A randomized, prospective pilot study of patient expectancy and antidepressant outcome.

BACKGROUND: This study is a randomized, prospective, investigation of the relationships between clinical trial design, patient expectancy and the outcome of treatment with antidepressant medication. Method Adult out-patients with major depressive disorder (MDD) were randomized to either placebo-controlled (PC, 50% probability of receiving active medication) or comparator (COMP, 100% probability of receiving active medication) administration of antidepressant medication. Independent-samples t tests and analysis of covariance (ANCOVA) were used to determine whether the probability of receiving active medication influenced patient expectancy and to compare medication response in the PC v. COMP conditions. We also tested the correlations between baseline expectancy score and final improvement in depressive symptoms across study groups. RESULTS: Subjects randomized to the COMP condition reported greater expectancy of improvement compared to subjects in the PC condition (t = 2.60, df = 27, p = 0.015). There were no statistically significant differences in the analyses comparing antidepressant outcomes between subjects receiving medication in the COMP condition and those receiving medication in the PC condition. Higher baseline expectancy of improvement was correlated with lower final depression severity scores (r = 0.53, p = 0.021) and greater improvement in depressive symptoms over the course of the study (r = 0.44, p = 0.058). CONCLUSIONS: The methods described represent a promising way of subjecting patient expectancy to scientific study. Expectancy of improvement is affected by the probability of receiving active antidepressant medication and seems to influence antidepressant response.

Adverse reactions to over-the-counter cough and cold products among children: the cases managed out of hospitals.

BACKGROUND AND OBJECTIVE: Prompted by continuing concerns about the safety of over-the-counter (OTC) cough and cold medications, we examined the frequency and severity of pediatric adverse drug reactions (ADRs) to OTC cough and cold products reported to a major poison control center. The goal was to focus on cases that are usually managed out of hospitals and may not be recognized by the traditional adverse events surveillance and reporting programs. METHODS: We conducted a retrospective review of electronic records on ADRs reported to the New Jersey Poison Information and Education System (NJPIES) through the National Poison Data System. Analyses included ADRs involving a single OTC cough and cold product. The number and proportion of reported ADRs to OTC cough and cold medicines were examined and compared by severity level between children <2 years of age, and children from 2 through 11 years of age. RESULTS: A total of 91 pediatric ADRs to OTC cough and cold products were reported to the NJPIES from 2000 through 2007. Of these, 61 cases (67%) were of minor severity. A larger proportion of the children 2-11 years of age (21.2%), compared with children <2 years of age (8.0%), experienced a reaction of moderate to major severity. CONCLUSIONS: While we found fewer ADR cases of moderate to major severity in younger children, our results call for a further review of the safety of OTC cough and cold medicines in children 2 years of age and older.

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide.

Suicide is a major public health problem with approximately 1 million victims each year worldwide. Up to 90% of adults who commit suicide have at least one psychiatric diagnosis such as major depression, bipolar disorder (BPD), schizophrenia (SZ), substance abuse or dependence. A question that has remained unanswered is whether the biological substrates of suicide are distinct from those of the psychiatric disorders in which it occurs. The serotonin 2C receptor (5-HT 2C R) has been implicated in depression and suicide. We, therefore, compared the frequencies of its mRNA editing variants in postmortem prefrontal cortical specimens from subjects who committed suicide or who died from other causes. All suicides occurred in the context of either SZ or BPD. The non-suicide cases included subjects with either SZ or BPD as well as subjects with no psychiatric diagnosis. We identified 5-HT 2CR mRNA editing variations that were associated with suicide but not with the comorbid psychiatric diagnoses, and were not influenced by demographic characteristics (age and sex) and alcohol or drug use. These variations consisted of a significant increase in the pool of mRNA variants (ACD and ABCD) that encode one of the most prevalent and highly edited isoforms of 5-HT 2C R, that is, VSV (Val156-Ser158-Val160). Because the VSV isoform of 5-HT 2C R exhibits low functional activity, an increase in its expression frequency may significantly influence the serotonergic regulation of the brain. Thus, at least in patients with SZ or BPD, overexpression of the VSV isoform in the prefrontal cortex may represent an additional risk factor for suicidal behavior.

Brief detection and co-occurrence of violence, depression and alcohol risk in prenatal care settings.

