Intergroup Differences In Incidence Research Articles

Efficacy and safety of 0.01% atropine for prevention of childhood myopia in a 2-year randomized placebo-controlled study.

Atropine eye drops prevent the progression of myopia, but their use has not been tested in the Japanese schoolchildren population. Here, we evaluate the efficacy and safety of 0.01% atropine eye drops for myopia control in Japanese children. Multicenter (7 university hospitals), randomized, double-masked, placebo-controlled trial. Participants were 171 Japanese schoolchildren aged 6 to 12years, with progressive myopia, spherical equivalence (SE) of -1.00 to -6.00 diopters (D), and astigmatism of ≤1.5 D. They were randomized to receive either 0.01% atropine (n=85) or placebo (n=86) eye drops once nightly OU for 24months. Primary and secondary efficacy endpoints were changes in SE and axial length (AL), respectively, from baseline to month 24. Data from 168 subjects were analyzed. At month 24, compliance was similar in both groups (atropine: 83.3%; placebo: 85.7%). The least squares mean change in SE and AL from baseline were, respectively, -1.26 D (95% confidence interval [CI]: -1.35, -1.17) and 0.63mm (0.59, 0.67) for atropine and -1.48 D (- 1.57, -1.39) and 0.77mm (0.73, 0.81) for placebo. Inter-group differences were 0.22 D (95% CI: 0.09, 0.35; P < 0.001) for SE and - 0.14mm (-0.20, -0.08; P < 0.001) for AL. Three patients experienced mild allergic conjunctivitis side effects, with no inter-group difference in incidence (atropine: 2.4%; 2/84 patients; placebo: 1.4%; 1/84 patients). With good compliance, 0.01% atropine is effective and safe for preventing the progression of childhood myopia.

Dexmedetomidine infusion as an analgesic adjuvant during laparoscopic \u0441holecystectomy: a randomized controlled study

BackgroundDexmedetomidine (DEX) has sedative, sympatholytic and analgesic effects and might be beneficial if used as an adjuvant to: improve analgesia; modulate haemodynamic responses to intubation and pneumoperitoneum and; reduce the number of opioid-associated adverse events. The aim of this study was to evaluate the efficacy and safety of DEX infusion during elective laparoscopic cholecystectomy (LC).MethodsA randomized, single-centre, parallel-group, placebo-controlled study was carried out between May 2016 and June 2017. Adult patients (18–79 years) with American Society of Anesthesiology (ASA) physical status I–II were randomly assigned to 0.5 μg/kg/h DEX infusion from induction of anaesthesia to extubation (Group D; n = 30) or normal saline infusion (Group C; n = 30). The primary efficacy outcomes were postoperative morphine consumption. Secondary efficacy outcomes included: time to first use of rescue analgesia; postoperative morphine consumption; intraoperative fentanyl consumption; time from end of surgery to extubation; lengths of intensive care unit (ICU) and general ward stay; degree of postoperative pain 3, 6, 12 and 24 h after surgery; incidence of persistent post-surgical pain.ResultsDEX infusion was associated with a decrease in postoperative morphine consumption (p = 0.001), lower incidence of severe postoperative pain (odds ratio [OR] 9, 95% confidence interval [CI] 1.1–77, p = 0.04) and significantly longer time to first use of rescue analgesia (p = 0.001). Group D also had significantly lower fentanyl consumption both intraoperatively (p = 0.001) and in the time from end of surgery to extubation (p = 0.001) plus decreased incidence of persistent post-surgical pain (OR 14.5, 95% CI 1.7–122, p = 0.005). The incidence of postoperative nausea and vomiting was lower in Group D than Group C (OR 5, 95% CI 1.1–26, p = 0.005). Median pain intensity did not differ between the groups 3, 6, 12 or 24 h after surgery and there were no inter-group differences in the lengths of ICU stay or overall hospital stay between groups. The incidence of hypertension was significantly higher in Group C (OR 13.8, 95% CI 4–48, p < 0.0001); there were no inter-group differences in incidences of hypotension and bradycardia.ConclusionsIntraoperative DEX infusion is safe and effective for improving analgesia during and after elective LC. DEX appears to significantly reduce the number of patients with severe postoperative pain, postoperative morphine consumption and prolong time to first use of rescue analgesia.Trial registrationClinicalTrials.gov: Retrospectively registered on July 7, 2017, NCT03211871.

