolescents’ cognitive biases related to social anxiety (Child-only condition); the second targeted parents’ biases associated with intrusive behavior (Parent-only condition); and the third targeted both youth and parents’ biases in tandem (Combo condition). The use of a multiple baseline design allowed for the efficient assessment of causal links between the intervention and reduction in social anxiety symptoms in youth. Results provided converging evidence indicating modest support for the efficacy of CBM-I, with no reliable differences across conditions. Taken together, results suggest that online CBM-I with anxious youth and/or their parents holds promise as an effective and easily administered component of treatment for child social anxiety that deserves further evaluation in a larger trial. PMID:25445075

Interpretation bias modification for youth and their parents: a novel treatment for early adolescent social anxiety.

PubMed

Reuland, Meg M; Teachman, Bethany A

2014-12-01

Social anxiety is the most prevalent anxiety disorder of late adolescence, yet current treatments reach only a minority of youth with the disorder. Effective and easy-to-disseminate treatments are needed. This study pilot tested the efficacy of a novel, online cognitive bias modification for interpretation (CBM-I) intervention for socially anxious youth and their parents. The CBM-I intervention targeted cognitive biases associated with early adolescents' maladaptive beliefs regarding social situations, and with parents' intrusive behavior, both of which have been theoretically linked with the maintenance of social anxiety in youth. To investigate the efficacy of intervening with parents and/or children, clinically diagnosed early adolescents (ages 10-15; N=18) and their mothers were randomly assigned to one of three conditions: the first targeted early adolescents' cognitive biases related to social anxiety (Child-only condition); the second targeted parents' biases associated with intrusive behavior (Parent-only condition); and the third targeted both youth and parents' biases in tandem (Combo condition). The use of a multiple baseline design allowed for the efficient assessment of causal links between the intervention and reduction in social anxiety symptoms in youth. Results provided converging evidence indicating modest support for the efficacy of CBM-I, with no reliable differences across conditions. Taken together, results suggest that online CBM-I with anxious youth and/or their parents holds promise as an effective and easily administered component of treatment for child social anxiety that deserves further evaluation in a larger trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Early Educational Intervention, Early Cumulative Risk, and the Early Home Environment as Predictors of Young Adult Outcomes within a High-Risk Sample

ERIC Educational Resources Information Center

Pungello, Elizabeth P.; Kainz, Kirsten; Burchinal, Margaret; Wasik, Barbara H.; Sparling, Joseph J.; Ramey, Craig T.; Campbell, Frances A.

2010-01-01

The extent to which early educational intervention, early cumulative risk, and the early home environment were associated with young adult outcomes was investigated in a sample of 139 young adults (age 21) from high-risk families enrolled in randomized trials of early intervention. Positive effects of treatment were found for education attainment,…

Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison.

PubMed

Rothwell, Peter M; Giles, Matthew F; Chandratheva, Arvind; Marquardt, Lars; Geraghty, Olivia; Redgrave, Jessica N E; Lovelock, Caroline E; Binney, Lucy E; Bull, Linda M; Cuthbertson, Fiona C; Welch, Sarah J V; Bosch, Shelley; Alexander, Faye C; Carasco-Alexander, Faye; Silver, Louise E; Gutnikov, Sergei A; Mehta, Ziyah

2007-10-20

The risk of recurrent stroke is up to 10% in the week after a transient ischaemic attack (TIA) or minor stroke. Modelling studies suggest that urgent use of existing preventive treatments could reduce the risk by 80-90%, but in the absence of evidence many health-care systems make little provision. Our aim was to determine the effect of more rapid treatment after TIA and minor stroke in patients who are not admitted direct to hospital. We did a prospective before (phase 1: April 1, 2002, to Sept 30, 2004) versus after (phase 2: Oct 1, 2004, to March 31, 2007) study of the effect on process of care and outcome of more urgent assessment and immediate treatment in clinic, rather than subsequent initiation in primary care, in all patients with TIA or minor stroke not admitted direct to hospital. The study was nested within a rigorous population-based incidence study of all TIA and stroke (Oxford Vascular Study; OXVASC), such that case ascertainment, investigation, and follow-up were complete and identical in both periods. The primary outcome was the risk of stroke within 90 days of first seeking medical attention, with independent blinded (to study period) audit of all events. Of the 1278 patients in OXVASC who presented with TIA or stroke (634 in phase 1 and 644 in phase 2), 607 were referred or presented direct to hospital, 620 were referred for outpatient assessment, and 51 were not referred to secondary care. 95% (n=591) of all outpatient referrals were to the study clinic. Baseline characteristics and delays in seeking medical attention were similar in both periods, but median delay to assessment in the study clinic fell from 3 (IQR 2-5) days in phase 1 to less than 1 (0-3) day in phase 2 (p<0.0001), and median delay to first prescription of treatment fell from 20 (8-53) days to 1 (0-3) day (p<0.0001). The 90-day risk of recurrent stroke in the patients referred to the study clinic was 10.3% (32/310 patients) in phase 1 and 2.1% (6/281 patients) in phase 2

Early Maladaptive Schemas and Aggression in Men Seeking Residential Substance Use Treatment

PubMed Central

Shorey, Ryan C.; Elmquist, Joanna; Anderson, Scott; Stuart, Gregory L.

2015-01-01

Social-cognitive theories of aggression postulate that individuals who perpetrate aggression are likely to have high levels of maladaptive cognitive schemas that increase risk for aggression. Indeed, recent research has begun to examine whether early maladaptive schemas may increase the risk for aggression. However, no known research has examined this among individuals in substance use treatment, despite aggression and early maladaptive schemas being more prevalent among individuals with a substance use disorder than the general population. Toward this end, we examined the relationship between early maladaptive schemas and aggression in men in a residential substance use treatment facility (N = 106). Utilizing pre-existing patient records, results demonstrated unique associations between early maladaptive schema domains and aggression depending on the type of aggression and schema domain examined, even after controlling for substance use, antisocial personality, age, and education. The Impaired Limits domain was positively associated with verbal aggression, aggressive attitude, and overall aggression, whereas the Disconnection and Rejection domain was positively associated with physical aggression. These findings are consistent with social-cognitive models of aggression and advance our understanding of how early maladaptive schemas may influence aggression. The implications of these findings for future research are discussed. PMID:25897180

Early growth hormone treatment start in childhood growth hormone deficiency improves near adult height: analysis from NordiNet® International Outcome Study.

PubMed

Polak, Michel; Blair, Jo; Kotnik, Primoz; Pournara, Effie; Pedersen, Birgitte Tønnes; Rohrer, Tilman R

2017-11-01

To investigate the effect of age at growth hormone (GH) treatment start on near adult height (NAH) in children with isolated GH deficiency (GHD). NordiNet® International Outcome Study (IOS) (Nbib960128), a non-interventional, multicentre study, evaluates the long-term effectiveness and safety of Norditropin® (somatropin) (Novo Nordisk A/S) in the real-life clinical setting. Patients ( n  = 172) treated to NAH (height at ≥18 years, or height velocity <2 cm/year at ≥16 (boys) or ≥15 (girls) years) were grouped by age (years) at treatment start (early (girls, <8; boys, <9), intermediate (girls, 8-10; boys, 9-11) or late (girls, >10; boys, >11)) and GHD severity (<3 ng/mL or 3 to ≤10 ng/mL). Multiple regression analysis was used to evaluate the effect of age at treatment start (as a categorical and continuous variable) on NAH standard deviation score (SDS). Age at treatment start had a marked effect on NAH SDS; NAH SDS achieved by patients starting treatment early ( n  = 40 (boys, 70.0%); least squares mean (standard error) -0.76 (0.14)) exceeded that achieved by those starting later (intermediate, n  = 42 (boys, 57.1%); -1.14 (0.15); late, n  = 90 (boys, 68.9%); -1.21 (0.10)). Multiple regression analysis showed a significant association between NAH SDS and age at treatment start ( P  < 0.0242), baseline height SDS (HSDS) ( P  < 0.0001), target HSDS ( P  < 0.0001), and GHD severity ( P  = 0.0012). Most (78.5%) patients achieved a normal NAH irrespective of age at treatment start. Early initiation of GH treatment in children with isolated GHD improves their chance of achieving their genetic height potential. © 2017 The authors.

EARLY Treatment with azilsartan compared to ACE-inhibitors in anti-hypertensive therapy – rationale and design of the EARLY hypertension registry

PubMed Central

2013-01-01

Background Arterial hypertension is highly prevalent but poorly controlled. Blood pressure (BP) reduction substantially reduces cardiovascular morbidity and mortality. Recent randomized, double-blind clinical trials demonstrated that azilsartan medoxomil (AZM) is more effective in reducing BP than the ubiquitary ACE inhibitor ramipril. Therefore, we aimed to test whether these can be verified under clinical practice conditions. Methods/Design The “Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy” (EARLY) registry is a prospective, observational, national, multicenter registry with a follow-up of up to 12 months. It will include up to 5000 patients on AZM or ACE-inhibitor monotherapy in a ratio of 7 to 3. A subgroup of patients will undergo 24-hour BP monitoring. EARLY has two co-primary objectives: 1) Description of the safety profile of azilsartan and 2) achievement of BP targets based on recent national and international guidelines for patients treated with azilsartan in comparison to those treated with ACE-inhibitors. The most important secondary endpoints are the determination of persistence with treatment and the documentation of cardiovascular and renal events. Recruitment commenced in January 2012 and will be completed by February 2013. Conclusions The data obtained will supplement previous results from randomized controlled trials to document the potential value of utilizing azilsartan medoxomil in comparison to ACE-inhibitor treatment for target BP achievement in clinical practice. PMID:23819631

Unexpected Decrease in Milk Production after Fenbendazole Treatment of Dairy Cows during Early Grazing Season

PubMed Central

Ravinet, Nadine; Chartier, Christophe; Bareille, Nathalie; Lehebel, Anne; Ponnau, Adeline; Brisseau, Nadine; Chauvin, Alain

2016-01-01

Gastrointestinal nematodes (GIN) infection can impair milk production (MP) in dairy cows. To investigate whether MP would be optimized by spring targeted-selective anthelmintic treatment in grazing cows, we assessed (1) the effect on MP of an anthelmintic treatment applied 1.5 to 2 months after turn-out, and (2) herd and individual indicators associated with the post-treatment MP response. A randomized controlled clinical trial was conducted in 13 dairy farms (578 cows) in western France in spring 2012. In each herd, lactating cows of the treatment group received fenbendazole orally, control cows remained untreated. Daily cow MP was recorded from 2 weeks before until 15 weeks after treatment. Individual serum pepsinogen and anti-Ostertagia antibody levels (expressed as ODR), faecal egg count and bulk tank milk (BTM) Ostertagia ODR were measured at treatment time. Anthelmintic treatment applied during the previous housing period was recorded for each cow. In each herd, information regarding heifers’ grazing and anthelmintic treatment history was collected to assess the Time of Effective Contact (TEC, in months) with GIN infective larvae before the first calving. The effect of treatment on weekly MP averages and its relationships with herd and individual indicators were studied using linear mixed models with two nested random effects (cow within herd). Unexpectedly, spring treatment had a significant detrimental effect on MP (-0.92 kg/cow/day on average). This negative MP response was particularly marked in high producing cows, in cows not treated during the previous housing period or with high pepsinogen levels, and in cows from herds with a high TEC or a high BTM ODR. This post-treatment decrease in MP may be associated with immuno-inflammatory mechanisms. Until further studies can assess whether this unexpected result can be generalized, non-persistent treatment of immunized adult dairy cows against GIN should not be recommended in early grazing season. PMID

Unexpected Decrease in Milk Production after Fenbendazole Treatment of Dairy Cows during Early Grazing Season.

PubMed

Ravinet, Nadine; Chartier, Christophe; Bareille, Nathalie; Lehebel, Anne; Ponnau, Adeline; Brisseau, Nadine; Chauvin, Alain

2016-01-01

Gastrointestinal nematodes (GIN) infection can impair milk production (MP) in dairy cows. To investigate whether MP would be optimized by spring targeted-selective anthelmintic treatment in grazing cows, we assessed (1) the effect on MP of an anthelmintic treatment applied 1.5 to 2 months after turn-out, and (2) herd and individual indicators associated with the post-treatment MP response. A randomized controlled clinical trial was conducted in 13 dairy farms (578 cows) in western France in spring 2012. In each herd, lactating cows of the treatment group received fenbendazole orally, control cows remained untreated. Daily cow MP was recorded from 2 weeks before until 15 weeks after treatment. Individual serum pepsinogen and anti-Ostertagia antibody levels (expressed as ODR), faecal egg count and bulk tank milk (BTM) Ostertagia ODR were measured at treatment time. Anthelmintic treatment applied during the previous housing period was recorded for each cow. In each herd, information regarding heifers' grazing and anthelmintic treatment history was collected to assess the Time of Effective Contact (TEC, in months) with GIN infective larvae before the first calving. The effect of treatment on weekly MP averages and its relationships with herd and individual indicators were studied using linear mixed models with two nested random effects (cow within herd). Unexpectedly, spring treatment had a significant detrimental effect on MP (-0.92 kg/cow/day on average). This negative MP response was particularly marked in high producing cows, in cows not treated during the previous housing period or with high pepsinogen levels, and in cows from herds with a high TEC or a high BTM ODR. This post-treatment decrease in MP may be associated with immuno-inflammatory mechanisms. Until further studies can assess whether this unexpected result can be generalized, non-persistent treatment of immunized adult dairy cows against GIN should not be recommended in early grazing season.

Early effects of equine FSH (eFSH) treatment on hormonal and reproductive parameters in mares intended to carry their own pregnancy.

PubMed

Raz, Tal; Gray, Allister; Hunter, Barbara; Card, Claire

2009-10-01

Superovulatory treatment may potentially increase the embryo recovery rate and the per-cycle pregnancy rate in normal or subfertile mares that are managed properly. However, some studies suggest a possible negative effect of superovulatory treatment on ovarian follicular maturation and embryo viability. Objectives of the present study were to investigate the early effects of eFSH treatment in reproductively normal mares in terms of: folliculogenesis, pregnancy rate, early embryonic development, reproductive tract parameters (tone and edema), and serum estradiol-17beta and progesterone concentrations. Reproductively sound mares (n=26) were evaluated daily by transrectal palpation and ultrasonography. Five days after spontaneous ovulation, mares were randomly assigned to one of two treatment groups. In the eFSH group, mares (n=16 estrous cycles) were administered eFSH twice daily; beginning when a follicle > or =20mm was detected, and continuing until at least one follicle reached a diameter of > or =35 mm. PGF2alpha was administered 2 days following initiation of eFSH therapy, and hCG was administered approximately 36h after cessation of eFSH therapy. In the control group, mares (n=26 estrous cycles) were administered PGF2alpha 7 days after spontaneous ovulation, and hCG when a follicle > or =35 mm was detected. All mares were bred with fresh semen, monitored for ovulation (Day 0), and evaluated for pregnancy on Days 11-16. Serum estradiol-17beta and progesterone concentrations were analyzed using radioimmunoassay on the Day of hCG administration, and Days 8, 11 and 16. Mares treated with eFSH had more follicles > or =30 mm at the time of hCG administration (2.6+/-0.4 compared with 1.1+/-0.1; P<0.01), and more ovulations (2.3+/-0.5 compared with 1.1+/-0.3; P<0.01). However, pregnancy rates were not significantly different between groups (50%; 8/16 compared with 62%; 16/26). Mean overall daily growth rate of embryonic vesicles from Day 11 to 16 was not statistically

Patterns of Early and Delayed Visual Response to Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration.

PubMed

Stoller, Glenn L; Kokame, Gregg T; Dreyer, Richard F; Shapiro, Howard; Tuomi, Lisa L

2016-05-12

12, early vs delayed responders in the PRN treatment groups received 7.5 vs 7.4 ranibizumab injections, respectively (P = .84). More than 80% of early responders receiving PRN treatment maintained 15-letter or greater gains at month 24. At baseline, early vs delayed responders had worse BCVA (49.8 vs 55.4 letters; P < .001) and greater CFT (374.9 vs 339.0 µm; P = .02), although anatomical results were comparable by month 3 (CFT, 187.7 vs 188.9 µm). Improvement of 15 letters or more from baseline occurred in 266 (25.2%) of 1057 patients within 3 months of beginning ranibizumab treatment, whereas an additional 135 (13.7%) of 988 patients achieved this gain by 12 months. The 2 cohorts had similar anatomical temporal response patterns. PRN treatment with monthly monitoring was effective in maintaining early vision gains and allowing delayed vision gains. These results suggest that vision improvement can continue in some patients after macular edema resolves and CFT decreases stabilize.

Effects of early thyroxine treatment on development and growth at age 10.7 years: follow-up of a randomized placebo-controlled trial in children with Down's syndrome.

PubMed

Marchal, Jan Pieter; Maurice-Stam, Heleen; Ikelaar, Nadine A; Klouwer, Femke C C; Verhorstert, Kim W J; Witteveen, M Emma; Houtzager, Bregje A; Grootenhuis, Martha A; van Trotsenburg, A S Paul

2014-12-01

In 2-year-old children with Down's syndrome (DS), early T4 treatment was found to result in slightly better motor development and growth. This study sought to determine long-term effects of early T4 treatment on development and growth in children with DS with either an elevated or normal neonatal TSH concentration. Patients received a single follow-up visit 8.7 years after a randomized placebo-controlled trial (RCT) comparing T4 and placebo treatment during the first 2 years of life. Dutch Academic Hospital. All children who completed the RCT (N = 181, of 196 randomly assigned children) were invited for the follow-up study. A total of 123 participants enrolled, at a mean age of 10.7 years. T4 or placebo treatment from the neonatal period until 2 years. Primary: mental and motor development. Secondary: communication skills, fine-motor coordination, height, weight, and head circumference (HC). Outcomes were compared between T4- and placebo-treated children, and between treatment groups with either a normal (<5 mIU/L), or elevated (≥ 5 mIU/L) TSH concentration at original trial entry. Mental or motor development, communication skills, or fine-motor coordination did not differ between T4- (N = 64) and placebo-treated children (N = 59). T4-treated children had a larger HC (50.4 vs 49.8 cm, P = .04) and tended to be taller (133.2 vs 131.1 cm, P = .06). These differences were somewhat greater in children with TSH ≥ 5 mIU/L (HC: T4, 50.5 vs placebo, 49.7 cm; P = .01; height: T4, 133.8 vs placebo, 130.8 cm; P = .02), but were not found in children with TSH <5 mIU/L (HC: T4, 50.1 vs placebo, 50.0 cm; P = .75; height: T4, 132.1 vs placebo, 131.6 cm; P = .22). Early T4 treatment of children with DS does not seem to benefit mental or motor development later in life. However, the positive effect on growth is still measurable, especially in children with an elevated plasma TSH concentration in the neonatal period.

Potential Adverse Effects of Amphetamine Treatment on Brain and Behavior: A Review

PubMed Central

Berman, Steven M.; Kuczenski, Ronald; McCracken, James T.; London, Edythe D.

2009-01-01

Rationale Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority 1. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Findings Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several-fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central

Very early withdrawal from treatment in patients starting peritoneal dialysis

PubMed Central

Luo, Qimei; Xia, Xi; Lin, Zhenchuan; Lin, Jianxiong; Yang, Xiao; Huang, Fengxian; Yu, Xueqing

2018-01-01

Abstract Introduction: Very early withdrawal from treatment in patients undergoing peritoneal dialysis (PD) is an increasingly important, but poorly understood, issue. Here, we identified the reasons and risk factors for very early withdrawal from PD. Methods: Incident PD patients from The First Affiliated Hospital of Sun Yat-sen University above 18 years who started treatment between January 1 2006 and December 31 2011 were included. Cessation of PD therapy within the first 90 days after beginning dialysis was classified as very early withdrawal. Results: Totally 1444 patients were enrolled. Of these, 71 (4.9%) withdrew from PD therapy during the first 90 days. Primary reasons for very early withdrawal included death (34 patients, 47.9%), transplantation (21 patients, 29.6%) and transfer to hemodialysis (14 patients, 19.7%). The leading reasons for death were cardiovascular and infectious disease, accounting for 41.2% (14 patients) and 23.5% (8 patients) of total deaths, respectively. Dialysate leakage (six patients, 42.9%) and catheter dysfunction (five patients, 35.7%) were the main reasons for transfer to hemodialysis. In multivariate analysis, predictors for very early PD withdrawal were older age (per decade increasing; hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.03–1.45; p = .019), higher systolic blood pressure (per 10 mmHg increasing; HR, 1.35; 95% CI, 1.20–1.50; p < .001), lower hemoglobin (per 10 g/l increasing; HR, 0.67; 95% CI, 0.57–0.78; p < .001), lower high-density lipoprotein cholesterol (HR, 0.24; 95% CI, 0.10–0.54; p = .001) and lower residual urine volume (per 100 ml/d increasing; HR, 0.90; 95% CI, 0.84–0.95; p = .001). Conclusions: Death was the primary reason for very early withdrawal from PD. Risk factors for very early withdrawal from PD were older in age, had higher systolic blood pressure, lower hemoglobin, lower high-density lipoprotein cholesterol and lower residual urine volume

Survival outcome of early versus delayed bevacizumab treatment in patients with recurrent glioblastoma

PubMed Central

Hamza, Mohamed A.; Mandel, Jacob J.; Conrad, Charles A.; Gilbert, Mark R.; Yung, W. K. Alfred; Puduvalli, Vinay K.; DeGroot, John F.

2015-01-01

Bevacizumab (BEV) is widely used for treatment of patients with recurrent glioblastoma. It is not known if there are differences in outcome between early versus delayed BEV treatment of recurrent glioblastoma. We examined the relationship between the time of starting BEV treatment and outcomes in patients with recurrent glioblastoma. In this retrospective chart review, we identified patients with recurrent glioblastoma diagnosed between 2005 and 2011 who were treated with BEV alone or BEV-containing regimens. Data was analyzed to determine overall survival (OS) from time of diagnosis and progression free survival (PFS) from time of starting BEV. A total of 298 patients were identified, 112 patients received early BEV, 133 patients received delayed BEV, and 53 patients were excluded because they either progressed within 3 months of radiation or received BEV at the time of diagnosis. There was no significant difference in PFS between patients that received early BEV and those that received delayed BEV (5.2 vs. 4.3 months, p = 0.2). Patients treated with delayed BEV had longer OS when compared to those treated with early BEV (25.9 vs. 20.8 months, p = 0.005). In patients with recurrent glioblastoma, there was no significant difference in PFS from the time of starting BEV between early and delayed BEV. Although patients treated with delayed BEV seemed to have longer OS, a conclusion regarding OS outcome requires further prospective trials. These results may indicate that delaying treatment with BEV is not detrimental for survival of patients with recurrent glioblastoma. PMID:24803001

Effects of an Early Numeracy Intervention on Struggling Kindergarteners' Mathematics Performance

ERIC Educational Resources Information Center

Bryant, Brian R.; Bryant, Diane Pedrotty; Roberts, Greg; Fall, Anna-Maria

2016-01-01

The purpose of this study was to investigate the effects of an early numeracy intervention delivered by kindergarten teachers to students identified as having mathematics difficulties. A multigroup growth-modeling-with-random-assignment-to-intervention-condition design was employed. Thirty-two teachers were randomly assigned to the treatment or…

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

PubMed

Lange, Marie; Heutte, Natacha; Noal, Sabine; Rigal, Olivier; Kurtz, Jean-Emmanuel; Lévy, Christelle; Allouache, Djelila; Rieux, Chantal; Lefel, Johan; Clarisse, Bénédicte; Leconte, Alexandra; Veyret, Corinne; Barthélémy, Philippe; Longato, Nadine; Tron, Laure; Castel, Hélène; Eustache, Francis; Giffard, Bénédicte; Joly, Florence

2018-06-22

Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. The sample consisted of women newly diagnosed with EBC ( n  = 118) and healthy controls ( n  = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant ( p  = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. The Oncologist IMPLICATIONS FOR PRACTICE: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced

Treatment of Early-stage Extracranial Arteriovenous Malformations with Intralesional Interstitial Bleomycin Injection: A Pilot Study.

PubMed

Jin, Yunbo; Zou, Yun; Hua, Chen; Chen, Hui; Yang, Xi; Ma, Gang; Chang, Lei; Qiu, Yajing; Lyu, Dongze; Wang, Tianyou; Chang, Shih-Jen; Qiao, Congzhen; Luo, Chunfen; Tremp, Mathias; Lin, Xiaoxi

2018-04-01

Purpose To assess the efficacy and safety of intralesional interstitial bleomycin injection in the treatment of early-stage (Schobinger stage I or II) extracranial arteriovenous malformations (AVMs). Materials and Methods This prospective study involved 34 patients with early-stage AVMs, as defined by the Schobinger staging system. The patients received intralesional interstitial bleomycin injected at a maximum dose of 15 000 IU or 1000 IU per kilogram of body weight for children who weighed less than 15 kg per procedure for a total of 6 months (once every month). Therapeutic outcome was evaluated by the degree of devascularization at angiography and the clinical outcome 3 months after the last treatment. Further follow-up was evaluated based on further clinical outcome. Adverse events were recorded according to the Society of Interventional Radiology classification. Results Of the 34 patients with early-stage AVM, 32 (mean age, 20.5 years; 24 female [75%]) completed the study. The results showed that 27 (84.4%, 95% confidence interval [CI]: 71.1, 97.7) patients were responsive to bleomycin injection, including nine (28.1%) with a complete response. Four (12.5%) patients showed no response, and one (3.1%) patient experienced worsening 3 months after the last treatment. During further follow-up (mean follow-up time, 20.7 months; range, 5-28 months), the outcome remained stable in 31 (96.9%) of the 32 patients. A major complication, anaphylactic shock, was observed in one (3.1%, 95% CI: 0, 9.5) patient. Common minor complications included hyperpigmentation, nausea, pruritus, and bullae. Conclusion Intralesional interstitial bleomycin injection is a feasible approach for early-stage AVMs and yields safe and effective outcomes. © RSNA, 2017.

Comparison of Percentage of Syllables Stuttered With Parent-Reported Severity Ratings as a Primary Outcome Measure in Clinical Trials of Early Stuttering Treatment.

PubMed

Onslow, Mark; Jones, Mark; O'Brian, Sue; Packman, Ann; Menzies, Ross; Lowe, Robyn; Arnott, Simone; Bridgman, Kate; de Sonneville, Caroline; Franken, Marie-Christine

2018-04-17

This report investigates whether parent-reported stuttering severity ratings (SRs) provide similar estimates of effect size as percentage of syllables stuttered (%SS) for randomized trials of early stuttering treatment with preschool children. Data sets from 3 randomized controlled trials of an early stuttering intervention were selected for analyses. Analyses included median changes and 95% confidence intervals per treatment group, Bland-Altman plots, analysis of covariance, and Spearman rho correlations. Both SRs and %SS showed large effect sizes from pretreatment to follow-up, although correlations between the 2 measures were moderate at best. Absolute agreement between the 2 measures improved as percentage reduction of stuttering frequency and severity increased, probably due to innate measurement limitations for participants with low baseline severity. Analysis of covariance for the 3 trials showed consistent results. There is no statistical reason to favor %SS over parent-reported stuttering SRs as primary outcomes for clinical trials of early stuttering treatment. However, there are logistical reasons to favor parent-reported stuttering SRs. We conclude that parent-reported rating of the child's typical stuttering severity for the week or month prior to each assessment is a justifiable alternative to %SS as a primary outcome measure in clinical trials of early stuttering treatment.

