No-treatment Interval Research Articles

Low-intensity extracorporeal shock wave therapy for patients with severe erectile dysfunction due to radical prostatectomy

Background: Phosphodiesterase type 5 inhibitor (PDE5I) was proved to be effective for normal treatment, but the response rate of PDE5I is significantly low in patients with erectile dysfunction (ED) due to radical prostatectomy (RP). Low-intensity extracorporeal shockwave therapy (LI-ESWT) was proved to be useful as a safe modality to treat ED. My objective is to determine the efficacy of LI-ESWT for patients with severe ED due to RP. Methods: This study was an open-label prospective pilot study. Between September 2012 and May 2014, 12 patients with severe ED due to RP were enrolled into this protocol. LI-ESWT comprised two treatment sessions per week for three weeks, which were repeated after a three-week no-treatment interval. LI-ESWT was applied to the penile shaft and crura at five different sites. Assessment of erectile and sexual function during LI-ESWT was determined using the international index of erectile function-erectile function domain (IIEF-EF) score, erection hardness score (EHS), nocturnal penile tumescence (NPT), flow-mediated vasodilation (FMD), and adverse events. We used FMD with the plethysmography technique for objective evaluation of the participant’s penile hemodynamics and endothelial function (EnF). Results: At the one-month follow up examination, the IIEF-EF scores did not change after LI-ESWT. However, the erectile function parameters significantly improved from 0.50±0.19 to 1.13±0.30 for EHS (P=0.0078) and from 0.36±0.14 to 1.06±0.36 for NPT (P=0.0156). Also, the FMD parameters significantly improved from 13.8±1.3 to 24.0±2.5 (P=0.0032). None of the patients reported adverse events. Conclusions: This is the first study that assessed the efficacy of LI-ESWT for patients with severe ED due to RP. Based on our results, LI-ESWT appeared to have the potential to be an effective treatment option for severe ED patients.

Penile Low-Intensity Shock Wave Therapy for Erectile Dysfunction: Personal Experience

Objective: Penile extracorporeal low-intensity shock wave therapy (LIST) to the penis has recently emerged as a novel and promising modality in the treatment of erectile dysfunction. LIST can improve penile blood flow and endothelial function by stimulating angiogenesis in the penis. Design and Method: We applied LIST to patients with mild to moderate vasculogenic ED who responded well to the use of PDE5i. The treatment protocol consisted of one treatment sessions per week for 6 weeks, a 6 -week no-treatment interval. Each session comprised the application of 3000 shock waves (energy intensity of 4 mJ/mm3) to each penile shaft and 1000 shock waves for each crura. Results: The results showed that 6 weeks after treatment, erectile function improved in the 85% of the cases, good result was achieved in 10% and no results in 5% of the patients. The average increase in the IIEF-EF domain score was 8.8 points. Furthermore, erectile function and penile blood flow were measured using nocturnal penile tumescence (NPT) and color-power Doppler of the penis. All NPT parameters improved as recorded by significant increases in the duration of the erections and penile rigidity. Conclusions: The treatment options for ED have greatly expanded and include PDE5i, intracavernosal injections, and penile prostheses. Our experience presented here demonstrate that LIST of the corpora cavernosa is a novel therapeutic option for ED. LIST may have a fundamental effect on penile endothelial function, increasing penile blood flow, and improving erectile function and consequently sexual satisfaction.

Low Intensity Extracorporeal Shock Wave Therapy Improves Erectile Function in a Model of Type II Diabetes Independently of NO/cGMP Pathway

Erectile dysfunction is highly prevalent in type II diabetes mellitus. Low intensity extracorporeal shock wave therapy improves erectile function in patients with erectile dysfunction of vasculogenic origin, including diabetes. However, its mode of action remains unknown. We investigated the effects of low intensity extracorporeal shock wave therapy compared to or combined with sildenafil on erectile dysfunction in a type II diabetes mellitus model. Our purpose was to test our hypothesis of a mode of action targeting the cavernous nitric oxide/cyclic guanosine monophosphate pathway. GK rats, a validated model of type II diabetes mellitus, and age matched Wistar rats were treated with low intensity extracorporeal shock wave therapy twice weekly for 3 weeks. Treatment was repeated after a 3-week no-treatment interval. The penis was stretched and dipped in a specifically designed water-filled cage. Shock waves were delivered by a calibrated probe yielding a controlled energy flux density (0.09 mJ/mm(2)). The probe was attached to an electrohydraulic unit with a focused shock wave source, allowing for accurate extrapolation to humans. Following a 4-week washout period erectile function was assessed as well as endothelium dependent and independent, and nitrergic relaxations of the corpus cavernosum of GK rats. Low intensity extracorporeal shock wave therapy significantly improved erectile function in GK rats to the same extent as sildenafil. Treatment effects were potentiated when combined with sildenafil. Shock wave effects were not associated with improved cavernous endothelium dependent or independent, or nitrergic reactivity. Low intensity extracorporeal shock wave therapy improved erectile function in GK rats. Unexpectedly, this was not mediated by a nitric oxide/cyclic guanosine monophosphate dependent mechanism. Sildenafil increased shock wave efficacy. This preclinical paradigm to deliver low intensity extracorporeal shock wave therapy to the rat penis should help further exploration of the mode of action of this therapy on erectile tissue.