Dilemmas in genetic counseling for low-penetrance neuro-susceptibility loci detected on prenatal chromosomal microarray analysis

Chromosomal microarray analysis is standard of care in fetuses with malformations, detecting clinically significant copy number variants in 5-7% of cases over conventional karyotyping. However, it also detects variants of uncertain significance in 1.6-4.2% of the cases, some of which are low-penetrance neuro-susceptibility loci. The interpretation of these variants in pregnancy is particularly challenging because the significance is often unclear and the clinical implications may be difficult to predict. The purpose of this study was to describe counseling dilemmas regarding low-penetrance neuro-susceptibility loci that are detected by prenatal chromosomal microarray analysis. During the study period (January 2014 to December 2015), 700 prenatal chromosomal microarray analyses were performed. Cases were categorized as "indicated" (n=375) if there were abnormal sonographic findings or suggestive medical history and "patient choice" (n=325) in the presence of a structurally normal fetus with no other particular indication. The laboratory reported on copy number variants ≥400 Kb in size in loci known to be associated with genetic syndromes and ≥1 Mb in other areas of genome. Results were classified as gross aneuploidy, copy number variants, and normal. Copy number variants were categorized according to the American College of Medical Genetics standards and guidelines: pathogenic, variants of uncertain significance, or benign. Variants of uncertain significance were further subdivided into categories of likely pathogenic, variants of uncertain significance with no subclassification, and likely benign. Statistical analysis was performed with the use of Chi square test and Fisher's exact test to compare intergroup differences in incidence of the different result categories and demographic data. Patient choice cases became more prevalent with time (35.5% in the beginning of the study, compared with 48.4% at the end of the study period). Clinically significant copy number variants were found in 14 of 375 (3.7%) of indicated cases vs only 2 of 325 (0.6%) of patient choice cases (P=.009). All "likely benign" variants consisted of low-penetrance neuro-susceptibility loci. The incidence thereof was similar between the indicated and patient choice groups (3.7% vs 3.4%; P=.85). In the indicated group, some variants of uncertain significance may have contributed to the abnormal anatomic findings. Conversely, in the patient choice group, the finding of low-penetrance neuro-susceptibility loci was often unexpected and confounding for prospective parents. Prenatal chromosomal microarray analysis added clinically significant information in both groups. However, it also detected low-penetrance neuro-susceptibility loci in approximately 3.5% of the cases. This fact should be conveyed during pretest counseling to allow patients to make informed choices, particularly when chromosomal microarray is to be performed for patient choice.

Investigation of carcinogenicity for levamisole administered in the diet to F344 rats

A two year carcinogenicity study of anthelmintic drug levamisole (LV) was performed using 50 male and 50 female F344 rats at dietary drug concentrations of 0, 60, or 300 ppm. The daily intakes of LV were calculated to be 2.6, 12.9 mg/kg b.w./day for males and 2.9, 14.1 mg/kg b.w./day for females, respectively. No significant differences in general condition and survival rate (82%, 74%, 80% in males and 84%, 84%, 84% in females, respectively) were observed. In the 300 ppm group, suppression of body weight gain was observed from the onset of treatment and reduction in final body weights was 6% in males and 11% in females. Significant increases in the absolute and/or relative weights of the lungs, heart, spleen, liver, kidneys, and adrenals were observed in males and/or females treated with 300 ppm. Some of high incidences neoplasms were observed, and there were also tendencies to increase for mammary gland fibroma and thoracic/abdominal cavity mesothelioma in males. However, there were no significant inter-group differences in incidences, histopathological types or differences compared with historical control data. Thus, it was concluded that LV was not carcinogenic to male and female F344 rats under the experimental conditions.