A new early cognitive screening measure to detect cognitive side-effects of electroconvulsive therapy?

PubMed

Martin, Donel M; Katalinic, Natalie; Ingram, Anna; Schweitzer, Isaac; Smith, Deidre J; Hadzi-Pavlovic, Dusan; Loo, Colleen K

2013-12-01

Cognitive side-effects from electroconvulsive therapy (ECT) can be distressing for patients and early detection may have an important role in guiding treatment decisions over the ECT course. This prospective study examined the utility of an early cognitive screening battery for predicting cognitive side-effects which develop later in the ECT course. The screening battery, together with the Mini Mental Status Examination (MMSE), was administered to 123 patients at baseline and after 3 ECT treatments. A more detailed cognitive battery was administered at baseline, after six treatments (post ECT 6) and after the last ECT treatment (post treatment) to assess cognitive side-effects across several domains: global cognition, anterograde memory, executive function, speed and concentration, and retrograde memory. Multivariate analyses examined the predictive utility of change on items from the screening battery for later cognitive changes at post ECT 6 and post treatment. Results showed that changes on a combination of items from the screening battery were predictive of later cognitive changes at post treatment, particularly for anterograde memory (p < 0.01), after controlling for patient and treatment factors. Change on the MMSE predicted cognitive changes at post ECT 6 but not at post treatment. A scoring method for the new screening battery was tested for discriminative ability in a sub-sample of patients. This study provides preliminary evidence that a simple and easy-to-administer measure may potentially be used to help guide clinical treatment decisions to optimise efficacy and cognitive outcomes. Further development of this measure and validation in a more representative ECT clinical population is required. Copyright © 2013 Elsevier Ltd. All rights reserved.

Functional Recovery in Major Depressive Disorder: Providing Early Optimal Treatment for the Individual Patient

PubMed Central

Katzman, Martin A; Habert, Jeffrey; McIntosh, Diane; MacQueen, Glenda M; Milev, Roumen V; McIntyre, Roger S; Blier, Pierre

2018-01-01

Abstract Major depressive disorder is an often chronic and recurring illness. Left untreated, major depressive disorder may result in progressive alterations in brain morphometry and circuit function. Recent findings, however, suggest that pharmacotherapy may halt and possibly reverse those effects. These findings, together with evidence that a delay in treatment is associated with poorer clinical outcomes, underscore the urgency of rapidly treating depression to full recovery. Early optimized treatment, using measurement-based care and customizing treatment to the individual patient, may afford the best possible outcomes for each patient. The aim of this article is to present recommendations for using a patient-centered approach to rapidly provide optimal pharmacological treatment to patients with major depressive disorder. Offering major depressive disorder treatment determined by individual patient characteristics (e.g., predominant symptoms, medical history, comorbidities), patient preferences and expectations, and, critically, their own definition of wellness provides the best opportunity for full functional recovery. PMID:29024974

Functional Recovery in Major Depressive Disorder: Providing Early Optimal Treatment for the Individual Patient.

PubMed

Oluboka, Oloruntoba J; Katzman, Martin A; Habert, Jeffrey; McIntosh, Diane; MacQueen, Glenda M; Milev, Roumen V; McIntyre, Roger S; Blier, Pierre

2018-02-01

Major depressive disorder is an often chronic and recurring illness. Left untreated, major depressive disorder may result in progressive alterations in brain morphometry and circuit function. Recent findings, however, suggest that pharmacotherapy may halt and possibly reverse those effects. These findings, together with evidence that a delay in treatment is associated with poorer clinical outcomes, underscore the urgency of rapidly treating depression to full recovery. Early optimized treatment, using measurement-based care and customizing treatment to the individual patient, may afford the best possible outcomes for each patient. The aim of this article is to present recommendations for using a patient-centered approach to rapidly provide optimal pharmacological treatment to patients with major depressive disorder. Offering major depressive disorder treatment determined by individual patient characteristics (e.g., predominant symptoms, medical history, comorbidities), patient preferences and expectations, and, critically, their own definition of wellness provides the best opportunity for full functional recovery. © The Author(s) 2017. Published by Oxford University Press on behalf of CINP.

Thin-plate spline analysis of treatment effects of rapid maxillary expansion and face mask therapy in early Class III malocclusions.

PubMed

Baccetti, T; Franchi, L; McNamara, J A

1999-06-01

An effective morphometric method (thin-plate spline analysis) was applied to evaluate shape changes in the craniofacial configuration of a sample of 23 children with Class III malocclusions in the early mixed dentition treated with rapid maxillary expansion and face mask therapy, and compared with a sample of 17 children with untreated Class III malocclusions. Significant treatment-induced changes involved both the maxilla and the mandible. Major deformations consisted of forward displacement of the maxillary complex from the pterygoid region and of anterior morphogenetic rotation of the mandible, due to a significant upward and forward direction of growth of the mandibular condyle. Significant differences in size changes due to reduced increments in mandibular dimensions were associated with significant shape changes in the treated group.

Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study.

PubMed

Ferrer, Ricard; Artigas, Antonio; Suarez, David; Palencia, Eduardo; Levy, Mitchell M; Arenzana, Angel; Pérez, Xose Luis; Sirvent, Josep-Maria

2009-11-01

Several Surviving Sepsis Campaign Guidelines recommendations are reevaluated. To analyze the effectiveness of treatments recommended in the sepsis guidelines. In a prospective observational study, we studied all adult patients with severe sepsis from 77 intensive care units. We recorded compliance with four therapeutic goals (central venous pressure 8 mm Hg or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, central venous oxygen saturation 70% or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, blood glucose greater than or equal to the lower limit of normal but less than 150 mg/dl, and inspiratory plateau pressure less than 30 cm H(2)O for mechanically ventilated patients) and four treatments (early broad-spectrum antibiotics, fluid challenge in the event of hypotension and/or lactate greater than 36 mg/dl, low-dose steroids for septic shock, drotrecogin alfa [activated] for multiorgan failure). The primary outcome measure was hospital mortality. The effectiveness of each treatment was estimated using propensity scores. Of 2,796 patients, 41.6% died before hospital discharge. Treatments associated with lower hospital mortality were early broad-spectrum antibiotic treatment (treatment within 1 hour vs. no treatment within first 6 hours of diagnosis; odds ratio, 0.67; 95% confidence interval, 0.50-0.90; P = 0.008) and drotrecogin alfa (activated) (odds ratio, 0.59; 95% confidence interval, 0.41-0.84; P = 0.004). Fluid challenge and low-dose steroids showed no benefits. In severe sepsis, early administration of broad-spectrum antibiotics in all patients and administration of drotrecogin alfa (activated) in the most severe patients reduce mortality.

Predictors of Positive Treatment Outcome in People With Anorexia Nervosa Treated in a Specialized Inpatient Unit: The Role of Early Response to Treatment.

PubMed

Wales, Jackie; Brewin, Nicola; Cashmore, Rebecca; Haycraft, Emma; Baggott, Jonathan; Cooper, Amy; Arcelus, Jon

2016-09-01

To investigate factors which predict positive treatment outcome in inpatients with anorexia nervosa (AN), particularly the role of early treatment response. 102 patients entering specialist inpatient treatment were assessed for eating disorder history, psychopathology, and motivation to change. Predictive factors assessed were: early treatment response defined as weight increase of at least 0.5-1 kg/week during the first 6 weeks of treatment (n=87), admission body mass index (BMI), onset age, chronicity, motivation to change, diagnosis, and previous hospitalization for AN. Positive treatment outcome was defined as achieving a BMI of 17.5 kg/m(2) within an individual time frame. Logistic regression indicated that patients were 18 times more likely to reach positive treatment outcome if they met the National Institute for Health and Care Excellence weight guidelines within the first 6 weeks of hospitalization. Higher admission BMI was also found to predict positive treatment outcome. Higher entry BMI and early weight gain predict positive treatment outcome in individuals receiving specialist AN inpatient treatment. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Cost-effectiveness of neurostimulation in Parkinson's disease with early motor complications.

PubMed

Dams, Judith; Balzer-Geldsetzer, Monika; Siebert, Uwe; Deuschl, Günther; Schuepbach, W M Michael; Krack, Paul; Timmermann, Lars; Schnitzler, Alfons; Reese, Jens-Peter; Dodel, Richard

2016-08-01

Recent research efforts have focused on the effects of deep brain stimulation of the subthalamic nucleus (STN DBS) for selected patients with mild-to-moderate PD experiencing motor complications. We assessed the cost utility of subthalamic DBS compared with the best medical treatment for German patients below the age of 61 with early motor complications of PD. We applied a previously published Markov model that integrated health utilities based on EuroQoL and direct costs over patients' lifetime adjusted to the German health care payer perspective (year of costing: 2013). Effectiveness was evaluated using the Parkinson's Disease Questionnaire 39 summary index. We performed sensitivity analyses to assess uncertainty. In the base-case analysis, the incremental cost-utility ratio for STN DBS compared to best medical treatment was 22,700 Euros per quality-adjusted life year gained. The time to, and costs for, battery exchange had a major effect on the incremental cost-utility ratios, but never exceeded a threshold of 50,000 Euros per quality-adjusted life year. Our decision analysis supports the fact that STN DBS at earlier stages of the disease is cost-effective in patients below the age of 61 when compared with the best medical treatment in the German health care system. This finding was supported by detailed sensitivity analyses reporting robust results. Whereas the EARLYSTIM study has shown STN DBS to be superior to medical therapy with respect to quality of life for patients with early motor complications, this further analysis has shown its cost-effectiveness. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

In vitro early changes in intercellular junctions by treatment with a chemical carcinogen.

PubMed

Tachikawa, T; Kohno, Y; Matsui, Y; Yoshiki, S

1986-06-01

To examine early intercellular junction changes caused by treatment with 9,10-dimethyl-1,2-benzanthracene (DMBA), rat lingual epithelium was cultivated in isolation and observed by electrophysiological, freeze-fracture and whole-mount electron microscopy. Electrophysiological measurements showed a transient decrease in membrane potential of -10.2 mV 6 h after the treatment. It returned to almost the same level as that of the control group 1 day later. Six hours after treatment, input resistance decreased rapidly to 5.3 M omega but increased to 18.0 M omega 12 h after treatment. Transient reduction of input resistance and membrane potential occurred prior to the decrease in the coupling ratio 6 h after treatment with DMBA. In freeze-fracture replicas, the number of gap junctions decreased by approximately 45% of the control value 6 h after treatment with DMBA. At 12 h and thereafter, the number and area of gap junctions subsequently decreased by 60-80% of the control value. Alterations in the number and area of desmosomes were similar to those of the gap junctions. The formation of epithelial cytoskeletons, partially devoid of the 2-4 and 5-8 nm filaments was also observed. A decrease in the density of filament networks beneath the plasma membranes was especially apparent. Treatment with a carcinogen brought about morphological cellular changes as early as 6 h after treatment, and such early changes might trigger metabolic cellular abnormalities. Affected cells appear to move away from normal cells in a process of repeated destruction and revision of intercellular junctions, and cytoskeletons.

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh

2016-01-01

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed themore » dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and

δ opioid receptor antagonist, ICI 174,864, is suitable for the early treatment of uncontrolled hemorrhagic shock in rats.

PubMed

Liu, Liangming; Tian, Kunlun; Zhu, Yu; Ding, Xiaoli; Li, Tao

2013-08-01

Fluid resuscitation is the essential step for early treatment of traumatic hemorrhagic shock. However, its implementation is greatly limited before hospital or during evacuation. The authors investigated whether δ opioid receptor antagonist ICI 174,864 was suitable for the early treatment of traumatic hemorrhagic shock. With uncontrolled hemorrhagic-shock rats, the antishock effects of six dosages of ICI 174,864 (0.1, 0.3, 0.5, 1, 3, and 5 mg/kg) infused with or without a small volume of lactated Ringer's solution (LR) before bleeding controlled or bleeding cessation at different times were observed. ICI 174,864 (0.1-3 mg/kg) with or without 1/4 volume of LR infusion showed dose-dependent increase in the mean arterial blood pressure, and significantly prolonged the survival time and 8-h survival rate, as compared with ICI 174,864 plus 1/2 volume of LR infusion. The best effect was shown with 3 mg/kg of ICI 174,864. Bleeding cessation at 1, 2, or 3 h during infusion of ICI 174,864 (3 mg/kg) plus 1/4 volume of LR improved subsequent treatment (70% 24-h survival rate vs. 50 and 10% 24-h survival rate in hypotensive resuscitation and LR group, respectively). There was significant improvement in hemodynamic parameters, oxygen delivery, and tissue perfusion of hemorrhagic-shock rats with 3 mg/kg of ICI 174,864 plus 1/4 volume of LR infusion. δ Opioid receptor antagonist ICI 174,864 alone or with small volume of fluid infusion has good beneficial effect on uncontrolled hemorrhagic shock. Its early application can "buy" time for subsequent treatment of traumatic shock.

The effect of hyperbaric oxygen treatment on early regeneration of sensory axons after nerve crush in the rat.

PubMed

Bajrović, Fajko F; Sketelj, Janez; Jug, Marko; Gril, Iztok; Mekjavić, Igor B

2002-09-01

Abstract The effect of hyperbaric oxygen treatment (HBO) on sensory axon regeneration was examined in the rat. The sciatic nerve was crushed in both legs. In addition, the distal stump of the sural nerve on one side was made acellular and its blood perfusion was compromised by freezing and thawing. Two experimental groups received hyperbaric exposures (2.5 ATA) to either compressed air (pO2 = 0.5 ATA) or 100% oxygen (pO2 = 2.5 ATA) 90 minutes per day for 6 days. Sensory axon regeneration in the sural nerve was thereafter assessed by the nerve pinch test and immunohistochemical reaction to neurofilament. HBO treatment increased the distances reached by the fastest regenerating sensory axons by about 15% in the distal nerve segments with preserved and with compromised blood perfusion. There was no significant difference between the rats treated with different oxygen tensions. The total number of regenerated axons in the distal sural nerve segments after a simple crush injury was not affected, whereas in the nerve segments with compromised blood perfusion treated by the higher pO2, the axon number was about 30% lower than that in the control group. It is concluded that the beneficial effect of HBO on sensory axon regeneration is not dose-dependent between 0.5 and 2.5 ATA pO2. Although the exposure to 2.5 ATA of pO2 moderately enhanced early regeneration of the fastest sensory axons, it decreased the number of regenerating axons in the injured nerves with compromised blood perfusion of the distal nerve stump.

Anti-early pregnancy by PDT

NASA Astrophysics Data System (ADS)

Ding, Ai-Hua; Chen, Hui-Ling

1993-03-01

The effect of laser on anti-early pregnancy in rabbits showed that laser in combination with HPD could induce necrosis of blastocysts and complete absorption. The anti-fertility efficiency of the combined treatment was more effective than that of the He-Ne laser or the HPD treatment alone. The fluorescence spectrum of HPD determined by PNQ3 showed that its affinity to embryonic tissue was about 4 times greater than that to uterine tissue. This may underlie the mechanisms of anti-early pregnancy of the laser. The operation of artificial abortion is a routine method to terminate early pregnancy. Though it is simple and easy, its syndrome and complications can not be absolutely avoided. Many antifertility drugs have been reported, however, they often bring in general reaction. Our present work is to explore a new way of anti-early pregnancy in rabbits by means of the light inhibitory and light sensitive effects of laser. It is a quite safe and painless treatment without expanding and scraping of the uterus.

Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jonasson, Sofia, E-mail: sofia.jonasson@foi.se; Wigenstam, Elisabeth; Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå

Chlorine (Cl{sub 2}) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl{sub 2}-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200 ppm Cl{sub 2} during 15 min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24 h or 14 days post-exposure. A single dose of themore » corticosteroid dexamethasone (10 or 100 mg/kg) was administered intraperitoneally 1, 3, 6, or 12 h following Cl{sub 2} exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6 h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1 h was dose-dependent; high-dose significantly reduced acute airway inflammation (100 mg/kg) but not treatment with the relatively low-dose (10 mg/kg). Both doses reduced AHR 14 days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl{sub 2} exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl{sub 2} exposure. - Highlights: • Inhalation of Cl{sub 2} may lead to a long-standing airway hyperresponsiveness. • The symptoms in Cl{sub 2}-exposed mice are similar to those described for RADS in humans. • Corticosteroids prevent delayed symptoms such as

Factors associated with current and severe physical side-effects after prostate cancer treatment: What men report.

PubMed

Steentjes, L; Siesling, S; Drummond, F J; van Manen, J G; Sharp, L; Gavin, A

2018-01-01

We identified patient and disease characteristics associated with (1) "current" physical side-effects of any severity; and (2) "severe" physical side-effects "ever" experienced by 3,348 (54%) prostate cancer (PCa) survivors in Ireland diagnosed 2-18 years previously. Postal questionnaires collected symptoms at diagnosis, post-biopsy complications, comorbidities, primary treatments and physical side-effects post-treatment (urinary incontinence, erectile dysfunction, libido loss, bowel problems, breast changes, hot flushes, and fatigue, "ever" and "current" at time of questionnaire completion). Men were grouped by "early" (localised) and "late" (locally advanced/advanced) disease at diagnosis. Multivariable logistic regression analysis identified patient and disease-related factors associated with post-treatment side-effects. Complications post-biopsy were associated with higher risk of "current" libido loss and impotence. Radical prostatectomy was associated with higher risk of "current" and "severe" incontinence, libido loss and impotence in both early and late disease. In early disease, brachytherapy was associated with lower risk of "current" fatigue and "severe" impotence. Comorbidities were associated with higher risk of "current" experience of four side-effects (incontinence, libido loss, bowel problems, fatigue). Men on active surveillance/watchful-waiting reported lower risk of sexual dysfunction. These findings could inform development of tailored information on side-effects, which, in turn, could inform treatment decision-making and post-treatment monitoring. © 2016 John Wiley & Sons Ltd.

Early weight gain predicts outcome in two treatments for adolescent anorexia nervosa.

PubMed

Le Grange, Daniel; Accurso, Erin C; Lock, James; Agras, Stewart; Bryson, Susan W

2014-03-01

Determine whether early weight gain predicts full remission at end-of-treatment (EOT) and follow-up in two different treatments for adolescent anorexia nervosa (AN), and to track the rate of weight gain throughout treatment and follow-up. Participants were 121 adolescents with AN (mean age = 14.4 years, SD = 1.6), from a two-site (Chicago and Stanford) randomized controlled trial. Adolescents were randomly assigned to family-based treatment (FBT) (n = 61) or individual adolescent focused therapy (AFT) (n = 60). Treatment response was assessed using percent of expected body weight (EBW) and the global score on the Eating Disorder Examination (EDE). Full remission was defined as having achieved ≥95% EBW and within one standard deviation of the community norms of the EDE. Full remission was assessed at EOT as well as 12-month follow-up. Receiver operating characteristic analyses showed that the earliest predictor of remission at EOT was a gain of 5.8 pounds (2.65 kg) by session 3 in FBT (area under the curve (AUC) = 0.670; p = .043), and a gain of 7.1 pounds (3.20 kg) by session 4 in AFT (AUC = 0.754, p = .014). Early weight gain did not predict remission at follow-up for either treatment. A survival analysis showed that weight was marginally superior in FBT as opposed to AFT (Wald chi-square = 3.692, df = 1, p = .055). Adolescents with AN who receive either FBT or AFT, and show early weight gain, are likely to remit at EOT. However, FBT is superior to AFT in terms of weight gain throughout treatment and follow-up. Copyright © 2013 Wiley Periodicals, Inc.

The role of the early therapeutic alliance in predicting drug treatment dropout.

PubMed

Meier, Petra S; Donmall, Michael C; McElduff, Patrick; Barrowclough, Christine; Heller, Richard F

2006-06-09

To investigate the role of the therapeutic alliance in predicting length of retention in residential drug treatment. The study recruited 187 clients starting residential rehabilitation treatment for drug misuse in three UK services. Counsellor and client information was assessed at intake, and the average total scores of client and counsellor ratings on the WAI-S (obtained during weeks 1-3) were use as the alliance measure. Length of retention and treatment completion (stay beyond 90 days) were used as measures of retention. Clients with weak counsellor rated alliances dropped out of treatment significantly sooner than clients with strong counsellor rated therapeutic alliances, whether or not the model adjusted for individual counsellor effects and potential confounders including psychological well-being, treatment motivation and readiness, coping strategies, and attachment style. The client rated alliance did not predict length of retention. Apart from the alliance, pre-treatment crack use, secure attachment style and better coping strategies were associated with shorter retention, whereas greater confidence in treatment, older client age and better education predicted treatment completion. Counsellors with greater experience of delivering drug counselling retained clients longer. The findings of this study stress the importance of treatment professionals attending to the therapeutic alliance in drug treatment, as counsellors' alliance ratings were found to be amongst the strongest predictors of dropout. Using alliance measures as clinical tools may help treatment practitioners to become aware of the risk of disengagement early on. Prospective studies are needed to evaluate whether strategies of reallocating clients with poor alliances to different counsellors lead to improvements in retention.

Relationship between plasma concentrations of lamotrigine and its early therapeutic effect of lamotrigine augmentation therapy in treatment-resistant depressive disorder.

PubMed

Kagawa, Shoko; Mihara, Kazuo; Nakamura, Akifumi; Nemoto, Kenji; Suzuki, Takeshi; Nagai, Goyo; Kondo, Tsuyoshi

2014-12-01

The relationship between plasma concentrations of lamotrigine and its therapeutic effects was prospectively studied on 34 (9 men and 25 women) inpatients with treatment-resistant depressive disorder during an 8-week treatment of lamotrigine augmentation using an open-study design. The subjects were depressed patients who had already shown insufficient response to at least 3 psychotropics, including antidepressants, mood stabilizers, and atypical antipsychotics. The diagnoses were major depressive disorder (n = 12), bipolar I disorder (n = 7), and bipolar II disorder (n = 15). The final doses of lamotrigine were 100 mg/d for 18 subjects who were not taking valproate and 75 mg/d for 16 subjects taking valproate. Depressive symptoms were evaluated by the Montgomery Åsberg Depression Rating Scale (MADRS) before and after the 8-week treatment. Blood sampling was performed at week 8. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography. There was a significant linear relationship between the plasma concentrations of lamotrigine and percentage improvements at week 8 (r = 0.418, P < 0.05). A stepwise multiple regression analysis showed that plasma lamotrigine concentrations alone had a significant effect on the percentage improvements at week 8 (standardized partial correlation coefficients = 0.454, P < 0.001). The receiver operating characteristics analysis indicated that a plasma lamotrigine concentration of 12.7 μmol/L or greater was significantly (P < 0.001) predictive of response (50% or more reduction in the MADRS score). The proportion of the responders was significantly higher in the groups with a lamotrigine concentration >12.7 μmol/L (11/15 versus 4/19, P < 0.01). The present study suggests that an early therapeutic response to lamotrigine is dependent on its plasma concentration and that a plasma lamotrigine concentration of 12.7 μmol/L may be a threshold for a good therapeutic response in treatment

Early-life antibiotic treatment enhances the pathogenicity of CD4+ T cells during intestinal inflammation.

PubMed

Scheer, Sebastian; Medina, Tiago S; Murison, Alex; Taves, Matthew D; Antignano, Frann; Chenery, Alistair; Soma, Kiran K; Perona-Wright, Georgia; Lupien, Mathieu; Arrowsmith, Cheryl H; De Carvalho, Daniel D; Zaph, Colby

2017-04-01

The incidence of inflammatory bowel diseases (IBDs) has steadily increased in recent decades-a phenomenon that cannot be explained by genetic mutations alone. Other factors, including the composition of the intestinal microbiome, are potentially important contributors to the increased occurrence of this group of diseases. Previous reports have shown a correlation between early-life antibiotic (Abx) treatment and an increased incidence of IBD. In this report, we investigated the effects of early-life Abx treatments on the pathogenicity of CD4 + T cells using an experimental T cell transfer model of IBD. Our results show that CD4 + T cells isolated from adult mice that had been treated with Abx during gestation and in early life induced a faster onset of IBD in Rag1 -deficient mice compared with CD4 + T cells of untreated mice. Ex vivo functional analyses of IBD-inducing CD4 + T cells did not show significant differences in their immunologic potential ex vivo, despite their in vivo phenotype. However, genome-wide gene-expression analysis revealed that these cells displayed dysregulated expression of genes associated with cell-cycle regulation, metabolism, and cellular stress. Analysis of Abx-treated CD4 + T cell donors showed systemically elevated levels of the stress hormone corticosterone throughout life compared with untreated donors. The cohousing of Abx-treated mice with untreated mice decreased serum corticosterone, and a consequent transfer of the cells from cohoused mice into Rag1 -deficient mice restored the onset and severity of disease to that of untreated animals. Thus, our results suggest that early-life Abx treatment results in a stress response with high levels of corticosterone that influences CD4 + T cell function. © Society for Leukocyte Biology.

Photodynamic therapy (PDT) utilizing PhotofrinR for treatment of early esophageal cancer

NASA Astrophysics Data System (ADS)

Overholt, Bergein F.; Panjehpour, Masoud; Teffeteller, Elmeria; Rose, S. Mark

1993-06-01

Four lesions of early carcinoma of the esophagus found during endoscopic biopsies in three patients were treated with photodynamic therapy. Follow-up biopsies over 9 - 24 months remain negative for carcinoma. Endoscopic ultrasonography is essential for proper staging and treatment planning for these patients. Photodynamic therapy may provide an alternative to surgical resection for early esophageal carcinoma or severe dysplasia in Barrett's esophagus.

Early treatment improves urodynamic prognosis in neurogenic voiding dysfunction: 20 years of experience.

PubMed

Costa Monteiro, Lucia M; Cruz, Glaura O; Fontes, Juliana M; Vieira, Eliane T R C; Santos, Eloá N; Araújo, Grace F; Ramos, Eloane G

To evaluate the association between early treatment and urodynamic improvement in pediatric and adolescent patients with neurogenic bladder. Retrospective longitudinal and observational study (between 1990 and 2013) including patients with neurogenic bladder and myelomeningocele treated based on urodynamic results. The authors evaluated the urodynamic follow-up (bladder compliance and maximum bladder capacity and pressure) considering the first urodynamic improvement in two years as the outcome variable and early referral as the exposure variable, using a descriptive and multivariate analysis with logistic regression model. Among 230 patients included, 52% had an early referral. The majority were diagnosed as overactive bladder with high bladder pressure (≥40cm H 2 O) and low bladder compliance (3mL/cmH 2 O) and were treated with oxybutynin and intermittent catheterization. Urodynamic follow-up results showed 68% of improvement at the second urodynamic examination decreasing bladder pressure and increasing bladder capacity and compliance. The percentage of incontinence and urinary tract infections decreased over treatment. Early referral (one-year old or less) increased by 3.5 the probability of urodynamic improvement in two years (95% CI: 1.81-6.77). Treatment onset within the first year of life improves urodynamic prognosis in patients with neurogenic bladder and triplicates the probability of urodynamic improvement in two years. The role of neonatologists and pediatricians in early referral is extremely important. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Cost-effectiveness of early versus delayed functional restoration for chronic disabling occupational musculoskeletal disorders.

