Efficacy and Safety of Propiverine and Solifenacin for the Treatment of Female Patients with Overactive Bladder: A Crossover Study

Objectives: To evaluate the clinical efficacy and tolerability of propiverine and solifenacin in female patients with overactive bladder (OAB). Methods: A prospective nonrandomized crossover study of propiverine 20 mg and solifenacin 5 mg was conducted. Female OAB patients were assigned alternately to treatment with propiverine for 8 weeks then solifenacin for 8 weeks (Group P‐S) or solifenacin for 8 weeks then propiverine for 8 weeks (Group S‐P). At baseline, 8th week and 16th week, symptoms were assessed using overactive bladder symptom score (OABSS). Results: A total of 121 patients were enrolled. Overall, 38 patients (31.4%) discontinued or dropped out and 83 patients were available for analysis (39 in Group P‐S and 44 in Group S‐P). In both groups, the total score and each score of OABSS were significantly improved after 8 weeks compared with baseline. In only Group P‐S (changing over from propiverine to solifenacin), urgency score in the 16th week was further improved significantly compared with the 8th week. The most bothersome symptom at baseline was urgency incontinence (50.6%), followed by urgency (37.3%). Even after symptom improvement, more than half of the patients were bothered by urgency or urgency incontinence. The incidence of adverse events of moderate and severe grade was higher during propiverine treatment than solifenacin (11.1% vs 2.9%, P = 0.039). Conclusion: Propiverine 20 mg and solifenacin 5 mg were effective for treating female OAB patients. Urgency was further improved after switching from propiverine to solifenacin, but not after switching from solifenacin to propiverine. Solifenacin was better tolerated than propiverine.     

Sacral Nerve Stimulation is more Effective than Optimal Medical Therapy for Severe Fecal Incontinence: A Randomized,Controlled Study

Purpose This randomized study was designed to compare the effect of sacral neuromodulation with optimal medical therapy in patients with severe fecal incontinence. Methods Patients (aged 39–86 years) with severe fecal incontinence were randomized to have sacral nerve stimulation (SNS group; n = 60) or best supportive therapy (control; n = 60), which consisted of pelvic floor exercises, bulking agent, and dietary manipulation. Full assessment included endoanal ultrasound, anorectal physiology, two-week bowel diary, and fecal incontinence quality of life index. The follow-up duration was 12 months. Results The sacral nerve stimulation group was similar to the control group with regard to gender (F:M = 11:1 vs. 14:1) and age (mean, 63.9 vs. 63 years). The incidence of a defect of ≤ 120° of the external anal sphincter and pudendal neuropathy was similar between the groups. Trial screening improved incontinent episodes by more than 50 percent in 54 patients (90 percent). Full-stage sacral nerve stimulation was performed in 53 of these 54 “successful” patients. There were no septic complications. With sacral nerve stimulation, mean incontinent episodes per week decreased from 9.5 to 3.1 (P < 0.0001) and mean incontinent days per week from 3.3 to 1 (P < 0.0001). Perfect continence was accomplished in 25 patients (47.2 percent). In the sacral nerve stimulation group, there was a significant (P < 0.0001) improvement in fecal incontinence quality of life index in all four domains. By contrast, there was no significant improvement in fecal continence and the fecal incontinence quality of life scores in the control group. Conclusions Sacral neuromodulation significantly improved the outcome in patients with severe fecal incontinence compared with the control group undergoing optimal medical therapy. *Deceased. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007.     

Effect of Blinding With a New Pragmatic Placebo Needle: A Randomized Controlled Crossover Study

