First Dose Of Study Medication Research Articles

Retrospective evaluation of ketamine versus droperidol on time to restraint removal in agitated emergency department patients

PurposeAcute agitation and violent behavior in the emergency department (ED) can lead to significant patient morbidity and contribute to the growing problem of workplace violence against health care providers. To our knowledge, there is no available literature directly comparing intramuscular ketamine to intramuscular droperidol in ED patients presenting with undifferentiated agitation. The purpose of this investigation was to compare the effectiveness and safety of these agents for acute agitation in the ED. MethodsThis was a retrospective observational study conducted at an urban, academic ED. The primary endpoint was time from the first dose of study medication to restraint removal. Safety endpoints included incidence of bradycardia (heart rate < 60 bpm), hypotension (systolic blood pressure < 90 mmHg), hypoxia (oxygen saturation < 90% or need for respiratory support), and incidence of intubation for ongoing agitation or respiratory failure. ResultsAn initial 189 patients were screened, of which, 92 met inclusion criteria. The median time from initial drug administration to restraint removal was 49 min (IQR 30, 168) in the ketamine group and 43 min (IQR 30, 80) in the droperidol group (Median difference 6 min; 95% CI [−7, 26]). There was no significant difference in rates of bradycardia (3% vs 3%, 95% CI [−7%, 8%]), hypotension (0% vs 2%, 95% CI [−5%, 2%]), or hypoxia (7% vs 10%, 95% CI [−15%, 9%]) in the ketamine versus droperidol groups respectively. One patient in the ketamine group was intubated for ongoing agitation, and one patient in the droperidol group was intubated for respiratory failure. ConclusionsIntramuscular droperidol and intramuscular ketamine were associated with similar times from drug administration to restraint removal in patients presenting to the ED with undifferentiated agitation. Prospective studies are warranted to evaluate IM droperidol and IM ketamine head-to-head as first line agents for acute agitation in the ED.

Fremanezumab for Chronic Migraine Prevention in Japanese Patients: Subgroup Analysis from Two International Trials.

Fremanezumab monoclonal antibody therapy has demonstrated efficacy for chronic migraine (CM) with rapid onset and good tolerability. This subgroup analysis of two clinical trials (Japanese and Korean CM Phase 2b/3 [NCT03303079] and HALO CM Phase 3 [NCT02621931]) aimed to evaluate the efficacy and safety of fremanezumab in Japanese patients. Both trials randomly assigned eligible patients at baseline (1:1:1 ratio) to subcutaneous monthly fremanezumab, quarterly fremanezumab, or placebo at 4-week intervals. The primary endpoint was the mean change from baseline in the monthly (28-day) average number of headache days of at least moderate severity during the 12-week period after the first dose of study medication (analyzed by ANCOVA over 12 weeks and MMRM over initial 4 weeks). Secondary endpoints examined other aspects of efficacy, including medication use and disability. A total of 479 and 109 patients were Japanese in the Japanese and Korean CM Phase 2b/3 and HALO CM trials, respectively. Baseline and treatment characteristics were generally similar between treatment groups for both trials. Results of subgroup analyses for the primary endpoint according to ANCOVA demonstrated the superiority of fremanezumab over placebo in Japanese patients (quarterly fremanezumab, p=0.0005; monthly fremanezumab, p=0.0002 in both trials). Results using the MMRM analysis confirmed the rapid onset of action in this population. Results of the secondary endpoints further supported the efficacy of fremanezumab in Japanese patients. Fremanezumab was well tolerated with nasopharyngitis and injection-site reactions representing the most common adverse events in all treatment groups. Despite the limitations of subgroup analyses, these consistent results confirm the efficacy and tolerability of fremanezumab in Japanese patients with CM.