PubMed

Theodore, Brian R; Mayer, Tom G; Gatchel, Robert J

2015-06-01

Despite extensive evidence for the treatment effectiveness of interdisciplinary functional restoration (FR) for chronic disabling occupational musculoskeletal disorders (CDOMD), there is little documentation on the cost-effectiveness of early rehabilitation using FR. A total of 1,119 CDOMD patients were classified according to duration of disability on FR entry, corresponding to early rehabilitation (ER: 4-8 months of disability, N = 373), intermediate duration (ID: 9-18 months, N = 373), and delayed rehabilitation (DR: >18 months, N = 373). Groups were matched on sex, age, ethnicity, and injured musculoskeletal region. One-year post-rehabilitation outcomes included return-to-work, work retention and healthcare utilization. Economic analyses included a cost-effectiveness analysis of the FR program, and estimation of the total cost-of-illness. At 1-year post-rehabilitation, all groups were comparable on return-to-work (overall 88%), work retention (overall 80%), and additional healthcare utilization (overall, 2.2% of patients received re-operations/new surgeries, 2 visits to new healthcare provider). Savings of up to 64% in medical costs, and up to 80% in disability benefits and productivity losses was associated with the ER group. The cost of rehabilitation was also up to 56% lower when administered early. Overall, ER resulted in estimated cost savings of up to 72% (or almost $170,000 per claim). Duration of disability does not negatively impact objective work or healthcare utilization outcomes following interdisciplinary FR. However, early rehabilitation is more likely to be a cost-effective solution compared to cases that progress >8 months and receiving FR as a treatment of "last resort".

Effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma (EAGLE): a randomised controlled trial.

PubMed

Azuara-Blanco, Augusto; Burr, Jennifer; Ramsay, Craig; Cooper, David; Foster, Paul J; Friedman, David S; Scotland, Graham; Javanbakht, Mehdi; Cochrane, Claire; Norrie, John

2016-10-01

Primary angle-closure glaucoma is a leading cause of irreversible blindness worldwide. In early-stage disease, intraocular pressure is raised without visual loss. Because the crystalline lens has a major mechanistic role, lens extraction might be a useful initial treatment. From Jan 8, 2009, to Dec 28, 2011, we enrolled patients from 30 hospital eye services in five countries. Randomisation was done by a web-based application. Patients were assigned to undergo clear-lens extraction or receive standard care with laser peripheral iridotomy and topical medical treatment. Eligible patients were aged 50 years or older, did not have cataracts, and had newly diagnosed primary angle closure with intraocular pressure 30 mm Hg or greater or primary angle-closure glaucoma. The co-primary endpoints were patient-reported health status, intraocular pressure, and incremental cost-effectiveness ratio per quality-adjusted life-year gained 36 months after treatment. Analysis was by intention to treat. This study is registered, number ISRCTN44464607. Of 419 participants enrolled, 155 had primary angle closure and 263 primary angle-closure glaucoma. 208 were assigned to clear-lens extraction and 211 to standard care, of whom 351 (84%) had complete data on health status and 366 (87%) on intraocular pressure. The mean health status score (0·87 [SD 0·12]), assessed with the European Quality of Life-5 Dimensions questionnaire, was 0·052 higher (95% CI 0·015-0·088, p=0·005) and mean intraocular pressure (16·6 [SD 3·5] mm Hg) 1·18 mm Hg lower (95% CI -1·99 to -0·38, p=0·004) after clear-lens extraction than after standard care. The incremental cost-effectiveness ratio was £14 284 for initial lens extraction versus standard care. Irreversible loss of vision occurred in one participant who underwent clear-lens extraction and three who received standard care. No patients had serious adverse events. Clear-lens extraction showed greater efficacy and was more cost-effective than

Effects of Early Chemotherapeutic Treatment on Learning in Adolescent Mice: Implications for Cognitive Impairment and Remediation in Childhood Cancer Survivors

PubMed Central

Bisen-Hersh, Emily B.; Hineline, Philip N.; Walker, Ellen A.

2013-01-01

Purpose Among children diagnosed with acute lymphoblastic leukemia (ALL) and given chemotherapy-only treatment, 40-70% of survivors experience neurocognitive impairment. The present study used a preclinical mouse model to investigate the effects of early exposure to common ALL chemotherapeutics methotrexate (MTX) and cytarabine (Ara-C) on learning and memory. Experimental Design Pre-weanling mouse pups were treated on postnatal day (PND) 14, 15, and 16 with saline, MTX, Ara-C, or a combination of MTX and Ara-C. Nineteen days following treatment (PND 35), behavioral tasks measuring different aspects of learning and memory were administered. Results Significant impairment in acquisition and retention over both short (1h) and long (24h) intervals, as measured by autoshaping and novel object recognition tasks, were found following treatment with MTX and Ara-C. Similarly, a novel conditional discrimination task revealed impairment in acquisition for chemotherapy-treated mice. No significant group differences were found following the extensive training component of this task, with impairment following the rapid training component occurring only for the highest MTX and Ara-C combination group. Conclusions Findings are consistent with clinical studies suggesting that childhood cancer survivors are slower at learning new information and primarily exhibit deficits in memory years after successful completion of chemotherapy treatment. The occurrence of mild deficits on a novel conditional discrimination task suggests that chemotherapy-induced cognitive impairment may be ameliorated through extensive training or practice. PMID:23596103

Effects of seawater acidification on the early development of sea urchin Glyptocidaris crenularis

NASA Astrophysics Data System (ADS)

Zhan, Yaoyao; Hu, Wanbin; Duan, Lizhu; Liu, Minbo; Zhang, Weijie; Chang, Yaqing; Li, Cong

2017-10-01

In this study, we evaluated the effects of CO2-induced seawater acidification on fertilization, embryogenesis and early larval development in the sea urchin Glyptocidaris crenularis, that inhabits subtidal coastal areas in northern China. The range in seawater pH used in experiments was based on the projections of the Intergovernmental Panel on Climate Change (IPCC), to the year 2100. A natural seawater treatment (pHnbs=7.98±0.03) and three laboratory-controlled acidified treatments (OA1, ΔpHnbs=-0.3 units; OA2, ΔpHnbs=-0.4 units; OA3, ΔpHnbs=-0.5 units) were used in experiments. Results show that: (1) there was a negative effect of seawater acidification on fertilization and on the percentage of abnormal fertilized eggs; (2) the size of early cleavage stage embryos decreased in a dose-dependent manner with decreasing pH; (3) both the hatching rate of blastulae and the survival rate of four-armed pluteus larvae decreased as pH declined; (4) larval abnormalities including asymmetrical development, changes in the length of skeletal elements, and corroded spicules were observed in all seawater acidified-treatments compared with the control. These data indicate that seawater acidification has a negative impact on the early development of G. crenularis, and supports the hypothesis that the response of echinoderms to ocean acidification (OA) varies among species. Further research is required to clarify the specific cellular mechanisms involved.

Early Intervention Services for Early-Phase Psychosis - Centre for integrative psychiatry in Psychiatric Hospital "Sveti Ivan", Croatia.

PubMed

Matić, Katarina; Gereš, Natko; Gerlach, Josefina; Prskalo-Čule, Diana; Zadravec Vrbanc, Tihana; Lovretić, Vanja; Librenjak, Dina; Vuk Pisk, Sandra; Ivezić, Ena; Šimunović Filipčić, Ivona; Jeleč, Vjekoslav; Filipčić, Igor

2018-06-01

There is a growing body of evidence suggesting that early and effective management in the critical early years of schizophrenia can improve long-term outcomes. The objective of this study was to evaluate time to relapse of the patients with early-phase psychosis treated in the Centre for integrative psychiatry (CIP). We performed a retrospective cohort study on the sample of 373 early-phase psychosis patients admitted to Psychiatric Hospital "Sveti Ivan", Zagreb Croatia: from January 1, 2015 to December 31, 2017. The primary outcome was time to relapse. Patients who were admitted to group psychotherapeutic program after the end of acute treatment had 70% lower hazard for relapse (HR=0.30; 95% CI 0.16-0.58). Patients who were included first in the psychotherapeutic program and then treated and controlled in the daily hospital had 74% lower hazard for relapse (HR=0.26; 95% CI 0.10-0.67). In early-phase psychosis, integrative early intervention service has relevant beneficial effects compare to treatment as usual. These results justified the implementation of multimodal early intervention services in treatment of patients with early-phase psychosis.

Early treatment of penile fractures: our experience.

PubMed

García Gómez, Borja; Romero, Javier; Villacampa, Felipe; Tejido, Angel; Díaz, Rafael

2012-09-01

To report our experience in early surgery of penile fractures. We review retrospectively all the cases that underwent surgery at our center from 1989 to 2009, with a total of 24. The cause of the fracture was sexual intercourse in most cases, and in all of them, surgical management was performed according to clinical presentation and physical exploration. In only 7 cases an ultrasound was performed as a complementary test. Early surgery allows prompt resolution of the problem with excellent functional outcomes and little side effects. The prognosis after emergency surgery was excellent in this review.

Predictors of premature termination from psychotherapy for anorexia nervosa: Low treatment credibility, early therapy alliance, and self-transcendence.

PubMed

Jordan, Jennifer; McIntosh, Virginia V W; Carter, Frances A; Joyce, Peter R; Frampton, Christopher M A; Luty, Suzanne E; McKenzie, Janice M; Carter, Janet D; Bulik, Cynthia M

2017-08-01

Failure to complete treatment for anorexia nervosa (AN) is- common, clinically concerning but difficult to predict. This study examines whether therapy-related factors (patient-rated pretreatment credibility and early therapeutic alliance) predict subsequent premature termination of treatment (PTT) alongside self-transcendence (a previously identified clinical predictor) in women with AN. 56 women aged 17-40 years participating in a randomized outpatient psychotherapy trial for AN. Treatment completion was defined as attending 15/20 planned sessions. Measures were the Treatment Credibility, Temperament and Character Inventory, Vanderbilt Therapeutic Alliance Scale and the Vanderbilt Psychotherapy Process Scale. Statistics were univariate tests, correlations, and logistic regression. Treatment credibility and certain early patient and therapist alliance/process subscales predicted PTT. Lower self-transcendence and lower early process accounted for 33% of the variance in predicting PTT. Routine assessment of treatment credibility and early process (comprehensively assessed from multiple perspectives) may help clinicians reduce PTT thereby enhancing treatment outcomes. © 2017 Wiley Periodicals, Inc.

A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

PubMed

Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

2014-09-01

Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids.

PubMed

L'Espérance, Sylvain; Bachvarova, Magdalena; Tetu, Bernard; Mes-Masson, Anne-Marie; Bachvarov, Dimcho

2008-02-26

Chemotherapy (CT) resistance in ovarian cancer (OC) is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155), following treatment with 10,0 microM cisplatin, 2,5 microM paclitaxel or 5,0 microM topotecan for 72 hours. Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism), signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes), cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular growth conditions that are known to alter gene

Effectiveness of a clinical practice intervention in early rheumatoid arthritis.

PubMed

Descalzo, Miguel Ángel; Carbonell, Jordi; González-Álvaro, Isidoro; Sanmartí, Raimon; Balsa, Alejandro; Hernandez-Barrera, Valentín; Román-Ivorra, José Andrés; Ivorra-Cortés, José; Lisbona, Pilar; Alperi, Mercedes; Jiménez-Garcia, Rodrigo; Carmona, Loreto

2012-03-01

To compare the outcome of early rheumatoid arthritis (RA) patients in a country where early clinics were established versus the outcome of patients in nonprotocolized clinics. We compared 2 multicenter cohorts: an RA cohort derived from an early arthritis registry set in 36 reference hospitals in which a specific intervention was established (Evaluation of a Model for Arthritis Care in Spain [SERAP]), and a historical control cohort of patients with early RA attending 34 rheumatology departments (Prognosis in Rheumatoid Arthritis [PROAR] cohort). Effectiveness was tested by comparing the change in the Disease Activity Score in 28 joints (DAS28), the change in the Health Assessment Questionnaire (HAQ), and the change in the Sharp/van der Heijde radiologic score using marginal structural models. A total of 161 early RA patients were recruited in the PROAR cohort and 447 in the SERAP cohort. Being a SERAP patient was inversely correlated with activity, resulting in a decrease of -0.24 (95% confidence interval [95% CI] -0.39, -0.08) units in the population average of the DAS28 after adjustment was made. Moreover, intervention may be seen as a protective factor of radiologic damage, with a decrease of -0.05 (95% CI -0.09, -0.01) units in the logarithm of the total Sharp/van der Heijde score. On the other hand, a decrease in functional impairment was detected, but intervention was not statistically associated with HAQ changes. Preventing major radiographic progression in a 2-year term inside structured and organized special programs for the management of disease, such as early arthritis clinics, are effective compared to nonprotocolized referrals, treatment, and followup. Copyright © 2012 by the American College of Rheumatology.

Early identification and treatment of communication and swallowing deficits in Parkinson disease.

PubMed

Ciucci, Michelle R; Grant, Laura M; Rajamanickam, Eunice S Paul; Hilby, Breanna L; Blue, Katherine V; Jones, Corinne A; Kelm-Nelson, Cynthia A

2013-08-01

Parkinson disease (PD) is a complex, progressive, neurodegenerative disorder that leads to a wide range of deficits including fine and gross sensorimotor impairment, autonomic dysfunction, mood disorders, and cognitive decline. Traditionally, the focus for diagnosis and treatment has been on sensorimotor impairment related to dopamine depletion. It is now widely recognized, however, that PD-related pathology affects multiple central nervous system neurotransmitters and pathways. Communication and swallowing functions can be impaired even in the early stages, significantly affecting health and quality of life. The purpose of this article is to review the literature on early intervention for communication and swallowing impairment in PD. Overarching themes were that (1) studies and interpretation of data from studies in early PD are limited; (2) best therapy practices have not been established, in part due to the heterogeneous nature of PD; and (3) as communication and swallowing problems are pervasive in PD, further treatment research is essential. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Early Identification and Treatment of Communication and Swallowing Deficits in Parkinson Disease

PubMed Central

Ciucci, Michelle R.; Grant, Laura M.; Paul Rajamanickam, Eunice S.; Hilby, Breanna L.; Blue, Katherine V.; Jones, Corinne A.; Kelm-Nelson, Cynthia A.

2015-01-01

Parkinson disease (PD) is a complex, progressive, neurodegenerative disorder that leads to a wide range of deficits including fine and gross sensorimotor impairment, autonomic dysfunction, mood disorders, and cognitive decline. Traditionally, the focus for diagnosis and treatment has been on sensorimotor impairment related to dopamine depletion. It is now widely recognized, however, that PD-related pathology affects multiple central nervous system neurotransmitters and pathways. Communication and swallowing functions can be impaired even in the early stages, significantly affecting health and quality of life. The purpose of this article is to review the literature on early intervention for communication and swallowing impairment in PD. Overarching themes were that (1) studies and interpretation of data from studies in early PD are limited; (2) best therapy practices have not been established, in part due to the heterogeneous nature of PD; and (3) as communication and swallowing problems are pervasive in PD, further treatment research is essential. PMID:24166192

Provider knowledge, attitudes and treatment preferences for early pregnancy failure

PubMed Central

Dalton, Vanessa K.; Harris, Lisa H.; Gold, Katherine J.; Kane-Low, Lisa; Schulkin, Jay; Guire, Ken; Fendrick, A. Mark

2010-01-01

Objective To describe health care provider knowledge, attitudes and treatment preferences for early pregnancy failure (EPF). Study Design We surveyed 976 obstetrician/gynecologists, midwives and family medicine practitioners on their knowledge and attitudes toward treatment options for EPF, and barriers to adopting misoprostol and office uterine evacuations. We used descriptive statistics to compare practices by provider specialty and logistic regression to identify associations between provider factors and treatment practices. Results Seventy percent of providers have not used misoprostol and 91% have not used an office uterine evacuation to treat EPF in the past 6 months. Beliefs about safety and patient preferences, and prior induced abortion training were significantly associated with use of both of these treatments. Conclusions Increasing education and training on the use of misoprostol and office uterine evacuation, and clarifying patient treatment preferences may increase the willingness of providers to adopt new practices for EPF treatment. PMID:20227674

[Operative treatment strategies for multiple trauma patients : early total care versus damage control].

PubMed

Klüter, T; Lippross, S; Oestern, S; Weuster, M; Seekamp, A

2013-09-01

The treatment of multiple trauma patients is a great challenge for an interdisciplinary team. After preclinical care and subsequent treatment in the emergency room the order of the interventions is prioritized depending of the individual risk stratification. For planning the surgery management it is essential to distinguish between absolutely essential operations to prevent life-threatening situations for the patient and interventions with shiftable indications, depending on the general condition of the patient. All interventions need to be done without causing significant secondary damage to prohibit hyperinflammation and systemic inflammatory response syndrome. The challenge consists in determination of the appropriate treatment at the right point in time. In general the early primary intervention, early total care, is differentiated from the damage control concept.

The effect of different treatments for early-lactation hyperketonemia on blood β-hydroxybutyrate, plasma nonesterified fatty acids, glucose, insulin, and glucagon in dairy cattle.

PubMed

Mann, S; Yepes, F A Leal; Behling-Kelly, E; McArt, J A A

2017-08-01

Despite increased efforts in preventing the occurrence of metabolic disorders in transition cows, hyperketonemia remains a frequent early-lactation metabolic disease affecting an average of 40% of cows in herds in the United States. Despite the demonstrated economic effect of this disorder, controlled clinical trials comparing different treatment strategies in affected cows are lacking. The objective of our study was to investigate the effect of treatment with intravenous glucose, oral propylene glycol, or a combination of both on the reduction in blood β-hydroxybutyrate (BHB) concentrations of early-lactation hyperketonemic dairy cows. Multiparous Holstein cows between 3 to 9 d in milk were screened for hyperketonemia using a handheld meter 3 times per week, and enrolled at whole blood BHB concentration ≥1.2 mmol/L to 1 of 4 treatment groups: (1) 500 mL of a 50% dextrose solution i.v. once daily for 3 d (GLU, n = 9), (2) 300 mL of propylene glycol as a drench once daily for 3 d (PG, n = 9), (3) a combination treatment of a 500 mL of 50% dextrose solution i.v. and 300 mL of propylene glycol orally once daily for 3 d (GLU+PG, n = 8), or (4) an untreated control group (CTRL, n = 8). Blood samples were collected immediately before as well as at 1, 2, 4, 8, 12, 24, 36, 48, 60, and 72 h after administration of the first treatment through a jugular catheter and 3 times per week thereafter from coccygeal vessels. Concentrations of BHB were measured in whole blood, and plasma samples were analyzed for glucose, fatty acid (NEFA), insulin, glucagon, and electrolyte concentrations. The EDTA-anticoagulated blood samples were assessed for red blood cell indices, and smears were made for evaluation of red blood cell morphology. Outcomes were analyzed using repeated measures analysis. Overall least squares means (95% CI) of whole blood BHB concentrations between 1 h and d 11 relative to first treatment were 1.11 (0.95 to 1.30), 1.26 (1.07 to 1.47), 0.96 (0.81 to 1.13), and 1

Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Dong Suk; Choi, Yoorim; Choi, Seong Mi

2015-11-27

Resveratrol is a sirtuin 1 (SIRT1) activator and can function as an anti-inflammatory and antioxidant factor. In mesenchymal stem cells (MSCs), resveratrol enhances the proliferation and differentiation potential and has an anti-aging effect. However, contradictory effects of resveratrol on MSC cultures have been reported. In this study, we found that resveratrol had different effects on MSC cultures according to their cell passage and SIRT1 expression. Resveratrol enhanced the self-renewal potential and multipotency of early passage MSCs, but accelerated cellular senescence of late passage MSCs. In early passage MSCs expressing SIRT1, resveratrol decreased ERK and GSK-3β phosphorylation, suppressing β-catenin activity. Inmore » contrast, in late passage MSCs, which did not express SIRT1, resveratrol increased ERK and GSK-3β phosphorylation, activating β-catenin. We confirmed that SIRT1-deficient early passage MSCs treated with resveratrol lost their self-renewal potential and multipotency, and became senescent due to increased β-catenin activity. Sustained treatment with resveratrol at early passages maintained the self-renewal potential and multipotency of MSCs up to passage 10. Our findings suggest that resveratrol can be effectively applied to early passage MSC cultures, whereas parameters such as cell passage and SIRT1 expression must be taken into consideration before applying resveratrol to late passage MSCs. - Highlights: • Resveratrol enhances self-renewal potential and multipotency of early passage MSCs. • Resveratrol accelerates the cellular senescence of late passage MSCs. • The effects of resveratrol on MSCs are dependent on the presence of SIRT1. • SIRT1 modulates ERK/GSK-3β/β-catenin signaling. • Sustained resveratrol treatment maintains MSC stemness up to P10.« less

[Use of magnetic therapy for treatment of early symptoms of vascular-type vibration syndrome in forestry workers].

PubMed

Karczewska, M

1996-01-01

The objective of the study was to evaluate the efficacy of the use of magnetic fields (ELF-MF) of therapeutic parameters in the treatment of early symptoms of vascular-type vibration syndrome in forestry workers. The study covered 96 forestry workers, and the control group was composed of 29 sawyers who underwent a simulated treatment. Each worker was granted sick leave and applied 20 procedures by employing an Aplhatron 4100 device under the ambulatory conditions. The outcome of the treatment was evaluated directly after the last procedure and 3 months later. A diversified positive influence on individual subjective and objective pathological changes in regard to both direct and late effects was observed. The abatement of subjective disorders right after termination of the treatment was observed in 67.7% and objective disorders in 57.3%. A long-term improvement (after 3 months) was found in a smaller proportion of persons as the abatement of subjective disorders was reported by 59.3% while objective disorders persisted in 43.7%. The results obtained prove that the application of variable magnetic fields (ELF-MF) of therapeutic parameters is useful in the prophylaxis and treatment of pathological changes during the period of prodromal symptoms and early pathological changes in vascular-type vibration syndrome induced by local magnetic vibrations.

Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant treatment with different epidermal growth factor receptor phenotypes.

PubMed

Wang, Tao; Liu, Yang; Zhou, Bin; Wang, Zhi; Liang, Naichao; Zhang, Yundong; Dong, Zhouhuan; Li, Jie

2016-01-01

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated efficacy in treating advanced non-small-cell lung cancer (NSCLC). Preliminary findings suggested that EGFR-TKIs might also be beneficial in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate the efficacy and safety of neoadjuvant therapy with icotinib in patients with early-stage NSCLC. We retrospectively reviewed the medical history of patients who were initially diagnosed with stage IA-IIIA NSCLC and were under icotinib administration before surgery between December 2011 and December 2014. Tumor assessment was conducted between the second and fourth week from initial icotinib treatment. The association between personal characteristics, smoking status, disease stage, EGFR mutation status, and clinical outcomes were investigated using multivariate logistic regression analysis. A total of 67 patients with NSCLC were reviewed, and approximately half (38/67) of them were identified as having EGFR-mutant tumors. The overall response rate of all patients was 26.7% at 2-4 weeks' assessment. Multivariate analysis showed that female sex (38.5% versus 10.7% in males, P=0.028) and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011) were independent predictive factors. The analysis also showed that the most common adverse effects were rash (43.3%) and dry skin (34.4%), which were tolerable. Icotinib induced clinical response with minimal toxicity as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR mutations. Further studies are warranted to confirm our findings.

Prognosis and response to laser treatment of early-onset hypertrophic port-wine stains (PWS).

PubMed

Passeron, Thierry; Salhi, Aicha; Mazer, Jean-Michel; Lavogiez, Céline; Mazereeuw-Hautier, Juliette; Galliot, Chrystèle; Collet-Villette, Anne-Marie; Labreze, Christine; Boon, Laurence; Hardy, Jean-Philippe; Fayard, Virginie; Livideanu, Cristina Bulai; Toubel, Gérard; Georgescou, Gabriela; Gral, Nathalie; Maza, Aude; Lacour, Jean-Philippe

2016-07-01

There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS). We sought to characterize patients with hypertrophic PWS presenting during childhood. Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded. A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS. As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation. PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Cost-effectiveness of early detection of breast cancer in Catalonia (Spain)

PubMed Central

2011-01-01

Background Breast cancer (BC) causes more deaths than any other cancer among women in Catalonia. Early detection has contributed to the observed decline in BC mortality. However, there is debate on the optimal screening strategy. We performed an economic evaluation of 20 screening strategies taking into account the cost over time of screening and subsequent medical costs, including diagnostic confirmation, initial treatment, follow-up and advanced care. Methods We used a probabilistic model to estimate the effect and costs over time of each scenario. The effect was measured as years of life (YL), quality-adjusted life years (QALY), and lives extended (LE). Costs of screening and treatment were obtained from the Early Detection Program and hospital databases of the IMAS-Hospital del Mar in Barcelona. The incremental cost-effectiveness ratio (ICER) was used to compare the relative costs and outcomes of different scenarios. Results Strategies that start at ages 40 or 45 and end at 69 predominate when the effect is measured as YL or QALYs. Biennial strategies 50-69, 45-69 or annual 45-69, 40-69 and 40-74 were selected as cost-effective for both effect measures (YL or QALYs). The ICER increases considerably when moving from biennial to annual scenarios. Moving from no screening to biennial 50-69 years represented an ICER of 4,469€ per QALY. Conclusions A reduced number of screening strategies have been selected for consideration by researchers, decision makers and policy planners. Mathematical models are useful to assess the impact and costs of BC screening in a specific geographical area. PMID:21605383

Effects of early developmental conditions on innate immunity are only evident under favourable adult conditions in zebra finches

NASA Astrophysics Data System (ADS)

de Coster, Greet; Verhulst, Simon; Koetsier, Egbert; de Neve, Liesbeth; Briga, Michael; Lens, Luc

2011-12-01

Long-term effects of unfavourable conditions during development can be expected to depend on the quality of the environment experienced by the same individuals during adulthood. Yet, in the majority of studies, long-term effects of early developmental conditions have been assessed under favourable adult conditions only. The immune system might be particularly vulnerable to early environmental conditions as its development, maintenance and use are thought to be energetically costly. Here, we studied the interactive effects of favourable and unfavourable conditions during nestling and adult stages on innate immunity (lysis and agglutination scores) of captive male and female zebra finches ( Taeniopygia guttata). Nestling environmental conditions were manipulated by a brood size experiment, while a foraging cost treatment was imposed on the same individuals during adulthood. This combined treatment showed that innate immunity of adult zebra finches is affected by their early developmental conditions and varies between both sexes. Lysis scores, but not agglutination scores, were higher in individuals raised in small broods and in males. However, these effects were only present in birds that experienced low foraging costs. This study shows that the quality of the adult environment may shape the long-term consequences of early developmental conditions on innate immunity, as long-term effects of nestling environment were only evident under favourable adult conditions.