HELP-SEEKING AND PATHWAYS TO CARE IN THE EARLY STAGES OF PSYCHOSIS: RESULTS FROM THE FEPSY STUDY

To systematically review evidence of the effects of the duration of untreated depression on the clinical outcomes of patients suffering from Unipolar Major Depression.A systematic review and meta-analysis of the evidence of duration of untreated depression and the effect it has on clinical outcomes in Unipolar Major Depression. Data used to this purpose were obtained from a literature search of the MEDLINE, Psychoinfo and Embase databases. Comparable data extracted from studies were entered and analysed using Cochrane Collaboration's Review Manager software Version 5.2.Ten studies were identified as meeting the inclusion criteria. Only three studies reported comparable data and were consequently used for the meta-analysis. Pooled data indicates the overall positive effect of shorter duration of untreated illness both in a patient's response to treatment (RR 1.70) and remission (RR 1.65).Other studies which were not included in the meta-analysis confirmed the importance of reducing delays in the treatment of depression in order to prevent the risk of worse outcomes and chronicity, in particular in patients presenting with a first episode of depression. Data regarding the association between the duration of untreated episode in recurrent depression and clinical outcomes are less evident.The heterogeneity of the selected studies was cause for limitations with regard to the carrying out of adequate meta-analysis.There is evidence highlighting the importance of a reduced no-treatment interval for patients suffering Unipolar Depression. In particular, there is emphasis on the first episode of depression corresponding to the notion of reducing the duration of untreated illness.

Low‐Intensity Extracorporeal Shock Wave Therapy—A Novel Effective Treatment for Erectile Dysfunction in Severe ED Patients Who Respond Poorly to PDE5 Inhibitor Therapy

Low-intensity shock wave therapy (LI-ESWT) has been reported as an effective treatment in men with mild and moderate erectile dysfunction (ED). The aim of this study is to determine the efficacy of LI-ESWT in severe ED patients who were poor responders to phosphodiesterase type 5 inhibitor (PDE5i) therapy. This was an open-label single-arm prospective study on ED patients with an erection hardness score (EHS) ≤ 2 at baseline. The protocol comprised two treatment sessions per week for 3 weeks, which were repeated after a 3-week no-treatment interval. Patients were followed at 1 month (FU1), and only then an active PDE5i medication was provided for an additional month until final follow-up visit (FU2). At each treatment session, LI-ESWT was applied on the penile shaft and crus at five different anatomical sites (300 shocks, 0.09 mJ/mm(2) intensity at 120 shocks/min). Each subject underwent a full baseline assessment of erectile function using validated questionnaires and objective penile hemodynamic testing before and after LI-ESWT. Outcome measures used are changes in the International Index of Erectile Function-erectile function domain (IIEF-ED) scores, the EHS measurement, and the three parameters of penile hemodynamics and endothelial function. Twenty-nine men (mean age of 61.3) completed the study. Their mean IIEF-ED scores increased from 8.8 ± 1 (baseline) to 12.3 ± 1 at FU1 (P = 0.035). At FU2 (on active PDE5i treatment), their IIEF-ED further increased to 18.8 ± 1 (P < 0.0001), and 72.4% (P < 0.0001) reached an EHS of ≥ 3 (allowing full sexual intercourse). A significant improvement (P = 0.0001) in penile hemodynamics was detected after treatment and this improvement significantly correlated with increases in the IIEF-ED (P < 0.05). No noteworthy adverse events were reported. Penile LI-ESWT is a new modality that has the potential to treat a subgroup of severe ED patients. These preliminary data need to be reconfirmed by multicenter sham control studies in a larger group of ED patients.