The purpose of the study was to examine the rates and inter-relationships among violence receipt, alcohol use problems, and depression in women seeking prenatal care. While waiting for their prenatal care appointment, women (n = 1054) completed measures of past year partner and non-partner violence receipt, alcohol misuse (TWEAK and quantity and frequency of alcohol use in past year), and depression (Center for Epidemiological Studies Depression Scale - CESD and prior history of depression). Over 30% of women reported either violence receipt, alcohol use problems or depression risk. Significant inter-relationships among all measured risk variables were found. Although violence receipt was significantly related to alcohol misuse, cigarette use, less education, and scoring above the cutoff on the CESD (>/= 16) was most strongly associated with violence. Practitioners should be well-equipped to provide assessment, interventions, or referrals as needed to the high numbers of women encountered in prenatal care settings experiencing psychosocial and behavioral problems that may affect their pregnancy.

A screening study of antidepressant treatment rates and mood symptoms in pregnancy.

STUDY DESIGN: As part of a large screening study of perinatal depression, pregnant women were screened for demographic, depression and treatment variables in obstetrics clinics. Women taking antidepressant medication prior to conception were included in the sample as the study aimed to document rates of antidepressant medication use, and relationship to depressive symptomatology. RESULTS: Among women who reported using antidepressant medications within 2 years prior to screening (n = 390, or 11% of all women), 22% reported current use of these medications. Women who reported using antidepressant medications (52%) and those who discontinued them (49%) evidenced elevated depressive symptoms during pregnancy. CONCLUSIONS: Both women who discontinue and some who continue antidepressants during pregnancy demonstrate depressive symptoms, suggesting sub-optimal management of both groups. Future studies should carefully assess the adequacy of treatments prescribed as well as the monitoring and adherence of recommended treatments. Full symptom remission should be the goal for antenatal and postnatal depression in order to minimize risk to mother and baby.

Postpartum mood disorders.

Depression is a common disorder in women of childbearing age. Many women experience depressive symptoms during the postpartum period, ranging from mild postpartum blues to significant mood disorders such as postpartum depression and postpartum psychosis. The 'baby blues' are extremely common, affecting 30-75% of new mothers. This form of postpartum mood change is self-limited and requires no specific treatment other than education and support. While less common, occurring in 10-15% of births, postpartum depression has the potential for significant impact on both the health of the mother and baby. Unfortunately, affective illness in women frequently goes unrecognized and untreated. While there are effective pharmacological treatments for postpartum depression, the treatments for postpartum depression are often not utilized due to concerns about lactation. Postpartum psychosis is extremely rare, affecting one to two women per 1000 births; each case represents a true psychiatric emergency. Identifying and treating postpartum affective illness in women is critical to the health of both mother and infant. This paper reviews the literature on the diagnosis and treatment of mood disorders in the postpartum period: postpartum blues, postpartum depression and postpartum psychosis.

Risk of venous thromboembolism from oral contraceptives containing gestodene and desogestrel versus levonorgestrel: a meta-analysis and formal sensitivity analysis.

Controversy exists regarding whether oral contraceptives (OCs) containing desogestrel and gestodene are associated with an increased risk of venous thromboembolism (VTE) versus OCs containing levonorgestrel. We were interested in synthesizing the available data, exploring explanations for mixed results, and characterizing the degree of uncontrolled confounding that could have produced a spurious association. We performed a meta-analysis and formal sensitivity analysis of studies that examined the relative risk of VTE for desogestrel and gestodene versus levonorgestrel. Twelve studies, all observational, were included. The summary relative risk (95% CI) was 1.7 (1.3-2.1; heterogeneity p = 0.09). If real, the incremental risk of VTE would be about 11 per 100,000 women per year. An association was present when accounting for duration of use and when restricted to the first year of use in new users. However, in the sensitivity analysis, the association abated in many, but not all, scenarios in which an unmeasured confounding factor increased the risk of VTE three to fivefold and in nearly all examined scenarios in which the factor increased the risk 10-fold. The summary relative risk of 1.7 does not appear to be caused by depletion of susceptibles, but is sensitive to a modest degree of unmeasured confounding. Whether such confounding occurred is unknown. However, given this sensitivity, this issue probably cannot be settled unequivocally with observational data. In the absence of a definitive answer, this apparent increased risk, together with its uncertainty and small magnitude and its important consequences, should be considered when selecting an OC for a given woman.

A sensitivity analysis for subverting randomization in controlled trials.