Oral cancer. The importance of early diagnosis and treatment.

PubMed

Sciubba, J J

2001-01-01

Oral cancer is an important health issue. The WHO predicts a continuing worldwide increase in the number of patients with oral cancer, extending this trend well into the next several decades. In the US the projected number of new cases of oral and oropharyngeal cancer will exceed 31,000 per year. Mortality due to cancers in this region exceeds the annual death rate is the US caused by either cutaneous melanoma or cervical cancer. Significant agents involved in the etiology of oral cancer in Western countries include sunlight exposure, smoking and alcohol consumption. Use of the areca or betel nut in many cultures is a major etiological factor outside of the USA. Other etiologic factors associated with oral squamous cell carcinoma, but far less significant statistically, include syphilis and sideropenic dysphagia. Recently, strong evidence for an etiological relationship between human papilloma virus and a subset of head and neck cancers has been noted. It is generally accepted that most sporadic tumors are the result of a multi-step process of accumulated genetic alterations. These alterations affect epithelial cell behavior by way of loss of chromosomal heterozygosity which in turn leads to a series of events progressing to the ultimate stage of invasive squamous cell carcinoma. The corresponding genetic alterations are reflected in clinical and microscopic pathology from hyperplasia through invasiveness. A wide range of mucosal alternations fall within the rubric of leukoplakia. Proliferative verrucous leukoplakia represents a relatively new type of leukoplakia that is separate from the more common or less innocuous form of this condition. Erythroplakia is particularly relevant considering its almost certain relationship with dysplasia or invasive carcinoma. Squamous cell carcinoma will develop from antecedent dysplastic oral mucosal lesions if an early diagnosis has not been made and treatment given. Early diagnosis within stages I and II correspond to a vastly

Early nerve repair in traumatic brachial plexus injuries in adults: treatment algorithm and first experiences.

PubMed

Pondaag, Willem; van Driest, Finn Y; Groen, Justus L; Malessy, Martijn J A

2018-01-26

OBJECTIVE The object of this study was to assess the advantages and disadvantages of early nerve repair within 2 weeks following adult traumatic brachial plexus injury (ATBPI). METHODS From 2009 onwards, the authors have strived to repair as early as possible extended C-5 to C-8 or T-1 lesions or complete loss of C-5 to C-6 or C-7 function in patients in whom there was clinical and radiological suspicion of root avulsion. Among a group of 36 patients surgically treated in the period between 2009 and 2011, surgical findings in those who had undergone treatment within 2 weeks after trauma were retrospectively compared with results in those who had undergone delayed treatment. The result of biceps muscle reanimation was the primary outcome measure. RESULTS Five of the 36 patients were referred within 2 weeks after trauma and were eligible for early surgery. Nerve ruptures and/or avulsions were found in all early cases of surgery. The advantages of early surgery are as follows: no scar formation, easy anatomical identification, and gap length reduction. Disadvantages include less-clear demarcation of vital nerve tissue and unfamiliarity with the interpretation of frozen-section examination findings. All 5 early-treatment patients recovered a biceps force rated Medical Research Council grade 4. CONCLUSIONS Preliminary results of nerve repair within 2 weeks of ATBPI are encouraging, and the benefits outweigh the drawbacks. The authors propose a decision algorithm to select patients eligible for early surgery. Referral standards for patients with ATBPI must be adapted to enable early surgery.

Early endoscopic treatment of blunt traumatic pancreatic injury.

PubMed

Björnsson, Bergthor; Kullman, Eric; Gasslander, Thomas; Sandström, Per

2015-01-01

Blunt pancreatic trauma is a rare and challenging situation. In many cases, there are other associated injuries that mandate urgent operative treatment. Morbidity and mortality rates are high and complications after acute pancreatic resections are common. The diagnosis of pancreatic injuries can be difficult and often requires multimodal approach including Computed Tomography scans, Magnetic resonance imaging and Endoscopic retrograde cholangiopancreaticography (ERCP). The objective of this paper is to review the application of endoprothesis in the settings of pancreatic injury. A review of the English literature available was conducted and the experience of our centre described. While the classical recommended treatment of Grade III pancreatic injury (transection of the gland and the pancreatic duct in the body/tail) is surgical resection this approach carries high morbidity. ERCP was first reported as a diagnostic tool in the settings of pancreatic injury but has in recent years been used increasingly as a treatment option with promising results. This article reviews the literature on ERCP as treatment option for pancreatic injury and adds further to the limited number of cases reported that have been treated early after the trauma.

The Effect of Aromatherapy Treatment on Fatigue and Relaxation for Mothers during the Early Puerperal Period in Japan: A Pilot Study.

PubMed

Asazawa, Kyoko; Kato, Yoshihiro; Yamaguchi, Atsuko; Inoue, Asako

2017-10-01

Early in the postpartum period, mothers are often nervous and tired from the delivery, breast-feeding and caring for a new-born. The aim of this study was to evaluate the process and outcome of using aromatherapy treatments to increase relaxation and decrease fatigue for mothers during the first to the seventh day of the postpartum period. This non-randomized controlled study with a quasi-experimental one-group pretest-posttest design was used to evaluate scores in relaxation and fatigue before and after the intervention. Aromatherapy hand treatments were performed on a purposive sample of 34 postpartum mothers in Tokyo, Japan, from May to July 2016. The single treatment included a choice of one of five essential aroma oils through hand and forearm massage. Relaxation and fatigue were measured by self-administered valid and reliable questionnaires. Wilcoxon signed-rank test was conducted to analyze the data before and after the intervention. The software programs SPSS, v. 23.0 (SPSS, Tokyo), was used to analyze the data, with the significance level set at 5%. Valid responses were obtained from 29 participants. A comparison of the scores before and after aroma treatment intervention indicated that the participants' relaxation scores increased significantly (P<0.001) and fatigue scores were significantly reduced (P<0.001). The majority of participants (77.8%) were satisfied with the treatment. The aroma treatments significantly improved relaxation and reduced fatigue for mothers in the early puerperal period and were well received. Therefore, a larger study using a pretest-posttest random control trial is recommended.

The Effect of Aromatherapy Treatment on Fatigue and Relaxation for Mothers during the Early Puerperal Period in Japan: A Pilot Study

PubMed Central

Asazawa, Kyoko; Kato, Yoshihiro; Yamaguchi, Atsuko; Inoue, Asako

2017-01-01

ABSTRACT Background: Early in the postpartum period, mothers are often nervous and tired from the delivery, breast-feeding and caring for a new-born. The aim of this study was to evaluate the process and outcome of using aromatherapy treatments to increase relaxation and decrease fatigue for mothers during the first to the seventh day of the postpartum period. Methods: This non-randomized controlled study with a quasi-experimental one-group pretest-posttest design was used to evaluate scores in relaxation and fatigue before and after the intervention. Aromatherapy hand treatments were performed on a purposive sample of 34 postpartum mothers in Tokyo, Japan, from May to July 2016. The single treatment included a choice of one of five essential aroma oils through hand and forearm massage. Relaxation and fatigue were measured by self-administered valid and reliable questionnaires. Wilcoxon signed-rank test was conducted to analyze the data before and after the intervention. The software programs SPSS, v. 23.0 (SPSS, Tokyo), was used to analyze the data, with the significance level set at 5%. Results: Valid responses were obtained from 29 participants. A comparison of the scores before and after aroma treatment intervention indicated that the participants’ relaxation scores increased significantly (P<0.001) and fatigue scores were significantly reduced (P<0.001). The majority of participants (77.8%) were satisfied with the treatment. Conclusion: The aroma treatments significantly improved relaxation and reduced fatigue for mothers in the early puerperal period and were well received. Therefore, a larger study using a pretest-posttest random control trial is recommended. PMID:29043282

Comparison of Growing Rod Instrumentation Versus Serial Cast Treatment for Early-Onset Scoliosis.

PubMed

Johnston, Charles E; McClung, Anna M; Thompson, George H; Poe-Kochert, Connie; Sanders, James O

2013-09-01

A comparison of 2 methods of early-onset scoliosis treatment using radiographic measures and complication rates. To determine whether a delaying tactic (serial casting) has comparable efficacy to a surgical method (insertion of growing rod instrumentation [GRI]) in the initial phase of early-onset deformity management. Serial casts are used in experienced centers to delay operative management of curves of surgical magnitude (greater than 50°) in children up to age 6 years. A total of 27 casted patients from 3 institutions were matched with 27 patients from a multicenter database according to age (within 6 months of each other), curve magnitude (within 10° of each other), and diagnosis. Outcomes were compared according to major curve magnitude, spine length (T1-S1), duration and number of treatment encounters, and complications. There was no difference in age (5.5 years) or initial curve magnitude (65°) between groups, which reflects the accuracy of the matching process. Six pairs of patients had neuromuscular diagnoses, 11 had idiopathic deformities, and 10 had syndromic scoliosis. Growing rod instrumentation patients had smaller curves (45.9° vs. 64.9°; p = .002) at follow-up, but there was no difference in absolute spine length (GRI = 32.0 cm; cast = 30.6 cm; p = .26), even though GRI patients had been under treatment for a longer duration (4.5 vs. 2.4 years; p < .0001) and had undergone a mean of 5.5 lengthenings compared with 4.0 casts. Growing rod instrumentation patients had a 44% complication rate, compared with 1 cast complication. Of 27 casted patients, 15 eventually had operative treatment after a mean delay of 1.7 years after casting. Cast treatment is a valuable delaying tactic for younger children with early-onset scoliosis. Spine deformity is adequately controlled, spine length is not compromised, and surgical complications associated with early GRI treatment are avoided. Copyright © 2013 Scoliosis Research Society. Published by Elsevier Inc

Investigation on the remineralization effect of arginine toothpaste for early enamel caries: nanotribological and nanomechanical properties

NASA Astrophysics Data System (ADS)

Yu, Ping; Arola, Dwayne D.; Min, Jie; Yu, Dandan; Xu, Zhou; Li, Zhi; Gao, Shanshan

2016-11-01

Remineralization is confirmed as a feasible method to restore early enamel caries. While there is evidence that the 8% arginine toothpaste has a good remineralization effect by increasing surface microhardness, the repair effect on wear-resistance and nanomechanical properties still remains unclear. Therefore, this research was conducted to reveal the nanotribological and nanomechanical properties changes of early caries enamel after remineralized with arginine toothpaste. Early enamel caries were created in bovine enamel blocks, and divided into three groups according to the treatment solutions: distilled and deionized water (DDW group), arginine toothpaste slurry (arginine group) and fluoride toothpaste slurry (fluoride group). All of the samples were subjected to pH cycling for 12 d. The nanotribological and nanomechanical properties were evaluated via the nanoscratch and nanoindentation tests. The wear depth and scratch morphology were observed respectively by scanning probe microscopic (SPM) and scanning electron microscopy (SEM). Finally, x-ray photoelectron spectroscopy (XPS) was used for element analysis of remineralized surfaces. Results showed that the wear depth of early caries enamel decreased after remineralization treatment and both the nanohardness and elastic modulus increased. Compared with the fluoride group, the arginine group exhibited higher nanohardness and elastic modulus with higher levels of calcium, fluoride, nitrogen and phosphorus; this group also underwent less wear and related damage. Overall, the synergistic effect of arginine and fluoride in arginine toothpaste achieves better nanotribological and nanomechanical properties than the single fluoride toothpaste, which could have significant impact on fight against early enamel caries.

Effect of three postmortem electrical stimulation treatments on the quality of early-deboned broiler breast meat

USDA-ARS?s Scientific Manuscript database

Electrical stimulation (ES) of animal carcasses during postmortem has been commonly used by beef industry to enhance meat tenderness, and has been recently adapted for commercial use with poultry. Majority of published investigations of ES effects on the tenderness of early-deboned poultry breast m...

Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect.

PubMed

Tillotson, S L; Fuggle, P W; Smith, I; Ades, A E; Grant, D B

1994-08-13

To assess whether early treatment of congenital hypothyroidism fully prevents intellectual impairment. A national register of children with congenital hypothyroidism who were compared with unaffected children from the same school classes and matched for age, sex, social class, and first language. First three years (1982-4) of a neonatal screening programme in England, Wales, and Northern Ireland. 361 children with congenital hypothyroidism given early treatment and 315 control children. Intelligence quotient (IQ) measured at school entry at 5 years of age with the Wechsler preschool and primary scale of intelligence. There was a discontinuous relation between IQ and plasma thyroxine concentration at diagnosis, with a threshold at 42.8 nmol/l (95% confidence interval 35.2 to 47.1 nmol/l). Hypothyroid children with thyroxine values below 42.8 nmol/l had a mean IQ 10.3 points (6.9 to 13.7 points) lower than those with higher values and than controls. None of the measures of quality of treatment (age at start of treatment (range 1-173 days), average thyroxine dose (12-76 micrograms in the first year), average thyroxine concentration during treatment (79-234 nmol/l in the first year), and thyroxine concentration less than 103 nmol/l at least once during the first year) influenced IQ at age 5. Despite early treatment in congenital hypothyroidism the disease severity has a threshold effect on brain development, probably determined prenatally. The 55% of infants with more severe disease continue to show clinically significant intellectual impairment; infants with milder disease show no such impairment. The findings predict that 10% of early treated infants with severe hypothyroidism, compared with around 40% of those who presented with symptoms in the period before screening began, are likely to require special education.

Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect.

PubMed Central

Tillotson, S. L.; Fuggle, P. W.; Smith, I.; Ades, A. E.; Grant, D. B.

1994-01-01

OBJECTIVES--To assess whether early treatment of congenital hypothyroidism fully prevents intellectual impairment. DESIGN--A national register of children with congenital hypothyroidism who were compared with unaffected children from the same school classes and matched for age, sex, social class, and first language. SETTING--First three years (1982-4) of a neonatal screening programme in England, Wales, and Northern Ireland. SUBJECTS--361 children with congenital hypothyroidism given early treatment and 315 control children. MAIN OUTCOME MEASURES--Intelligence quotient (IQ) measured at school entry at 5 years of age with the Wechsler preschool and primary scale of intelligence. RESULTS--There was a discontinuous relation between IQ and plasma thyroxine concentration at diagnosis, with a threshold at 42.8 nmol/l (95% confidence interval 35.2 to 47.1 nmol/l). Hypothyroid children with thyroxine values below 42.8 nmol/l had a mean IQ 10.3 points (6.9 to 13.7 points) lower than those with higher values and than controls. None of the measures of quality of treatment (age at start of treatment (range 1-173 days), average thyroxine dose (12-76 micrograms in the first year), average thyroxine concentration during treatment (79-234 nmol/l in the first year), and thyroxine concentration less than 103 nmol/l at least once during the first year) influenced IQ at age 5. CONCLUSIONS--Despite early treatment in congenital hypothyroidism the disease severity has a threshold effect on brain development, probably determined prenatally. The 55% of infants with more severe disease continue to show clinically significant intellectual impairment; infants with milder disease show no such impairment. The findings predict that 10% of early treated infants with severe hypothyroidism, compared with around 40% of those who presented with symptoms in the period before screening began, are likely to require special education. PMID:7920127

Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)

PubMed Central

Herrick, Ariane L; Pan, Xiaoyan; Peytrignet, Sébastien; Lunt, Mark; Hesselstrand, Roger; Mouthon, Luc; Silman, Alan; Brown, Edith; Czirják, László; Distler, Jörg H W; Distler, Oliver; Fligelstone, Kim; Gregory, William J; Ochiel, Rachel; Vonk, Madelon; Ancuţa, Codrina; Ong, Voon H; Farge, Dominique; Hudson, Marie; Matucci-Cerinic, Marco; Balbir-Gurman, Alexandra; Midtvedt, Øyvind; Jordan, Alison C; Jobanputra, Paresh; Stevens, Wendy; Moinzadeh, Pia; Hall, Frances C; Agard, Christian; Anderson, Marina E; Diot, Elisabeth; Madhok, Rajan; Akil, Mohammed; Buch, Maya H; Chung, Lorinda; Damjanov, Nemanja; Gunawardena, Harsha; Lanyon, Peter; Ahmad, Yasmeen; Chakravarty, Kuntal; Jacobsen, Søren; MacGregor, Alexander J; McHugh, Neil; Müller-Ladner, Ulf; Riemekasten, Gabriela; Becker, Michael; Roddy, Janet; Carreira, Patricia E; Fauchais, Anne Laure; Hachulla, Eric; Hamilton, Jennifer; İnanç, Murat; McLaren, John S; van Laar, Jacob M; Pathare, Sanjay; Proudman, Susannah; Rudin, Anna; Sahhar, Joanne; Coppere, Brigitte; Serratrice, Christine; Sheeran, Tom; Veale, Douglas J; Grange, Claire; Trad, Georges-Selim; Denton, Christopher P

2017-01-01

Objectives The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or ‘no immunosuppressant’. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: −4.0 (−5.2 to −2.7) units for methotrexate, −4.1 (−5.3 to −2.9) for MMF, −3.3 (−4.9 to −1.7) for cyclophosphamide and −2.2 (−4.0 to −0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed. Trial registration number NCT02339441. PMID:28188239

Effect of acarbose to delay progression of carotid intima-media thickness in early diabetes.

PubMed

Patel, Y R; Kirkman, M S; Considine, R V; Hannon, T S; Mather, K J

2013-10-01

The anti-diabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. The Early Diabetes Intervention Program was a randomized trial of acarbose versus placebo in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 h after a 75 g oral glucose load and a mean HbA1c of 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years. Progressive increases in IMT were seen in both treatment groups, but progression was reduced in participants randomized to acarbose (p = 0.047). In age, sex and smoking-adjusted analyses, IMT progression was associated with greater fasting and oral glucose tolerance test-excursion glucose, fasting insulin, cholesterol and glycated low-density lipoprotein concentrations. IMT progression was reduced with study-related changes in weight, insulin and non-esterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression. Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects. Copyright © 2013 John Wiley & Sons, Ltd.

Effects of Acarbose to Delay Progression of Carotid Intima-Media Thickness in Early Diabetes

PubMed Central

Patel, YR; Kirkman, MS; Considine, RV; Hannon, TS; Mather, KJ

2014-01-01

Background The antidiabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. Methods The Early Diabetes Intervention Program (EDIP) was a randomized trial of acarbose versus placebo, in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 hours after a 75g oral glucose load, and mean HbA1c 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years. Results Progressive increases in IMT were seen in both treatment groups, but this was reduced in participants randomized to acarbose (p=0.047). In age, sex and smoking-adjusted analyses IMT progression was associated with greater fasting and OGTT-excursion glucose, fasting insulin, cholesterol, and glycated LDL concentrations. IMT progression was reduced with study-related changes in weight, insulin, and nonesterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression. Conclusions Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects. PMID:23908125

78 FR 9396 - Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-08

...] Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early Stage Disease; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and... ``Alzheimer's Disease: Developing Drugs for the Treatment of Early Stage Disease.'' This guidance outlines FDA...

Reducing Readmissions among Heart Failure Patients Discharged to Home Health Care: Effectiveness of Early and Intensive Nursing Services and Early Physician Follow-Up.

PubMed

Murtaugh, Christopher M; Deb, Partha; Zhu, Carolyn; Peng, Timothy R; Barrón, Yolanda; Shah, Shivani; Moore, Stanley M; Bowles, Kathryn H; Kalman, Jill; Feldman, Penny H; Siu, Albert L

2017-08-01

To compare the effectiveness of two "treatments"-early, intensive home health nursing and physician follow-up within a week-versus less intense and later postacute care in reducing readmissions among heart failure (HF) patients discharged to home health care. National Medicare administrative, claims, and patient assessment data. Patients with a full week of potential exposure to the treatments were followed for 30 days to determine exposure status, 30-day all-cause hospital readmission, other health care use, and mortality. An extension of instrumental variables methods for nonlinear statistical models corrects for nonrandom selection of patients into treatment categories. Our instruments are the index hospital's rate of early aftercare for non-HF patients and hospital discharge day of the week. All hospitalizations for a HF principal diagnosis with discharge to home health care between July 2009 and June 2010 were identified from source files. Neither treatment by itself has a statistically significant effect on hospital readmission. In combination, however, they reduce the probability of readmission by roughly 8 percentage points (p < .001; confidence interval = -12.3, -4.1). Results are robust to changes in implementation of the nonlinear IV estimator, sample, outcome measure, and length of follow-up. Our results call for closer coordination between home health and medical providers in the clinical management of HF patients immediately after hospital discharge. © Health Research and Educational Trust.

Early versus later response to treatment in patients with community-acquired pneumonia: analysis of the REACH study.

PubMed

Blasi, Francesco; Ostermann, Helmut; Racketa, Jill; Medina, Jesús; McBride, Kyle; Garau, Javier

2014-01-22

Key goals in the treatment of CAP include early response to treatment and achievement of clinical stability. The US FDA recommends early response endpoints (72 hours after initiation of treatment) in clinical trials for the treatment of community-acquired bacterial pneumonia. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe Complicated Skin and Soft Tissue Infections [cSSTI] or CAP in the Hospital Setting) was a retrospective observational study, providing current data on the clinical management and resource burden of CAP in real-life settings in European hospitals. This analysis reviews the characteristics and outcomes of patients showing early positive response to treatment (time to clinical stability [TCS] ≤4 days, as assessed by Halm's criteria) compared with patients with later positive response (TCS >4 days). Patients were adults, hospitalized with CAP (2010-2011) and requiring in-hospital treatment with intravenous antibiotics. Of the 2039 patients included in REACH, 585 (28.7%) had TCS assessed by Halm's criteria: 332 (56.8%) showed early response (median 3.0 days), and 253 (43.2%) showed later response to treatment (median 7.0 days). Use of Halm's criteria varied across participating countries, ranging from 0% (Belgium) to 49.1% (UK). Patient characteristics and relevant medical history were similar between the two groups. There were no notable differences in initial antibiotic therapy between groups, except that more early responders had been treated with amoxicillin-clavulanate and amoxicillin monotherapy (22.6%; 7.5%, respectively) than later responders (5.9%; 1.2%, respectively). Initial treatment modification and re-infection or recurrences were less frequent in early responders compared with later responders (14.2% and 3.3% vs. 34.8% and 5.9%, respectively). Early responders had a shorter duration of hospitalization (mean 9.4 ± SD 7.0; median 8.0 days vs. mean 15.6 ± SD 10.5; median 12

No alterations of brain GABA after 6 months of treatment with atypical antipsychotic drugs in early-stage first-episode schizophrenia.

PubMed

Goto, Naoki; Yoshimura, Reiji; Kakeda, Shingo; Moriya, Junji; Hori, Hikaru; Hayashi, Kenji; Ikenouchi-Sugita, Atsuko; Nakano-Umene, Wakako; Katsuki, Asuka; Nishimura, Joji; Korogi, Yukunori; Nakamura, Jun

2010-12-01

We investigated the effects of atypical antipsychotic drugs on GABA concentrations in early-stage, first-episode schizophrenia patients. Sixteen (8 males, 8 females; age, 30±11 years old) patients were followed up for six months. We also included 18 sex- and age-matched healthy control subjects. All patients were treated with atypical antipsychotic drugs (5 patients with risperidone, 5 patients with olanzapine, 4 patients with aripiprazole, and 2 patients with quetiapine). In all three regions measured (frontal lobe, left basal ganglia, and parieto-occipital lobe), no differences in GABA concentrations were observed in a comparison of pre-treatment levels and those six months after treatment. These results suggest that relatively short-term treatment with atypical antipsychotic drugs may not affect GABAergic neurotransmission; however, it is also possible that such treatment prevents further reductions in brain GABA levels in people with early-stage, first-episode schizophrenia. Copyright © 2010 Elsevier Inc. All rights reserved.

The impact of early symptom change and therapeutic alliance on treatment outcome in cognitive-behavioural therapy for eating disorders.

PubMed

Turner, Hannah; Bryant-Waugh, Rachel; Marshall, Emily

2015-10-01

The present study explored the impact of early symptom change (cognitive and behavioural) and the early therapeutic alliance on treatment outcome in cognitive-behavioural therapy (CBT) for the eating disorders. Participants were 94 adults with diagnosed eating disorders who completed a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment, following the 6th session and at the end of treatment. They also completed a measure of therapeutic alliance following the 6th session. Greater early reduction in dietary restraint and eating concerns, and smaller levels of change in shape concern, significantly predicted later reduction in global eating pathology. The early therapeutic alliance was strong across the three domains of tasks, goals and bond. Early symptom reduction was a stronger predictor of later reduction in eating pathology than early therapeutic alliance. The early therapeutic alliance did not mediate the relationship between early symptom reduction and later reduction in global eating pathology. Instead, greater early symptom reduction predicted a strong early therapeutic alliance. Early clinical change was the strongest predictor of treatment outcome and this also facilitated the development of a strong early alliance. Clinicians should be encouraged to deliver all aspects of evidence-based CBT, including behavioural change. The findings suggest that this will have a positive impact on both the early therapeutic alliance and later change in eating pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early onset of action and sleep-improving effect are crucial in decreasing suicide risk: the role of quetiapine XR in the treatment of unipolar and bipolar depression.

PubMed

Pompili, Maurizio; Rihmer, Zoltan; Gonda, Xenia; Serafini, Gianluca; Sher, Leo; Girardi, Paolo

2012-01-01

Although the possibilities of antidepressive pharmacotherapy are continuously improving, the rate of nonresponders or partial responders is still relatively high. Suicidal behavior, the most tragic consequence of untreated or unsuccessfully treated depression, commonly observed in the first few weeks of antidepressive treatment before the onset of therapeutic action, is strongly related to certain symptoms of depression like insomnia. The present paper reviews the newly discovered and well-documented antidepressive effect of quetiapine in bipolar and unipolar depression with special focus on its early onset of action and its sleep-improving effects. Both beneficial effects play an important role in the reduction of suicidal risk frequently observed in depressed patients.

Initial Treatment for Nonsyndromic Early-Life Epilepsy: An Unexpected Consensus.