Imiquimod 3.75% cream (Zyclara) for the treatment of actinic keratoses

Introduction: Actinic keratosis is a premalignant disease with a high incidence and is a strong predictor for the development of squamous cell carcinoma. Various treatment options have been established over recent years, including topical treatment with imiquimod, 5-fluorouracil, diclofenac or photodynamic therapy, cryotherapy and surgical procedures.Areas covered: This review covers basic and clinical experiences with imiquimod 3.75% for topical treatment of actinic keratosis of the face and balding scalp and its comparators with special focus on imiquimod 5%. It also covers pharmacology of imiquimod 3.5% and its contribution to the current treatment options of actinic keratoses.Expert opinion: Imiquimod 3.75% is an interesting, safe and well-tolerated treatment option for actinic keratoses of the face or balding scalp especially in respect of compliance, as it is indicated for daily use for a shorter time period (2 times, 2-week cycles) and approved for use on larger areas compared with imiquimod 5%. Data from current trials indicate lower efficacy compared with imiquimod 5% cream when applied three times a week for 16 weeks or for two 4-week cycles with a 4-week no-treatment interval, but indicate similar efficacy when compared with a twice-weekly schedule for 16 weeks. An additive effect was observed when combining cryosurgery followed by imiquimod 3.75%.

Can Low-Intensity Extracorporeal Shockwave Therapy Improve Erectile Function? A 6-Month Follow-up Pilot Study in Patients with Organic Erectile Dysfunction

BackgroundLow-intensity extracorporeal shockwave therapy (LI-ESWT) is currently under investigation regarding its ability to promote neovascularization in different organs. ObjectiveTo evaluate the effect of LI-ESWT on men with erectile dysfunction (ED) who have previously responded to oral phosphodiesterase type 5 inhibitors (PDE5-I). Design, setting, and participantsWe screened 20 men with vasculogenic ED who had International Index of Erectile Function ED (IIEF-ED) domain scores between 5–19 (average: 13.5) and abnormal nocturnal penile tumescence (NPT) parameters. Shockwave therapy comprised two treatment sessions per week for 3 wk, which were repeated after a 3-wk no-treatment interval. InterventionLI-ESWT was applied to the penile shaft and crura at five different sites. MeasurementsAssessment of erectile function was performed at screening and at 1 mo after the end of the two treatment sessions using validated sexual function questionnaires, NPT parameters, and penile and systemic endothelial function testing. The IIEF-ED questionnaire was answered at the 3- and 6-mo follow-up examinations. Results and limitationsWe treated 20 middle-aged men (average age: 56.1 yr) with vasculogenic ED (mean duration: 34.7 mo). Eighteen had cardiovascular risk factors. At 1 mo follow-up, significant increases in IIEF-ED domain scores were recorded in all men (20.9±5.8 vs 13.5±4.1, p<0.001); these remained unchanged at 6 mo. Moreover, significant increases in the duration of erection and penile rigidity, and significant improvement in penile endothelial function were demonstrated. Ten men did not require any PDE5-I therapy after 6-mo follow-up. No pain was reported from the treatment and no adverse events were noted during follow-up. ConclusionsThis is the first study that assessed the efficacy of LI-ESWT for ED. This approach was tolerable and effective, suggesting a physiologic impact on cavernosal hemodynamics. Its main advantages are the potential to improve erectile function and to contribute to penile rehabilitation without pharmacotherapy. The short-term results are promising, yet demand further evaluation with larger sham-control cohorts and longer follow-up.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 3-week cycles

Imiquimod 5% cream is approved as a 16-week regimen for the treatment of actinic keratoses involving a 25-cm(2) area of skin. We sought to evaluate imiquimod 2.5% and 3.75% creams for short-course treatment of the entire face and scalp. In two identical studies, adults with 5 to 20 lesions were randomized to placebo, or imiquimod 2.5% or 3.75% cream (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 3-week treatment cycles, with a 3-week, no-treatment interval. Efficacy was assessed at 8 weeks posttreatment. In all, 490 subjects were randomized to placebo, or imiquimod 2.5% or 3.75% cream. Median baseline lesion counts for the treatment groups were 9 to 10. Complete and partial clearance rates were 5.5% and 12.8% for placebo, 25.0% and 42.7% for imiquimod 2.5%, and 34.0% and 53.7% for imiquimod 3.75% (P < .001, each imiquimod vs placebo; P = .034, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion count were 23.6%, 66.7%, and 80.0% for the placebo, imiquimod 2.5%, and imiquimod 3.75% groups, respectively (P < .001 each imiquimod vs placebo). There were few treatment-related discontinuations. Temporary treatment interruption (rest) rates were 0%, 17.1%, and 27.2% for the placebo, imiquimod 2.5%, and imiquimod 3.75%, respectively. Local effects of imiquimod, including erythema, may have led to investigator and subject bias. Both imiquimod 2.5% and 3.75% creams were more effective than placebo and had an acceptable safety profile when administered daily as a 3-week on/off/on regimen.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles

