Randomized controlled trials in cancer: improving the quality of their reports will also facilitate better conduct

BACKGROUND: The 1994 Centers for Disease Control and Prevention draft Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities did not exempt pediatric facilities from instituting controls to prevent nosocomial tuberculosis (TB) transmission. Many researchers contend that TB disease in children does not require such rigid controls. We surveyed acute-care pediatric facilities in the United States to determine adherence to environmental and administrative control recommendations. METHODS: The study included 4 mailings of a survey to infection control professionals at 284 US children's hospitals and adult acute-care hospitals with > 30 pediatric beds. RESULTS: Isolation rooms (IRs) generally conformed to recommended guidelines; 92% of respondents reported IRs with > or = 6 air changes per hour, 90% reported 1-pass air and negative pressure, and 89% reported that IRs were private rooms. A sufficient number of inpatient IRs were reported by 88%, but only 42% had IRs in outpatient areas, and 19% had IRs in off-site clinics. Employee tuberculin skin-test programs were in place at 98% of facilities, but policies pertaining to implementation varied. Employees' use of personal respirators increased at respondent hospitals from 1991 to 1994, but as late as 1994, nearly one third still used surgical masks for high-risk procedures. CONCLUSIONS: Environmental and administrative controls used by respondent hospitals largely conformed to published guidelines. Because definitive studies that quantify the risk of nosocomial M tuberculosis transmission in pediatric settings have yet to be performed, pediatric facilities are required to have the same protections in place as do their adult counterparts.     

Benefit of screening mammography in women aged 40-49: a new meta-analysis of randomized controlled trials

Eight randomized controlled trials (RCTs) of screening mammography have been conducted involving women aged 40-49 at entry. Current data are now available from these trials at 10.5 to 18 years of follow-up (average follow-up time: 12.7 years). Meta-analysis has been performed using a Mantel-Haenszel estimator method to combine current follow-up data from the eight RCTs of mammography that included women aged 40-49 at entry, including new follow-up data presented at the NIH Consensus Development Conference held January 21-23, 1997. Combining the most recent follow-up data on women aged 40-49 at entry into all eight RCTs yields a statistically significant 18% mortality reduction among women invited to screening mammography (relative risk: 0.82; 95% confidence interval: 0.71-0.95). Combining all current follow-up data on women aged 40-49 at entry into the five Swedish RCTs yields a statistically significantly 29% mortality reduction among women invited to screening (relative risk: 0.71; 95% confidence interval: 0.57-0.89). Meta-analysis including the most recent follow-up data from all eight RCTs involving women aged 40-49 at entry demonstrates for the first time a statistically significant mortality reduction due to regular screening mammography in women of this age group.     

Breast cancer in Norway 1970-1993: a population-based study on incidence, mortality and survival

The incidence, mortality and survival of breast cancer patients from 1970 to 1993 were studied using data from the Cancer Registry of Norway. The age-adjusted incidence rate increased from 62.0 to 76.9 per 100,000 person-years during the period, and more than 2000 cases are now registered annually. The increase tends to be highest in the age group below 40 years. The increase is mainly found in cases with localized tumours at the time of diagnosis. The mortality rate has been almost unchanged in the period; the age adjusted mortality rate is 27.0 per 100,000 person-years at the end of the study period. The 5-year overall survival has increased among cases with axillary lymph node metastases at the time of diagnosis; the other stages show only little improvement.     

The prevalence and timing of obstetric ultrasound in Victoria 1991-1992: a population-based study

Viscosupplementation is a relatively new treatment concept for restoring the normal rheologic properties of the osteoarthritic joint. It is most often used for the knee. This case report describes results that were achieved using viscosupplementation following conservative therapy for a patient with osteoarthritis of the temporomandibular joint. Further study in the use of these treatments is recommended.     

Antimicrobial prophylaxis in colorectal surgery: a systematic review of randomized controlled trials

BACKGROUND: A systematic review was carried out to assess the relative efficacy of antimicrobial prophylaxis for the prevention of postoperative wound infection in patients undergoing colorectal surgery. METHODS: MEDLINE, EMBASE, the Cochrane Trials Register and the references cited in retrieved studies were searched to identify relevant trials published between 1984 and 1995. RESULTS: Some 147 relevant trials were identified. The quality of trials has improved over the past 12 years. The results confirm that the use of antimicrobial prophylaxis is effective for the prevention of surgical wound infection after colorectal surgery. There was no significant difference in the rate of surgical wound infections between many different regimens. However, certain regimens appear to be inadequate (e.g. metronidazole alone, doxycycline alone, piperacillin alone, oral neomycin plus erythromycin on the day before operation). A single dose administered immediately before the operation (or short-term use) is as effective as long-term postoperative antimicrobial prophylaxis (odds ratio 1.17 (95 per cent confidence interval (c.i.) 0.90-1.53)). There is no convincing evidence to suggest that the new-generation cephalosporins are more effective than first-generation cephalosporins (odds ratio 1.07 (95 per cent c.i. 0.54-2.12)). CONCLUSION: Antibiotics selected for prophylaxis in colorectal surgery should be active against both aerobic and anaerobic bacteria. Administration should be timed to make sure that the tissue concentration of antibiotics around the wound area is sufficiently high when bacterial contamination occurs. Guidelines should be developed locally in order to achieve a more cost-effective use of antimicrobial prophylaxis in colorectal surgery.     