PubMed

Shellhaas, Renée A; Berg, Anne T; Grinspan, Zachary M; Wusthoff, Courtney J; Millichap, John J; Loddenkemper, Tobias; Coryell, Jason; Saneto, Russell P; Chu, Catherine J; Joshi, Sucheta M; Sullivan, Joseph E; Knupp, Kelly G; Kossoff, Eric H; Keator, Cynthia; Wirrell, Elaine C; Mytinger, John R; Valencia, Ignacio; Massey, Shavonne; Gaillard, William D

2017-10-01

There are no evidence-based guidelines on the preferred approach to treating early-life epilepsy. We examined initial therapy selection in a contemporary US cohort of children with newly diagnosed, nonsyndromic, early-life epilepsy (onset before age three years). Seventeen pediatric epilepsy centers participated in a prospective cohort study of children with newly diagnosed epilepsy with onset under 36 months of age. Details regarding demographics, seizure types, and initial medication selections were obtained from medical records. About half of the 495 enrolled children with new-onset, nonsyndromic epilepsy were less than 12 months old at the time of diagnosis (n = 263, 53%) and about half (n = 260, 52%) had epilepsy with focal features. Of 464 who were treated with monotherapy, 95% received one of five drugs: levetiracetam (n = 291, 63%), oxcarbazepine (n = 67, 14%), phenobarbital (n = 57, 12%), topiramate (n = 16, 3.4%), and zonisamide (n = 13, 2.8%). Phenobarbital was prescribed first for 50 of 163 (31%) infants less than six months old versus seven of 300 (2.3%) of children six months or older (P < 0.0001). Although the first treatment varied across study centers (P < 0.0001), levetiracetam was the most commonly prescribed medication regardless of epilepsy presentation (focal, generalized, mixed/uncertain). Between the first and second treatment choices, 367 (74%) of children received levetiracetam within the first year after diagnosis. Without any specific effort, the pediatric epilepsy community has developed an unexpectedly consistent approach to initial treatment selection for early-life epilepsy. This suggests that a standard practice is emerging and could be utilized as a widely acceptable basis of comparison in future drug studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Outcomes of management of early temporomandibular joint disorders: How effective is nonsurgical therapy in the long-term?

PubMed Central

Mortazavi, Seyed Hossein; Motamedi, Mohammad Hosein Kalantar; Navi, Fina; Pourshahab, Majid; Bayanzadeh, Seyed Masoud; Hajmiragha, Habib; Isapour, Mona

2010-01-01

, severity of symptoms and duration of the treatment did not influence treatment results in this group of patients with early TMD. Conclusion: In this population, TMD was significantly higher in females. Treatment of early TMD with IOS was effective and moderately effective in long-term in over 80% of the patients during the follow-up period of 1–9 years. Bruxism had a significant etiologic role in TMD; occlusal attrition of the dentition, pain of all the teeth, early morning pain of the masticatory muscles and the TMJ are signs and symptoms to suspect nocturnal bruxism. Use of an IOS is recommended to prevent potential damage to the dentition, periodontium and the TMJ in early TMD. PMID:22442579

Trans-generational Effects of Early Life Stress: The Role of Maternal Behavior

PubMed Central

Schmauss, Claudia; Lee-McDermott, Zoe; Medina, Liorimar Ramos

2014-01-01

Using a rodent paradigm of early life stress, infant maternal separation (IMS), we examined whether IMS-triggered behavioral and epigenetic phenotypes of the stress-susceptible mouse strain Balb/c are propagated across generations. These phenotypes include impaired emotional behavior and deficits in executive cognitive functions in adulthood, and they are associated with increased acetylation of histone H4K12 protein (acH4K12) in the forebrain neocortex. These behavioral and epigenetic phenotypes are transmitted to the first progeny of IMS Balb/c mothers, but not fathers, and cross-fostering experiments revealed that this transmission is triggered by maternal behavior and modulated by the genetic background of the pups. In the continued absence of the original stressor, this transmission fades in later progenies. An adolescent treatment that lowers the levels of acH4K12 in IMS Balb/c mice augments their emotional abnormality but abolishes their cognitive deficits. Conversely, a treatment that further elevates the levels of acH4K12 improved the emotional phenotype but had no effects on the cognitive deficits. Moreover, treatments that prevent the emergence of either emotional or cognitive deficits in the mother also prevent the establishment of such deficits in her offspring, indicating that trans-generational effects of early life stress can be prevented. PMID:24786242

Grazing effects on aboveground primary production and root biomass of early-seral, mid-seral, and undisturbed semiarid grassland

USGS Publications Warehouse

Milchunas, D.G.; Vandever, M.W.

2013-01-01

Annual/perennial and tall/short plant species differentially dominate early to late successional shortgrass steppe communities. Plant species can have different ratios of above-/below-ground biomass distributions and this can be modified by precipitation and grazing. We compared grazing effects on aboveground production and root biomass in early- and mid-seral fields and undisturbed shortgrass steppe. Production averaged across four years and grazed and ungrazed treatments were 246, 134, and 102 g m−2 yr−1 for the early-, mid-seral, and native sites, respectively, while root biomass averaged 358, 560, and 981 g m−2, respectively. Early- and mid-seral communities provided complimentary forage supplies but at the cost of root biomass. Grazing increased, decreased, or had no effect on aboveground production in early-, mid-seral, and native communities, and had no effect on roots in any. Grazing had some negative effects on early spring forage species, but not in the annual dominated early-seral community. Dominant species increased with grazing in native communities with a long evolutionary history of grazing by large herbivores, but had no effects on the same species in mid-seral communities. Effects of grazing in native communities in a region cannot necessarily be used to predict effects at other seral stages.

Best practices in the treatment of early cystic fibrosis lung disease.

PubMed

Proesmans, Marijke

2017-02-01

For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection. In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized.

Response to Early Intensive Behavioral Intervention for autism--an umbrella approach to issues critical to treatment individualization.

PubMed

Fava, Leonardo; Strauss, Kristin

2014-12-01

Integrating knowledge across the disciplines of genetics, neurological, and behavioral science targets, so far, early identification of children with autism and thus early access to intervention. Cross-discipline collaboration might be substantially improve treatment efficacy via individualized treatment based on the child and family needs, consistency across treatment providers and careful planning of skill curricula, setting and techniques. This paper documents the current state of five main issues critical to treatment individualization where cross-discipline collaboration is warranted: (1) developmental timing, (2) treatment intensity, (3) heterogeneity in treatment response, (4) program breath and flexibility, and (5) formats of treatment provision. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study.

PubMed

Alahdab, Fares; Farah, Wigdan; Almasri, Jehad; Barrionuevo, Patricia; Zaiem, Feras; Benkhadra, Raed; Asi, Noor; Alsawas, Mouaz; Pang, Yifan; Ahmed, Ahmed T; Rajjo, Tamim; Kanwar, Amrit; Benkhadra, Khalid; Razouki, Zayd; Murad, M Hassan; Wang, Zhen

2018-03-01

To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials. We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta-analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables. We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5-48] RCTs per MA) with average follow-up of 24 (range, 1-168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37%. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95% CI, 2.12-3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow-up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow-up or the test for publication bias. Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Early Prediction of Acute Antidepressant Treatment Response and Remission in Pediatric Major Depressive Disorder

ERIC Educational Resources Information Center

Tao, Rongrong; Emslie, Graham; Mayes, Taryn; Nakonezny, Paul; Kennard, Betsy; Hughes, Carroll

2009-01-01

The rate of symptom improvement during the early weeks of acute fluoxetine treatment is a good indicator of remission. This finding was made after evaluating the outcome of the fluoxetine treatment on 168 children and adults with depression.

Deficits in adult prefrontal cortex neurons and behavior following early post-natal NMDA antagonist treatment.

PubMed

Coleman, Leon G; Jarskog, L Fredrik; Moy, Sheryl S; Crews, Fulton T

2009-09-01

The prefrontal cortex (PFC) is associated with higher cognitive functions including attention and working memory and has been implicated in the regulation of impulsivity as well as the pathology of complex mental illnesses. N-methyl D-aspartate (NMDA) antagonist treatment with dizocilpine induces cell death which is greatest in the frontal cortex on post-natal day seven (P7), however the long-term structural and behavioral effects of this treatment are unknown. This study investigates both the acute neurotoxicity of P7 dizocilpine and the persistent effects of this treatment on pyramidal cells and parvalbumin interneurons in the adult PFC, a brain region involved in the regulation of impulsivity. Dizocilpine treatment on P7 increased cleaved caspase-3 immunoreactivity (IR) in the PFC on P8. In adult mice (P82), P7 dizocilpine treatment resulted in 50% fewer parvalbumin-positive interneurons (p<0.01) and 42% fewer layer V pyramidal neurons (p<0.01) in the PFC. Double immunohistochemistry revealed cleaved caspase-3 IR in both GAD67 IR interneurons and GAD67 (-) neurons. Following dizocilpine treatment at P7, adults showed reduced time in the center of the open field suggesting increased anxiety-like behavior. These findings indicate that early brain insults affecting glutamatergic neurotransmission lead to persistent brain pathology that could contribute to impulsivity and cognitive dysfunction.

Opportunity cost for early treatment of Chagas disease in Mexico.

PubMed

Ramsey, Janine M; Elizondo-Cano, Miguel; Sanchez-González, Gilberto; Peña-Nieves, Adriana; Figueroa-Lara, Alejandro

2014-04-01

Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations. A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment. In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient's quality of life.

Opportunity Cost for Early Treatment of Chagas Disease in Mexico

PubMed Central

Ramsey, Janine M.; Elizondo-Cano, Miguel; Sanchez-González, Gilberto; Peña-Nieves, Adriana; Figueroa-Lara, Alejandro

2014-01-01

Background Given current neglect for Chagas disease in public health programs in Mexico, future healthcare and economic development policies will need a more robust model to analyze costs and impacts of timely clinical attention of infected populations. Methodology/Principal Findings A Markov decision model was constructed to simulate the natural history of a Chagas disease cohort in Mexico and to project the associated short and long-term clinical outcomes and corresponding costs. The lifetime cost for a timely diagnosed and treated Chagas disease patient is US$ 10,160, while the cost for an undiagnosed individual is US$ 11,877. The cost of a diagnosed and treated case increases 24-fold from early acute to indeterminate stage. The major cost component for lifetime cost was working days lost, between 44% and 75%, depending on the program scenario for timely diagnosis and treatment. Conclusions/Significance In the long term, it is cheaper to diagnose and treat chagasic patients early, instead of doing nothing. This finding by itself argues for the need to shift current policy, in order to prioritize and attend this neglected disease for the benefit of social and economic development, which implies including treatment drugs in the national formularies. Present results are even more relevant, if one considers that timely diagnosis and treatment can arrest clinical progression and enhance a chronic patient's quality of life. PMID:24743112

[Comparison of effect between early and delayed in primary intramedullary nailing combined with locked plate fixation for the treatment of multi-segments tibial fractures of type].

PubMed

Gao, Wei-qiang; Hu, Jiang-hai; Gu, Zhu-chao; Zhang, Huai-xian; Min, Peng; Zhang, Lin-jun; Yu, Wen-wen; Wang, Guang-lin

2015-02-01

locked plating does not significantly increase the postoperative incidence of soft tissue complications for patients. The early and delayed primary intramedullary nailing and locked plating for treatment of AO/ASIF-42C2 proximal third tibial fractures can get similar curative effect.

Internet-Delivered, Family-Based Treatment for Early-Onset OCD: A Preliminary Case Series

PubMed Central

Comer, Jonathan S.; Furr, Jami M.; Cooper-Vince, Christine E.; Kerns, Caroline E.; Chan, Priscilla T.; Edson, Aubrey L.; Khanna, Muniya; Franklin, Martin E.; Garcia, Abbe M.; Freeman, Jennifer B.

2014-01-01

Given the burdens of early-onset obsessive-compulsive disorder (OCD), limitations in the broad availability and accessibility of evidence-based care for affected youth present serious public health concerns. The growing potential for technological innovations to transform care for the most traditionally remote and underserved families holds enormous promise. This article presents the rationale, key considerations, and a preliminary case series for a promising behavioral telehealth innovation in the evidence-based treatment of early-onset OCD. We developed an Internet-based format for the delivery of family-based treatment for early-onset OCD directly to families in their homes, regardless of their geographic proximity to a mental health facility. Videoteleconferencing (VTC) methods were used to deliver real-time cognitive-behavioral therapy centering on exposure and response prevention to affected families. Participants in the preliminary case series included 5 children between the ages of 4 and 8 (MAge = 6.5) who received the Internet-delivered treatment format. All youth completed a full treatment course, all showed OCD symptom improvements and global severity improvements from pre- to posttreatment, all showed at least partial diagnostic response, and 60% no longer met diagnostic criteria for OCD at posttreatment. No participants got worse, and all mothers characterized the quality of services received as “excellent.” The present work adds to a growing literature supporting the potential of VTC and related computer technology for meaningfully expanding the reach of supported treatments for OCD and lays the foundation for subsequent controlled evaluations to evaluate matters of efficacy and engagement relative to standard in-office evidence-based care. PMID:24295036

The Effect of Growing Rod Treatment on Hemoglobin and Hematocrit Levels in Early-onset Scoliosis.

PubMed

Barrett, Kody K; Lee, Christopher; Myung, Karen; Johnston, Charles; Shah, Suken A; Akbarnia, Behrooz A; Skaggs, David L

2016-09-01

This study examines preoperative hemoglobin (Hgb) and hematocrit (Hct) levels in a group of early-onset scoliosis (EOS) patients and the effect of distraction-based growing rods (GRs) on these levels. Children with EOS are at risk for respiratory insufficiency and chronic hypoxemia. Increased Hgb and Hct levels have been identified as surrogate markers for chronic hypoxemia. A study of patients who underwent VEPTR surgery showed a significant decrease in Hgb levels following surgery. Data were retrospectively collected on 66 EOS patients without confounding respiratory issues or oxygen dependence who were treated with GRs at 5 institutions. Average age at initial surgery was 5.5 years. Patients were followed for a minimum of 2 years (average 3.7 y). Preoperative and postoperative Hgb and Hct levels were converted to Z-scores based on age-adjusted mean blood indices and were compared using a paired t test. The prevalence of elevated Hgb and Hct levels (Z-score >2) preoperatively was 15% (10/66) and 19% (12/64), respectively. The average Hgb Z-score decreased from 0.20 to -0.31 (P=0.005) 6 to 24 months following surgery and the Hct Z-score decreased from 0.31 to -0.28 (P=0.002) 6 to 24 months following surgery. Following distraction-based GR treatment of children with EOS there was a significant decrease in both their Hgb and Hct. This is a physiological marker of decreased hypoxemia and improved pulmonary function. Level III-therapeutic study.

Cost-effectiveness of early intervention in first-episode psychosis: economic evaluation of a randomised controlled trial (the OPUS study).

PubMed

Hastrup, Lene Halling; Kronborg, Christian; Bertelsen, Mette; Jeppesen, Pia; Jorgensen, Per; Petersen, Lone; Thorup, Anne; Simonsen, Erik; Nordentoft, Merete

2013-01-01

Information about the cost-effectiveness of early intervention programmes for first-episode psychosis is limited. To evaluate the cost-effectiveness of an intensive early-intervention programme (called OPUS) (trial registration NCT00157313) consisting of enriched assertive community treatment, psychoeducational family treatment and social skills training for individuals with first-episode psychosis compared with standard treatment. An incremental cost-effectiveness analysis of a randomised controlled trial, adopting a public sector perspective was undertaken. The mean total costs of OPUS over 5 years (€123,683, s.e. = 8970) were not significantly different from that of standard treatment (€148,751, s.e. = 13073). At 2-year follow-up the mean Global Assessment of Functioning (GAF) score in the OPUS group (55.16, s.d. = 15.15) was significantly higher than in standard treatment group (51.13, s.d. = 15.92). However, the mean GAF did not differ significantly between the groups at 5-year follow-up (55.35 (s.d. = 18.28) and 54.16 (s.d. = 18.41), respectively). Cost-effectiveness planes based on non-parametric bootstrapping showed that OPUS was less costly and more effective in 70% of the replications. For a willingness-to-pay up to €50,000 the probability that OPUS was cost-effective was more than 80%. The incremental cost-effectiveness analysis showed that there was a high probability of OPUS being cost-effective compared with standard treatment.

Early Treatment in HCV: Is it a Cost-Utility Option from the Italian Perspective?

PubMed

Marcellusi, Andrea; Viti, Raffaella; Damele, Francesco; Cammà, Calogero; Taliani, Gloria; Mennini, Francesco Saverio

2016-08-01

In Italy, the Italian Pharmaceutical Agency (AIFA) criteria used F3-F4 fibrosis stages as the threshold to prioritise the treatment with interferon (IFN)-free regimens, while in genotype 1 chronic hepatitis C (G1 CHC) patients with fibrosis of liver stage 2, an approach with pegylated interferon (PEG-IFN)-based triple therapy with simeprevir was suggested. The key clinical question is whether, in an era of financial constraints, the application of a universal IFN-free strategy in naïve G1 CHC patients is feasible within a short time horizon. The aim of this study is to perform an economic analysis to estimate the cost-utility of the early innovative therapy in Italy for managing hepatitis C virus (HCV)-infected patients. The incremental cost-utility analysis was carried out to quantify the benefits of the early treatment approach in HCV subjects. A Markov simulation model including direct and indirect costs and health outcomes was developed from an Italian National Healthcare Service and societal perspective. A total of 5000 Monte Carlo simulations were performed on two distinct scenarios: standard of care (SoC) which includes 14,000 genotype 1 patients in Italy treated with innovative interferon-free regimens in the fibrosis of liver stages 3 and 4 (F3-F4) versus early-treatment scenario (ETS) where 2000 patients were additionally treated with simeprevir plus PEG-IFN and ribavirin in the fibrosis stage 2 (F2) (based on Italian Medicines Agency AIFA reimbursement criteria). A systematic literature review was carried out to identify epidemiological and economic data, which were subsequently used to inform the model. Furthermore, a one-way probabilistic sensitivity was performed to measure the relationship between the main parameters of the model and the cost-utility results. The model shows that, in terms of incremental cost-effectiveness ratio (ICER) per quality adjusted life year (QALY) gained, ETS appeared to be the most cost-utility option compared with both

Acute Cutaneous Necrosis: A Guide to Early Diagnosis and Treatment.

PubMed

Karimi, Karen; Odhav, Ashika; Kollipara, Ramya; Fike, Jesse; Stanford, Carol; Hall, John C

Acute cutaneous necrosis is characterised by a wide range of aetiologies and is associated with significant morbidity and mortality, warranting complex considerations in management. Early recognition is imperative in diagnosis and management of sudden gangrenous changes in the skin. This review discusses major causes of cutaneous necrosis, examines the need for early assessment, and integrates techniques related to diagnosis and management. The literature, available via PubMed, on acute cutaneous necrotic syndromes was reviewed to summarise causes and synthesise appropriate treatment strategies to create a clinician's guide in the early diagnosis and management of acute cutaneous necrosis. Highlighted in this article are key features associated with common causes of acute cutaneous necrosis: warfarin-induced skin necrosis, heparin-induced skin necrosis, calciphylaxis, pyoderma gangrenosum, embolic phenomena, purpura fulminans, brown recluse spider bite, necrotising fasciitis, ecthyma gangrenosum, antiphospholipid syndrome, hypergammaglobulinemia, and cryoglobulinemia. This review serves to increase recognition of these serious pathologies and complications, allowing for prompt diagnosis and swift limb- or life-saving management.

Fire decreases arthropod abundance but increases diversity: Early and late season prescribed fire effects in a Sierra Nevada mixed-conifer forest

USGS Publications Warehouse

Ferrenberg, Scott; Schwilk, Dylan W.; Knapp, Eric E.; Groth, Eric; Keeley, Jon E.

2006-01-01

Prior to fire suppression in the 20th century, the mixed-conifer forests of the Sierra Nevada, California, U.S.A., historically burned in frequent fires that typically occurred during the late summer and early fall. Fire managers have been attempting to restore natural ecosystem processes through prescription burning, and have often favored burning during the fall in order to mimic historical fire regimes. Increasingly, however, prescription burning is also being done during the late spring and early summer in order to expand the window of opportunity for needed fuel reduction burning. The effect of prescribed fires outside of the historical fire season on forest arthropods is not known. The objective of this study was to compare the short-term effects of prescribed fires ignited in the early and late fire season on forest floor arthropods. Arthropod abundance and diversity were assessed using pitfall trapping in replicated burn units in Sequoia National Park, California. Overall, abundance of arthropods was lower in the burn treatments than in the unburned control. However, diversity tended to be greater in the burn treatments. Fire also altered the relative abundances of arthropod feeding guilds. No significant differences in arthropod community structure were found between early and late season burn treatments. Instead, changes in the arthropod community appeared to be driven largely by changes in fuel loading, vegetation, and habitat heterogeneity, all of which differed more between the burned and unburned treatments than between early and late season burn treatments.

Bcl2-independent chromatin cleavage is a very early event during induction of apoptosis in mouse thymocytes after treatment with either dexamethasone or ionizing radiation.

PubMed

Hahn, Peter J; Lai, Zhi-Wei; Nevaldine, Barbara; Schiff, Ninel; Fiore, Nancy C; Silverstone, Allen E

2003-11-01

We have quantified the emergence of early chromatin breaks during the signal transduction phase of apoptosis in mouse thymocytes after treatment with either ionizing radiation or dexamethasone. Dexamethasone at 1 microM can induce significant levels of DNA breaks (equivalent to the amount induced directly by 7.5 Gy ionizing radiation) within 0.5 h of treatment. The execution phase of apoptosis was not observed until 4-6 h after the same treatment. The presence of the Bcl2 transgene under the control of the p56lck promoter almost completely inhibited apoptosis up to 24 h after treatment, but it had virtually no effect on the early chromatin cleavage occurring in the first 6 h. Ionizing radiation induced chromatin cleavage both directly by damaging DNA and indirectly with kinetics similar to the induction of chromatin cleavage by dexamethasone. The presence of the Bcl2 transgene had no effect on the direct or indirect radiation-induced cleavage in the first 6 h, but after the first 6 h, the Bcl2 gene inhibited further radiation-induced chromatin cleavage. These results suggest that endonucleases are activated within minutes of treatment with either dexamethasone or ionizing radiation as part of the very early signal transduction phase of apoptosis, and prior to the irreversible commitment to cell death.

Effects of early chemotherapeutic treatment on learning in adolescent mice: implications for cognitive impairment and remediation in childhood cancer survivors.

PubMed

Bisen-Hersh, Emily B; Hineline, Philip N; Walker, Ellen A

2013-06-01

Among children diagnosed with acute lymphoblastic leukemia (ALL) and given chemotherapy-only treatment, 40% to 70% of survivors experience neurocognitive impairment. The present study used a preclinical mouse model to investigate the effects of early exposure to common ALL chemotherapeutics methotrexate (MTX) and cytarabine (Ara-C) on learning and memory. Preweanling mouse pups were treated on postnatal day (PND) 14, 15, and 16 with saline, MTX, Ara-C, or a combination of MTX and Ara-C. Nineteen days after treatment (PND 35), behavioral tasks measuring different aspects of learning and memory were administered. Significant impairment in acquisition and retention over both short (1 hour) and long (24 hours) intervals, as measured by autoshaping and novel object recognition tasks, was found following treatment with MTX and Ara-C. Similarly, a novel conditional discrimination task revealed impairment in acquisition for chemotherapy-treated mice. No significant group differences were found following the extensive training component of this task, with impairment following the rapid training component occurring only for the highest MTX and Ara-C combination group. Findings are consistent with those from clinical studies suggesting that childhood cancer survivors are slower at learning new information and primarily exhibit deficits in memory years after successful completion of chemotherapy. The occurrence of mild deficits on a novel conditional discrimination task suggests that chemotherapy-induced cognitive impairment may be ameliorated through extensive training or practice. ©2013 AACR

Triple DMARD treatment in early rheumatoid arthritis modulates synovial T cell activation and plasmablast/plasma cell differentiation pathways

PubMed Central

Wechalekar, Mihir D.; Guo, Yanxia; Yin, Xuefeng; Weedon, Helen; Proudman, Susanna M.; Smith, Malcolm D.; Nagpal, Sunil

2017-01-01

Objectives This study sought to investigate the genome-wide transcriptional effects of a combination of disease modifying anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine and hydroxychloroquine) in synovial tissues obtained from early rheumatoid arthritis (RA) patients. While combination DMARD strategies have been investigated for clinical efficacy, very little data exists on the potential molecular mechanism of action. We hypothesized that tDMARD would impact multiple biological pathways, but the specific pathways were unknown. Methods Paired synovial biopsy samples from early RA patients before and after 6 months of tDMARD therapy were collected by arthroscopy (n = 19). These biopsies as well as those from subjects with normal synovium (n = 28) were profiled by total RNA sequencing. Results Large differences in gene expression between RA and control biopsies (over 5000 genes) were identified. Despite clinical efficacy, the expression of a restricted set of less than 300 genes was reversed after 6 months of treatment. Many genes remained elevated, even in patients who achieved low disease activity. Interestingly, tDMARD downregulated genes included those involved in T cell activation and signaling and plasmablast/plasma cell differentiation and function. Conclusions We have identified transcriptomic signatures that characterize synovial tissue from RA patients with early disease. Analysis after 6 months of tDMARD treatment highlight consistent alterations in expression of genes related to T cell activation and plasmablast/plasma cell differentiation. These results provide novel insight into the biology of early RA and the mechanism of tDMARD action and may help identify novel drug targets to improve rates of treatment-induced disease remission. PMID:28863153

Triple DMARD treatment in early rheumatoid arthritis modulates synovial T cell activation and plasmablast/plasma cell differentiation pathways.

PubMed

Walsh, Alice M; Wechalekar, Mihir D; Guo, Yanxia; Yin, Xuefeng; Weedon, Helen; Proudman, Susanna M; Smith, Malcolm D; Nagpal, Sunil

2017-01-01

This study sought to investigate the genome-wide transcriptional effects of a combination of disease modifying anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine and hydroxychloroquine) in synovial tissues obtained from early rheumatoid arthritis (RA) patients. While combination DMARD strategies have been investigated for clinical efficacy, very little data exists on the potential molecular mechanism of action. We hypothesized that tDMARD would impact multiple biological pathways, but the specific pathways were unknown. Paired synovial biopsy samples from early RA patients before and after 6 months of tDMARD therapy were collected by arthroscopy (n = 19). These biopsies as well as those from subjects with normal synovium (n = 28) were profiled by total RNA sequencing. Large differences in gene expression between RA and control biopsies (over 5000 genes) were identified. Despite clinical efficacy, the expression of a restricted set of less than 300 genes was reversed after 6 months of treatment. Many genes remained elevated, even in patients who achieved low disease activity. Interestingly, tDMARD downregulated genes included those involved in T cell activation and signaling and plasmablast/plasma cell differentiation and function. We have identified transcriptomic signatures that characterize synovial tissue from RA patients with early disease. Analysis after 6 months of tDMARD treatment highlight consistent alterations in expression of genes related to T cell activation and plasmablast/plasma cell differentiation. These results provide novel insight into the biology of early RA and the mechanism of tDMARD action and may help identify novel drug targets to improve rates of treatment-induced disease remission.

