Randomized clinical trial of efficacy of self-monitoring techniques to treat urinary incontinence in women

AIM: To assess the efficacy of self-monitoring techniques to reduce urine loss and increase quality of life for women with urinary incontinence. METHODS: The design was a two arm, randomized, clinical trial with a wait list control group and 3-week intervention. Participants were 224 community-dwelling women 18 and older with UI. Self-monitoring was individualized counseling about fluid and caffeine intake, quick pelvic floor muscle contraction, voiding frequency, and management of constipation. The primary outcome measure was grams of urine loss. Secondary outcomes included episodes of urine loss, quality of life, and caffeine and fluid consumption. RESULTS: The main effect of self-monitoring on grams of urine loss was significant. After adjusting for baseline urine loss, time in the intervention or in wait list group, age, hormone status, and race the self- monitoring group lost an average of 13.3 g less urine and had improved 26.1 points in quality of life compared to the wait list group. The effect of self-monitoring on episodes of urine loss was not significant in the total sample but was more effective for women who had 9 or more episodes of urine loss, were 65 years or older, and were premenopausal or taking hormone replacement therapy. Participants in the self-monitoring group reduced their caffeine intake, but did not increase their fluid intake compared to the wait list control group. CONCLUSIONS: Since self-monitoring techniques are simple, safe, inexpensive, and within the scope of practice for most health professionals, they should be considered as first steps to treat women with UI.     

Prompt closure versus gradual weaning of external ventricular drainage for hydrocephalus following aneurysmal subarachnoid haemorrhage: Protocol for the DRAIN randomised clinical trial

Background

Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease caused by rupture of an intracranial aneurysm. A common complication following aSAH is hydrocephalus, for which placement of an external ventricular drain (EVD) is an important first-line treatment. Once the patient is clinically stable, the EVD is either removed or replaced by a ventriculoperitoneal shunt. The optimal strategy for cessation of EVD treatment is, however, unknown. Gradual weaning may increase the risk of EVD-related infection, whereas prompt closure carries a risk of acute hydrocephalus and redundant shunt implantations. We designed a randomised clinical trial comparing the two commonly used strategies for cessation of EVD treatment in patients with aSAH.

Methods

DRAIN is an international multi-centre randomised clinical trial with a parallel group design comparing gradual weaning versus prompt closure of EVD treatment in patients with aSAH. Participants are randomised to either gradual weaning which comprises a multi-step increase of resistance over days, or prompt closure of the EVD. The primary outcome is a composite outcome of VP-shunt implantation, all-cause mortality, or ventriculostomy-related infection. Secondary outcomes are serious adverse events excluding mortality, functional outcome (modified Rankin scale), health-related quality of life (EQ-5D) and Fatigue Severity Scale (FSS). Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, type I error 5%, power 80%), 122 patients are needed in each intervention group. Outcome assessment for the primary outcome, statistical analyses and conclusion drawing will be blinded.

Trial Registration

ClinicalTrials.gov identifier: NCT03948256.     

Gal alpha(1-3)Gal expression of the cornea in vitro, in vivo and in xenotransplantation

BACKGROUND: To investigate alpha Gal (Gal alpha1-3Gal beta 1-4GlcNAc-R) expression of the porcine cornea in vitro, in vivo and after xenotransplantation. METHODS: Using the GS-IB4 lectin (Griffonia simplifolia I isolectin B4), the expression of alpha Gal was evaluated in the normal porcine cornea and in cultured corneal stromal and endothelial cells of the second passages. The distribution of alpha Gal epitopes was also evaluated in corneal grafts at 4, 7 and 10 days after pig-to-rat orthotopic corneal transplantation. RESULTS: The expression of alpha Gal was mostly confined to the anterior stromal keratocytes of the normal porcine cornea. However, reactivity for GS-IB4 was markedly increased during cell culture passage (P)-by 18.0% (P1) and 39.0% (P2) in cultivated keratocytes, and by 62.1% (P1) and 87.1% (P2) in cultured endothelial cells. The expression of alpha Gal epitopes was gradually enhanced in all corneal layers of the graft after transplantation. CONCLUSION: Alpha Gal expression in the cornea was gradually induced during in vitro culture and after xenotransplantation, suggesting a role of putative Gal-related acute humoral rejection in porcine corneal xenotransplantation.     