Salmonella typhimurium DT104 infection in people and animals in Scotland: a collaborative epidemiological study 1993-96

This paper describes a comparative analysis of human and farm animal salmonellosis in Scotland between 1993 and 1996, with particular reference to Salmonella typhimurium definitive type 104 (DT104). Cattle were the main reservoir, accounting for 73.1 per cent of incidents involving all salmonellae and 69.5 per cent of those involving S typhimurium DT104. The annual rates of incidence in people and cattle were recorded in each Health Board area. Dumfries and Galloway had the highest rate of incidence in cattle for all salmonellae (19.0 per 100,000) but people were affected uniformly across mainland Scotland. However, the rate of incidence of S typhimurium DT104 was highest in Dumfries and Galloway for both people (10.1 per 100,000) and cattle (13.0 per 100,000). In Dumfries and Galloway, Wigtownshire had the highest rates for all salmonellae and for S typhimurium DT104 in both people and cattle. In Dumfries and Galloway, 37.8 per cent of the adult cases of S typhimurium DT104 in people were among those known to have had regular contact with animals, and children under six years of age accounted for 36.3 per cent of the human infections in this region.     

Calciphylaxis in patients on hemodialysis: a prevalence study

BACKGROUND: Calciphylaxis is characterized by painful, violaceous, mottled skin lesions (livedo reticularis) that may progress to tissue necrosis, nonhealing ulcers, gangrene, and potentially amputation, sepsis, or death. The prevalence and characteristics of patients who have calciphylaxis need further identification to predict which patients on dialysis may benefit from close monitoring or early surgical intervention. METHODS: All 242 patients undergoing hemodialysis in an outpatient unit were reviewed retrospectively during a 15-month cross-sectional study of the prevalence and characteristics of calciphylaxis. RESULTS: Ten patients (prevalence, 4.1%) had calciphylaxis. Patients with calciphylaxis were significantly younger (49 versus 60 years; p = 0.01), had undergone hemodialysis longer (80 versus 20 months; p < 0.0001), and had higher median serum calcium (9.7 versus 9.2 mg/dl; p = 0.03), phosphate (8.2 versus 5.7 mg/dl; p = 0.001), calcium phosphate product (81.5 versus 52.9; p = 0.0004), parathyroid hormone (1496 versus 138 pg/ml; p < 0.0001), and alkaline phosphatase levels (188 versus 89 IU/L; p = 0.0001). Bone surveys were positive in all 10 patients with calciphylaxis compared with 49 (21%) of the 232 patients without calciphylaxis (p < 0.0001). All patients who underwent parathyroidectomy for calciphylaxis had dramatic healing of the ulcers. CONCLUSIONS: The presence of calciphylaxis is higher among younger patients who had undergone longer periods of hemodialysis. Therefore this group of patients should be monitored aggressively and treated expeditiously for complications of secondary hyperparathyroidism.     

Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials

CONTEXT: Aspirin has been widely used to prevent myocardial infarction and ischemic stroke but some studies have suggested it increases risk of hemorrhagic stroke. OBJECTIVE: To estimate the risk of hemorrhagic stroke associated with aspirin treatment. DATA SOURCES: Studies were retrieved using MEDLINE (search terms, aspirin, cerebrovascular disorders, and stroke), bibliographies of the articles retrieved, and the authors' reference files. STUDY SELECTION: All trials published in English-language journals before July 1997 in which participants were randomized to aspirin or a control treatment for at least 1 month and in which the incidence of stroke subtype was reported. DATA EXTRACTION: Information on country of origin, sample size, duration, study design, aspirin dosage, participant characteristics, and outcomes was abstracted independently by 2 authors who used a standardized protocol. DATA SYNTHESIS: Data from 16 trials with 55462 participants and 108 hemorrhagic stroke cases were analyzed. The mean dosage of aspirin was 273 mg/d and mean duration of treatment was 37 months. Aspirin use was associated with an absolute risk reduction in myocardial infarction of 137 events per 10000 persons (95% confidence interval [CI], 107-167; P<.001) and in ischemic stroke, a reduction of 39 events per 10000 persons (95% CI, 17-61; P<.001). However, aspirin treatment was also associated with an absolute risk increase in hemorrhagic stroke of 12 events per 10000 persons (95% CI, 5-20; P<.001). This risk did not differ by participant or study design characteristics. CONCLUSIONS: These results indicate that aspirin therapy increases the risk of hemorrhagic stroke. However, the overall benefit of aspirin use on myocardial infarction and ischemic stroke may outweigh its adverse effects on risk of hemorrhagic stroke in most populations.     