Stroke Prevention by Cilostazol in Patients with Atherothrombosis: Meta-analysis of Placebo-controlled Randomized Trials

Cilostazol is an antiplatelet agent that inhibits phosphodiesterase III in platelets and vascular endothelium. Previous randomized controlled trials of cilostazol for prevention of cerebrovascular events have garnered mixed results. We performed a systematic review and meta-analysis of the randomized clinical trials in patients with atherothrombotic diseases to determine the effects of cilostazol on cerebrovascular, cardiac, and all vascular events, and on all major hemorrhagic events. Relevant trials were identified by searching MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry for titles and abstracts. Data from 12 randomized controlled trials, involving 5674 patients, were analyzed for end points of cerebrovascular, cardiac, and major bleeding events. Searching, determination of eligibility, data extraction, and meta-analyses were conducted by multiple independent investigators. Data were available in 3782, 1187, and 705 patients with peripheral arterial disease, cerebrovascular disease, and coronary stenting, respectively. Incidence of total vascular events was significantly lower in the cilostazol group compared with the placebo group (relative risk [RR], 0.86; 95% confidence interval [CI], 0.74-0.99; P=.038). This was particularly influenced by a significant decrease of incidence of cerebrovascular events in the cilostazol group (RR, 0.58; 95% CI, 0.43-0.78; P < .001). There was no significant intergroup difference in incidence of cardiac events (RR, 0.99; 95% CI, 0.83-1.17; P=.908) and serious bleeding complications (RR, 1.00; 95% CI, 0.66-1.51; P=.996). This first meta-analysis of cilostazol in patients with atherothrombosis demonstrated a significant risk reduction for cerebrovascular events, with no associated increase of bleeding risk.

Rat medium-term multi-organ carcinogenesis bioassay of Agaricus blazei Murrill fruit-body extract

The modifying potential of Agaricus blazei Murrill fruit-body extract (ABFE) on tumor development was investigated in a medium-term multi-organ carcinogenesis bioassay. Male 6-week-old F344 rats were treated with N-nitrosodiethylamine (DEN), N-methyl- N-nitrosourea (MNU), 1,2-dimethylhydrazine dihydrochloride (DMH), N-butyl- N-(hydroxybutyl)-nitrosamine (BBN), and diisopropanolnitrosamine (DHPN) for initiation (DMBDD treatment). After a 1-week withdrawal period, the animals received distilled water (vehicle control) or ABFE A, gamma-amino butyric acid (GABA) at 0.8 mg/kg, ABFE B (GABA level of 3.0 mg/kg) or ABFE C (GABA level of 12.0 mg/kg) by gavage for 24 weeks. There were no effects of ABFE on survival rate, general condition, body weight, food and water consumption, and organ weights. The multiplicity of large intestinal nodules, smaller than 2 mm was significantly increased in the ABFE C group with DMBDD treatment. However, there were no significantly inter-group differences in incidences of hyperplastic or neoplastic lesions in colon or other organs, or in immunohistochemically identified preneoplastic lesions in the liver. In conclusion, A. blazei Murrill fruit-body extract, even at a GABA level up to 12 mg/kg, did not exert modifying potential in the present medium-term multi-organ carcinogenesis bioassay in male F344 rats (DMBDD method).

A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial Comparing the Efficacy and Tolerability of Levocabastine-Oxymetazoline Nasal Spray with Levocabastine and Oxymetazoline Alone in the Symptomatic Treatment of Seasonal Allergic Rhinitis

A total of 1015 patients participated in three 1-week, multicenter, double-blind, randomized, placebo-controlled trials undertaken to assess the therapeutic efficacy and tolerability of twice daily administration of a nasal spray containing a combination of levocabastine (0.5 mg/mL) and oxymetazoline (0.5 mg/mL) (levocabastine-D) versus that of either agent alone in the treatment of ragweed-induced seasonal allergic rhinitis. As these studies shared a common protocol, the data have been pooled. Patient assessments revealed that the mean change in area under the curve (AUC) from baseline over the entire treatment period was significantly greater in patients treated with levocabastine or levocabastine-D than in those receiving placebo for all symptoms evaluated (nasal congestion; P &lt; 0.05 and sneezing, rhinorrhea, nasal itching, ocular symptoms, total key symptoms, total all symptoms; P &lt; 0.001). Corresponding changes in patients treated with oxymetazoline alone did not attain statistical significance. Day-by-day analysis demonstrated that the beneficial effects seen with levocabastine and levocabastine-D were maintained throughout the treatment period for all symptoms except nasal congestion (Days 1 and 2 only); oxymetazoline provided significant relief from nasal congestion only and only on the first day of treatment. Investigator assessments revealed similar trends. Global evaluations of therapeutic efficacy revealed that 44% of levocabastine-treated patients and 52% of patients treated with levocabastine-D considered therapeutic efficacy to be excellent or good compared with 39% of those on oxymetazoline and 26% on placebo (P &lt; 0.01 versus placebo). Adverse experiences were reported by 30% of levocabastine-treated patients, 40% of patients treated with levocabastine-D and oxymetazoline, and 32% of placebo controls, with no statistically significant intergroup differences in incidence or type. In conclusion, twice daily levocabastine nasal spray is effective and well-tolerated for the treatment of ragweed-induced seasonal allergic rhinitis with an adverse effect profile comparable with that of placebo. Addition of oxymetazoline to the topical antihistamine does not appear to provide significant additional clinical benefit compared to that observed with levocabastine alone, and tachyphylaxis to the decongestant effect of the topical vasoconstrictor occurs within days of treatment initiation.