In some randomized controlled trials, subjects with a better prognosis may be diverted into the treatment group. This subverting of randomization results in an unobserved non-compliance with the originally intended treatment assignment. Consequently, the estimate of treatment effect from these trials may be biased. This paper clarifies the determinants of the magnitude of the bias and gives a sensitivity analysis that associates the amount that randomization is subverted and the resulting bias in treatment effect estimation. The methods are illustrated with a randomized controlled trial that evaluates the efficacy of a culturally sensitive AIDS education video.

Treatment guidelines for depression in pregnancy.

Depression is a ubiquitous disorder in childbearing women with up to 10% of women experiencing depression in pregnancy. Postpartum depression occurs in 12-16% of pregnancies making it a common complication. Moreover, these illnesses are frequently underdiagnosed in obstetric settings, and a recent report of the Surgeon General's Office confirms that many women do not access services, or receive treatment of inadequate intensity or duration. This paper provides current treatment guidelines to aid in appropriate diagnosis and treatment of depression in pregnancy and postpartum. Review of current literature on psychotropic medication use in pregnancy is also provided.

Factors associated with home environmental problems among community-living older people.

PURPOSE: This paper describes the types of difficulties older people have with their home environments and the factors associated with having such difficulties. METHOD: Data were used from 296 study participants of the University at Buffalo's Consumer Assessments Study that examines the home modification needs and environmental difficulties of older people. A combination of socio-demographic variables, health and functional status indicators and measures of psychosocial well-being were used to predict environmental problems. RESULTS: An average of 13 problems with the environment that posed as a barrier to safe and independent performance was observed in homes. It was found that most difficulties occurred in bathrooms, kitchens, bedrooms and access to entryways and rooms. Hierarchical multiple regression analysis showed that having home environmental problems was most strongly associated with younger age, being female, being of minority status, having pain, and greater physical disability. CONCLUSION: The findings show that a combination of conditions that include demographic and functional conditions place older people at risk for problems with the home environment that impede performance of daily living activities.

Strictureplasty for Crohn's disease: meta-analysis.

PURPOSE: The objective of this study was to analyze patient outcome after strictureplasty for management of intestinal stricture caused by Crohn's disease based on differences in surgical procedures. METHODS: A MEDLINE search was performed using a medical subject heading analysis for strictureplasty in Crohn's disease. Meta-analysis of multiple variables for outcome was performed using random-effects models. RESULTS: Five hundred six patients underwent 1,825 strictureplasties for Crohn's disease with minimal morbidity and zero mortality. Ninety percent of strictures were less than 10 cm in length. Approximately 85 percent of these procedures used the Heineke-Mikulicz technique and 13 percent used Finney strictureplasty. Forty-four percent of procedures included concurrent bowel resection. Recurrence rate of Crohn's disease after strictureplasty was increased in patients with longer study duration after surgery (P = 0.04), who showed symptoms of active disease (P = 0.02), who experienced preoperative weight loss (P = 0.02), or who received the Heineke-Mikulicz procedure (P = 0.008). The proportion of patients requiring additional surgery was increased with longer study duration (P = 0.006), with preoperative weight loss (P = 0.001), or with the Heineke-Mikulicz procedure (P = 0.005). The proportion of patients requiring additional surgery was decreased when a Finney strictureplasty was used (P = 0.008) as compared with those treated by the Heineke-Mikulicz procedure. CONCLUSION: Although the Heineke-Mikulicz technique is most often used for Crohn's strictureplasty, outcome analysis revealed the Finney strictureplasty may reduce the reoperation rate.

Adherence by African American men to prostate cancer education and early detection.

BACKGROUND: This study was designed to identify factors that predict adherence by African American men to prostate cancer education and early detection. METHODS: In the spring of 1995, the authors identified 548 African American men who were patients at the University Health Services of the University of Chicago, were ages 40-70 years, and did not have a personal history of prostate cancer. Baseline telephone survey data were collected from 413 men (75%). Participants were randomly assigned to either a minimal or an enhanced intervention group. Men in the former group were mailed a letter and a reminder that invited them to a urology clinic for prostate cancer education and early detection. Men in the enhanced intervention group were sent the same correspondence and were also given print material and telephone contacts, which were tailored to each recipient. RESULTS: Adherence was significantly higher (OR = 2.6, CI: 1.7-3.9) in the enhanced intervention group than in the minimal intervention group (51% and 29%, respectively). Men who were age 50 years or older (OR = 1.7, CI: 1.1-2.8), were married (OR = 1.8, CI: 1.2-2.9), believed that prostate cancer early detection examination should be performed in the absence of symptoms (OR = 2.3, CI: 1.3-4.0), and self-reported an intention to have an early detection examination (OR = 1.9, CI: 1.2-2.9) were also more likely to adhere. CONCLUSIONS: A tailored behavioral intervention can influence adherence to prostate cancer early detection among African American men. Individual background and cognitive and psychosocial characteristics may also affect behavior. Future studies should assess the impact of this type of intervention on cognitive and psychologic correlates of decision-making and behavior along the continuum of prostate cancer care. [See editorial on pages 1-2, this issue.]