Safety and efficacy of early varenicline prescription in hospitalized patients with acute myocardial infarction: East Asian population

Smoking is a strong risk factor for patients with acute myocardial infarction (AMI). Varenicline is commonly used as a smoking cessation medication, but little is known about its usage in patients with AMI, particularly in hospitalized patients. This is a prospective observational, single-center study collected from May 2018 to July 2021. Study patients underwent percutaneous coronary intervention for AMI.The primary end point was set as safety of varenicline, focusing on any serious adverse cardiac events within 24 weeks after treatment. Efficacy of smoking abstinence was also assessed through self-reports of complete abstinence over a week before the 24- week clinic visit. A total of 162 patients hospitalized with AMI were enrolled in our study. Mean age was 56.7 ± 9.95 years and 97% of the patients were male. Most patients (93.2%) received their first dose of varenicline during hospitalization. Time from admission to first dose of study medication was 2.31 ± 2.73 days and duration of drug intake was 7.41 ± 5.18 weeks. At week 24, only one patient had recurrent myocardial infarction, five patients had undergone revascularization for target lesion failure, and no additional patients developed stroke or died. In terms of efficacy, the rate of smoking abstinence was 79%. Light smokers found it easier to quit smoking than heavy smokers. This study may represent the first report on the safety and efficacy of early initiation of varenicline treatment in East Asian population hospitalized due to AMI who recently underwent percutaneous coronary intervention.

Treatment with fluvoxamine in nonhospitalized coronavirus disease 2019 patients

Context Fluvoxamine may have a potential immune-regulatory action and a therapeutic role in severe acute respiratory syndrome-coronavirus (SARS-CoV-2) infection that may prevent progression and/or hospitalization. Aims Trial that compared fluvoxamine versus placebo in nonhospitalized adults with confirmed SARS-CoV-2 infection (mild and moderate coronavirus disease 2019 cases). Settings and design This is a double-blinded, randomized clinical trial. Patients and methods The study enrolled 162 cases with positive PCR assay for SARS-CoV-2 infection and who were symptomatic within 7 days of the first dose of study medication. Statistical analysis The demographic, clinical, and laboratory data gathered together will be tabulated and statistically analyzed. The statistical analysis of data was carried out using Excel and the SPSS programs statistical package for AQ8 Social Sciences, version 17. Quantitative data were described as median (minimum–maximum). An analysis of the data was carried out to test statistically significant differences between groups. Quantitative data were presented as mean±SD and the Student’s t test was used to compare between two groups. Results In all, 162 patients completed the study; 72 patients were of mild severity; 90 patients were moderate cases and each group was randomized to receive fluvoxamine or placebo besides standard care. In the mild group, no significant difference was recorded while slight significance exists in the moderate severity group. Conclusions Fluvoxamine may have an added value besides the current standard care in reducing the need for hospitalization in outpatient cases, especially pneumonic ones; however, more larger studies are needed.

Feasibility of gabapentin as an intervention for neurorecovery after an acute spinal cord injury: Protocol.

This protocol is describing the first ever prospective, mock-efficacy, dose exploration trial design testing the feasibility of administering gabapentin in the acute setting as an intervention for neurorecovery. Gabapentin is an FDA-approved medication for treating seizures and postherpetic neuralgia and is used broadly off-label for neuropathic pain management for many conditions, including spinal cord injury. Emerging data suggests that when given early after spinal cord injury onset and in low-medium doses, gabapentin may have properties that promote recovery of neurological function. The objective of this trial is to assess the feasibility of conducting an efficacy trial in which gabapentin is started early after injury, is restricted in its dose, and is not used for pain management. Forty-two people aged 18 years or older with any level and any severity of spinal cord injury induced by a trauma will be enrolled, randomized, and have the first dose of study medication by 120 h post-injury onset. Participants will be randomly assigned to one of three groups: 600, 1,800 mg/day gabapentin, or placebo. Study medication will be given for a 90-day duration. Blinded assessments will be obtained at 7 days post-injury (baseline), 30 days post-injury (interim), after the 90-day treatment duration/approximately 3 months post-injury (end of treatment), and at 6 months post-injury (end of study). The key analysis parameters will evaluate feasibility of recruitment of target population, delivery of drug treatment protocol, maintenance of blinding, and retention of participants. Outputs from this trial will inform research and clinical practice on the effects of manipulating gabapentin for non-pain management purposes in the acute setting and will guide the development of a properly powered efficacy trial of gabapentin as an intervention for neurorecovery in spinal cord injury. The study was approved by the MetroHealth Institutional Review Board (IRB21-00609) and registered at clinicaltrials.gov prior to enrolling any participants. Dissemination will include peer-reviewed publications, presentations at professional conferences and in the community, and through other healthcare and public venues. www.ClinicalTrials.gov, identifier: NCT05302999; protocol version 1.1 approved 05/23/2022. National Institute on Disability, Independent Living and Rehabilitation Research.