Placebo control is a useful method for determining the efficacy of a therapy. In acupuncture researches, the preferred method for placebo control is acupuncture using a placebo needle that has a blunt tip and achieves no skin penetration.We performed a crossover study to validate the blinding effect of a new type of placebo needle. Sixty volunteers were randomized to receive acupuncture using 2 types of needles with different sequences: sequence AB, involving first the pragmatic placebo needle and then the real needle, and sequence BA, in a reverse order. Placebo acupuncture was performed by administering the placebo needle through an adhesive pad without skin penetration on the acupoints LI4, RN12, BL25, and BL36. Real acupuncture was performed by needling through the pad and penetrating the skin to 15 mm using a real needle on the same acupoints. The acupuncture was administered every other day with 3 sessions for 1 type of needle. The primary outcome was the perception of needle penetration. Besides degree of acupuncture pain, type, and degree of needle sensation, needle acceptability and factors influencing the subject blinding effect were assessed.Needle penetration was felt by 100%, 90% (54/60), 88.3% (53/60), and 95% (57/60) of volunteers receiving placebo acupuncture and 98.3% (59/60), 96.7% (58/60), 95% (57/60), and 95% (57/60) of volunteers receiving real acupuncture on LI4, RN12, BL25, and BL36, respectively. Differences of the volunteers’ perception of needle penetration between the placebo needle and real needle were not significant for the 4 acupoints (all P > 0.05). Volunteers experienced fewer distension sensations (P = 0.01), a lower degree of needle sensation (P = 0.007), and less pain (P = 0.006) during placebo acupuncture than during real acupuncture. The placebo needle was more easily accepted than the real needle (OR = 1.63, 95% CI, 1.01–2.64). The influences of age, sex, educational level, acupuncture experience, needle sensation, acupuncture pain, and needle acceptability on volunteers’ perception of needle penetration were not significant.The pragmatic placebo needle is a valid control for acupuncture research. It produces a good subject blinding effect with a similar appearance to conventional acupuncture needles and no skin penetration when applied.     

The effects of transcranial direct current stimulation on attention and inhibitory control of children and adolescents with attention-deficit/hyperactivity disorder (ADHD): Study protocol for a randomized,sham-controlled,triple-blind,cross-over trial

Attention-deficit/hyperactivity disorder (ADHD) is characterized by a persistent pattern of inattention and hyperactivity/impulsivity. Despite the proven efficacy of pharmacological treatment, many individuals continue to suffer socially and academically and some experience significant side effects that negate the use psychotropic drugs. Transcranial direct current stimulation (tDCS) is a cortical neuromodulation feature that has shown positive results in the treatment of various neuropsychiatric conditions.Objectives:To investigate the effect of tDCS on the performance of children and adolescents with ADHD in the neuropsychological tests of visual attention, verbal, and inhibitory control.Methodology:Triple blind, randomized, sham-controlled, cross-over trial involving tDCS in children and adolescents with ADHD. Initial screening will be performed using Swanson, Nolan, and Pelham – IVand Wechsler intelligence scale for children fourth edition vocabulary and cube subtests. Individuals will be evaluated pre-tDCS and post-tDCS with the Wechsler intelligence scale for children fourth edition Digitus subtest, neuropsychological assessment battery second edition inhibiting responses subtest, Corsi cubes, and visual attention test-4.     

Temporary Sacral Nerve Stimulation for Treatment of Irritable Bowel Syndrome: A Pilot Study

Purpose  This study was designed to evaluate the effect of temporary sacral nerve stimulation in patients with diarrhea-predominant irritable bowel syndrome. Methods  Symptoms of diarrhea-predominant irritable bowel syndrome and disease-specific quality of life was evaluated in six patients before and during percutaneous sacral nerve evaluation test. Primary end points were differences between total irritable bowel syndrome symptom score and total quality of life score before and during stimulation. Secondary end points were differences between the variable domains. Results  Percutaneous sacral nerve evaluation test was performed in five women and one man (median age, 33 (range, 26–54) years). The irritable bowel syndrome symptom score decreased from 48.9 to 28.3 (P = 0.004). Pain, bloating, and diarrhea were significantly reduced from 7.9, 13.5, and 17.3 to 4.4, 7.2, and 10.6, respectively (P = 0.02, P = 0.01, P = 0.03). The irritable bowel syndrome quality of life score decreased from 99.3 to 59.6 (P = 0.009). Daily activities, emotional distress, eating habits, and fatigue were significantly reduced from 26.9, 22.2, 15.2, and 23.2 to 16.9, 13.3, 8, and 14.4, respectively (P = 0.02, P = 0.02, P = 0.02, P = 0.007). Two weeks after cessation of stimulation, the patients had symptoms as before stimulation. Conclusions  Temporary sacral nerve stimulation provides a significant reduction in diarrhea-predominant irritable bowel symptoms and improves quality of life. Further studies with permanent implantation and double-blind crossover ON-and-OFF-stimulation to evaluate the impact of placebo effect are needed.     

