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Protocol Violations (protocol + violation)
Selected AbstractsFailure of Helicobacter pylori Treatment After Regimes Containing Clarithromycin: New Practical Therapeutic OptionsHELICOBACTER, Issue 6 2008Bruno Sanches Abstract Failure of Helicobacter pylori treatment is a growing problem in daily practice. Aim:, To evaluate the efficacy of two new regimes as second-line options in a randomized and prospective study. Methods:, Patients in whom a first eradication regime containing clarithromycin had failed were included. After performing gastroscopy and a 13C-urea breath test (UBT), the patients were randomized to receive a combination of 20 mg of rabeprazole, 500 mg of levofloxacin, and 200 mg (two tablets) of furazolidone administered once daily for 10 days (RLF) or the combination of 20 mg of rabeprazole, 120 mg (two tablets) of bismuth subcitrate, 100 mg of doxycycline, and 200 mg of furazolidone, administered twice daily for 10 days (RBDF). Clinical examinations and new UBT were performed 60 days after therapy. Results:, Sixty patients were included (mean age, 46 years, 57% females). Two patients were excluded: one because of adverse effects and another as a result of protocol violation. Compliance was similar in both groups (90% took all medications correctly). Side-effects (96% mild) were observed in 87% of the patients and were comparable between groups, except diarrhea, which was more frequent in group RLF (p= .025). Intention-to-treat cure rates were 77% (95% confidence interval (CI): 62,93%) in the RLF group and 83% (95% CI: 68,97%) in the RBDF group (p= .750). Per-protocol cure rates were 80% (95% CI: 65,95%) in the RLF group and 82% (95% CI: 67,96%) in the RBDF group (p= 1.0). Conclusions:, Both once-daily triple (rabeprazole, levofloxacin, and furazolidone) and twice-daily quadruple therapy (rabeprazole, bismuth subcitrate, doxycycline, and furazolidone) for 10 days achieved encouraging results. Subsequent studies should be performed to evaluate antibiotic resistance, doses, dosing intervals, duration of treatment, and safety of these two regimes. [source] Unilateral groin surgery in children: will the addition of an ultrasound-guided ilioinguinal nerve block enhance the duration of analgesia of a single-shot caudal block?PEDIATRIC ANESTHESIA, Issue 9 2009NARASIMHAN JAGANNATHAN MD Summary Background:, Inguinal hernia repair, hydrocelectomy, and orchidopexy are commonly performed surgical procedures in children. Postoperative pain control is usually provided with a single-shot caudal block. Blockade of the ilioinguinal nerve may lead to additional analgesia. The aim of this double-blind, randomized controlled trial was to evaluate the efficacy of an adjuvant blockade of the ilioinguinal nerve using ultrasound (US) guidance at the end of the procedure with local anesthetic vs normal saline and to explore the potential for prolongation of analgesia with decreased need for postoperative pain medication. Methods:, Fifty children ages 1,6 years scheduled for unilateral inguinal hernia repair, hydrocelectomy, orchidopexy, or orchiectomy were prospectively randomized into one of two groups: Group S that received an US-guided ilioinguinal nerve block with 0.1 ml·kg,1 of preservative-free normal saline and Group B that received an US-guided nerve block with 0.1 ml·kg,1 of 0.25% bupivacaine with 1 : 200 000 epinephrine at the conclusion of the surgery. After induction of anesthesia but prior to surgical incision, all patients received caudal anesthesia with 0.7 ml·kg,1 of 0.125% bupivacaine with 1 : 200 000 epinephrine. Patients were observed by a blinded observer for (i) pain scores using the Children and Infants Postoperative Pain Scale, (ii) need for rescue medication in the PACU, (iii) need for oral pain medications given by the parents at home. Results:, Forty-eight patients, consisting of 46 males and two females, with a mean age of 3.98 (sd ± 1.88) were enrolled in the study. Two patients were excluded from the study because of study protocol violation and/or alteration in surgical procedure. The average pain scores reported for the entire duration spent in the recovery room for the caudal and caudal/ilioinguinal block groups were 1.92 (sd ± 1.59) and 1.18 (sd ± 1.31), respectively. The average pain score difference was 0.72 (sd ± 0.58) and was statistically significant (P < 0.05). In addition, when examined by procedure type, it was found that the difference in the average pain scores between the caudal and caudal/ilioinguinal block groups was statistically significant for the inguinal hernia repair patients (P < 0.05) but not for the other groin surgery patients (P = 0.13). For all groin surgery patients, six of the 23 patients in the caudal group and eight of the 25 patients in the caudal/ilioinguinal block group required pain rescue medications throughout their entire hospital stay or at home (P = 0.76). Overall, the caudal group received an average of 0.54 (sd ± 1.14) pain rescue medication doses, while the caudal/ilioinguinal block group received an average of 0.77 (sd ± 1.70) pain rescue medication doses; this was, however, not statistically significant (P = 0.58). Conclusions:, The addition of an US-guided ilioinguinal nerve block to a single-shot caudal block decreases the severity of pain experienced by pediatric groin