Effects of psychotherapeutic treatments for PTSD: a meta-analysis of controlled clinical trials

This meta-analysis synthesized the results from controlled, clinical trials of psychotherapeutic treatments for posttraumatic stress disorder (PTSD). Psychotherapeutic modalities included behavioral, cognitive, and psychodynamic treatments, in group and individual settings. Participants in the studies included combat veterans from the Vietnam and Lebanon Wars, crime-related victims, and severe bereavement sufferers. The impact of psychotherapy on PTSD and psychiatric symptomatology was significant, d = .52, r = .25, when measured immediately after treatments were administered. Similarly, there was no decay in the effect of treatment at follow-up, d = .64, r = .31. Moreover, for target symptomes of PTSD and general psychological symptomes (intrusion, avoidance, hyperarousal, anxiety, and depression), effect sizes were significant, ranging from r's of .2-.49. Results suggest substantial promise for improving psychological health and decreasing related symptoms for those suffering from PTSD.     

The quality of clinical trials published in The Journal of Family Practice, 1974-1991

The contact area between an antibody (Ab) and the antigen (Ag) is called antigenic determinant or epitope. The first step in the characterization of an Ag by using monoclonal antibodies (MAb) is to map the relative distribution of the corresponding epitopes on the Ag surface. The computer program MAPAG has been devised to automatically construct antigenic maps. MAPAG is fed with a binary matrix of experimental data indicating the ability of paired MAb to bind or not simultaneously to the Ag. The program is interactive menu-driven and allows the user an easy data handling. MAPAG utilizes iterative processes to construct and to adjust the final map, which is graphically shown as a 2- or a 3-dimensional model. Additionally, the antigenic map obtained can be optionally modified by the user or readjusted by the program. The suitability of MAPAG was illustrated by running experimental data from literature and comparing antigenic maps constructed by the program with those elaborated by the investigators without the assistance of a computer. Furthermore, since some MAb could present negative allosteric effects leading to misinterpretation of data, MAPAG has been provided with an approximate reasoning module to solve such anomalous situations. Results indicated that the program can be successfully employed as a simple, fast and reliable antigenic model-builder.     

A rejoinder to "Psychotherapy research ethics: Continuing the debate on controlled clinical trials."

Responds to C. A. Heflinger's (1987) critique of the present authors (1986) by reiterating their concern for the principle of autonomy. The present authors note that all patients were fully informed about the research plan and their right to withdraw. Nonetheless, the ethical criticism offered by Heflinger regarding randomization cannot be entirely dismissed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mortality as a function of temperature. A study in Valencia, Spain, 1991-1993

BACKGROUND: Increased mortality is associated with both very low and very high ambient temperatures. This study assesses the relationship between daily numbers of deaths and variations in ambient temperature within the city of Valencia. METHODS: The daily number of deaths from all causes (total deaths and only those occurring in people aged over 70), as well as those deaths from specific causes (e.g. cardiovascular and respiratory diseases, malignant tumours and all causes except external ones) occurring within the city of Valencia were related to the average daily temperature using autoregressive Poisson regression controlling for seasonality, day of the week, holidays, air pollution, influenza incidence, and humidity. Temperature was measured within the regression model as two complementary variables: 'Heat' and 'Cold'; also taken into account were their delayed effects up to 2 weeks after measurement. RESULTS: Graphical analysis revealed a relationship between temperature and mortality according to the time of year. For the cooler months (November-April), the temperature at which mortality was lowest was the 'minimum' (i.e. around 15 degrees C), while for the warmer months (May-October), it occurred at around 24 degrees C. Because of this, a stratified analysis was undertaken with different values for the 'Heat' and 'Cold' variables according to which of the two seasons was involved. During the colder months of the year, higher temperatures tended to exert a rapid influence on mortality and the lower temperatures a more delayed relation. During the hot season it is the heat variable which more clearly manifests an effect, and this is prolonged over the two following weeks. Variations also occur according to age and cause of death. The effect of temperature is greater in persons aged over 70 years of age, and it is also greater in cases of circulatory and respiratory diseases. CONCLUSIONS: A statistically significant association has been found between temperature and mortality. This relationship is not monotonic, but mortality increases in proportion to the variance in ambient temperature from a range of temperatures that varies from winter to summer.     

Statistical and Practical Significance in the IJPT: A Research Review from 1993-2003.