The approved imiquimod 5% cream regimen for treating actinic keratoses requires a long treatment time and is limited to a small area of skin. We sought to evaluate imiquimod 2.5% and 3.75% for short-course treatment of the full face or balding scalp. In two identical studies, adults with 5 to 20 lesions were randomized to placebo, imiquimod 2.5%, or imiquimod 3.75% (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed at 8 weeks posttreatment. A total of 479 patients were randomized to placebo, or imiquimod 2.5% or 3.75%. Complete and partial clearance (> or =75% lesion reduction) rates were 6.3% and 22.6% for placebo, 30.6% and 48.1% for imiquimod 2.5%, and 35.6% and 59.4% for imiquimod 3.75%, respectively (P < .001 vs placebo, each; P = .047, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion counts were 25.0% for placebo, 71.8% for imiquimod 2.5%, and 81.8% for imiquimod 3.75% (P < .001, each active vs placebo; P = .048 3.75% vs 2.5%). There were few treatment-related discontinuations. Patient rest period rates were 0% for placebo, 6.9% for imiquimod 2.5%, and 10.6% for imiquimod 3.75%. Local pharmacologic effects of imiquimod, including erythema, may have limited concealment of treatment assignment in some patients. Both imiquimod 2.5% and 3.75% creams were more effective than placebo and were well tolerated when administered daily as a 2-week on/off/on regimen to treat actinic keratoses.

A short duration of untreated illness (DUI) improves response outcomes in first-depressive episodes

Background Few studies have addressed the implication of the duration of untreated illness (DUI) on the clinical outcome of mood disorders. Although not focusing on DUI, previous findings suggest that the longer it takes to start appropriate treatment, the worse will be the evolution of depressive disorder. We sought to determine the effect of the duration of untreated episode (DUE) on 1) rates of response to treatment, 2) time to attain a sustained response and 3) rates of remission of MDD, dealing specially with first-depressive episodes. Methods 141 patients with MDD were grouped into long DUE (> 8 weeks) and short DUE (≤ 8). Statistical analyses were performed to determine differences in outcome variables. The same analyses were repeated by splitting the sample between first-episode and recurrent depression. Results The percentage of patients who achieved a sustained response was significantly higher in the group with a short DUE [OR = 2.6; 95% CI 1.3–5.1]. Survival analyses showed that patients with a long DUE delayed longer time to attain a sustained response [39 vs. 20 days, p = 0.012]. Once the sample was split, these results were even more pronounced in the subsample of first-depressive episode patients. Limitations Given that the sample was originally recruited for two clinical trials, the follow-up period of this study is only six weeks long. Conclusions Our results indicate that response to antidepressant treatments is faster when the no-treatment interval is reduced. The earliest treatment of first-depressive episodes seems to be crucial since a shorter duration of untreated illness implies better response outcomes.

An Investigation of Treatment Scheduling for Phonemic Awareness With Kindergartners Who Are at Risk for Reading Difficulties

This study examined 2 schedules of treatment for phonemic awareness. Forty-one 5- to 6-year-old kindergartners, including 22 English learners, with low letter-name and first-sound knowledge received 11 hr of phonemic awareness treatment: concentrated (CP, 3x/wk to December), dispersed (DP, 1x/wk to March), and dispersed vocabulary control (CON). English learners performed similarly to native English speakers. Participants with moderate deficits in letter-names and first sounds showed significant benefits after both treatment conditions. Three times the intensity had no additional effect on phonemic awareness. CP continued to increase significantly during the no-treatment interval. In March, CP and DP were significantly greater than CON, but the 2 conditions did not differ other than with a minor DP advantage on last sounds. By May, there were no significant differences among the 3 conditions in meeting grade-level expectations for phoneme segmenting. For phonemic awareness, over the course of a school year, with concomitant classroom instruction, the gains made from short, intense treatment were similar to those made from continuous weekly treatment. At-risk kindergartners with moderate deficits benefited more than those with mild deficits. Children, particularly those with mild deficits, may improve substantially with only classroom instruction and incidental self-regulatory gains from treatment for another area.