surgery patients. The decrease in pain scores were particularly pronounced in inguinal hernia repair patients. [source] An open-label, multinational, multicenter study of G17DT vaccination combined with cisplatin and 5-fluorouracil in patients with untreated, advanced gastric or gastroesophageal cancer : The GC4 studyCANCER, Issue 9 2006Jaffer A. Ajani M.D. Abstract BACKGROUND Gastrin hormone is trophic to in vitro gastric cancer, and the antigastrin antibodies (AGAs) are antiproliferative and antimetastatic. Human gastric cancers overexpress gastrin genes and receptors that react to gastrin's trophic effects. Immunogen G17DT elicits a specific and high-affinity AGA. The authors evaluated G17DT vaccination given with cisplatin plus 5-fluorouracil for the treatment gastric adenocarcinoma. METHODS In this multicenter, Phase II study, patients received G17DT vaccination intramuscularly on Weeks 1, 5, 9 and 25 and cisplatin plus 5-fluorouracil every 28 days. Eligible patients had untreated, metastatic, or unresectable gastric or gastroesophageal adenocarcinoma with near-normal organ function. The primary endpoint of the study was the over response rate (ORR), and secondary endpoints included overall survival (OS), safety, and the impact of successful vaccination on patient outcome. RESULTS In total, 103 patients were enrolled in 5 countries. Seven patients who were overdosed inadvertently with 5-fluorouracil (a major protocol violation) were removed from the analysis. The confirmed ORR was 30% in 79 patients who were evaluated for response. The median time-to-progression (TTP) was 5.4 months, and the median survival (MS) was 9.0 months (n = 96 patients). Sixty-five of 94 patients who were vaccinated (69%) had 2 consecutive AGA titers of ,1 units (successfully vaccinated patients or immune-responders). The TTP was longer in immune-responders than in immune-nonresponders (P = .0005). Similarly, the MS was longer in immune-responders than in immune-nonresponders (10.3 months vs. 3.8 months; P ,.0001). In a multivariate analysis, successful vaccination was an independent OS prognosticator (P = .0001). G17DT did not have an adverse effect on safety. CONCLUSIONS The results demonstrated that successful G17DT vaccination was correlated with longer TTP and MS. AGA response was an independent OS prognosticator. A Phase III evaluation of G17DT in gastric cancer is warranted. Cancer 2006. © 2006 American Cancer Society. [source] Therapeutic Yield and Outcomes of a Community Teaching Hospital Code Stroke ProtocolACADEMIC EMERGENCY MEDICINE, Issue 4 2004Andrew W. Asimos MD Objectives: To describe the experience of a community teaching hospital emergency department (ED) Code Stroke Protocol (CSP) for identifying acute ischemic stroke (AIS) patients and treating them with tissue plasminogen activator (tPA) and to compare outcome measures with those achieved in the National Institute of Neurological Disorders and Stroke (NINDS) trial. Methods: This study was a retrospective review from a hospital CSP registry. Results: Over a 56-month period, CSP activation occurred 255 times, with 24% (n= 60) of patients treated with intravenous (IV) tPA. The most common reasons for thrombolytic therapy exclusion were mild or rapidly improving symptoms in 37% (n= 64), intracerebral hemorrhage (ICH) in 23% (n= 39), and unconfirmed symptom onset time for 14% (n= 24) of patients. Within 36 hours of IV tPA treatment, 10% (NINDS = 6%) of patients (n= 6) sustained a symptomatic ICH (SICH). Three months after IV tPA treatment, 60% of patients had achieved an excellent neurologic outcome, based on a Barthel Index of ,95 (NINDS = 52%), while mortality measured 12% (NINDS = 17%). Among IV tPA-treated patients, those developing SICH were significantly older and had a significantly higher mean initial glucose value. Treatment protocol violations occurred in 32% of IV tPA-treated patients but were not significantly associated with SICH (Fisher's exact test). Conclusions: Over the study period, the CSP yielded approximately one IV tPA-treated patient for every four screened and, despite prevalent protocol violations, attained three-month functional outcomes equal to those achieved in the NINDS trial. For community teaching hospitals, ED-directed CSPs are a feasible and effective means to screen AIS patients for treatment with thrombolysis. [source] A Combination of Midazolam and Ketamine for Procedural Sedation and Analgesia in Adult Emergency Department PatientsACADEMIC EMERGENCY MEDICINE, Issue 3 2000Carl R. Chudnofsky MD Abstract Objective: To describe the clinical characteristics of a combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department (ED) patients. Methods: This was a prospective, observational trial, conducted in the ED of an urban level II trauma center. Patients , 18 years of age requiring procedural sedation and analgesia were eligible, and enrolled patients received 0.07 mg/kg of intravenous midazolam followed by 2 mg/kg of intravenous ketamine. Vital signs were recorded at regular intervals. The adequacy of sedation, adverse effects, patient satisfaction, and time to reach discharge alertness were determined. Descriptive statistics were calculated using statistical analysis software. Results: Seventy-seven patients were enrolled. Three were excluded due to protocol violations, three due to lack of