Controlled,double-blind,multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability

Our objectives were to ascertain the tolerability and efficacy of trospium chloride in doses of 20 mg twice daily for long-term therapy (52 weeks) in patients with urge syndrome. The trial comprised a total of 358 patients with urge syndrome or urge incontinence. After randomisation in the ratio of 3:1, participants were treated continuously for 52 weeks with either trospium chloride (20 mg twice daily) or oxybutynin (5 mg twice daily). At intervals of 4-8 weeks, patients were physically examined with measurements of blood pressure and pulse rate, were questioned about any adverse events, checked for compliance and underwent relevant laboratory tests. As an additional safety measure, an ECG was made at 26 and 52 weeks. Urodynamic measurements were performed at the beginning, and at 26 and 52 weeks to determine the maximal cystometric bladder capacity. Among others things, the frequencies of micturition, incontinence and number of urgency events were recorded in patient diary protocols in weeks 0, 2, 26 and 52. The evaluation of vital parameters, laboratory results and ECGs did not show any relevant changes attributable to the action of the anticholinergics. Analysis of the micturition diary clearly indicated a reduction of the micturition frequency, incontinence frequency, and a reduction of the number of urgencies in both treatment groups. Mean maximum cystometric bladder capacity increased during treatment with trospium chloride by 92 ml after 26 weeks and 115 ml after 52 weeks (P=0.001). Further comparison with oxybutynin did not reveal any statistically significant differences in urodynamic variables between the drugs. Adverse events occurred in 64.8% of the patients treated with trospium chloride and 76.7% of those treated with oxybutynin. The main symptom encountered in both treatment group was dryness of the mouth. For patients on trospium chloride, the estimated risk of an unexpected adverse event was 0.027 per patient per week for all adverse events and 0.009 for dryness of the mouth, resulting in a considerably lower risk during treatment given with trospium chloride than with oxybutynin (0.045 and 0.021, respectively). An overall assessment for each of the drugs reveals a comparable efficacy level and a better benefit-risk ratio for trospium chloride than for oxybutynin due to better tolerability.     

前列安栓治疗慢性前列腺炎的安全性和有效性:随机双盲安慰剂对照试验

目的　评价前列安栓治疗各型慢性前列腺炎的安全性、有效性和依从性。　方法　多中心随机双盲安慰剂对照研究。 12 5例慢性前列腺炎患者根据美国国立卫生院 (NIH)前列腺炎分型标准分型后随机分为治疗组和对照组 ,治疗组 (6 5例 )前列安栓 1粒 ,对照组 (6 0例 )安慰剂 1粒 ,肛内用药每晚 1次 ,疗程 1个月。以NIH慢性前列腺炎症状评分 (NIH CPSI)和前列腺按摩液 (EPS)白细胞计数为疗效评价指标。　结果　试验结束时 ,12 4例可评价病例中Ⅱ型 4 8例 (38.7% ) ,Ⅲa型 4 5例 (36 .3% ) ,Ⅲb型 31例 (2 5 .0 % )。治疗组NIH CPSI总分用药前后分别为 (2 5 .4 5± 5 .82 )和 (15 .0 8± 7.84 )分 ,平均降低 10 .37分 ,症状程度评分用药前后分别为 (16 .76± 4 .0 7)和 (9.4 2± 5 .38)分 ,平均降低 7.34分 ;对照组NIH CPSI总分用药前后分别为 (2 2 .87± 5 .79)和 (16 .2 2± 6 .2 3)分 ,平均降低 6 .6 5分 ,症状程度评分用药前后分别为 (15 .2 7± 3.86 )和 (10 .5 5± 4 .2 9)分 ,平均降低 4 .72分 ;治疗组NIH CPSI总分与症状程度评分的下降幅度均较对照组更明显 (P <0 .0 1)。治疗组总显效率2 8.1% (18/ 6 4 ) ,总有效率 71.9% (4 6 / 6 4 ) ,对照组总显效率 13.3% (8/ 6 0 ) ,总有效率 4 1.7% (2 5 / 6 0 )     

A prospective randomized clinical trial to investigate the effect of silicone gel sheeting (Cica-Care) on post-traumatic hypertrophic scar among the Chinese population