First admissions for depression: is the `no-treatment interval' a critical predictor of time to remission?

Background: This study aimed to replicate findings that length of episode prior to adequate antidepressant treatment (the `no-treatment interval') and premorbid neuroticism predict time to remission from the institution of adequate treatment for depression. Methods: Eighty-three inpatients meeting ICD-10 criteria for a depressive illness were entered into an 18-month prospective follow-up study of illness course. Subjects were assessed using the Schedules for Clinical Assessment in Neuropsychiatry, Maudsley Personality Inventory (MPI) and the Hamilton Rating Scale for Depression (HRSD). Remission was defined as an HRSD score of <8 for 2 consecutive weeks. Results Twenty-two patients (27%) remained depressed 12 months after the onset of adequate treatment. Significantly longer times to remission were predicted by a longer no-treatment interval and higher premorbid neuroticism scores. Limitations: Adequate antidepressant treatment was commenced prior to admission in half the cases, requiring a retrospective assessment of illness course prior to study entry. Twenty-four patients (29%) had not remitted at the time of completion of the MPI. Conclusions: These results replicate previous findings identifying a longer time to treatment and higher neuroticism scores as predictors of chronicity in depression.

Alterations of Cell Cycle Regulators in Rat and Mouse Urinary Bladder Carcinogenesis Models.

Both genotoxic and non-genotoxic carcinogens may cause changes in cell cycle regulatory mechanisms. One of the most frequent genetic alterations observed in human malignancies, including urinary bladder carcinomas, involves the p53 tumor suppressor gene. The H- and K-ras oncogenes also appear to be prime targets in man and experimental animals. In rat urinay bladder carcinogenesis models using N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), most transitional cell car-cinomas (TCCs) produced are of papillary type and invasion is rare. While p53 mutations are relatively frequent in animals continuously exposed to BBN, they are less common when tumors are generated by protocols with a no-treatment interval before terminal sacrifice. The ras gene alterations do not vary under these conditions. In two-stage (initiation-promotion) rat models, p53 mutations are rare but cyclin D1 overexpression is frequently observed in TCCs. No mutations are generally found in rat tumors due to the non-genotoxic carcinogen, uracil. In contrast to rat tumors, mouse urinary bladder tumors induced by BBN aggressively invade and demonstrate occasionally metastasis. In one series, p53 mutations were found in 14 of 18 invasive tumors. Moreover, urinary bladder carcinomas with metastasis harbored more frequent alterations. Loss of heterozygosity of the p53 gene was also evident in about 14% of such carcinomas. In conclusion, genetic alterations differ according to the experimental protocol, the species, and the type of carcinogen used.

Effects of eye-movement desensitization versus no treatment on repeated measures of fear of spiders

Multiple measures of fear of spiders were acquired during in vivo tests once before and several times after 7 subjects were exposed to an experimental rendition of eye-movement desensitization. The pre- and posttreatment measures were compared with corresponding measures acquired from 7 other subjects once before and several times after a concurrent no-treatment interval. There was no evidence from the in vivo tests that eye-movement desensitization affected fear of spiders.

Time to remission in major depression. Is there a link between ‘no-treatment interval’ and outcome?

Time to remission in major depression. Is there a link between ‘no-treatment interval’ and outcome?

A study of group communication intervention with chronically aphasic persons

Abstract Aten et al (1982) demonstrated that a group of mild moderate chronically aphasic individuals made statistically significant improvement on the CADL subsequent to group treatment emphasizing functional communication skills. However, no improvement was apparent on the PICA. The present study investigated the effects of a relatively more structured group treatment programme on the communication ability of chronically aphasic patients. Ten aphasics, a minimum of 18 months post-onset, participated in a 60-week programme that included two series of 20 weeks of group treatment and 10 weeks of treatment withdrawal. The chronic aphasic subjects in this study did make gains in overall communication ability after 20 weeks of structured group treatment, and initial gains were retained throughout treatment withdrawals. Reinitiation of structured treatment after a no-treatment interval resulted in a significant gain in communication ability as measured by the PICA. Significant CADL gains were limited to the fi...