Endoscopic laser-induced steam generator: a new method of treatment for early gastric cancer

NASA Astrophysics Data System (ADS)

Hayashi, Takuya; Arai, Tsunenori; Tajiri, Hisao; Nogami, Yashiroh; Hino, Kunihiko; Kikuchi, Makoto

1996-05-01

The minimum invasive endoscopic treatment for early gastric cancer has been popular in Japan. The endoscopic mucosal resection and laser coagulation by Nd:YAG laser irradiation has been the popular treatment method in this field. However, the submucosal cancer has not been successfully treated by these methods. To treat the submucosal cancer endoscopically, we developed a new coagulation therapy using hot steam generated by Nd:YAG laser. The steam of which temperature was over 10 deg. in Celsius was generated by the laser power of 30 W with 5 ml/min. of saline. The steam was emitted to canine gastric wall under laparotomy or endoscopy for 50 s respectively. Follow up endoscopy was performed on 3, 7, 14, 28 days after the treatment. Histological examination was studied on 7, 28 days, and just after the emission. In the acute observation, the submucosal layer was totally coagulated. On the 7th day, ulceration with white coat was seen. The mucosal defect, submucosal coagulation, and marked edema without muscle degeneration were found by the histological study. On the 14th day, the ulcer advanced in the scar stage. On the 28th day, it completely healed into white scar with mucosal regeneration and mucosal muscle thickening. We could obtain reproducible coagulation up to deep submucosal layer with large area in a short operation time. Moreover there were no degeneration of proper muscle. This treatment effectiveness could be easily controlled by the steam temperature and emission duration. We think that this method can be applied to early gastric cancer including the submucosal cancer, in particular poor risk case for operation. Further study should be done to apply this method to clinical therapy.

Effects of child development accounts on early social-emotional development: an experimental test.

PubMed

Huang, Jin; Sherraden, Michael; Kim, Youngmi; Clancy, Margaret

2014-03-01

This study, based on Oklahoma's statewide Child Development Accounts (CDAs) program, presents findings from the first experimental test of the hypothesis that creating lifelong savings accounts for children at birth promotes their long-term well-being. To examine the effects of CDAs, an innovative social policy to encourage lifelong saving and asset building for long-term development, on parent-reported social-emotional development in early childhood. A statewide randomized experiment of CDAs was conducted in 2008, drawing a probability sample of 7328 children from all infants born in two 3-month periods in Oklahoma (April 1 through June 30 and August 1 through October 31, 2007). After agreeing to participate in the experiment, caregivers of 2704 infants completed a baseline survey and were randomly assigned to treatment (n = 1358) and control groups (n = 1346). Approximately 84% of participants completed a follow-up survey in the spring of 2011. The intervention offered CDAs, built on the existing Oklahoma 529 college-savings plan, to treatment participants. It also provided additional financial incentives and information. The primary outcome-child social-emotional development-is measured by scores from a 17-item version of the Ages and Stages Questionnaire: Social-Emotional. Caregivers completed it in the 3-year follow-up survey. Lower scores indicate better functioning. The CDAs have positive effects on social-emotional development for children at approximately age 4 years. The nonweighted treatment-control difference is -1.56 (90% CI, -2.87 to -0.22; P = .06), but the weighted difference is nonsignificant. The effects appear to be greater for disadvantaged subsamples, such as low-income households (weighted mean difference, -2.21; 90% CI, -4.01 to -0.42; P = .04). As a complement to other early education and health interventions, CDAs may improve social-emotional development in early childhood. Their effects may be explained as a mediating

Are improvements in shame and self-compassion early in eating disorders treatment associated with better patient outcomes?

PubMed

Kelly, Allison C; Carter, Jacqueline C; Borairi, Sahar

2014-01-01

Compassion-focused therapy (CFT; Gilbert, 2005, 2009) is a transdiagnostic treatment approach focused on building self-compassion and reducing shame. It is based on the theory that feelings of shame contribute to the maintenance of psychopathology, whereas self-compassion contributes to the alleviation of shame and psychopathology. We sought to test this theory in a transdiagnostic sample of eating disorder patients by examining whether larger improvements in shame and self-compassion early in treatment would facilitate faster eating disorder symptom remission over 12 weeks. Participants were 97 patients with an eating disorder admitted to specialized day hospital or inpatient treatment. They completed the Eating Disorder Examination-Questionnaire, Experiences of Shame Scale, and Self-Compassion Scale at intake, and again after weeks 3, 6, 9, and 12. Multilevel modeling revealed that patients who experienced greater decreases in their level of shame in the first 4 weeks of treatment had faster decreases in their eating disorder symptoms over 12 weeks of treatment. In addition, patients who had greater increases in their level of self-compassion early in treatment had faster decreases in their feelings of shame over 12 weeks, even when controlling for their early change in eating disorder symptoms. These results suggest that CFT theory may help to explain the maintenance of eating disorders. Clinically, findings suggest that intervening with shame early in treatment, perhaps by building patients' self-compassion, may promote better eating disorders treatment response. Copyright © 2013 Wiley Periodicals, Inc.

Cognitive effects of bilateral high frequency repetitive transcranial magnetic stimulation in early phase psychosis: a pilot study.

PubMed

Francis, Michael M; Hummer, Tom A; Vohs, Jenifer L; Yung, Matthew G; Visco, Andrew C; Mehdiyoun, Nikki F; Kulig, Teresa C; Um, Miji; Yang, Ziyi; Motamed, Mehrdad; Liffick, Emily; Zhang, Ying; Breier, Alan

2018-05-31

Cognitive dysfunction is a core facet of schizophrenia that is present early in the course of the illness and contributes to diminished functioning and outcomes. Repetitive transcranial magnetic stimulation (rTMS) is a relatively new neuropsychiatric intervention. Initially used in treatment resistant depression, investigators are now studying rTMS for other psychiatric diseases such as schizophrenia. In this study we examined the effect of high frequency rTMS on cognitive function in a group of individuals with early phase psychosis. Twenty subjects were randomized (1:1) in double-blind fashion to rTMS or sham condition. Over two weeks subjects underwent ten sessions of high frequency, bilateral, sequential rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Prior to beginning and following completion of study treatment, subjects completed a cognitive assessment and magnetic resonance imaging. Subjects receiving rTMS, compared to sham treatment, displayed improvement on a standardized cognitive battery both immediately following the course of study treatment and at follow-up two weeks later. Imaging results revealed that left frontal cortical thickness at baseline was correlated with treatment response. The study treatment was found to be safe and well tolerated. These results suggest that rTMS may hold promise for the treatment of cognitive dysfunction in the early phase of psychosis, and that MRI may provide biomarkers predicting response to the treatment.

The effects of very early mirror therapy on functional improvement of the upper extremity in acute stroke patients.

PubMed

Yeldan, Ipek; Huseyınsınoglu, Burcu Ersoz; Akıncı, Buket; Tarakcı, Ela; Baybas, Sevim; Ozdıncler, Arzu Razak

2015-11-01

[Purpose] The aim of the study was to evaluate the effects of a very early mirror therapy program on functional improvement of the upper extremity in acute stroke patients. [Subjects] Eight stroke patients who were treated in an acute neurology unit were included in the study. [Methods] The patients were assigned alternatively to either the mirror therapy group receiving mirror therapy and neurodevelopmental treatment or the neurodevelopmental treatment only group. The primary outcome measures were the upper extremity motor subscale of the Fugl-Meyer Assessment, Motricity Index upper extremity score, and the Stroke Upper Limb Capacity Scale. Somatosensory assessment with the Ayres Southern California Sensory Integration Test, and the Barthel Index were used as secondary outcome measures. [Results] No statistically significant improvements were found for any measures in either group after the treatment. In terms of minimally clinically important differences, there were improvements in Fugl-Meyer Assessment and Barthel Index in both mirror therapy and neurodevelopmental treatment groups. [Conclusion] The results of this pilot study revealed that very early mirror therapy has no additional effect on functional improvement of upper extremity function in acute stroke patients. Multicenter trials are needed to determine the results of early application of mirror therapy in stroke rehabilitation.

Cost-effectiveness analysis of interferon beta-1b for the treatment of patients with a first clinical event suggestive of multiple sclerosis.

PubMed

Caloyeras, John P; Zhang, Bin; Wang, Cheng; Eriksson, Marianne; Fredrikson, Sten; Beckmann, Karola; Knappertz, Volker; Pohl, Christoph; Hartung, Hans-Peter; Shah, Dhvani; Miller, Jeffrey D; Sandbrink, Rupert; Lanius, Vivian; Gondek, Kathleen; Russell, Mason W

2012-05-01

To assess, from a Swedish societal perspective, the cost effectiveness of interferon β-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment). A Markov model was developed, using patient level data from the BENEFIT trial and published literature, to estimate health outcomes and costs associated with IFNB-1b for hypothetical cohorts of patients after an initial clinical event suggestive of MS. Health states were defined by Kurtzke Expanded Disability Status Scale (EDSS) scores. Model outcomes included quality-adjusted life years (QALYs), total costs (including both direct and indirect costs), and incremental cost-effectiveness ratios. Sensitivity analyses were performed on key model parameters to assess the robustness of model results. In the base case scenario, early IFNB-1b treatment was economically dominant (ie, less costly and more effective) versus delayed IFNB-1b treatment when QALYs were used as the effectiveness metric. Sensitivity analyses showed that the cost-effectiveness results were sensitive to model time horizon. Compared with the delayed treatment strategy, early treatment of MS was also associated with delayed EDSS progressions, prolonged time to CDMS diagnosis, and a reduction in frequency of relapse. Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Early Educational Intervention, Early Cumulative Risk, and the Early Home Environment as Predictors of Young Adult Outcomes Within a High-Risk Sample

PubMed Central

Pungello, Elizabeth P.; Kainz, Kirsten; Burchinal, Margaret; Wasik, Barbara H.; Sparling, Joseph J.; Ramey, Craig T.; Campbell, Frances A.

2009-01-01

The extent to which early educational intervention, early cumulative risk, and the early home environment were associated with young adult outcomes was investigated in a sample of 139 young adults (age 21) from high-risk families enrolled in randomized trials of early intervention. Positive effects of treatment were found for education attainment, attending college, and skilled employment; negative effects of risk were found for education attainment, graduating high school, being employed and avoiding teen parenthood. The home mediated the effects of risk for graduating high school, but not being employed or teen parenthood. Evidence for moderated mediation was found for educational attainment; the home mediated the association between risk and educational attainment for the control group, but not the treated group. PMID:20331676

Therapeutic effect of the compound Danshen dripping pill combined with laser acupoint irradiation on early diabetic retinopathy

NASA Astrophysics Data System (ADS)

Liu, Hui-Hui; Xiong, Guo-Xin; Zhang, Li-Ping

2017-06-01

To investigate the therapeutic effect of the compound Danshen dripping pill combined with laser acupoint irradiation on early diabetic retinopathy, 19 patients with early diabetic retinopathy were randomly divided into a treatment group and a control group. The TaiYang, YangBai, YuYao and ZanZhu acupoints of patients in the treatment group were irradiated with a semiconductor laser combined with the oral compound Danshen dropping pills, while those in the control group only used the oral compound Danshen dropping pills. The indicators of vision, mean defect of light sensitivity in the visual field, renal function and fasting blood glucose, were examined to evaluate the efficacy. After treatment, the above indicators of patients in the two groups were significantly improved and there was a significant difference between the two groups. This showed that the compound Danshen dripping pills combined with the laser acupoint irradiation can improve the ischemic and anoxic state of early diabetic retinopathy and improve the visual field.

Atypical antipsychotics in the treatment of early-onset schizophrenia

PubMed Central

Hrdlicka, Michal; Dudova, Iva

2015-01-01

Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. PMID:25897226

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study.

PubMed

Nabieva, N; Fehm, T; Häberle, L; de Waal, J; Rezai, M; Baier, B; Baake, G; Kolberg, H-C; Guggenberger, M; Warm, M; Harbeck, N; Wuerstlein, R; Deuker, J-U; Dall, P; Richter, B; Wachsmann, G; Brucker, C; Siebers, J W; Popovic, M; Kuhn, T; Wolf, C; Vollert, H-W; Breitbach, G-P; Janni, W; Landthaler, R; Kohls, A; Rezek, D; Noesselt, T; Fischer, G; Henschen, S; Praetz, T; Heyl, V; Kühn, T; Krauss, T; Thomssen, C; Hohn, A; Tesch, H; Mundhenke, C; Hein, A; Hack, C C; Schmidt, K; Belleville, E; Brucker, S Y; Kümmel, S; Beckmann, M W; Wallwiener, D; Hadji, P; Fasching, P A

2018-06-01

Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84). These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. CFEM345DDE19. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of early human handling on the pain sensitivity of young lambs.

PubMed

Guesgen, Mirjam J; Beausoleil, Ngaio J; Stewart, Mairi

2013-01-01

Pain sensitivity of lambs changes over the first weeks of life. However, the effects of early treatments such as human handling on pain sensitivity are unknown for this species. This study investigated the effects of regular early gentle human handling on the pain sensitivity of lambs, indicated by their behavioural responses to tail docking. Prospective part-blinded experimental study. Twenty-nine singleton Coopworth lambs (females n=14, males n=15). Starting at one day of age, lambs were either handled twice daily for 2 weeks (Handled), were kept in the presence of lambs who were being handled but were not handled themselves (Presence), or were exposed to a human only during routine feeding and care (Control). At 3 weeks of age, all lambs were tail docked using rubber rings. Changes in behaviour due to docking were calculated and change data were analyzed using two-way anova with treatment and test pen as main factors. All lambs showed significant increases in the frequency and duration of behaviours indicative of pain, including 'abnormal' behaviours, and decreases in the frequency and duration of 'normal' behaviours after docking. Handled lambs showed a smaller increase in the time spent lying abnormally after docking than did Control lambs (mean transformed change in proportion of 30 minutes spent±SE: Control 0.55±0.04; Handled 0.38±0.03; Presence 0.48±0.03; C versus H t=3.45, p=0.007). These results provide some evidence that handling early in life may reduce subsequent pain sensitivity in lambs. While the behavioural effects of handling on pain behaviour were subtle, the results suggest, at the very least, that early handling does not increase pain sensitivity in lambs and suggests there is still flexibility postnatally in the pain processing system of a precocial species. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

[Laparoscopic Proximal Gastrectomy as a Surgical Treatment for Upper Third Early Gastric Cancer].

PubMed

Park, Do Joong; Park, Young Suk; Ahn, Sang Hoon; Kim, Hyung Ho

2017-09-25

Recently, the incidence of upper third gastric cancer has increased, and with it the number of endoscopic submucosal dissection (ESD) procedures performed has been increasing. However, if ESD is not indicated or non-curable, surgical treatment may be necessary. In the case of lower third gastric cancer, it is possible to preserve the upper part of the stomach; however, in the case of upper third gastric cancer, total gastrectomy is still the standard treatment option, regardless of the stage. This is due to the complications associated with upper third gastric cancer, such as gastroesophageal reflux after proximal gastrectomy rather than oncologic problems. Recently, the introduction of the double tract reconstruction method after proximal gastrectomy has become one of the surgical treatment methods for upper third early gastric cancer. However, since there has not been a prospective comparative study evaluating its efficacy, the ongoing multicenter prospective randomized controlled trial (KLASS-05) comparing laparoscopic proximal gastrectomy with double tract reconstruction and laparoscopic total gastrectomy is expected to be important for determining the future of treatment of upper third early gastric cancer.

Effect of socioeconomic status disparity on child language and neural outcome: how early is early?

PubMed

Hurt, Hallam; Betancourt, Laura M

2016-01-01

It is not news that poverty adversely affects child outcome. The literature is replete with reports of deleterious effects on developmental outcome, cognitive function, and school performance in children and youth. Causative factors include poor nutrition, exposure to toxins, inadequate parenting, lack of cognitive stimulation, unstable social support, genetics, and toxic environments. Less is known regarding how early in life adverse effects may be detected. This review proposes to elucidate "how early is early" through discussion of seminal articles related to the effect of socioeconomic status on language outcome and a discussion of the emerging literature on effects of socioeconomic status disparity on brain structure in very young children. Given the young ages at which such outcomes are detected, the critical need for early targeted interventions for our youngest is underscored. Further, the fiscal reasonableness of initiating quality interventions supports these initiatives. As early life adversity produces lasting and deleterious effects on developmental outcome and brain structure, increased focus on programs and policies directed to reducing the impact of socioeconomic disparities is essential.

Preliminary evaluation of the effects of photobiomodulation therapy and physical rehabilitation on early postoperative recovery of dogs undergoing hemilaminectomy for treatment of thoracolumbar intervertebral disk disease.

PubMed

Bennaim, Michael; Porato, Mathilde; Jarleton, Astrid; Hamon, Martin; Carroll, James D; Gommeren, Kris; Balligand, Marc

2017-02-01

OBJECTIVE To evaluate the effects of postoperative photobiomodulation therapy and physical rehabilitation on early recovery variables for dogs after hemilaminectomy for treatment of intervertebral disk disease. ANIMALS 32 nonambulatory client-owned dogs. PROCEDURES Dogs received standard postoperative care with photobiomodulation therapy (n = 11), physical rehabilitation with sham photobiomodulation treatment (11), or sham photobiomodulation treatment only (10) after surgery. Neurologic status at admission, diagnostic and surgical variables, duration of postoperative IV analgesic administration, and recovery grades (over 10 days after surgery) were assessed. Time to reach recovery grades B (able to support weight with some help), C (initial limb movements present), and D (ambulatory [≥ 3 steps unassisted]) was compared among groups. Factors associated with ability to ambulate on day 10 or at last follow-up were assessed. RESULTS Time to reach recovery grades B, C, and D and duration of postoperative IV opioid administration did not differ among groups. Neurologic score at admission and surgeon experience were negatively associated with the dogs' ability to ambulate on day 10. The number of disk herniations identified by diagnostic imaging before surgery was negatively associated with ambulatory status at last follow-up. No other significant associations and no adverse treatment-related events were identified. CONCLUSIONS AND CLINICAL RELEVANCE This study found no difference in recovery-related variables among dogs that received photobiomodulation therapy, physical rehabilitation with sham photobiomodulation treatment, or sham photobiomodulation treatment only. Larger studies are needed to better evaluate effects of these postoperative treatments on dogs treated surgically for intervertebral disk disease.

Sport and early osteoarthritis: the role of sport in aetiology, progression and treatment of knee osteoarthritis.

PubMed

Vannini, F; Spalding, T; Andriolo, L; Berruto, M; Denti, M; Espregueira-Mendes, J; Menetrey, J; Peretti, G M; Seil, R; Filardo, G

2016-06-01

Sports activities are considered favourable for general health; nevertheless, a possible influence of sports practice on the development of early osteoarthritis (OA) is a cause for concern. A higher incidence of OA in knees and ankles of former high-impact sports players than in those of the normal population has been shown and it is still debatable whether the cause is either to be recognized generically in the higher number of injuries or in a joint overload. The possibility to address knee OA in its early phases may be strictly connected to the modification of specific extrinsic or intrinsic factors, related to the patient in order to save the joint from further disease progression; these include sport practice, equipment and load. Non-surgical therapies such as continuative muscles reinforce and training play a strong role in the care of athletes with early OA, particularly if professional. There is an overall agreement on the need of an early restoring of a proper meniscal, ligament and cartilage integrity in order to protect the knee and resume sports safely, whereas alignment is a point still strongly debatable especially for professional athletes. Remaining questions still to be answered are the risks of different sports in relation to one another, although an actual protective effect of low-impact sports, such as walking, swimming or cycling, has been recognized on the appearance or worsening of OA, the effect of continuing or ceasing to practice a sport on the natural history of early OA, and even following appropriate treatment is still unknown.

Effects of Multidimensional Treatment Foster Care on Psychotic Symptoms in Girls

PubMed Central

Poulton, Richie; Van Ryzin, Mark J.; Harold, Gordon T.; Chamberlain, Patricia; Fowler, David; Cannon, Mary; Arseneault, Louise; Leve, Leslie D.

2014-01-01

Objective Neurodevelopmental theories of psychosis highlight the potential benefits of early intervention, prevention, and/or preemption. How early intervention should take place has not been established, nor if interventions based on social learning principles can have preemptive effects. The objective was to test if a comprehensive psychosocial intervention can significantly alter psychotic symptom trajectories during adolescence – a period of heightened risk for a wide range of psychopathology. Method This study was a randomized controlled trial (RCT) of Multidimensional Treatment Foster Care (MTFC) for delinquent adolescent girls. Assessment of psychotic symptoms took place at baseline and then 6, 12, 18, and 24 months post-baseline using a standardized self-report instrument (Brief Symptom Inventory). A second source of information about psychotic symptoms was obtained at baseline or 12 months, and again at 24 months using a structured diagnostic interview (the Diagnostic Interview Schedule for Children [DISC]). Results Significant benefits for MTFC over treatment-as-usual for psychosis symptoms were observed over a 24-month period. Findings were replicated across both measures. Effects were independent of substance use and initial symptom severity, and persisted beyond the initial intervention period. Conclusion Ameliorating non-clinical psychotic symptoms trajectories beginning in early adolescence via a multifaceted psychosocial intervention is possible. Developmental research on non-clinical psychotic symptoms and their prognostic value should be complemented by more psychosocial intervention research aimed at modifying these symptom trajectories early in their natural history. PMID:25457926

Cognitive Remediation for the Treatment of Cognitive Dysfunction in the Early Course of Psychosis.

PubMed

Lewandowski, Kathryn E

2016-01-01

The development of cognitive remediation programs has been a key step toward the creation of a treatment approach to address the cognitive-symptom domain in psychosis. Studies support the efficacy of cognitive remediation in producing moderate effects on cognition at the group level in patients with schizophrenia. Cognitive remediation may harness neuroplasticity in relevant systems that underpin the cognitive functions being addressed. Since neuroplasticity may be greater in people who (1) are younger and (2) have not yet experienced the consequences of long-term psychosis, cognitive remediation may be particularly effective in people in the early course of illness or in the prodrome, prior to the onset of frank symptoms. The present article reviews the evidence for implementing cognitive remediation in patients with recent-onset psychosis and people identified as being at high risk for developing schizophrenia, and also the evidence for cognitive remediation to modify neural targets. Promising findings suggest that cognitive remediation may be useful in addressing cognitive deficits in early-course and prodromal participants. Additionally, a growing literature using neuroimaging techniques demonstrates the ability of cognitive remediation paradigms to engage neural targets.

Cognitive load effects on early visual perceptual processing.

PubMed

Liu, Ping; Forte, Jason; Sewell, David; Carter, Olivia

2018-05-01

Contrast-based early visual processing has largely been considered to involve autonomous processes that do not need the support of cognitive resources. However, as spatial attention is known to modulate early visual perceptual processing, we explored whether cognitive load could similarly impact contrast-based perception. We used a dual-task paradigm to assess the impact of a concurrent working memory task on the performance of three different early visual tasks. The results from Experiment 1 suggest that cognitive load can modulate early visual processing. No effects of cognitive load were seen in Experiments 2 or 3. Together, the findings provide evidence that under some circumstances cognitive load effects can penetrate the early stages of visual processing and that higher cognitive function and early perceptual processing may not be as independent as was once thought.

Historical and regulatory perspectives on the treatment effect of antibacterial drugs for community-acquired pneumonia.

PubMed

Singer, M; Nambiar, S; Valappil, T; Higgins, K; Gitterman, S

2008-12-01

A noninferiority margin based on the treatment effect of antibacterial drugs is required for noninferiority studies of community-acquired pneumonia. A quantitative estimate of treatment effect is generally determined from placebo-controlled trials, but, since the mid-to-late 1930s, no studies have compared outcomes for patients who received placebo (or no specific therapy) with those for patients who received an antibacterial drug for treatment of community-acquired pneumonia. In this article, early controlled studies, as well as observational data, are reviewed, and the beneficial effect of antibacterial drugs on mortality rates among patients with pneumococcal pneumonia is demonstrated. However, because these data were obtained in the early 20th century, several important factors have changed, including patient populations, the etiological agents of pneumonia, and medical standards of care. Thus, the applicability of these studies to the determination of a noninferiority margin for contemporary trials for community-acquired pneumonia remains in question.

Very early disengagement and subsequent re-engagement in primary care Office Based Opioid Treatment (OBOT) with buprenorphine.

PubMed

Hui, David; Weinstein, Zoe M; Cheng, Debbie M; Quinn, Emily; Kim, Hyunjoong; Labelle, Colleen; Samet, Jeffrey H

2017-08-01

Patients with opioid use disorder often require multiple treatment attempts before achieving stable recovery. Rates of disengagement from buprenorphine are highest in the first month of treatment and termination of buprenorphine therapy results in return to use rates as high as 90%. To better characterize these at-risk patients, this study aims to describe: 1) the frequency and characteristics of patients with very early disengagement (≤1month) from Office Based Opioid Treatment (OBOT) with buprenorphine and 2) the frequency and characteristics of patients who re-engage in care at this same OBOT clinic within 2years, among the subset of very early disengagers. This is a retrospective cohort study of adult patients enrolled in a large urban OBOT program. Descriptive statistics were used to characterize the sample and the proportion of patients with very early (≤1month) disengagement and their re-engagement. Multivariable logistic regression models were used to identify patient characteristics associated with the outcomes of very early disengagement and re-engagement. Potential predictors included: sex, age, race/ethnicity, education, employment, opioid use history, prior substance use treatments, urine drug testing, and psychiatric diagnoses. Overall, very early disengagement was unusual, with only 8.4% (104/1234) of patients disengaging within the first month. Among the subset of very early disengagers with 2years of follow-up, the proportion who re-engaged with this OBOT program in the subsequent 2years was 11.9% (10/84). Urine drug test positive for opiates within the first month (AOR: 2.01, 95% CI: 1.02-3.93) was associated with increased odds of very early disengagement. Transferring from another buprenorphine prescriber (AOR: 0.09, 95% CI: 0.01-0.70) was associated with decreased odds of very early disengagement. No characteristics were significantly associated with re-engagement. Early disengagement is uncommon; however, continued opioid use appeared to

A systematic review and mixed treatment comparison of monotherapy in early Parkinson's disease: implications for Latin America.

PubMed

Márquez-Cruz, Maribel; Díaz-Martínez, Juan Pablo; Soto-Molina, Herman; De Saráchaga, Adib Jorge; Cervantes-Arriaga, Amin; Llorens-Arenas, Rodrigo; Rodríguez-Violante, Mayela

2016-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disease. There are no clinical trials comparing all available pharmacological therapies for the treatment of early PD. The objective of this review is to indirectly analyze the efficacy of antiparkinson drugs currently available in Latin America. A systematic review was performed exploring only placebo-controlled randomized trials comparing antiparkinson monotherapy (levodopa, pramipexole, rasagiline, or selegiline) in patients with PD on Hoehn and Yahr stages I through III published from January 1994 to May 2014. The primary outcome was the mean change in the Unified PD Rating Scale (UPDRS) I, II and III. A mixed treatment comparison analysis (indirect comparisons) through a random-effects model was performed. Levodopa demonstrated the highest effects in terms of UPDRS score improvement both from baseline and when compared to other treatments. Levodopa showed a 60.1% probability of granting the greatest reduction in UPDRS I, II and III.

A 37-year-old Menkes disease patient-Residual ATP7A activity and early copper administration as key factors in beneficial treatment.