documentation, and one due to subcutaneous infiltration of ketamine, leaving 70 patients for analysis. The average age was 31 years, and 41 (59%) were female. Indications for procedural sedation and analgesia included abscess incision and drainage (66%), fracture/joint reduction (26%), and other (8%). The mean dose of midazolam was 5.6 ± 1.4 mg and the mean dose of ketamine was 159 ± 42 mg. The mean time to achieve discharge criteria was 64 ± 24 minutes. Fivepatients experienced mild emergence reactions, but there were no episodes of hallucinations, delirium, or other serious emergence reactions. Eighteen (25%) patients recalled dreaming while sedated; twelve (17%) were described as pleasant, two (3%) unpleasant, three (4%) both pleasant and unpleasant, and one (1%) neither pleasant nor unpleasant. There were four (6%) cases of respiratory compromise, two (3%) episodes of emesis, and one (1%) case of myoclonia. All of these were transient and did not result in a change in the patient's disposition. Only one (1%) patient indicated that she was not satisfied with the sedation regimen. Conclusions: The combination of midazolam and ketamine provides effective procedural sedation and analgesia in adult ED patients, and appears to be safe. [source] Promoting acute thrombolysis for ischaemic stroke (PRACTISE)INTERNATIONAL JOURNAL OF STROKE, Issue 2 2007Protocol for a cluster randomised controlled trial to assess the effect of implementation strategies on the rate, effects of thrombolysis for acute ischaemic stroke (ISRCTN 20405426) Rationale Thrombolysis with intravenous rtPA is an effective treatment for patients with ischaemic stroke if given within 3 h from onset. Generally, more than 20% of stroke patients arrive in time to be treated with thrombolysis. Nevertheless, in most hospitals, only 1,8% of all stroke patients are actually treated. Interorganisational, intraorganisational, medical and psychological barriers are hampering broad implementation of thrombolysis for acute ischaemic stroke. Aims To evaluate the effect of a high-intensity implementation strategy for intravenous thrombolysis in acute ischaemic stroke, compared with regular implementation; to identify success factors and obstacles for implementation and to assess its cost-effectiveness, taking into account the costs of implementation. Design The PRACTISE study is a national cluster-randomised-controlled trial. Twelve hospitals have been assigned to the regular or high-intensity intervention by random allocation after pair-wise matching. The high-intensity implementation consists of training sessions in conformity with the Breakthrough model, and a tool kit. All patients who are admitted with acute stroke and onset of symptoms not longer than 24 h are registered. Study outcomes The primary outcome measure is treatment with thrombolysis. Secondary outcomes are admission within 4 h after onset of symptoms, death or disability at 3 months, the rate of haemorrhagic complications in patients treated with thrombolysis, and costs of implementation and stroke care in the acute setting. Tertiary outcomes are derived from detailed criteria for the organisational characteristics, such as door-to-needle time and protocol violations. These can be used to monitor the implementation process and study the effectiveness of specific interventions. Discussion This study will provide important information on the effectiveness and cost-effectiveness of actively implementing an established treatment for acute ischaemic stroke. The multifaceted aspect of the intervention will make it difficult to attribute a difference in the primary outcome measure to a specific aspect of the intervention. However, careful monitoring of intermediate parameters as well as monitoring of accomplished SMART tasks can be expected to provide useful insights into the nature and role of factors associated with implementation of thrombolysis for acute ischaemic stroke, and of effective acute interventions in general. [source] Accrediting radiation technique in a multicentre trial of chemoradiation for pancreatic cancerJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 6 2008N Spry Summary Before a multicentre trial of 3-D conformal radiotherapy to treat cancer of the pancreas, participating clinicians were asked to complete an accreditation exercise. This involved planning two test cases according to the study protocol, then returning hard copies of the plans and dosimetric data for review. Any radiation technique that achieved the specified constraints was allowed. Eighteen treatment plans were assessed. Seven plans were prescribed incorrect doses and two of the planning target volumes did not comply with protocol guidelines. All plans met predefined normal tissue dose constraints. The identified errors were attributable to unforeseen ambiguities in protocol documentation. They were addressed by feedback and corresponding amendments to protocol documentation. Summary radiobiological measures including total weighted normal tissue equivalent uniform dose varied significantly between centres. This accreditation exercise successfully identified significant potential sources of protocol violations, which were then easily corrected. We believe that this process should be applied to all clinical trials involving radiotherapy. Due to the limitations of data analysis with hard-copy