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder

Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy. In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD. Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy. The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance. A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin. Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD. ClinicalTrials.gov Identifier: NCT02061293.

Pharmacokinetics of ciprofloxacin and fluocinolone acetonide otic solution in pediatric patients

PurposeTo describe the pharmacokinetics (PK) of ciprofloxacin 0.3 % and fluocinolone acetonide 0.025 % otic solution (CIPRO+FLUO), ciprofloxacin 0.3 % otic solution alone (CIPRO), and fluocinolone acetonide 0.025 % otic solution alone (FLUO) administered into the middle ears of pediatric patients with Acute Otitis Media with Tympanostomy Tubes (AOMT). Materials and methodsWe performed a PK analysis of patients who participated in two multicenter, randomized, double-blind AOMT clinical trials (SALVAT studies CIFLOTIII/10IA02 and CIFLOTIII/10IA04). Each patient received 0.25 mL of CIPRO+FLUO, CIPRO, or FLUO twice a day instilled into the ear canal(s) for 7 days to treat AOMT. Blood samples of patients with unilateral AOMT were collected before the administration of the first dose of study medication at Visit 1 (day 1) and within 1–2 h after the last dose on day 7. Blood samples were analyzed to detect ciprofloxacin and fluocinolone acetonide concentrations using two validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods, with the lower limit of quantification for ciprofloxacin and fluocinolone acetonide in plasma samples being 1 ng/mL. Thirty randomly selected patients between 10 months and 10 years of age (mean age, 4.4 years) were included in the study. Although all available samples were analyzed, only PK data of the 22 patients with both samples and unilateral disease were considered for study purposes. ResultsNo detectable concentrations of ciprofloxacin or fluocinolone acetonide in plasma were observed (<1 ng/mL). ConclusionsThese results demonstrated negligible systemic exposure to ciprofloxacin and fluocinolone acetonide following topical otic administration in pediatric patients with AOMT.

Pembrolizumab treatment of advanced cervical cancer: updated results from the phase II KEYNOTE-158 study