BACKGROUND: This study aimed to determine the efficacy of silicone gel (Cica-Care) on severe post-traumatic hypertophic scars among the Chinese population. METHOD AND MATERIALS: A randomized clinical trial (RCT) was conducted on 45 Chinese patients with post-traumatic hypertrophic scars. Twenty-two subjects were placed in the experimental group with silicone gel sheeting (SGS) applied 24h per day for 6 months while all subjects were taught to massage the scar daily for 15 min serving as the control intervention. Scar assessments were conducted regularly to measure the changes in thickness, pigmentation, vascularity, pliability, itchiness and pain. RESULTS: Two-way repeated ANOVA showed a significant difference between MT group and SGS group on scar thickness. The post hoc comparison analysis showed that the difference was significant at the post-2-month (p=0.008) and post-6-month (p<0.001) intervention. The SGS group also showed changes in pigmentation which resembled normal skin but no statistical significance was found. Pain, itchiness and pliability were also improved after intervention. CONCLUSION: This study indicated that silicone gel sheeting (Cica-Care) was effective to reduce thickness, pain, itchiness and pliability of the severe hypertrophic scar among the Chinese population. The moisturization effect of the tough and hard scar might contribute to the reduction of the skin thickness after 6 month's intervention.     

A prospective clinical trial investigating the efficacy of a method of preparing subpopulations of antibody-free spermatozoa from the ejaculates of antibody-positive patients

Couples undergoing in vitro fertilization treatment (IVF) were invited to take part in a controlled prospective clinical trial. The aim was to determine the effect on the fertilization rate of a technique devised to obtain an antibody-free preparation of spermatozoa from an antibody-positive ejaculate. Oocytes collected during IVF were allocated into one of two groups, ensuring that quality and maturity were comparable in each. One group, the control, was inseminated with Percoll-processed spermatozoa. The experimental group was inseminated with identical numbers of Percoll-processed spermatozoa which had been treated to obtain an antibody-free preparation. The treatment was found to have no beneficial effect on the fertilization rate at IVF. Laboratory studies were also performed on the ejaculates of antibody-positive volunteers to determine whether this treatment led to any effects, whether beneficial or detrimental, on sperm function. Membrane integrity was found to be unaffected, as was the percentage of spermatozoa undergoing the spontaneous acrosome reaction following overnight incubation. The percentage of spermatozoa undergoing the ionophore-induced acrosome reaction following treatment, however, was higher than that of the controls. The results of sperm–zona pellucida binding studies were equivocal. The findings indicated that the treatment procedure could not be justified for use in IVF, but may be beneficial for intrauterine insemination.     

Monitoring and modifying recruitment and retention strategies for an ongoing randomised clinical trial with venous leg ulcer patients: Overcoming barriers to participation

Venous leg ulcers (VLUs) are open skin lesions of the lower legs arising in areas affected by venous hypertension that are associated with substantial morbidity. Clinical trials testing innovative approaches to improve healing outcomes are critically needed because standard therapies are often ineffective. However, patients with VLUs frequently have multiple physical, emotional and socioeconomic challenges that can negatively impact their decision to enrol in a clinical trial. To benefit clinical researchers and ultimately the community of patients with chronic wounds, this paper describes the monitoring and modification of recruitment strategies in an ongoing clinical trial testing effects of omega-3 fatty acid oral supplementation on VLU healing in ageing adults (n = 208). Multiple modifications over time in this study have targeted participation barriers identified through data monitoring and include expanding inclusion criteria, adding recruitment sites, enhancing communication methods, and meeting patients' transportation needs. Recruitment activities from January 2019 to June 2022 have resulted in 57 participants (mean age: 63.7 years). Overall, the recruitment rate is 42.5% of patients contacted during face-to-face visits. Overcoming barriers to participation is key to helping patients with VLUs interested in research enrol in clinical trials aiming to improve healing outcomes in this vulnerable population.     

The renoprotective effects of structured care in a clinical trial setting in type 2 diabetic patients with nephropathy.