information only, it is recommended that complete planning datasets from treatment-planning systems be collected through a digital submission process. [source] A quality assurance audit: Phase III trial of maximal androgen deprivation in prostate cancer (TROG 96.01)JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 1 2000A Steigler SUMMARY In 1997 the Trans-Tasman Radiation Oncology Group (TROG) performed a quality assurance (QA) audit of its phase III randomized clinical trial investigating the effectiveness of different durations of maximal androgen deprivation prior to and during definitive radiation therapy for locally advanced carcinoma of the prostate (TROG 96.01). The audit reviewed a total of 60 cases from 15 centres across Australia and New Zealand. In addition to verification of technical adherence to the protocol, the audit also incorporated a survey of centre planning techniques and a QA time/cost analysis. The present report builds on TROG's first technical audit conducted in 1996 for the phase III accelerated head and neck trial (TROG 91.01) and highlights the significant progress TROG has made in the interim period. The audit provides a strong validation of the results of the 96.01 trial, as well as valuable budgeting and treatment planning information for future trials. Overall improvements were detected in data quality and quantity, and in protocol compliance, with a reduction in the rate of unacceptable protocol violations from 10 to 4%. Audit design, staff education and increased data management resources were identified as the main contributing factors to these improvements. In addition, a budget estimate of $100 per patient has been proposed for conducting similar technical audits. The next major QA project to be undertaken by TROG during the period 1998,1999 is an intercentre dosimetry study. Trial funding and staff education have been targeted as the key major issues essential to the continued success and expansion of TROG's QA programme. [source] Effect of Desonide Hydrogel 0.05% on the Hypothalamic-Pituitary-Adrenal Axis in Pediatric Subjects with Moderate to Severe Atopic DermatitisPEDIATRIC DERMATOLOGY, Issue 3 2007Lawrence F. Eichenfield M.D. A recent formulation advance has enabled the development of desonide 0.05% into a novel moisturizing aqueous gel (hydrogel) that is free of alcohol and surfactants. This multicenter, open-label study evaluated the hypothalamic-pituitary-adrenal axis suppression potential, tolerability, and efficacy of this new Class VI topical steroid formulation in pediatric subjects with moderate-to-severe atopic dermatitis (mean body surface area = 51%). Forty children, aged 6 months to 6 years were enrolled and treated twice daily for 4 weeks. Desonide hydrogel 0.05% was well tolerated and no treatment-related adverse events were reported. No suppression of adrenal function was observed in subjects who completed the study without protocol violations related to cosyntropin administration or cortisol testing (n = 34). Of the subjects who completed the study with complications in cortisol testing (n = 3), there was one subject (1/37 = 3%) who had a low poststimulation cortisol level at week 4. Efficacy was demonstrated by marked improvement in overall disease state and in the signs and symptoms of atopic dermatitis. This study validates the systemic safety of a novel desonide hydrogel formulation in young pediatric patients and confirms the longstanding tolerability and efficacy profile of desonide. [source] Natural course of sensitization to cow's milk and hen's egg in childhood atopic dermatitis: ETACTM Study GroupCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2002A. Wolkerstorfer Background Sensitization to food allergens has been implicated in the pathogenesis of atopic diseases, in particular atopic dermatitis (AD). The aim of the present paper is to investigate the natural course of sensitization to egg and to cow's milk and its relationship with the severity of AD. Methods The placebo intention-to-treat population of the ETACTM (Early Treatment of the Atopic Child) study consisted of 397 children with AD aged 12,24 months (mean±,SD: 17.2 ± 4.1 months) who were followed for 18 months. All children were examined for objective SCORing Atopic Dermatitis (SCORAD) and specific IgE amongst other, to egg and to cow's milk at inclusion and after 3, 12 and 18 months. Fifteen patients were excluded from this analysis due to major protocol violations thus leaving 382 patients in the analysed population. Results Sensitization to egg and to cow's milk was more common in atopic children with severe AD at all time-points. At inclusion, children sensitized to both egg and to cow's milk had the most severe AD (Kruskall-Wallis test P = 0.007). The degree of sensitization expressed in RAST classes was significantly related to the severity of AD. Furthermore, children sensitized to egg or to cow's milk at inclusion had a higher risk of persistence of AD (84% and 67%, respectively, vs. 57% in those not sensitized) and a higher objective SCORAD after 18 months follow-up. Conclusion We found an association between severity of AD and sensitization to egg or to cow's milk. Moreover, sensitization to egg, and to a lesser extent cow's milk, indicates a worse outcome of AD in terms of persistence and severity of the disease. [source] | ||||||||||