<h3>Objectives:</h3> Pembrolizumab (pembro) showed durable antitumor activity and manageable safety in patients (pts) with advanced cervical cancer in an earlier interim analysis of KEYNOTE-158 (NCT02628067). Based on those results, the US FDA granted accelerated approval of pembro for pts with advanced, PD-L1-positive cervical cancer that progressed on or after chemotherapy. We present an updated analysis of pts included in the cervical cancer cohort of KEYNOTE-158 based on 17 months of additional follow-up. <h3>Methods:</h3> KEYNOTE-158 is a phase 2 basket study investigating the antitumor activity of pembro across several cancer types. Key eligibility criteria for the cervical cancer cohort included histologically or cytologically confirmed disease, progression on or intolerance to ≥1 line of standard therapy, an ECOG PS of 0 or 1, and provision of a tumor sample for biomarker analysis. Pts received pembro 200 mg once every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision. Tumor imaging was performed every 9 weeks for the first 12 months, and every 12 weeks thereafter. PD-L1 positivity, defined as a combined positive score (CPS) ≥1, was evaluated retrospectively by immunohistochemistry. The primary endpoint was the objective response rate (ORR) assessed per RECIST v1.1 by independent central radiology review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. <h3>Results:</h3> A total of 98 pts were treated. Median age was 46 (range, 24 to 75) years, 65.3% had ECOG PS 1, and 94.9% had stage M1 disease. A total of 83.7% of enrolled pts had PD-L1–positive tumors. As of the June 27, 2019 data cutoff, the median follow-up duration, defined as first dose of study medication to data cutoff, was 36.9 (range, 34.3 to 41.0) months. In the updated analysis, 2 partial responses (PR) converted to complete responses (CR) and 2 additional PR occurred for a total of 5 CR and 9 PR; ORR was 14.3% (95% CI, 8.0% to 22.8%). A total of16 pts had stable disease (SD), and the disease control rate (CR+PR+SD) was 30.6%. All 14 responses were in pts with PD-L1–positive tumors, resulting in an ORR of 17.1% (95% CI, 9.7% to 27.0%) in the PD-L1–positive cohort (N=82) and 0.0% (95% CI, 0.0% to 21.8%) in the PD-L1–negative cohort. A total of 7 of 14 responses were ongoing after ≥24 months of follow-up. Median DOR had not been reached (range, 3.7+ to 35.2+). Median (95% CI) PFS and OS were 2.1 (2.1 to 2.2) months and 9.3 (7.6 to 11.7) months, respectively. Treatment-related adverse events (AEs) occurred in 65.3% of pts, and the most common were hypothyroidism (11.2%), fatigue (11.2%), and decreased appetite (9.2%). 12.2% of pts had treatment-related grade 3-4 AEs; there were no grade 5 AEs. <h3>Conclusions:</h3> With 17 months of additional follow-up, pembro continues to show durable antitumor activity and manageable safety in pts with advanced cervical cancer, similar to the previous report.

Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial

Selinexor combined with dexamethasone has shown activity in patients with heavily pre-treated multiple myeloma. In a phase 1b/2 study, the combination of oral selinexor with bortezomib (a proteasome inhibitor) and dexamethasone induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezomib. We aimed to evaluate the clinical benefit of weekly selinexor, bortezomib, and dexamethasone versus standard bortezomib and dexamethasone in patients with previously treated multiple myeloma. This phase 3, randomised, open-label trial was done at 123 sites in 21 countries. Patients aged 18 years or older, who had multiple myeloma, and who had previously been treated with one to three lines of therapy, including proteasome inhibitors, were randomly allocated (1:1) to receive selinexor (100 mg once per week), bortezomib (1·3 mg/m2 once per week), and dexamethasone (20 mg twice per week), or bortezomib (1·3 mg/m2 twice per week for the first 24 weeks and once per week thereafter) and dexamethasone (20 mg four times per week for the first 24 weeks and twice per week thereafter). Randomisation was done using interactive response technology and stratified by previous proteasome inhibitor therapy, lines of treatment, and multiple myeloma stage. The primary endpoint was progression-free survival in the intention-to-treat population. Patients who received at least one dose of study treatment were included in the safety population. This trial is registered at ClinicalTrials.gov, NCT03110562. The trial is ongoing, with 55 patients remaining on randomised therapy as of Feb 20, 2020. Of 457 patients screened for eligibility, 402 were randomly allocated-195 (49%) to the selinexor, bortezomib, and dexamethasone group and 207 (51%) to the bortezomib and dexamethasone group-and the first dose of study medication was given between June 6, 2017, and Feb 5, 2019. Median follow-up durations were 13·2 months [IQR 6·2-19·8] for the selinexor, bortezomib, and dexamethasone group and 16·5 months [9·4-19·8] for the bortezomib and dexamethasone group. Median progression-free survival was 13·93 months (95% CI 11·73-not evaluable) with selinexor, bortezomib, and dexamethasone and 9·46 months (8·11-10·78) with bortezomib and dexamethasone (hazard ratio 0·70 [95% CI 0·53-0·93], p=0·0075). The most frequent grade 3-4 adverse events were thrombocytopenia (77 [39%] of 195 patients in the selinexor, bortezomib, and dexamethasone group vs 35 [17%] of 204 in the bortezomib and dexamethasone group), fatigue (26 [13%] vs two [1%]), anaemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Peripheral neuropathy of grade 2 or above was less frequent with selinexor, bortezomib, and dexamethasone (41 [21%] patients) than with bortezomib and dexamethasone (70 [34%] patients; odds ratio 0·50 [95% CI 0·32-0·79], p=0·0013). 47 (24%) patients in the selinexor, bortezomib, and dexamethasone group and 62 (30%) in the bortezomib and dexamethasone group died. A once-per-week regimen of selinexor, bortezomib, and dexamethasone is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received one to three previous lines of therapy. Karyopharm Therapeutics.