PubMed

Tümer, Z; Petris, M; Zhu, S; Mercer, J; Bukrinski, J; Bilz, S; Baerlocher, K; Horn, N; Møller, L B

2017-11-01

Menkes disease (MD) is a lethal disorder characterized by severe neurological symptoms and connective tissue abnormalities; and results from malfunctioning of cuproenzymes, which cannot receive copper due to a defective intracellular copper transporting protein, ATP7A. Early parenteral copper-histidine supplementation may modify disease progression substantially but beneficial effects of long-term treatment have been recorded in only a few patients. Here we report on the eldest surviving MD patient (37 years) receiving early-onset and long-term copper treatment. He has few neurological symptoms without connective tissue disturbances; and a missense ATP7A variant, p.(Pro852Leu), which results in impaired protein trafficking while the copper transport function is spared. These findings suggest that some cuproenzymes maintain their function when sufficient copper is provided to the cells; and underline the importance of early initiated copper treatment, efficiency of which is likely to be dependent on the mutant ATP7A function. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of early measles vaccine on pneumococcal colonization: A randomized trial from Guinea-Bissau

PubMed Central

Byberg, Stine; Hervig Jacobsen, Lars; Bjerregaard-Andersen, Morten; Jensen, Aksel Karl Georg; Martins, Cesario; Aaby, Peter; Skov Jensen, Jørgen; Stabell Benn, Christine; Whittle, Hilton

2017-01-01

Background Measles vaccine (MV) may have non-specific beneficial effects for child health and particularly seems to prevent respiratory infections. Streptococcus pneumoniae is the leading cause of bacterial pneumonia among children worldwide, and nasopharyngeal colonization precedes infection. Objective We investigated whether providing early MV at 18 weeks of age reduced pneumococcal colonization and/or density up to 9 months of age. Method The study was conducted in 2013–2014 in Guinea-Bissau. Pneumococcal vaccine was not part of the vaccination program. Infants aged 18 weeks were block-randomized 2:1 to early or no early MV; at age 9 months, all children were offered MV as per current policy. Nasopharyngeal swabs were taken at baseline, age 6.5 months, and age 9 months. Pneumococcal density was determined by q-PCR. Prevalence ratios of pneumococcal colonization and recent antibiotic treatment (yes/no) by age 6.5 months (PR6.5) and age 9 months (PR9) were estimated using Poisson regression with robust variance estimates while the pneumococcal geometric mean ratio (GMR6.5 and GMR9) was obtained using OLS regression. Results Analyses included 512 children; 346 early MV-children and 166 controls. At enrolment, the pneumococcal colonization prevalence was 80% (411/512). Comparing early MV-children with controls, the PR6.5 was 1.02 (95%CI = 0.94–1.10), and the PR9 was 1.04 (0.96–1.12). The GMR6.5 was 1.02 (0.55–1.89), and the GMR9 was 0.69 (0.39–1.21). Early MV-children tended to be less frequently treated with antibiotics prior to follow up (PR6.5 0.60 (0.34–1.05) and PR9 0.87 (0.50–1.53)). Antibiotic treatment was associated with considerably lower colonization rates, PR6.5 0.85 (0.71–1.01) and PR9 0.66 (0.52–0.84), as well as lower pneumococcal density, GMR6.5 0.32 (0.12–0.86) and GMR9 0.52 (0.18–1.52). Conclusion Early MV at age 18 weeks had no measurable effect on pneumococcal colonization prevalence or density. Higher consumption of

Initial Weight Loss Response as an Indicator for Providing Early Rescue Efforts to Improve Long-term Treatment Outcomes.

PubMed

Unick, Jessica L; Pellegrini, Christine A; Demos, Kathryn E; Dorfman, Leah

2017-09-01

There is a large variability in response to behavioral weight loss (WL) programs. Reducing rates of obesity and diabetes may require more individuals to achieve clinically significant WL post-treatment. Given that WL within the first 1-2 months of a WL program is associated with long-term WL, it may be possible to improve treatment outcomes by identifying and providing additional intervention to those with poor initial success (i.e., "early non-responders"). We review the current literature regarding early non-response to WL programs and discuss how adaptive interventions can be leveraged as a strategy to "rescue" early non-responders. Preliminary findings suggest that adaptive interventions, specifically stepped care approaches, offer promise for improving outcomes among early non-responders. Future studies need to determine the optimal time point and threshold for intervening and the type of early intervention to employ. Clinicians and researchers should consider the discussed factors when making treatment decisions.

[Effects of early enteral nutrition in the treatment of patients with severe burns].

PubMed

Wu, Y W; Liu, J; Jin, J; Liu, L J; Wu, Y F

2018-01-20

Objective: To investigate the effects of early enteral nutrition (EEN) in the treatment of patients with severe burns. Methods: Medical records of 52 patients with severe burns hospitalized in the three affiliations of authors from August to September in 2014 were retrospectively analyzed and divided into EEN group ( n =28) and non-early enteral nutrition (NEEN) group ( n =24) according to the initiation time of enteral nutrition. On the basis of routine treatment, enteral nutrition was given to patients in group EEN within post injury day (POD) 3, while enteral nutrition was given to patients in group NEEN after POD 3. The following items were compared between patients of the two groups, such as the ratio of enteral nutrition intake to total energy intake, the ratio of parenteral nutrition intake to total energy intake, the ratio of total energy intake to energy target on POD 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28, the levels of prealbumin, serum creatinine, blood urea nitrogen, total bilirubin, direct bilirubin, and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score on POD 1, 3, 7, 14, and 28, the first operation time, the number of operations, and the frequencies of abdominal distension, diarrhea, vomiting, aspiration, catheter blockage, and low blood sugar within POD 28. Data were processed with χ (2)test, t test, Wilcoxon rank sum test, and Bonferroni correction. Results: (1) The ratio of parenteral nutrition intake to total energy intake of patients in group EEN on POD 1 was obviously lower than that in group NEEN ( Z =2.078, P <0.05). The ratio of enteral nutrition intake to total energy intake and the ratio of total energy intake to energy target of patients in group EEN on POD 2 and 3 were obviously higher than those in group NEEN ( Z =5.766, 6.404, t =4.907, 6.378, P <0.01). The ratio of total energy intake to energy target of patients in group EEN was obviously lower than that in group NEEN on POD 4, 5, 6, and 7 ( t =4.635, 2.547, 3

Prevention and early treatment of influenza in healthy adults.

PubMed

Demicheli, V; Jefferson, T; Rivetti, D; Deeks, J

2000-01-06

We present three systematic reviews carried out within the Cochrane Collaboration, focusing on a different influenza intervention in healthy adults: Vaccines; Ion Channel Inhibitor antivirals and Neuraminidase Inhibitor (NIs) antivirals. The objectives were to identify, retrieve and assess all studies evaluating the effects of these interventions in prophylaxis and early treatments of influenza and the frequency of adverse events. Additionally we present the results of the economic evaluation of effective alternatives in order to define the most cost-effective intervention. The economic evaluation is set in the context of the British Army. Studies were identified using a standard Cochrane search strategy. Any randomised or quasi-randomised studies in healthy individuals aged 14-60 years were considered for inclusion in the systematic review. Those which met inclusion criteria were assessed for quality and their data meta-analysed. The economic model was constructed using Cost-effectiveness and Cost-utility study designs. Live aerosol vaccines reduced cases of clinical influenza A with virological confirmation (by serology and/or viral isolation) by 48% (95%CI: 24-64%), whilst recommended inactivated parenteral vaccines have an efficacy of 68% (95%CI: 49-79%). Vaccine effectiveness in reducing clinical influenza cases (i.e. without virological confirmation) was lower, with efficacies of 13 and 24% respectively. Use of the vaccine significantly reduced time off work, but only by 0.4 days (95%CI: 0. 1-0.8 days). Analysis of vaccines matching the circulating strain gave higher estimates of efficacy, whilst inclusion of all other vaccines reduced the efficacy. When compared to placebo for the prevention of influenza, oral amantadine was 61% (95%CI: 51-69%) efficacious (RR 0.39 - 95%CI: 0.31-0.49), and oral rimantadine was 64% (95%CI: 41-78%) efficacious (RR 0.36 -95%CI: 0.22-0.59). When compared to placebo for the treatment of influenza, oral amantadine significantly

Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids.

PubMed

Jonasson, Sofia; Wigenstam, Elisabeth; Koch, Bo; Bucht, Anders

2013-09-01

Chlorine (Cl2) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl2-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200ppm Cl2 during 15min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24h or 14days post-exposure. A single dose of the corticosteroid dexamethasone (10 or 100mg/kg) was administered intraperitoneally 1, 3, 6, or 12h following Cl2 exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1h was dose-dependent; high-dose significantly reduced acute airway inflammation (100mg/kg) but not treatment with the relatively low-dose (10mg/kg). Both doses reduced AHR 14days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl2 exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl2 exposure. Copyright © 2013 Elsevier Inc. All rights reserved.

[Effectiveness of N-acetylcysteine in the treatment of schizophrenia].

PubMed

Miyake, Nobumi; Miyamoto, Seiya

2016-04-01

Oxidative stress and neuroinflammation have recently been focused on the pathological hypotheses of schizophrenia. N-acetylcysteine (NAC) is a precursor of endogenous antioxidant glutathione and has antioxidant, anti-inflammatory, and neuroprotective properties. NAC is widely available as an over-the-counter nutritional supplement. Increasing lines of evidence suggest that NAC is effective for various mental disorders. In randomized controlled trials, treatment with NAC as an add-on to antipsychotics showed beneficial effects and safety profiles in patients with chronic schizophrenia. The results of a recent preclinical study using a neurodevelopmental model of schizophrenia suggest that NAC may have promising effects in an early stage of schizophrenia and an at-risk mental state. However, there is little clinical evidence for the efficacy and safety of NAC at these stages of schizophrenia. In this review, we summarize the evidence regarding the effectiveness of NAC for the treatment of schizophrenia and its prodromal stage. We also introduce the preliminary results of our research on NAC.

Early improvement as a resilience signal predicting later remission to antidepressant treatment in patients with Major Depressive Disorder: Systematic review and meta-analysis.

PubMed

Wagner, Stefanie; Engel, Alice; Engelmann, Jan; Herzog, David; Dreimüller, Nadine; Müller, Marianne B; Tadić, André; Lieb, Klaus

2017-11-01

Early improvement of depressive symptoms during the first two weeks of antidepressant treatment has been discussed to be a resilience signal predicting a later positive treatment outcome in patients with Major Depressive Disorder (MDD). However, the predictive value of early improvement varies between studies, and the use of different antidepressants may explain heterogeneous results. The objective of this review was to assess the predictive value of early improvement on later response and remission and to identify antidepressants with the highest chance of early improvement. We included 17 randomized controlled trials investigating early improvement in 14,779 adult patients with MDD comparing monotherapy with an antidepressant against placebo or another antidepressant drug. 62% (range: 35-85%) of patients treated with an antidepressant and 47% (range: 21-69%) with placebo were early improver, defined as a >20%/25% symptom reduction after two weeks of treatment. Early improvement predicted response and remission after 5-12 weeks of treatment with high sensitivity (85%; 95%-CI: 84.3 to 85.7) and low to moderate specificity (54%; 95%-CI: 53.1 to 54.9). Early improver had a 8.37 fold (6.97-10.05) higher likelihood to become responder and a 6.38 fold (5.07-8.02) higher likelihood to be remitter at endpoint than non-improver. The highest early improver rates were achieved in patients treated with mirtazapine or a tricyclic antidepressant. This finding of a high predictive value of early improvement on treatment outcome may be important for treatment decisions in the early course of antidepressant treatment. Further studies should test the efficacy of such early treatment decisions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial.

PubMed

Rouzé, Anahita; Loridant, Séverine; Poissy, Julien; Dervaux, Benoit; Sendid, Boualem; Cornu, Marjorie; Nseir, Saad

2017-11-01

The aim of this study was to determine the impact of a biomarker-based strategy on early discontinuation of empirical antifungal treatment. Prospective randomized controlled single-center unblinded study, performed in a mixed ICU. A total of 110 patients were randomly assigned to a strategy in which empirical antifungal treatment duration was determined by (1,3)-β-D-glucan, mannan, and anti-mannan serum assays, performed on day 0 and day 4; or to a routine care strategy, based on international guidelines, which recommend 14 days of treatment. In the biomarker group, early stop recommendation was determined using an algorithm based on the results of biomarkers. The primary outcome was the percentage of survivors discontinuing empirical antifungal treatment early, defined as a discontinuation strictly before day 7. A total of 109 patients were analyzed (one patient withdraw consent). Empirical antifungal treatment was discontinued early in 29 out of 54 patients in the biomarker strategy group, compared with one patient out of 55 in the routine strategy group [54% vs 2%, p < 0.001, OR (95% CI) 62.6 (8.1-486)]. Total duration of antifungal treatment was significantly shorter in the biomarker strategy compared with routine strategy [median (IQR) 6 (4-13) vs 13 (12-14) days, p < 0.0001). No significant difference was found in the percentage of patients with subsequent proven invasive Candida infection, mechanical ventilation-free days, length of ICU stay, cost, and ICU mortality between the two study groups. The use of a biomarker-based strategy increased the percentage of early discontinuation of empirical antifungal treatment among critically ill patients with suspected invasive Candida infection. These results confirm previous findings suggesting that early discontinuation of empirical antifungal treatment had no negative impact on outcome. However, further studies are needed to confirm the safety of this strategy. This trial was registered at Clinical

Oral health-related quality of life following dental treatment under general anaesthesia for early childhood caries - a UK-based study.

PubMed

de Souza, Michelle C; Harrison, Mike; Marshman, Zoe

2017-01-01

To assess parental reports of changes in oral health-related quality of life (OHRQoL) of young children in the UK with early childhood caries (ECC) following dental treatment under general anaesthesia (DGA). To compare the impact of oral rehabilitation (OR) and extraction-only (Exo) treatment approaches on this. Data were collected using the proxy reported components of the Child Oral Health-Related Quality of Life (COHRQoL ® ) questionnaire: the Parent-Caregivers Perceptions questionnaire (P-CPQ) and Family Impact Scale (FIS), from a convenience sample of parents of children receiving DGA at a UK Paediatric Dental Department. Mean scores and prevalence impacts were compared pre- and postoperatively with mean change score and effect sizes calculations. Seventy-eight parents were recruited (51 children undergoing OR, 27 Exo) with 6 lost to follow-up (92.3%). Following treatment, changes in mean P-CPQ and FIS scores were statistically significant (P < 0.0001) with medium to large effect sizes (0.45-1.39). The differences in change scores between the two treatment approaches were not statistically different. DGA for young children with early childhood caries resulted in substantial improvements in parent's ratings of their child's OHRQoL and of the impact on their families. Larger cohort studies are needed to validate these preliminary findings. © 2016 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation.

PubMed

Vujosevic, Stela; Bottega, Elisa; Casciano, Margherita; Pilotto, Elisabetta; Convento, Enrica; Midena, Edoardo

2010-06-01

effective as modified Early Treatment Diabetic Retinopathy Study laser photocoagulation in the treatment of clinically significant diabetic macular edema. Micropulse diode laser treatment does not determine any change on FAF showing (at least) nonclinically visible damage of the retinal pigment epithelium. Microperimetry data encourage the use of a new, less aggressive laser therapeutic approach in the treatment of clinically significant diabetic macular edema.

Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Dalbeth, Nicola; Saag, Kenneth G; Palmer, William E; Choi, Hyon K; Hunt, Barbara; MacDonald, Patricia A; Thienel, Ulrich; Gunawardhana, Lhanoo

2017-12-01

To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline -0.43 versus -0.07; P <0.001), decreased the overall incidence of gout flares (29.3% versus 41.4%; P < 0.05), and improved serum UA control (62.8% versus 5.7%; P < 0.001). No major safety concerns were reported. Urate-lowering therapy with febuxostat improved magnetic resonance imaging-determined synovitis and reduced the incidence of gout flares in subjects with early gout. © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Beyond usual care: the economic consequences of expanding treatment options in early pregnancy loss.

PubMed

Dalton, Vanessa K; Liang, Angela; Hutton, David W; Zochowski, Melissa K; Fendrick, A Mark

2015-02-01

The objective of this study was to estimate the economic consequences of expanding options for early pregnancy loss (EPL) treatment beyond expectant management and operating room surgical evacuation (usual care). We constructed a decision model using a hypothetical cohort of women undergoing EPL management within a 30 day horizon. Treatment options under the usual care arm include expectant management and surgical uterine evacuation in an operating room (OR). Treatment options under the expanded care arm included all evidence-based safe and effective treatment options for EPL: expectant management, misoprostol treatment, surgical uterine evacuation in an office setting, and surgical uterine evacuation in an OR. Probabilities of entering various treatment pathways were based on previously published observational studies. The cost per case was US $241.29 lower for women undergoing treatment in the expanded care model as compared with the usual care model (US $1033.29 per case vs US $1274.58 per case, expanded care and usual care, respectively). The model was the most sensitive to the failure rate of the expectant management arm, the cost of the OR surgical procedure, the proportion of women undergoing an OR surgical procedure under usual care, and the additional cost per patient associated with implementing and using the expanded care model. This study demonstrates that expanding women's treatment options for EPL beyond what is typically available can result in lower direct medical expenditures. Copyright © 2015 Elsevier Inc. All rights reserved.

Cost effectiveness of letrozole versus anastrozole in postmenopausal women with HR+ early-stage breast cancer.

PubMed

Lipsitz, Michael; Delea, Thomas E; Guo, Amy

2010-10-01

The Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen Alone or in Combination (ATAC) trials demonstrated that, in postmenopausal women with hormone receptor positive (HR+) early-stage breast cancer, 5 years of initial adjuvant endocrine therapy with letrozole or anastrozole is superior to tamoxifen. With expected generic availability of anastrozole in July 2010 and letrozole in June 2011, there may be financial pressures prior to letrozole's generic availability to start treatment-naïve patients on anastrozole vs. letrozole or to switch patients already receiving letrozole to anastrozole. A Markov model was used to estimate cost per quality-adjusted life-year (QALY) gained with letrozole vs. anastrozole from the US healthcare system perspective. Cost effectiveness was examined separately in treatment-naïve patients and in patients already receiving letrozole. For the latter, cost effectiveness of continued letrozole vs. therapeutic substitution (TS) to generic anastrozole was evaluated separately in cohorts defined on years of endocrine therapy remaining. TS to generic anastrozole was assumed to result in an additional 5% of patients discontinuing endocrine therapy. Probabilities of distant recurrence and death were taken from reports of BIG 1-98, ATAC, the Early Breast Cancer Trialists' Collaborative Group meta-analysis of tamoxifen, and other published sources. Carry-over effects of aromatase inhibitors were assumed to be proportional to treatment duration. Costs of aromatase inhibitors were assumed to decline by 75% with generic availability. In treatment-naïve patients, total expected lifetime costs are $3916 greater with letrozole vs. anastrozole. However, initiation of treatment with letrozole results in a gain of 0.15 QALYs. Cost per QALY gained with letrozole vs. anastrozole is $25,846. In patients already receiving letrozole, the increase in total expected lifetime costs with continued letrozole vs. TS to anastrozole is between $4200 and

Neurocognitive Outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study

ERIC Educational Resources Information Center

Frazier, Jean A.; Giuliano, Anthony J.; Johnson, Jacqueline L.; Yakutis, Lauren; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.; Hooper, Stephen R.

2012-01-01

Objective: To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Method: Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated…

Clinical effectiveness of decongestive treatments on excess arm volume and patient-centered outcomes in women with early breast cancer-related arm lymphedema: a systematic review

PubMed Central

Jeffs, Eunice; Ream, Emma; Taylor, Cath; Bick, Debra

2018-01-01

outcome measures were not pooled in statistical meta-analysis. A narrative and tabular format was used to synthesize results from identified and included studies. Results: Seven studies reporting results for outcomes of interest were critically appraised and included in the review: five randomized controlled trials and two descriptive (uncontrolled) studies. Reported outcomes included excess arm volume (five studies), health-related quality of life (three studies), arm heaviness (one study), arm function (two studies) and patient-perceived benefit (two studies). There was some evidence that decongestive treatments were effective for women presenting within either 12 months or a mean of nine months of developing breast cancer-related arm lymphedema, but the wide range of data prevented comparison of treatment findings which limited our ability to answer the review questions. Conclusions: Weak evidence (grade B) for the impact of decongestive lymphedema treatment on women with early lymphedema (i.e. less than 12 months duration of BCRL symptoms) did not allow any conclusions to be drawn about the most effective treatment to be offered when these women first present for treatment. Findings provided no justification to support change to current practice. Future primary research needs to focus on the most effective treatment for women when they first present with lymphedema symptoms, e.g. treatment provided within 12 months of developing symptoms. Studies should be adequately powered and recruit women exclusively with less than 12 months duration of breast cancer-related lymphedema symptoms, provide longer follow-up to monitor treatment effect over time, with comparable treatment protocols, outcome measures and reporting methods. PMID:29419623

Is early intervention in psychosis cost-effective over the long term?

PubMed

Mihalopoulos, Cathrine; Harris, Meredith; Henry, Lisa; Harrigan, Susy; McGorry, Patrick

2009-09-01

This study assesses the long-term cost-effectiveness of a comprehensive model of mental health care for first-episode psychosis. The study is an extension of a previous economic evaluation of the Early Psychosis Prevention and Intervention Centre (EPPIC) that assessed the first-year costs and outcomes of treatment. The current study used a matched, historical control group design with a follow-up of approximately 8 years. Complete follow-up data were available for 65 of the original 102 participants. Direct public mental health service costs incurred subsequent to the first year of treatment and symptomatic and functional outcomes of 32 participants initially treated for up to 2 years at EPPIC were compared with a matched cohort of 33 participants initially treated by generic mental health services. Treatment-related resource use was measured and valued using Australian published prices. Almost 8 years after initial treatment, EPPIC subjects displayed lower levels of positive psychotic symptoms (P = .007), were more likely to be in remission (P = .008), and had a more favorable course of illness (P = .011) than the controls. Fifty-six percent of the EPPIC cohort were in paid employment over the last 2 years compared with 33% of controls (P = .083). Each EPPIC patient costs on average A$3445 per annum to treat compared with controls, who each costs A$9503 per annum. Specialized early psychosis programs can deliver a higher recovery rate at one-third the cost of standard public mental health services. Residual methodological limitations and limited sample size indicate that further research is required to verify this finding.

T42. WHEN SHOULD EARLY INTERVENTION START, AND FOR HOW LONG SHOULD IT LAST?

PubMed Central

Albert, Nikolai; Melau, Marianne; Jensen, Heidi; Hastrup, Lene Halling; Hjorthøj, Carsten; Nordentoft, Merete

2018-01-01

Abstract Background Early intervention in psychosis facilities have often failed to integrate the two main elements of early intervention. While some facilities have focused on early, and have had Duration of Untreated Psychosis (DUP) as their main target, others have focused on the intervention and the treatment provided when patients were diagnosed. As both DUP reduction and specialized early intervention (SEI) has proved to have an effect on the treatment of patients with first-episode psychosis one could hope of a synergetic effect if the two strategies were integrated. In this study, we use data from a randomized clinical trial testing the effect of prolonged early intervention (5 years) compared to standard specialized early intervention (2 years). Overall the study found that both treatment groups remained stable or improved in psychopathology, functioning and cognition and that there was no further beneficial effect of the prolonged the treatment. Participants had a long DUP (median 52 weeks). For this specific sub-study we hypothesized that patients who were treated early in their course of illness would have a beneficial effect of the prolonged treatment compared to those who only received 2 years of specialized treatment. Methods 296 participants with a psychotic diagnosis within the schizophrenia spectrum (ICD 10 – F2x, excluding F21) were included. DUP start was assessed from first psychotic symptom equivalent to 3 or above on a global SAPS item. DUP stop was when patients started antipsychotic treatment or specialized early intervention treatment. To assess if there were a delay within the mental health referral system we used the national register to identify when participants first were diagnosed with a schizophrenia spectrum diagnosis and calculated the time until they started SEI treatment. Finally, we added the DUP and the treatment delay together to assess the time from first psychotic symptom until the start of adequate treatment (both

Is alternate rapid maxillary expansion and constriction an effective protocol in the treatment of Class III malocclusion? A systematic review

PubMed Central

Pithon, Matheus Melo; Santos, Nathalia de Lima; dos Santos, Camila Rangel Barreto; Baião, Felipe Carvalho Souza; Pinheiro, Murilo Costa Rangel; Matos, Manoel; Souza, Ianderlei Andrade; de Paula, Rafael Pereira

2016-01-01

ABSTRACT Introduction: the treatment of Class III malocclusion in early age is one of the greatest challenges for orthodontists, and the establishment of more effective treatment method is a constant concern for these professionals. Thus, the objective of this systematic review is to verify the effectiveness of the therapy protocol for alternate rapid maxillary expansion and constriction (Alt-RAMEC) in the early treatment of Class III malocclusion. Methods: searches were performed in the following electronic databases: Cochrane Library, Medline (EBSCO and PubMed), SciELO, LILACS and Scopus. The following inclusion criteria were used: in vivo studies conducted with early intervention (patient in craniofacial development phase) with the use of the Alt-RAMEC protocol. Reviews, case reports, editorials, and studies with syndromic patients or under use of systemic drug were excluded. Duplicates were also excluded. The studies were assessed for methodological quality using the Cochrane tool for assessment of risk of bias, and classified as high or low risk of bias. Results: 53 articles were found. Duplicates exclusion was thus performed and 35 articles remained. After inclusion analysis, only 5 matched the criteria. Two articles were classified as low risk of bias and three as high risk of bias. It was observed that the Alt-RAMEC enable protraction in less time and with better results, promoting greater effectiveness in the protraction treatment of Class III malocclusion. Conclusions: Although there is positive evidence of the effectiveness of early treatment with the Alt-RAMEC protocol in patients with Class III malocclusion, further studies are needed to confirm its effectiveness using long-term methodology. PMID:28125138

Effect of bone mesenchymal stem cells transplantation on the micro-environment of early osteonecrosis of the femoral head.

PubMed

Song, Huanjin; Tao, Li; Wang, Fang; Wang, Weizhuo; Wei, Yongchang; Shen, Wenjun; Zhou, Fuling

2015-01-01

Autologous implantation of bone mesenchymal stem cells (BMSCs) has achieved promising clinical efficacy for the treatment of early-stage osteonecrosis of the femoral head (ONFH). However, the underlying mechanisms are not completely elucidated. Here, we investigated the effect of BMSCs on the early ONFH in vitro and in vivo. In co-cultured system, primary BMSCs enhanced the activity and inhibited the apoptosis of primary OB. The concentrations of VEGF and BMP-2 in the co-cultured medium were significantly higher than those without co-culture. Importantly, BMSCs implantation increased OB, capillaries and VEGF and BMP-2 expressions of the necrotic areas of femoral head in the ONFH rabbits. In conclusion, our results indicated that BMSCs treated the early ONFH possibly through increasing OB and capillaries, as well as VEGF and BMP-2 expression in the femoral head. These results provided possible mechanisms for the treatment of early-stage ONFH with BMSCs transplantation.