A Lack of Clinical Effect of High‐frequency rTMS to Dorsolateral Prefrontal Cortex on Bulimic Symptoms: A Randomised,Double‐blind Trial

Studies suggest that stimulation of the left dorsolateral prefrontal cortex (DLPFC) reduces food craving in bulimic patients, but evidence supporting repetitive transcranial magnetic stimulation (rTMS) as a therapeutic tool is lacking. We investigated the safety and therapeutic efficacy of an adjunct high‐frequency rTMS programme targeting the left DLPFC. Forty‐seven women with bulimia nervosa were randomised to a real or sham stimulation group. The real group underwent 10 rTMS sessions, each consisting of 20 trains of 5 seconds with 55‐second intervals between trains, at a frequency of 10 Hz. The main outcome was the number of binge episodes in the 15 days following the end of stimulation. Overall, no significant improvement in bingeing and purging symptoms was noted after the programme. rTMS was well tolerated. This suggests that 10 sessions of high‐frequency rTMS to the left DLPFC provide no greater benefit than placebo. Future studies should consider methodological issues as well as alternative targets. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.     

Effect of Insulin Feedback on Closed-Loop Glucose Control: A Crossover Study

Background

Closed-loop (CL) insulin delivery systems utilizing proportional-integral-derivative (PID) controllers have demonstrated susceptibility to late postprandial hypoglycemia because of delays between insulin delivery and blood glucose (BG) response. An insulin feedback (IFB) modification to the PID algorithm has been introduced to mitigate this risk. We examined the effect of IFB on CL BG control.

Methods

Using the Medtronic ePID CL system, four subjects were studied for 24 h on PID control and 24 h during a separate admission with the IFB modification (PID + IFB). Target glucose was 120 mg/dl; meals were served at 8:00 AM, 1:00 PM, and 6:00 PM and were identical for both admissions. No premeal manual boluses were given. Reference BG excursions, defined as incremental glucose rise from premeal to peak, and postprandial BG area under the curve (AUC; 0–5 h) were compared. Results are reported as mean ± standard deviation.

Results

The PID + IFB control resulted in higher mean BG levels compared with PID alone (153 ± 54 versus 133 ± 56 mg/dl; p < .0001). Postmeal BG excursions (114 ± 28 versus 114 ± 47 mg/dl) and AUCs (285 ± 102 versus 255 ± 129 mg/dl/h) were similar under both conditions. Total insulin delivery averaged 57 ± 20 U with PID versus 45 ± 13 U with PID + IFB (p = .18). Notably, eight hypoglycemic events (BG < 60 mg/dl) occurred during PID control versus none during PID + IFB.

Conclusions

Addition of IFB to the PID controller markedly reduced the occurrence of hypoglycemia without increasing meal-related glucose excursions. Higher average BG levels may be attributable to differences in the determination of system gain (Kp) in this study. The prevention of postprandial hypoglycemia suggests that the PID + IFB algorithm may allow for lower target glucose selection and improved overall glycemic control.     

The Impact of CPAP on Cardiovascular Biomarkers in Minimally Symptomatic Patients with Obstructive Sleep Apnea: A Pilot Feasibility Randomized Crossover Trial

Background Previous, largely uncontrolled studies demonstrated the substantial effects of continuous positive airway pressure ventilation (CPAP) on a variety of physiologic and biochemical markers known to be risk factors for cardiovascular disease in patients with obstructive sleep apnea (OSA). In this pilot crossover study, we assessed (1) the feasibility of using CPAP in a group of minimally symptomatic patients with OSA, assessed through patient compliance and (2) CPAP therapy’s effect on biomarkers in these patients. Methods We studied patients with minimal daytime sleepiness who were referred to the University of British Columbia’s Hospital Sleep Clinic with suspected OSA and an apnea-hypopnea index (AHI) > 15 events/h. Patients were randomized to either CPAP or no therapy for 4 weeks followed by a washout of 4 weeks, and then a crossover to the other intervention. Fasting morning blood and urine, 24-h blood pressure (BP) measurements, and endothelial function (peak flow-mediated dilation to nitroglycerin-mediated dilation ratio) were assessed before and after each study intervention. Results Nine adult male and four female patients were studied. Mean (SD) age was 55 (7) years, mean AHI = 27.9/h, mean Epworth Sleepiness Score = 6.8 (11/13 had a score < 10), and mean BMI = 31.1 kg/m². Mean compliance with CPAP therapy was 5.53 h/night. Compared to no therapy, potential improvements were observed with CPAP for urinary microalbumin, norepinephrine, and epinephrine to creatinine ratios (decreased by 3.51 mg/mmol, 1.70 nmol/mmol, and 0.95 nmol/mmol, respectively); 24-h BP (systolic decreased by 3.60 mmHg, diastolic by 0.70 mmHg); homeostasis model for insulin resistance score (decreased by 1.11); and endothelial function (increased by 7.4%). However, none of the above differences was significant (p > 0.10). Conclusion In this pilot study there were potential improvements in a variety of cardiovascular biomarkers with CPAP. CPAP compliance was reasonably good even though patients were not particularly sleepy. Accordingly, larger randomized controlled trials in this area appear feasible and warranted.     