Fluticasone furoate/vilanterol versus fluticasone propionate in patients with asthma and exercise-induced bronchoconstriction

Objective: To investigate whether once-daily (OD) fluticasone furoate (FF)/vilanterol (VI) provides greater long-term protection from postexercise fall in forced expiratory volume in 1 s (FEV1) than twice-daily (BD) fluticasone propionate (FP) in patients with asthma and exercise-induced bronchoconstriction. Methods: A randomized, double-blind, crossover study was conducted in patients (aged 12–50 years) on low-/mid-dose maintenance inhaled corticosteroid. Following a 4-week run-in period (FP 250 µg BD), patients with a ≥ 20% decrease in postexercise FEV1 received FF/VI 100/25 µg OD or FP 250 µg BD for 2 weeks. Exercise challenges were carried out 23 h after the first dose of study medication, and 12 and 23 h after evening clinic dose at the end of the 2-week treatment period. After a 2-week washout period (FP 250 µg), patients crossed over treatments, with procedures and tests repeated. The primary endpoint was mean maximal percentage decrease from pre-exercise FEV1 following exercise challenge 12-h postevening dose on Day 14. Results: The mean maximal percentage decrease from pre-exercise FEV1 after the 12-h exercise challenge (Day 14) was 15.02% with FF/VI, and 16.71% with FP (difference, −1.69; 95% confidence interval, −3.76 to 0.39; p = 0.109). After the 23-h exercise challenge (Day 14), respective mean maximal decreases were 11.90% and 14.05% (difference, −2.15; 95% confidence interval, −4.31 to 0.01). Conclusion: The study failed to show a difference between FF/VI and FP at providing long-term protection from exercise-induced bronchoconstriction.

Uterine Artery Doppler in Pregnancy: Women with PCOS Compared to Healthy Controls.

The objective of this study was to investigate possible differences in uterine artery pulsatility index (UtAPI) between pregnant women with PCOS and healthy controls and to explore possible effects of metformin on UtAPI. Material and Methods. The study was conducted in a tertiary center. Forty-eight pregnant women diagnosed with PCOS before pregnancy and 124 healthy pregnant women were included. Women with PCOS were randomly assigned to metformin 2000 mg daily or a placebo. UtAPI was measured five times during 1st and 2nd trimesters of pregnancy in women with PCOS and four times in healthy controls. Results. There was no difference in UtAPI between PCOS women and healthy controls at any point in time (p = 0.34–0.77). In women with PCOS, randomly assigned to metformin 2000 mg or placebo, UtAPI was unaffected by metformin two hours after intake of the first dose of study medication (p = 0.34). All PCOS women, regardless of randomization, had higher UtAPI two hours after intake of study medication and a meal compared to before a meal (p = 0.02). Conclusions. In the first and second trimesters of pregnancy, there was no difference in UtAPI between women with PCOS and healthy controls. Metformin had no immediate effect on the UtAPI. Interestingly, blood flow decreased after a meal, suggesting that time since last meal should be taken into consideration when interpreting the results of UtAPI measurements in pregnancy. This trial is registered with ClinicalTrials.gov (NCT00466622) Metformin in Pregnant PCOS women (PregMet) (NCT00159536).