Anxious Depression and early changes in the HAMD-17 anxiety-somatization factor items and antidepressant treatment outcome

PubMed Central

Farabaugh, Amy H.; Bitran, Stella; Witte, Janet; Alpert, Jonathan; Chuzi, Sarah; Clain, Alisabet J.; Baer, Lee; Fava, Maurizio; McGrath, Patrick J.; Dording, Christina; Mischoulon, David; Papakostas, George I

2010-01-01

Objective To assess the relationship between early changes in anxiety/somatization symptoms and treatment outcome among MDD subjects during a 12-week trial of fluoxetine. We also examined the relationship between anxious depression and treatment response. Methods 510 MDD patients received 12 weeks of fluoxetine with flexible dosing (target dosages: 10 mg/day (week 1), 20 mg/day (weeks 2–4), 40 mg/day (weeks 4–8), and 60 mg/day (weeks 5–12)). We assessed the relationship between early changes in HAMD-17- anxiety/somatization factor items and depressive remission, as well as whether anxious depression at baseline predicted remission at study endpoint. . Baseline HAMD-17 scores were considered as covariates and the Bonferroni correction (p ≤ .008) was used for multiple comparisons. Results Adjusting for baseline HAMD-17 scores, patients who experienced greater early improvement in somatic symptoms (gastrointestinal) were significantly more likely to attain remission (HAMD-17 < 8) at endpoint than those without early improvement (p = .006). Early changes in the remaining items did not predict remission, nor did anxious depression at baseline. Conclusions Among the anxiety/somatization factor items, only early changes in somatic symptoms (gastrointestinal) predicted remission. Future studies are warranted to further investigate this relationship, as well as that between anxious depression and treatment outcome. PMID:20400905

Cimetidine as a novel adjunctive treatment for early stage Lyme disease.

PubMed

Shemenski, Justin

2016-04-09

Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most common vector-borne illness in the United States. It is a complex disease which may affect the skin, joints, heart, eyes, and central nervous system. Prompt diagnosis and treatment is curative in most instances. However, a significant percentage of patients experience ongoing symptoms after treatment. Currently, there is much controversy regarding the diagnosis, pathophysiology, and treatment of Lyme disease. Pathogen persistence despite treatment lies at the heart of this debate. Many believe that the ongoing symptoms are due to factors such as autoimmunity or permanent damage that is incurred during the active infection. However, there is an emerging school of thought that states that ongoing symptoms are due to a persistent infection that is able to survive both the immune response and antibiotic therapy. Numerous studies have shown that Bb can indeed persist within the host despite treatment and several mechanisms have been proposed to explain Bb's persistence capabilities. These include: polymorphism, antigenic variance, biofilm formation, persister cells, and immunomodulation. There is evidence that Bb is able to alter cytokine profiles within the host which may allow the organism to survive the immune response. This immunomodulation follows a pattern of T-helper 1 (TH1) suppression in favor of T-helper 2 (TH2) processes. In contrast, it has been shown that the optimal immune response to Bb infection involves an early, robust TH1 response and a later conversion to TH2 dominance once the infection is controlled or cleared. It has been proposed that a reconstitution of proper immune-competency in the infected host may improve clinical outcomes in Lyme disease. Cimetidine (CIM) is an over-the-counter histamine-2 (H2) antagonist that is primarily used to lower acid secretions in the stomach. T-regulatory (Treg) cells also possess the H2 receptor, which has spurred interest in CIM as a

Early response to venlafaxine antidepressant correlates with lower ACTH levels prior to pharmacological treatment.

PubMed

Araya, A V; Rojas, P; Fritsch, R; Rojas, R; Herrera, L; Rojas, G; Gatica, H; Silva, H; Fiedler, J L

2006-12-01

A link between stressful life events and development or exacerbation of depression has been established via a large body of evidence. An alteration in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression has also been associated with an increase in cortisol secretion. As arginine-vasopressin (AVP) plays an important role in the activation of HPA axis during stress, the present study investigated ACTH and cortisol secretory response induced by an AVP-related peptide desmopressin (ddAVP) in patients with major depression. Prior to antidepressant treatment, endocrinological parameters were evaluated and correlated with the clinical response to venlafaxine treatment, which offers a dual antidepressant action. Depressive patients with no other psychiatric pathology were evaluated with 17-item Hamilton Depression Scale (HAM-D) in order to follow-up the response to venlafaxine. After 1 wk of treatment, 60% of patients reduced their initial HAM-D score to at least 25%; this group was classified as early responders. The other group (40%) started to reduce significantly their HAM-D score after 3 wk of treatment and was classified as late responders. After 6 wk of treatment both groups have reduced HAM-D score to at least 25% of the baseline score. Prior to the pharmacological treatment, both early and late responders showed salivary cortisol rhythm and urinary free cortisol (UFC) in 24-h similar to healthy subjects. However, we did observe differences in basal ACTH secretion, showing that the late responder group had higher basal ACTH than both early responders and controls. The ddAVP challenge promoted a robust secretion of ACTH only in late responders, suggesting a different sensitivity of pituitary vasopressin receptor. The differences in clinical response to venlafaxine among depressive patients seem to be related to endocrinological parameters.

Treatment of early non-small cell lung cancer, stage IA, by image-guided robotic stereotactic radioablation--CyberKnife.

PubMed

Brown, William T; Wu, Xiaodong; Amendola, Beatriz; Perman, Mark; Han, Hoke; Fayad, Fahed; Garcia, Silvio; Lewin, Alan; Abitbol, Andre; de la Zerda, Alberto; Schwade, James G

2007-01-01

To evaluate the efficacy of using image-guided robotic stereotactic radioablation as an alternative treatment modality for patients with surgically resectable, but medically inoperable, T1 N0 M0, stage IA non-small cell lung cancer. Between January 2004 and May 2006, 19 patients, 11 women and 8 men ranging in age from 52 to 88 years, with stage IA non-small cell lung cancer were treated. Tumor volume ranged from 1.7 to 13 mL. Total doses ranged from 24 to 60 Gy delivered in 3 fractions. Eleven patients received 60 Gy. Real-time target localization was accomplished by radiographic detection of fiducial marker(s) implanted within the tumor combined with respiratory motion tracking. All patients tolerated radioablation well with fatigue as the main side effect. Fourteen patients are alive from 1 to 25 months posttreatment. Four patients died: 2 of comorbid disease and 2 of cancer progression (status post 60 and 55.5 Gy). Three patients developed grade I radiation pneumonitis. Two patients have stable disease. In 3 patients, cancer recurred in the planning treatment volume: in 2 patients after treatment with 60 Gy and in 1 patient after treatment with 55.5 Gy. One patient had local control in the target volume but developed metastasis to the ipsilateral hilum. Nine patients had a complete response and show no evidence of disease. In our early experience, stereotactic radioablation using the CyberKnife system appears to be a safe, minimally invasive, and effective modality for treating early stage lung cancer in patients with medically inoperable disease. Dose escalation and/or increasing the treatment volumes, with the aid of the high conformality of this technique, may help to achieve further improvements in these promising results.

The influence of rapamycin on the early cardioprotective effect of hypoxic preconditioning on cardiomyocytes

PubMed Central

Wang, Jiang; Maimaitili, YiLiyaer; Yu, Jin; Guo, Hai; Ma, Hai-Ping; Chen, Chun-ling

2016-01-01

Introduction The purpose of this study was to examine the effects of rapamycin on the cardioprotective effect of hypoxic preconditioning (HPC) and on the mammalian target of rapamycin (mTOR)-mediated hypoxia-inducible factor 1 (HIF-1) signaling pathway. Material and methods Primary cardiomyocytes were isolated from rat pups and underwent rapamycin and/or HPC, followed by hypoxia/re-oxygenation (H/R) injury. Cell viability and cell injury were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and qRT-PCR was used to measure HIF-1α and mTOR mRNA expression. A Langendorff heart perfusion model was conducted to observe the effect of rapamycin. Results Rapamycin treatment nearly abolished the cardioprotective effect of HPC in cardiomyocytes, reduced cell viability (p = 0.007) and increased cell damage (p = 0.032). HIF-1α and mTOR mRNA expression increased in cardiomyocytes undergoing I/R injury within 2 h after HPC. After rapamycin treatment, mTOR mRNA expression and HPC-induced HIF-1α mRNA expression were both reduced (p < 0.001). A Langendorff heart perfusion model in rat hearts showed that rapamycin greatly attenuated the cardioprotective effect of HPC in terms of heart rate, LVDP, and dp/dtmax (all, p < 0.029). Conclusions Rapamycin, through inhibition of mTOR, reduces the elevated HIF-1α expression at an early stage of HPC, and attenuates the early cardioprotective effect of HPC. PMID:28721162

Effective Treatment of Transmissible Venereal Tumors in Dogs with Vincristine and IL2.

PubMed

DEN Otter, Willem; Hack, Margot; Jacobs, John J L; Tan, Jurgen F V; Rozendaal, Lawrence; VAN Moorselaar, R Jeroen A

2015-06-01

To improve treatment of inoperable transmissible venereal tumors (TVTs) in dogs. Recently, we showed that TVT is sensitive to intratumoral treatment with interleukin-2 (IL2). In addition it is known that TVT is sensitive to intravenous treatment with vincristine. In the present study we tried to establish the therapeutic effect of intratumoral treatment with vincristine and IL2. We treated 12 dogs with TVT with 1-4 intratumoral treatments with vincristine and IL-2. Per treatment we used vincristine (0.5-0.7 mg/m(2)) and IL2 (2×10(6) units). The injections were given at weekly intervals. Early therapeutic effects were: three complete regressions, four partial regressions, three stable disease, and two progressive disease. Late therapeutic effects were established 45-60 months after the first presentation; there were five complete regressions, no partial regressions, nor stable or progressive diseases. Interestingly, all five dogs with late therapeutic effects were in good health. No tumor recurrence was noted. Intratumoral treatment of TVT with vincristine and IL2 appears to have impressive therapeutic effects. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Are both early egg introduction and eczema treatment necessary for primary prevention of egg allergy?

PubMed

Matsumoto, Kenji; Mori, Rintaro; Miyazaki, Celine; Ohya, Yukihiro; Saito, Hirohisa

2018-06-01

The Learning Early About Peanut Allergy (LEAP) study proved that early introduction of peanut significantly prevented the development of peanut allergy. However, in regard to similar attempts to prevent egg allergy through early egg introduction, the Prevention of Egg Allergy in High-risk Infants with Eczema (PETIT) study is the only randomized intervention trial to show a statistically significant effect. Meta-analysis of those studies indicated that neither the total amount nor pretreatment of egg showed any effect on egg allergy at the age of 12 months. However, raw egg powder resulted in a significantly higher prevalence of allergic reactions at initial introduction, whereas use of boiled egg was much safer. The prevalence of atopic dermatitis/eczema at introduction of egg correlated significantly with the subsequent prevalence of allergic reactions at initial introduction. In addition, the prevalence of egg allergy in the late introduction group correlated significantly with the prevalence of atopic dermatitis at introduction, even when the atopic dermatitis was proactively treated with a topical corticosteroid ointment. It is definitely true that the number of trials and number of participants in each trial are insufficient for drawing firm conclusions, especially regarding the optimal dose, raw versus boiled, when to start, and for whom to intervene. Therefore we propose various studies that should be performed to generate stronger data and conclusions. However, on the basis of the most recent results, we postulate that simultaneous intervention by both early boiled egg introduction and eczema treatment is probably indispensable for primary prevention of egg allergy. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Dual effects of fluoxetine on mouse early embryonic development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Chang-Woon; Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University, Changwon 630-723; Choe, Changyong

2012-11-15

Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50 μM) for different durations. When late 2-cells were incubated with 5 μM fluoxetine for 6 h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetinemore » (5 μM) over 24 h showed a reduction in blastocyst formation. The addition of fluoxetine (5 μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K{sup +} channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ∼ 30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Highlights: ► Short-term exposure of 2-cells to fluoxetine enhances mouse blastocyst formation. ► The enhancive effect of fluoxetine is resulted from Ca

Understanding Treatment Effect Estimates When Treatment Effects Are Heterogeneous for More Than One Outcome.

PubMed

Brooks, John M; Chapman, Cole G; Schroeder, Mary C

2018-06-01

Patient-centred care requires evidence of treatment effects across many outcomes. Outcomes can be beneficial (e.g. increased survival or cure rates) or detrimental (e.g. adverse events, pain associated with treatment, treatment costs, time required for treatment). Treatment effects may also be heterogeneous across outcomes and across patients. Randomized controlled trials are usually insufficient to supply evidence across outcomes. Observational data analysis is an alternative, with the caveat that the treatments observed are choices. Real-world treatment choice often involves complex assessment of expected effects across the array of outcomes. Failure to account for this complexity when interpreting treatment effect estimates could lead to clinical and policy mistakes. Our objective was to assess the properties of treatment effect estimates based on choice when treatments have heterogeneous effects on both beneficial and detrimental outcomes across patients. Simulation methods were used to highlight the sensitivity of treatment effect estimates to the distributions of treatment effects across patients across outcomes. Scenarios with alternative correlations between benefit and detriment treatment effects across patients were used. Regression and instrumental variable estimators were applied to the simulated data for both outcomes. True treatment effect parameters are sensitive to the relationships of treatment effectiveness across outcomes in each study population. In each simulation scenario, treatment effect estimate interpretations for each outcome are aligned with results shown previously in single outcome models, but these estimates vary across simulated populations with the correlations of treatment effects across patients across outcomes. If estimator assumptions are valid, estimates across outcomes can be used to assess the optimality of treatment rates in a study population. However, because true treatment effect parameters are sensitive to correlations

Effectiveness of brief VR treatment for PTSD in war-fighters: a case study.

PubMed

Miyahira, Sarah D; Folen, Raymond A; Hoffman, Hunter G; Garcia-Palacios, Azucena; Schaper, Kim M

2010-01-01

War-fighters exposed to combat are at high risk for developing posttraumatic stress disorder (PTSD), a complex and challenging condition to treat. Cognitive behavioral therapies (CBT) have been empirically validated as effective treatments for PTSD resulting from sexual assault, vehicular accidents, and disasters. Exposure, imaginal or in vivo, to the traumatic event is a central component of successful CBT treatment. Early studies indicate that CBT with brief virtual reality exposure (VRE) is beneficial in treating PTSD. The case study examined the effectiveness of brief VRE in treating combat-related PTSD.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib.

PubMed

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib

PubMed Central

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib. PMID:28744140

[Conservative treatment of idiopathic scoliosis with effective braces: early response to trunk asymmetry may avoid curvature progress].

PubMed

Matussek, J; Dingeldey, E; Wagner, F; Rezai, G; Nahr, K

2014-07-01

Vertical posture of the growing child requires minute central nervous control mechanisms in order to maintain symmetry of the torso in its various activities. Scoliosis describes a constant deviation in the frontal, transverse and sagittal planes from the dynamic symmetry of the trunk. Early intervention with effective bracing, physiotherapy and sports can reverse curve progression during growth spurts, once these are identified in screening. Modern braces have a derotating and reducing effect (mirror effect) on asymmetric body volumes, thus influencing the growing torso and restoring lasting symmetry. Recent data support the use of braces to reverse progressing scoliosis.

Effect of generalised access to early diagnosis and treatment and targeted mass drug administration on Plasmodium falciparum malaria in Eastern Myanmar: an observational study of a regional elimination programme.

PubMed

Landier, Jordi; Parker, Daniel M; Thu, Aung Myint; Lwin, Khin Maung; Delmas, Gilles; Nosten, François H

2018-05-12

Potentially untreatable Plasmodium falciparum malaria threatens the Greater Mekong subregion. A previous series of pilot projects in Myanmar, Laos, Cambodia, and Vietnam suggested that mass drug administration was safe, and when added to provision of early diagnosis and treatment, could reduce the reservoir of P falciparum and interrupts transmission. We examined the effects of a scaled-up programme of this strategy in four townships of eastern Myanmar on the incidence of P falciparum malaria. The programme was implemented in the four townships of Myawaddy, Kawkareik, Hlaingbwe, and Hpapun in Kayin state, Myanmar. Increased access to early diagnosis and treatment of malaria was provided to all villages through community-based malaria posts equipped with rapid diagnostic tests, and treatment with artemether-lumefantrine plus single low-dose primaquine. Villages were identified as malarial hotspots (operationally defined as >40% malaria, of which 20% was P falciparum) with surveys using ultrasensitive quantitative PCR either randomly or targeted at villages where the incidence of clinical cases of P falciparum malaria remained high (ie, >100 cases per 1000 individuals per year) despite a functioning malaria post. During each survey, a 2 mL sample of venous blood was obtained from randomly selected adults. Hotspots received targeted mass drug administration with dihydroartemisinin-piperaquine plus single-dose primaquine once per month for 3 consecutive months in addition to the malaria posts. The main outcome was the change in village incidence of clinical P falciparum malaria, quantified using a multivariate, generalised, additive multilevel model. Malaria prevalence was measured in the hotspots 12 months after mass drug administration. Between May 1, 2014, and April 30, 2017, 1222 malarial posts were opened, providing early diagnosis and treatment to an estimated 365 000 individuals. Incidence of P falciparum malaria decreased by 60 to 98% in the four townships

Preliminary Evaluation on the Effects of Feeds on the Growth and Early Reproductive Performance of Zebrafish (Danio rerio)

PubMed Central

2012-01-01

This study evaluated the effects of several commercially available feeds and different feeding regimes on the growth and early reproductive performance of zebrafish (Danio rerio). Juvenile zebrafish (n= 20; 5.06 ± 0.69 mg) were stocked into each of 24 tanks (volume, 2 L); 3 tanks were assigned to each of 8 feeding combinations for a period of 60 d. At the end of 60 d, 2 male and 2 female fish from each tank were pooled by dietary treatment (n = 6) and used to evaluate the effects of feeding combinations on early reproductive performance. Zebrafish fed dietary treatments 3 and 7 had significantly greater weight gain than zebrafish fed diet 5. Mean spawning success was significantly greater in zebrafish fed the control diet (Artemiaonly) than in those fed diet 1. Mean hatch rates were greater in zebrafish fed the control feed and diets 1, 2, 3, 5, and 6 than zebrafish fed diet 4. Additional results suggest that female zebrafish are sexually mature after 90 d post fertilization and that fertilization rates are the limiting factor in early reproduction. PMID:23043806

Creep grazing and early weaning effects on cow and calf productivity.

PubMed

Harvey, R W; Burns, J C

1988-05-01

One hundred fifty Simmental-Hereford cows and calves were used in a 3-yr study to evaluate three creep grazing treatments and an early weaning treatment on cow and calf performance during midsummer (July to September). Calves were approximately 150 d of age and averaged 178.6 kg when treatments were initiated. Tifleaf pearl millet (Pennisetum Americanum L. Leeke) was used as the forage for two of the creep treatments, representing two cow stocking intensities of .466 (TLM1) and .239 (TLM2) ha of base hill land pasture/cow, and as pasture for early weaned calves. A red clover (Trifolium pratense L.)-Kentucky bluegrass (Poa pratensis L.) mixture was used as the other creep forage. Hill land pastures were similar for the mature cow units in all creep treatments. Calf average daily gains ranged from .93 to 1.10 kg and were not influenced (P greater than .05) by treatment. Calf gains per hectare were similar for the control, red clover and TLM1 treatments. The TLM2 and early weaning treatments resulted in increases of 105.4 and 39.1 kg of calf gain/ha (P less than .05) compared with the control. When calves were allowed to creep graze millet, decreasing the forage area from .466 to .239 ha per cow-calf unit resulted in an increase of 97.7 kg of calf gain/ha with no reduction in calf gain. Cows on the more intensively grazed millet creep treatment (TLM2) lost more weight (P less than .05) during midsummer than those on the TLM1 treatment, but they gained 18.5 kg more (P less than .10) weight than TLM1 cows between weaning and the start of winter feeding.

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

ERIC Educational Resources Information Center

Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

2007-01-01

Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

[Acupotomy and acupuncture in the treatment of avascular necrosis of femoral head at the early and middle stages:a clinical randomized controlled trial].

PubMed

Wang, Zhanyou; Zhou, Xuelong; Xie, Lishuang; Liang, Dongyue; Wang, Ying; Zhang, Hong-An; Zheng, Jinghong

2016-10-12

To compare the efficacy difference between acupotomy and acupuncture in the treatment of avascular necrosis of femoral head at the early and middle stages. The randomized controlled prospective study method was adopted. Sixty cases of avascular necrosis of femoral head at Ficat-ArletⅠto Ⅱ stages were randomized into an acupotomy group (32 cases) and an acupuncture group (28 cases) by the third part. In the acupotomy group, the acupotomy was adopted for the loose solution at the treatment sites of hip joint, once every two weeks, totally for 3 times. In the acupuncture group, ashi points around the hip joint were selected and stimulated with warm acupuncture therapy, once every day, for 6 weeks. Harris hip score was observed before and after treatment. The efficacy was evaluated in the two groups. Harris hip score was improved significantly after treatment in the two groups (both P <0.05). The result in acupotomy group was better than that in the acupuncture group ( P <0.05). The effective rate was 90.6% (29/32) in the acupotomy group, better than 75.0% (21/28) in the acupuncture group after treatment ( P <0.05). Harris hip score and the effective rate in the acupotomy group are better than those in the treatment with routine acupuncture for avascular necrosis of femoral head at the early and middle stages.

Weight changes after adjuvant treatment in Korean women with early breast cancer.

PubMed

Han, Hye-Suk; Lee, Keun-Wook; Kim, Jee Hyun; Kim, Sung-Won; Kim, In-Ah; Oh, Do-Youn; Im, Seock-Ah; Bang, Soo-Mee; Lee, Jong Seok

2009-03-01

Weight gain is a common problem in breast cancer patients and is reported to be associated with poorer survival. However, most data are limited to Western women. We evaluated weight changes after adjuvant treatment in Korean women with early breast cancer. The authors reviewed the records of 260 patients with stage I-III breast cancer treated between June 2003 and February 2006. Body weight, body mass index (BMI) and menopausal status at baseline and after 3, 6, 12 and 24 months of adjuvant treatment were reviewed. Mean patient age was 47.0 years and 61.1% of women were premenopausal. Among them, 195 patients (75.8%) received chemotherapy and 186 (71.5%) received hormonal therapy. Mean baseline weight was 57.5 +/- 9.8 kg and mean BMI was 23.5 +/- 1.6 kg/m(2) (22.8 +/- 3.0 vs. 24.7 +/- 3.2 kg/m(2) for pre- vs. post-menopausal women, P = 0.286). Mean weight changes were; 0.30 kg at 3 months (P = 0.019); 0.16 kg at 6 months (P = 0.367); -0.34 kg at 1 year (P = 0.082); -0.40 kg at 2 years (P = 0.097). Twenty-three patients (10.4%) gained more than 5% of baseline body weight at 1 year, but no clinical variable was found to be associated with these weight gains. This study shows that Korean women with early breast cancer do not gain weight after adjuvant treatment. Further studies are needed to determine differences between Asian and Western women in terms of weight changes and prognosis in early breast cancer.

Early life stress determines the effects of glucocorticoids and stress on hippocampal function: Electrophysiological and behavioral evidence respectively.

PubMed

Pillai, Anup G; Arp, Marit; Velzing, Els; Lesuis, Sylvie L; Schmidt, Mathias V; Holsboer, Florian; Joëls, Marian; Krugers, Harm J

2018-05-01

Exposure to early-life adversity may program brain function to prepare individuals for adaptation to matching environmental contexts. In this study we tested this hypothesis in more detail by examining the effects of early-life stress - induced by raising offspring with limited nesting and bedding material from postnatal days 2-9 - in various behavioral tasks and on synaptic function in adult mice. Early-life stress impaired adult performance in the hippocampal dependent low-arousing object-in-context recognition memory task. This effect was absent when animals were exposed to a single stressor before training. Early-life stress did not alter high-arousing context and auditory fear conditioning. Early-life stress-induced behavioral modifications were not associated with alterations in the dendritic architecture of hippocampal CA1 pyramidal neurons or principal neurons of the basolateral amygdala. However, early-life stress reduced the ratio of NMDA to AMPA receptor-mediated excitatory postsynaptic currents and glutamate release probability specifically in hippocampal CA1 neurons, but not in the basolateral amygdala. These ex vivo effects in the hippocampus were abolished by acute glucocorticoid treatment. Our findings support that early-life stress can hamper object-in-context learning via pre- and postsynaptic mechanisms that affect hippocampal function but these effects are counteracted by acute stress or elevated glucocorticoid levels. Copyright © 2018. Published by Elsevier Ltd.

Aspherical Supernovae: Effects on Early Light Curves

NASA Astrophysics Data System (ADS)

Afsariardchi, Niloufar; Matzner, Christopher D.

2018-04-01

Early light from core-collapse supernovae, now detectable in high-cadence surveys, holds clues to a star and its environment just before it explodes. However, effects that alter the early light have not been fully explored. We highlight the possibility of nonradial flows at the time of shock breakout. These develop in sufficiently nonspherical explosions if the progenitor is not too diffuse. When they do develop, nonradial flows limit ejecta speeds and cause ejecta–ejecta collisions. We explore these phenomena and their observational implications using global, axisymmetric, nonrelativistic FLASH simulations of simplified polytropic progenitors, which we scale to representative stars. We develop a method to track photon production within the ejecta, enabling us to estimate band-dependent light curves from adiabatic simulations. Immediate breakout emission becomes hidden as an oblique flow develops. Nonspherical effects lead the shock-heated ejecta to release a more constant luminosity at a higher, evolving color temperature at early times, effectively mixing breakout light with the early light curve. Collisions between nonradial ejecta thermalize a small fraction of the explosion energy; we will address emission from these collisions in a subsequent paper.

The Effects of Early Bilateral Otitis Media with Effusion on Educational Attainment: A Prospective Cohort Study.

ERIC Educational Resources Information Center

Peters, Sylvia A. F.; And Others

1994-01-01

Examination of the relationship between educational attainment and long-lasting, bilateral otitis media with effusion (OME) in 270 Dutch children (ages 2 to 4) found that, at age 7, early bilateral OME affected spelling ability but not reading ability. Effects of treatment with ventilation tubes were not found. (DB)

Controlling grape must fermentation in early winemaking phases: the role of electrochemical treatment.

PubMed

Lustrato, G; Alfano, G; Belli, C; Grazia, L; Iorizzo, M; Maiuro, L; Massarella, F; Zanardini, E; Ranalli, G

2003-01-01

To contribute to an understanding of the phenomena related to the effect of low electric current (LEC) in grape must fermentation during laboratory and pilot plant scale winemaking, with selected co-culture yeasts (Saccharomyces cerevisiae strain 404 and Hanseniaspora guilliermodii strain 465). LEC (10, 30, 50 and 100 mA) was applied to fresh grape must as an alternative method to the usual addition of SO2. Parameters such as polarity, treatment duration (24-96 h) and type of inoculum yeast were varied one at a time. LEC decreased the survival time and increased the death rate of H. guilliermondii strain 465 in co-cultures, whereas it did not affect the growth and survival of S. cerevisiae strain 40. A final comparison was made of the main physico-chemical parameters on wine obtained after the different tests. The results have demonstrated that the low voltage treatment using a pair of graphite electrodes had a positive effect on grape juice fermentation (yeast microflora) during the early stages of winemaking, even with the potential of being an alternative method to the usual addition of SO2. These results could be of significant importance in developing new winemaking technologies for an innovative yeast fermentation control process for 'biological wine'.