Effect of Visual Cues, Vital Signs, and Protocols on Triage: A Prospective Randomized Crossover Trial

Study objectives: We sought to compare triage designations derived from in-person and telephone interviews and systematically examine the effect of visual cues, vital signs, and complaint-based protocols on the triage process. Methods: We conducted a 2-phase, prospective, observational study employing a randomized, crossover design in a university teaching hospital emergency department. In both phases, every eligible patient underwent sequential in-person and telephone triage interviews conducted by certified ED triage nurses. After taking a history, each nurse chose 1 of 5 hypothetical triage designations and, after being told the patient’s vital signs, again selected a designation. Phase 1 designations were based solely on nurses’ clinical expertise. In phase 2, both nurses used complaint-based protocols. Results: Agreement between telephone and in-person designations was poor (percent agreement, 43.1% to 48.8%; κ, .19 to .26; τ_b , .34 to .45 for the 4 primary comparisons). Knowledge of vital signs and use of protocols did not improve agreement or increase identification of patients requiring admission to hospital. Conclusion: These data establish that telephone and in-person triage are not equivalent and suggest that visual cues may play an important role in the triage process. It is unclear whether telephone triage is an adequate method of assigning patients to an appropriate level of care. [Salk ED, Schriger DL, Hubbell KA, Schwartz BL: Effect of visual cues, vital signs, and protocols on triage: A prospective randomized crossover trial. Ann Emerg Med December 1998;32:655-664.]     

Effects of Isometric Handgrip Training on Home Blood Pressure Measurements in Hypertensive Patients: A Randomized Crossover Study

Objective We aimed to examine the effects of isometric handgrip (IHG) training on home blood pressure (BP) levels in hypertensive Japanese patients undergoing treatment. Methods Fifty-three hypertensive patients (mean age, 61.7 years; 56.6% men) with a home systolic BP ≥135 mmHg and/or a home diastolic BP ≥85 mmHg were randomly assigned to either group A or B. As per the crossover design, group A performed 8 weeks of IHG training, followed by an equivalent training-free, control period, while the reverse protocol was performed by group B. The baseline characteristics were similar between both groups. The individualized daily IHG training comprised four sets of 2-min isometric contractions at 30% of the individual’s maximum voluntary contraction capacity, including 1 min of rest between sets, for ≥3 days/week. The outcome measure was morning and evening home BP readings taken over the last 2 weeks of the training and control periods. Results A combined data analysis for both groups showed that IHG training was significantly associated with the lowering of both systolic and diastolic BP in the morning (137.9±9.3 vs. 135.3±9.5 mmHg, p=0.007 and 83.0±9.5 vs. 81.2±9.3 mmHg, p＜0.001, respectively) and evening (130.0±10.7 vs. 127.6±10.1 mmHg, p=0.003 and 75.8±10.4 vs. 73.8±9.2 mmHg, p＜0.001, respectively), while no significant change was observed after the control period. A larger increase in the maximum grip strength due to IHG training was associated with greater BP reductions. Conclusion An 8-week period of IHG training significantly lowered both the morning and evening home BP in hypertensive Japanese patients undergoing treatment.     

Comparison of Pharmacodynamics between Tegoprazan and Dexlansoprazole Regarding Nocturnal Acid Breakthrough: A Randomized Crossover Study