BACKGROUND: The RENAAL Study has confirmed the renoprotective effects of Losartan in type 2 diabetes. In this subgroup analysis from the RENAAL Study, we hypothesized that the intensive care received by patients in a clinical trial setting also reduced the rate of decline in renal function through optimization of all risk factors. METHODS: We compared the rate of deterioration in renal function, expressed as the regression coefficient of the monthly serum creatinine (SeCr) reciprocal (beta-1/Cr) in 55 Chinese type 2 diabetic patients before and after entry into the RENAAL Study. RESULTS: Of the 55 patients, 44 had at least three out-patient SeCr measurements both before (2.9+/-2.4 years) and after (3.3+/-0.8 years) entry into the study for evaluation. In the Losartan group (n = 24), the median beta-1/Cr fell from -11.4 x 10(-5) l micro mol(-1) month(-1) before entry into the trial to -4.7 x 10(-5) l micro mol(-1) month(-1) following entry (P = 0.001). The respective figures were -9.1 x 10(-5) and -5.0 x 10(-5) l micro mol(-1) month(-1) (P = 0.01) in the placebo group (n = 20). A decrease in beta-1/Cr was observed in 21 (87.5%) and 14 (70.0%) patients in the Losartan and placebo groups, respectively. Spot urinary albumin-to-creatinine ratio was reduced by 56% (P = 0.001) in the Losartan group but the change was not significant in the placebo group. At the end of the study, patients in both groups had lower blood pressure and better lipid control. The frequency of patient visits to doctors and nurses were doubled. CONCLUSIONS: The rate of renal function decline was significantly reduced in the majority of patients allocated to either Losartan or placebo following entry into the RENAAL study. These results suggest that in patients with diabetic nephropathy, implementation of a structured care protocol in a clinical trial setting facilities intensive treatment of risk factors confering renoprotective effects in addition to those resulting from Losartan treatment.     

An open-label randomized trial of the safety and efficacy of sirolimus vs. azathioprine in living related renal allograft recipients receiving cyclosporine and prednisone combination

BACKGROUND: The ability of sirolimus (SRL), in combination with reduced exposure of cyclosporine, was investigated to prevent acute rejection and associated side effects. METHODS: Between June 1999 and February 2000, 70 recipients of primary one-haplotype living-related donor renal allografts were randomized to receive SRL (2 mg/d) or azathioprine (AZA) (2 mg/kg/d) combined with cyclosporine and prednisone. The primary end-point was a composite of first occurrence of biopsy-confirmed acute rejection, graft loss, or death during the first 3 months after transplantation. RESULTS: From week 4 to month 12, SRL patients received lower cyclosporine (week 4: 364 mg/d vs. 455 mg/d, p = 0.004; month 12: 195 mg/d vs. 255 mg/d, p = 0.038) doses and showed lower cyclosporine concentrations (week 4: 247 ng/mL vs. 309 ng/mL, p = 0.04; month 12: 143 ng/mL vs. 188 ng/mL, p = 0.045). Compared with AZA, SRL patients showed reduced 3-month primary end point (0% vs. 17.1%, p = 0.025), and reduced incidence of biopsy-confirmed acute rejection at 3 months (0% vs. 14.3%, p = 0.01) but not at 12 months (11.4% vs. 14.3%, NS). Mean creatinine at 12 months were not different (1.8 +/- 0.6 vs. 1.6 +/- 0.6, p = 0.23). Hyperlipidemia was the only adverse event more frequent among SRL patients (49% vs. 17%, p = 0.01). There were no differences in infections and no malignancies in both groups. CONCLUSIONS: The combination of 2 mg fixed doses of SRL, reduced cyclosporine exposure and prednisone was associated with a low incidence of acute rejection and did not result in significantly impaired graft function compared with patients receiving AZA, standard doses of cyclosporine and prednisone.     

甲磺酸酚妥拉明片/胶囊治疗阴茎勃起功能障碍的临床研究

目的 :为了解甲磺酸酚妥拉明在治疗阴茎勃起功能障碍 ( ED)中的有效性和安全性。方法 :采用随机安慰剂对照试验研究的方法进行分析。试验分为片剂组 ( A组 )、胶囊组 ( B组 )、安慰剂的片剂和胶囊组并为一组 ( C组 )。组间比例为 1∶ 1∶ 1 ( A∶B∶C)。共有 2 41例参加了临床试验 ,其中 2 1 7例完成试验。试验药物 (片剂或胶囊 )必须在性交前 1h服用 ,每次服 1片 ( 4 0 mg) ;两周内至少有 3次服药并尝试性交以保证达到统计学要求 ,但服药不能超过 8次 ;整个试验持续 1 0周。药物的有效性按国际性功能量表 ( IIEF)衡量 ,安全性以监测试验过程中的不良反应来反映。结果 :有效率 ,A组为 6 8% ,B组为 6 2 % ,C组为 45%。 A、B组和 C组比效有显著性差异。整个试验未发生严重不良反应。结论 :甲磺酸酚妥拉明片和胶囊是一种治疗勃起功能障碍的有效且安全的药物     