Comparison of Epidurally Administered Sufentanil, Morphine, and Sufentanil-Morphine Combination for Postoperative Analgesia

Postoperative analgesia provided by epidurally administered sufentanil and/or morphine was evaluated in 45 patients recovering from major gynecologic surgery. At the first complaint of pain in the Postanesthesia Care Unit, patients received a single epidural bolus of 30 micrograms sufentanil (group A), 5 mg morphine (group B), or 30 micrograms sufentanil plus 3 mg morphine (group C) in a randomized blinded fashion. Analgesic efficacy was assessed throughout the 24-h study period with 10-cm visual analog scales. The need for additional postoperative analgesia (patient-controlled analgesia, 1 mg of morphine every 6 min as necessary) and the incidence of adverse effects were also assessed. Patients receiving sufentanil (groups A and C) had significantly faster onset of analgesia than did patients given morphine alone (group B, P less than 0.05). Group B subjects experienced the longest duration of analgesia (B vs A and C, P less than 0.05) and required significantly less patient-controlled analgesia (morphine) than patients in group A (P less than 0.05). No patient developed clinically significant respiratory depression or excessive sedation, and there were no intergroup differences in incidence of pruritus or nausea (P value not significant). The data indicate that a mixture of sufentanil and morphine provides either a more rapid onset of epidural analgesia or reduced patient-controlled analgesia narcotic requirement than respective doses of each agent administered alone.

歯科・口腔外科領域感染症に対するＭｉｄｅｃａｍｙｃｉｎ ａｃｅｔａｔｅ（ＭＯＭ）の薬効評価 Ｊｏｓａｍｙｃｉｎを対照とする二重盲検比較試験成績

Clinical efficacy and safety of Midecamycin acetate (MOM) were compared with those of Josamycin (JM) in patients with oral and maxillofacial infections under multicentered double-blind controlled study, and the following results were obtained.1. The overall clinical effectiveness rate was 77.4% for MOM group and 77.4% for JM group, judged by committee members with no significant difference.2. Clinical effectiveness rate classified by diagnosis was 78.8% for MOM group and 78.0% for JM in periodontal infections but no significant difference was observed.In pericoronitis, clinical effectiveness rate was 76.3% for MOM and 62. 5% for JM, but no significant difference was observed.In osteitis of jaws, clinical effectiveness rate was 76.3% for MOM and 85.9% for JM, but no significant difference was observed.3. As to improvement rate of clinical signs and symptoms, no significant difference was observed.4. Some side effects were observed in 7 patients (3.3%) in the MOM group and 12 patients (5.6%) in the JM group with no significant intergroup difference in incidence of these side effects.5. Some abnormal laboratory findings were observed in 4 patients (4%) in the MOM group and one patient (0.9%) in the JM group with no significant intergroup difference in incidence of these abnormal laboratory findings.6. The clinical usefulness rate judged by doctors in charge was 72.9% for MOM group and 76.2% for JM group, with no significant difference.From the above results, it was concluded that MOM had the same efficacy as JM for the treatment of oral and maxillofacial infections with half doses of JM.

Acute Respiratory Failure

The hospital and ICU course of 98 patients who required mechanical ventilatory support longer than 72 h was reviewed to determine if mortality rates were influenced by admitting diagnosis. Patients with malignant diagnoses were compared to patients with nonmalignant diagnoses and to those admitted to the ICU after myocardial infarction or cardiorespiratory arrest. Although there was no significant intergroup difference in incidence of multiple organ system failure, age, and length of ICU and hospital stay, there was a much higher incidence of sepsis (p less than .05) and mortality (p less than .01) in the cancer group. Cancer patients and their families should be made aware of the extremely poor prognosis if prolonged acute respiratory failure develops.