Background/AimsTegoprazan, a novel potassium-competitive acid blocker, is expected to overcome the limitations of proton pump inhibitors and effectively control nocturnal acid breakthrough. To evaluate the pharmacodynamics of tegoprazan versus dexlansoprazole regarding nocturnal acid breakthrough in healthy subjects.MethodsIn a randomized, open-label, single-dose, balanced incomplete block crossover study, 24 healthy male volunteers were enrolled and randomized to receive oral tegoprazan (50, 100, or 200 mg) or dexlansoprazole (60 mg) during each of two administration periods, separated by a 7- to 10-day washout period. Blood samples were collected for pharmacokinetic parameter analysis; gastric monitoring was performed for pharmacodynamic parameter evaluation.ResultsAll 24 subjects completed the study. Average maximum plasma concentration, area under the plasma concentration–time curve, and mean time with gastric pH >4 and pH >6 for tegoprazan demonstrated dose-dependent incremental increases. All the tegoprazan groups reached mean pH ≥4 within 2 hours, whereas the dexlansoprazole group required 7 hours after drug administration. Based on pharmacodynamic parameters up to 12 hours after evening dosing, 50, 100, and 200 mg of tegoprazan presented a stronger acid-suppressive effect than 60 mg of dexlansoprazole. Moreover, the dexlansoprazole group presented a comparable acid-suppressive effect with the tegoprazan groups 12 hours after dosing.ConclusionsAll the tegoprazan groups demonstrated a significantly faster onset of gastric pH increase and longer holding times above pH >4 and pH >6 up to 12 hours after evening dosing than the dexlansoprazole group.     

Role of Bladder Dysfunction in Men with Lower Urinary Tract Symptoms Refractory to Alpha‐blocker Therapy: A Video‐urodynamic Analysis

Objectives

Lower urinary tract symptoms (LUTS) in men result from a complex interplay of pathophysiology, including bladder and bladder outlet dysfunction. This study retrospectively analyzed bladder dysfunction in men with LUTS based on the results of video‐urodynamic studies (VUDS).

Methods

Male patients (aged ≥40 years), with LUTS and an International Prostate Symptom Score of 8 or more, who were refractory to alpha‐blocker treatment were retrospectively recruited and evaluated with VUDS and total prostate volume (TPV). Patients were further divided into subgroups of bladder dysfunction and bladder outlet dysfunction according to characteristic VUDS findings. Age, TPV and VUDS findings were compared among different subgroups.

Results

After VUDS, bladder outlet obstruction (BOO) was only noted in 48.6% of men. Of patients, 919 of 2991 (30.7%) had bladder dysfunction including detrusor underactivity (DU, 5.1%), detrusor overactivity and inadequate contractility (DHIC, 5.3%), detrusor overactivity (DO, 17%) and hypersensitive bladder (HSB, 3.3%). In addition, 1941 (64.9%) had bladder outlet dysfunction including BOO + DO (33.8%), BOO alone (14.8%), and poor urethral sphincter relaxation (PRES, 16.3%). Among the 1519 patients with DO, 66.6% (1012) had BOO while, among 1454 patients with BOO, 69.5% (1010) had DO. Patients with DHIC, DU and DO were 5 years older than patients with HSB and normal men. TPV was significantly smaller in patients with DHIC, DU and DO as compared with BOO + DO.

Conclusion

Approximately one‐third of male LUTS was due to bladder dysfunction. A man older than 70 years with LUTS and TPV less than 30 mL usually indicates the presence of bladder dysfunction rather than BOO.     

中低频治疗在肩关节周围炎老年患者生活质量和抑郁状态中的相关性研究

目的观察TENS80C中低频治疗仪在提高患者生活质量及减轻抑郁障碍中的临床有效性,为TENS80C中低频治疗仪能够提高患者生活质量及减轻抑郁障碍提供依临床依据。方法本研究将有疼痛、肌力减退表现的肩关节周围炎患者,在常规康复治疗的基础上,随机入组TENS80C中低频治疗组、调制中频治疗组各30例。每位人组的受试者治疗1次／d,5次／w,共4w,共20次。分别在入组时和治疗第7次、14次、20次时对患者进行SF-36、ZUNG氏抑郁自评量表（SDS）评定,共计4次。结果康复组和对照组治疗前各项观察指标经统计学分析差异无统计学意义（P〉0．05）,SF-36第4次评分实验组与第4次评分对照组经独立样本t检验P〈0．05,显示差异有统计学意义,第1次评分实验组（疗前）与第4次评分实验组（疗后）经独立样本t检验显示差异有统计学意义（P〈0．01）。SDS抑郁评分第4次评分实验组与第4次评分对照组经独立样本t检验,显示差异有统计学意义（P〈O．01）。第1次评分实验组（疗前）与第4次评分实验组（疗后）经独立样本t检验显示差异有统计学意义（P〈0．01）。结论TENS80C中低频治疗仪在提高患者日常生活能力及减轻抑郁障碍中有显著效果。