Comparison of glycopyrronium versus tiotropium on the time to clinically important deteriorations in patients with COPD: a post-hoc analysis of randomized trials

Glycopyrronium is a once-daily, inhaled long-acting muscarinic antagonist (LAMA) demonstrating similar efficacy to inhaled tiotropium in patients with moderate-to-severe COPD; however, the benefit of LAMAs on COPD symptoms has been variable. COPD is a progressive disease in which many patients develop an acute or sustained deterioration. Data on the prevention of clinically important deteriorations (CID) using LAMAs are limited. A pooled analysis was performed on four Phase III trials (n = 2936) that compared the efficacy of glycopyrronium (n = 1859) with tiotropium (n = 1077). The primary endpoint was significant delay and/or reduction in the occurrence of CID. CID was defined as any of the following: ≥100 mL decrease from baseline in pre-dose forced expiratory volume in 1 second (FEV1), ≥4 point increase in St George’s Respiratory Questionnaire score or a moderate-to-severe COPD exacerbation occurring after the first dose of study medication. A sustained CID was a CID occurring on ≥2 consecutive visits 4 weeks apart or for ≥50% of all available subsequent visits. Baseline characteristics for the overall population were similar. Patients had moderate (62%) or severe (38%) COPD. Mean post-bronchodilator FEV1 was approximately 55% predicted, and mean FEV1 reversibility was 16.7 and 18.6% in the glycopyrronium and tiotropium groups, respectively. Both glycopyrronium and tiotropium significantly reduced time to CID and sustained CID versus placebo (p < 0.001). No statistically significant differences were found between the glycopyrronium and tiotropium treatment groups in time to CID or sustained CID. Glycopyrronium is effective in delaying time to clinically important deteriorations, with similar efficacy to tiotropium.

A Double-blind, Randomized, Placebo-controlled Trial of Lactobacillus acidophilus for the Treatment of Acute Watery Diarrhea in Vietnamese Children.

Probiotics are the most frequently prescribed treatment for children hospitalized with diarrhea in Vietnam. We were uncertain of the benefits of probiotics for the treatment of acute watery diarrhea in Vietnamese children. We conducted a double-blind, placebo-controlled, randomized trial of children hospitalized with acute watery diarrhea in Vietnam. Children meeting the inclusion criteria (acute watery diarrhea) were randomized to receive either 2 daily oral doses of 2 × 10 CFUs of a local probiotic containing Lactobacillus acidophilus or placebo for 5 days as an adjunct to standard of care. The primary end point was time from the first dose of study medication to the start of the first 24-hour period without diarrhea. Secondary outcomes included the total duration of diarrhea and hospitalization, daily stool frequency, treatment failure, daily fecal concentrations of rotavirus and norovirus, and Lactobacillus colonization. One hundred and fifty children were randomized into each study group. The median time from the first dose of study medication to the start of the first 24-hour diarrhea-free period was 43 hours (interquartile range, 15-66 hours) in the placebo group and 35 hours (interquartile range, 20-68 hours) in the probiotic group (acceleration factor 1.09 [95% confidence interval, 0.78-1.51]; P = 0.62). There was also no evidence that probiotic treatment was efficacious in any of the predefined subgroups nor significantly associated with any secondary end point. This was a large double-blind, placebo-controlled trial in which the probiotic underwent longitudinal quality control. We found under these conditions that L. acidophilus was not beneficial in treating children with acute watery diarrhea.

Evaluation of Gelatin Tannate Against Symptoms of Acute Diarrhea in Pediatric Patients