The reporting and interpretation of effect sizes in addition to statistical significance tests is becoming increasingly recognized as good research practice, as evidenced by the editorial policies of at least 23 journals that now require effect sizes. Statistical significance tests are limited in the information they provide readers about results, and effect sizes can be useful when evaluating result importance. The current article (a) summarizes statistical versus practical significance, (b) briefly discusses various effect size options, (c) presents a review of research articles published in the International Journal of Play Therapy (1993-2003) regarding use of effect sizes and statistical significance tests, and (d) provides recommendations for improved research practice in the journal and elsewhere. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transcranial magnetic stimulation in mania: a controlled study

OBJECTIVE: Left prefrontal transcranial magnetic stimulation has been reported to have ECT-like effects in depression; therefore, the authors planned a study of transcranial magnetic stimulation in mania. METHOD: Sixteen patients completed a 14-day double-blind, controlled trial of right versus left prefrontal transcranial magnetic stimulation at 20 Hz (2-second duration per train, 20 trains/day for 10 treatment days). Mania was evaluated with the Mania Scale, the Brief Psychiatric Rating Scale, and the Clinical Global Impression. RESULTS: Significantly more improvement was observed in patients treated with right than with left prefrontal transcranial magnetic stimulation. CONCLUSIONS: The therapeutic effect of transcranial magnetic stimulation in mania may show laterality opposite to its effect in depression.     

Randomized controlled trial of omeprazole or endoscopy in patients with persistent dyspepsia: a cost-effectiveness analysis

BACKGROUND: Cost-effectiveness analysis, Helicobacter pylori research and the development of proton pump inhibitors are having an increasing impact on the management of dyspepsia. However, clinical trials have not always included both H. pylori diagnosis and proton pump inhibitors in their protocols. METHODS: Patients who were referred for upper gastrointestinal endoscopy by their general practitioner were randomized to either prompt endoscopy followed by directed medical treatment (conventional group, n=38), or to empirical treatment with omeprazole and, in the case of symptom relapse, serological screening for H. pylori infection followed by eradication therapy in seropositive patients (empirical group, n=42). The study lasted for up to 1 year. RESULTS: In the empirical group, only 13 patients (31%) underwent endoscopy. The average number of days for which the patients kept records of their dyspeptic symptoms was 266 (95% CI: 226-307) in the empirical group, of which 166 (95% CI: 128-204) were symptom-free. In the conventional group, 159 (95% CI: 119-198) out of 255 days (95% CI: 209-302) were recorded as symptom-free. The average medical cost in the empirical group was $284 (95% CI: 218-350) and in the conventional group $491 (95% CI: 383-600). In the empirical group, two malignancies were found, whereas in the conventional group one malignancy was found. CONCLUSIONS: The empirical drug treatment strategy in patients with persistent dyspeptic symptoms resulted in 69% fewer diagnostic endoscopies with lower medical costs and equal effectiveness in the first year, compared to prompt endoscopy followed by directed medical treatment.     

Alcohol habits in Swedish women: observations from the population study of women in Gothenburg, Sweden 1968-1993

Plasmalogen rather than diacyl phospholipids are the preferred substrate for the cardiac phospholipase A2 (PLA2) isoform activated during ischemia. The diacyl metabolite, lysophosphatidylcholine, is arrhythmogenic, but the effects of the plasmalogen metabolite, lysoplasmenylcholine (LPLC), are essentially unknown. We found that 2.5 and 5 micromol/L LPLC induced spontaneous contractions of intact isolated rabbit ventricular myocytes (median times, 27.4 and 16.4 minutes, respectively) significantly faster than lysophosphatidylcholine (>60 and 37.8 minutes, respectively). Whole-cell recordings revealed that LPLC depolarized the resting membrane potential from -83.5+/-0.2 to -21.5+/-1.0 mV. Depolarization was due to a guanidinium toxin-insensitive Na+ influx. The LPLC-induced current reversed at -18.5+/-0.9 mV and was shifted 26.7+/-4.2 mV negative by a 10-fold reduction of bath Na+ (Na+/K+ permeability ratio, approximately 0.12+/-0.06). In contrast, block of Ca2+ channels with Cd2+ and reducing bath Cl failed to affect the current. The actions of LPLC were opposed by lanthanides. Gd3+ and La3+ were equally effective inhibitors of the LPLC-induced current and equally delayed the onset of spontaneous contractions. However, the characteristics of lanthanide block imply that Gd3+-sensitive, poorly selective, stretch-activated channels were not involved. Instead, the data are consistent with the view that lanthanides increase phospholipid ordering and may thereby oppose membrane perturbations caused by LPLC. Plasmalogens constitute a significant fraction of cardiac sarcolemmal choline phospholipids. In light of their subclass-specific catabolism by phospholipase A2 and the present results, it is suggested that LPLC accumulation may contribute to ventricular dysrhythmias during ischemia.