Effectiveness and safety of olive oil preparation for topical use in pressure ulcer prevention: Multicentre,controlled, randomised,and double‐blinded clinical trial

This non‐inferiority, multicentre, randomised, controlled, and double‐blinded clinical trial compared the therapeutic effectiveness of the topical application of an olive oil solution with that of a hyperoxygenated fatty acid compound for the prevention of pressure ulcers in at‐risk nursing home residents. The study population comprised 571 residents of 23 nursing homes with pressure ulcer risk, randomly assigned to a hyperoxygenated fatty acid group (n = 288) or olive oil solution group (n = 283). Both solutions were applied on at‐risk skin areas every 12 hours for 30 days or until pressure ulcer onset. The main outcome variable was the pressure ulcer incidence. The absolute risk difference was estimated (with 95% CI) using Kaplan‐Meier survival and Cox regression curves. The groups did not significantly differ in any study variable at baseline. The pressure ulcer incidence was 4.18% in the olive oil group vs 6.57% in the control group, with an incidence difference of −2.39% (95% CI = −6.40 to 1.56%), which is within the pre‐established non‐inferiority margin of ±7%, thus supporting the study hypothesis. We present the first evidence of the effectiveness and safety of the topical application of olive oil to prevent pressure ulcers in the institutionalised elderly.     

Effect of a platelet-activating factor receptor antagonist, E5880, on cerebral vasospasm after aneurysmal subarachnoid hemorrhage--open clinical trial to investigate efficacy and safety

The efficacy and safety of a new platelet-activating factor receptor antagonist, E5880, were investigated for preventing cerebral vasospasm after subarachnoid hemorrhage (SAH) in 71 patients with SAH who underwent surgery for ruptured aneurysms within 3 days. Intravenous E5880 administration (300 micrograms or 1200 micrograms twice daily) was begun within 4 days and continued for 14 days. The incidence of symptomatic vasospasm, low-density area on computed tomography, and angiographic vasospasm was lower than in placebo groups in previous studies. Clinical outcome was favorable compared with previous studies. No clinically important adverse events were observed. These results suggest that E5880 is safe and effective in the treatment of patients with cerebral vasospasm due to SAH.     

First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes—Chapter 6: patient selection for pilot clinical trials of islet xenotransplantation

Patients in whom type 1 diabetes is complicated by impaired awareness of hypoglycemia and recurrent episodes of severe hypoglycemia are candidates for islet or pancreas transplantation if severe hypoglycemia persists after completion of a structured stepped care approach or a formalized medical optimization run‐in period that provides access to hypoglycemia‐specific education including behavioral therapies, insulin analogs, and diabetes technologies under the close supervision of a specialist hypoglycemia service. Patients with type 1 diabetes and end‐stage renal failure who cannot meet clinically appropriate glycemic goals or continue to experience severe hypoglycemia after completion of a formalized medical optimization program under the guidance of an expert diabetes care team are candidates for islet or pancreas transplantation either simultaneously with or after a previous kidney transplant. Similarly, patients with type 2 diabetes and problematic hypoglycemia or renal failure who meet these criteria are considered candidates for islet replacement. Likewise, patients with pancreatectomy‐induced diabetes in whom an islet autograft was not available or deemed inappropriate are candidates for islet or pancreas transplantation if extreme glycemic lability persists despite best medical therapy. To justify participation of these transplant candidates in early‐phase trials of porcine islet cell products, lack of timely access to islet or pancreas allotransplantation due to allosensitization, high islet dose requirements, or other factors, or alternatively, a more favorable benefit–risk determination associated with the xenoislet than the alloislet or allopancreas transplant must be demonstrated. Additionally, in non‐uremic xenoislet recipients, the risks associated with diabetes must be perceived to be more serious than the risks associated with the xenoislet product and the rejection prophylaxis, and in xenoislet recipients with renal failure, the xenoislet product and immunosuppression must not impact negatively on renal transplant outcomes. The most appropriate patient group for islet xenotransplantation trials will be defined by the specific characteristics of each investigational xenoislet product and related technologies applied for preventing rejection. Selecting recipients who are more likely to experience prolonged benefits associated with the islet xenograft will help these patients comply with lifelong monitoring and other public health measures.