BackgroundAcute diarrhea is the second most common cause of morbidity and mortality worldwide, especially in children aged ≤3 years. Some drugs (e.g., the mucoprotector gelatin tannate) plus a reduced osmolality oral rehydration solution (ORS) may effectively reduce symptom duration and severity. The current trial was therefore designed to assess the efficacy and safety of gelatin tannate in pediatric patients with acute diarrhea.Material/MethodsThis was a randomized, controlled, double-blind, parallel-group, single-center study comparing gelatin tannate plus ORS (103 patients) with ORS plus placebo (100 patients) in children aged 3 months to 12 years with infectious or noninfectious acute diarrhea. Details about stool consistency and total time to resolution of diarrhea comprised the primary study endpoints. Secondary study endpoints included symptoms of diarrhea at 12, 24, 36, 48, and 72 hours after the first dose of study medication.ResultsFrom 12 hours onwards, the incidence of watery stools was significantly lower in the gelatin tannate group than in the ORS group (at 12 hours: 59.2% vs. 77.0%; p=0.01). The same was true for stool frequency (at 12 hours: mean 2 vs. 3 stool productions in the previous 12 hours; p<0.01). At all timepoints during the study, the proportion of patients with Stool Decrease Index improvement was significantly greater (p<0.01) in the gelatin tannate group than in the placebo group (at 12 hours: 66.6% vs. 33.3%; p<0.01).ConclusionsGelatin tannate plus ORS is an effective and safe option for the treatment of acute diarrhea in children. Significant symptom relief is evident 12 hours after starting treatment.

High-Dose Methylprednisolone to Prevent Platelet Decline in Preeclampsia: A Randomized Controlled Trial.

To evaluate whether early administration of high-dose methylprednisolone limits the fall of platelets in preeclampsia. A randomized trial of 180 mg methylprednisolone or placebo administered in divided doses over 36 hours was conducted in women admitted for preeclampsia and platelet counts below 150×10/L in four French academic centers. Patients were not included when platelet counts were below 50×10/L or when immediate delivery was required. The primary study outcome was the proportion of patients with platelet counts above 100×10/L 36 hours after the first dose of study medication. The total sample size needed to detect a 23% difference in the rate of this outcome between groups with a one-tailed α of 0.05 and 90% power was 94 patients. Thirty-six patients were randomly assigned to receive methylprednisolone and 34 placebo between October 2007 and May 2011. Platelet counts above 100×10/L at 36 hours after the first dose of study medication were recorded in 30 (83%) in the active group and 29 (85%) in the placebo group (relative risk 0.98, 95% confidence interval 0.80-1.20; P=.82). The only adverse potentially study-related event was hyperglycemia in one woman allocated to methylprednisolone. In women with preeclampsia and platelet counts under 150×10/L, methylprednisolone was not effective in maintaining platelet counts above 100×10/L. EU Clinical Trials Register, http://clinicaltrialsregister.eu, EudraCT 2006-004881-15-FR.

Clinical Assessment of Treatment Outcomes Following &amp;lt;i&amp;gt;Borago officinalis&amp;lt;/i&amp;gt; Extract Therapy in Patients Presenting with Cyclical Mastalgia

In order to evaluate the safety and efficacy of Borago officinalis (900 mg borage oil capsules) in the treatment of patients presenting with cyclic mastalgia, 91 subjects were included in the study. Ef- ficacy assessments were performed based on data obtained prior to the start of treatment (Pre- treatment), and after each menstrual cycle (Assessment 2—following 45 days of treatment; and Assessment 3—at the end of the 90-day treatment period). Primary efficacy measures considered the results of the Mastalgia Questionnaire, including a 100 mm visual analog pain scale assessing mean, most intense mastalgia severity, and impact on work, sleep, and sexual activity. Safety and tolerability measures included any changes in vital signs and physical exam in relation to pre- treatment, any changes in clinical laboratory exams in relation to pretreatment, and the occur- rence of adverse events after the first dose of study medication. The VAS scores of the mean mas- talgia and most severe mastalgia both showed statistically significant (p < 0.0001) reductions from Pretreatment to Assessment 3. Mean mastalgia scores improved among 92.3% of the treated patients, while most severe mastalgia scores improved among 93.4% of patients. There were sta- * Corresponding author.

THU0336 Lower-Dose Solumatrix® Indomethacin Efficacy in Acute Pain: Results from Two Phase 3 Studies

BackgroundIndomethacin is used to treat acute gouty arthritis and other acute pain conditions, but similar to other NSAIDs, is associated with dose-related gastrointestinal, cardiovascular, and renal complications. International health authorities...

S123 Increased risk of upper respiratory infection with addition of intermittent bolus-dose vitamin D supplementation to a daily low-dose regimen

Introduction and ObjectivesMeta-analysis of clinical trials of vitamin D supplementation for the prevention of acute respiratory infection (ARI) shows a protective effect in the general population, but there is controversy...

Naproxen Twice Daily Versus as Needed (PRN) Dosing: Efficacy and Tolerability for Treatment of Acute Ankle Sprain, a Randomized Clinical Trial.

This study was conducted to compare the efficacy and safety of naproxen 500 mg twice daily (BID) versus naproxen 500 mg as needed (PRN) for treatment of ankle sprain. In this seven-day, randomized, parallel group trial, 135 patients with ankle sprain occurring less than 48 hours prior to the first dose of study medication were randomized to receive naproxen 500 mg BID (67 patients) and naproxen 500 mg as needed (PRN) (68 patients). The ankle pain was assessed at rest and on full weight bearing using Numeric Rating Scale (NRS) from 0 (no pain) to 10 (the worst imaginable pain). Ankle swelling was assessed as a 4-point scale ranging from 0 (no swelling) to 3 (severe swelling) rated by the investigator. The primary efficacy end point was the patient's assessment of ankle pain via NRS and the degree of swelling on day seven. Results showed a significant decrease in pain on weight bearing, pain at rest and the extent of swelling (P<0.001) in both groups, but there was no substantial difference between the two groups (P>0.05) after seven days. Assessing the safety profile of the two different dosing, 13.3% of the naproxen BID group and 6.7% of the as needed group had adverse events, showing that the as needed regimen was safer (P<0.001). Results showed that naproxen as needed may reduce the pain and edema of the sprained ankle with no significant difference compared to the BID regimen, while it possesses better safety profile and lower total drug use.

An oral preparation of Lactobacillus acidophilus for the treatment of uncomplicated acute watery diarrhoea in Vietnamese children: study protocol for a multicentre, randomised, placebo-controlled trial.

BackgroundDiarrhoeal disease is a major global health problem, particularly affecting children under the age of 5 years. Besides oral rehydration solution, probiotics are also commonly prescribed to children with acute watery diarrhoea in some settings. Results from randomised clinical trials (RCTs) in which investigators studied the effect of probiotics on diarrhoeal symptoms have largely shown a positive effect; yet, the overall quality of the data is limited. In Vietnam, probiotics are the most frequently prescribed treatment for children hospitalised with acute watery diarrhoea, but there is little justification for this treatment in this location. We have designed a RCT to test the hypothesis that an oral preparation of Lactobacillus acidophilus is superior to placebo in the treatment of acute watery diarrhoea in Vietnamese children.MethodsThis RCT was designed to study the effect of treatment with L. acidophilus (4 × 109 colony-forming units/day) for 5 days for acute watery diarrhoea against a placebo in 300 children ages 9 to 60 months admitted to hospitals in Vietnam. Clinical and laboratory data plus samples will be collected on admission, daily during hospitalisation, at discharge, and at follow-up visits for a subset of participants. The primary end point will be defined as the time from the first dose of study medication to the start of the first 24-hour period without diarrhoea as assessed by the on-duty nurse. Secondary endpoints include the time to cessation of diarrhoea as recorded by parents or guardians in an hourly checklist, stool frequency over the first 3 days, treatment failure, rotavirus and norovirus viral loads, and adverse events.DiscussionThe existing evidence for the use of probiotics in treating acute watery diarrhoea seems to favour their use. However, the size of the effect varies across publications. An array of different probiotic organisms, doses, treatment durations, study populations, designs, settings, and aetiologies have been described. In this trial, we will investigate whether probiotics are beneficial as an adjuvant treatment for children with acute watery diarrhoea in Vietnam, with the aim of guiding clinical practice through improved regional evidence.Trial registrationCurrent Controlled Trials ISRCTN88101063