Treatment of superficial basal cell carcinoma and squamous cell carcinoma in situ with a high-energy pulsed carbon dioxide laser.

BACKGROUND: High-energy pulsed carbon dioxide (CO2) lasers have been used extensively to resurface wrinkled and photodamaged skin with a low risk of scarring. Results of histological studies demonstrate precise ablation depths in treated skin with minimal thermal damage to underlying tissue. Our objective was to determine if a pulsed CO2 laser could effectively ablate superficial malignant cutaneous neoplasms (superficial multifocal basal cell carcinoma [BCC] and squamous cell carcinoma [SCC] in situ). OBSERVATIONS: Thirty superficial neoplasms (17 BCCs and 13 SCCs) and their surrounding 3-mm margins were treated with either 2 or 3 passes of a pulsed CO2 laser (500 mJ, 2-4 W) using a 3-mm collimated handpiece. The treated areas were subsequently excised and evaluated histologically by serial sectioning at 5-micron intervals for residual tumor at the deep and lateral margins. Average patient age was greater for those with SCCs than for those with BCCs (76.5 vs 56.7 years; P = .001). The average tumor thickness of SCC in situ was significantly greater than that of superficial BCC (0.57 vs 0.34 mm; P = .01). All (9 of 9 patients) BCCs were completely ablated with 3 passes, and residual tumor in the deep margins was seen in 5 of 8 patients treated with 2 passes of the pulsed CO2 laser (P = .005). Incomplete vaporization of the SCC depth was seen in 3 of 7 patients treated with 3 passes and in 2 of 6 patients treated with 2 passes. Those SCCs incompletely treated were significantly thicker than those completely ablated (0.65 vs 0.41 mm; P = .01). Positive lateral margins were seen in 1 BCC and 3 SCC specimens. CONCLUSIONS: Pulsed CO2 laser treatment can be effective in ablating superficial BCC. Treatment of the neoplasm and a minimum of 4-mm margins with 3 passes (500 mJ, 2-4 W) is recommended for complete vaporization using this laser system. Because 3 passes did not completely ablate all SCC in situ, use of this modality alone is not recommended for treatment of thick or keratotic lesions. No direct comparison of efficacy can be made with other destructive modalities that have not been evaluated with comparably sensitive histological techniques. Further study is needed to establish any cosmetic advantage of pulsed CO2 lasers over other destructive modalities for treatment of superficial malignant neoplasms and long-term cure rates.

Does surgical approach affect the incidence of inflatable penile prosthesis infection?

OBJECTIVES: To review retrospectively the rate of infection in 380 consecutive organically impotent men implanted with a Mentor Alpha I inflatable penile prosthesis, stratified by surgical approach (scrotal or infrapubic). METHODS: Data were obtained from review of medical records. One hundred percent of cases were available for a minimum postoperative follow-up of 6 months. RESULTS: Twenty patients had a prior penile prosthetic operation and were excluded, leaving 360 primary implants for review. Overall, 6 patients (1.7%) developed periprosthetic infection. Four of these 6 patients were diabetic. Four of 139 infrapubic cases (2.9%) and 2 of 221 scrotal cases (0.9%) developed periprosthetic infection. This difference was not statistically significant (P = 0.15). Equal proportions of the infrapubic (39.6%) and scrotal cases (40.3%) were diabetic patients. The infection rate in patients with and without diabetes was 4 of 144 (2.8%) and 2 of 216 (0.9%), respectively. This difference was not statistically significant (P = 0.18). CONCLUSIONS: This study indicates that there is no statistically significant difference in the infection rate when the scrotal and infrapubic approaches to inflatable penile prosthesis insertion are compared.

Should we adjust for covariates in nonlinear regression analyses of randomized trials?

The analyses of the primary objectives of randomized clinical trials often are not adjusted for covariates, except possibly for stratification variables. For analyses with linear models, adjustment is a precision issue only. We review the literature regarding logistic and Cox (proportional hazards) regression models. For these nonlinear analyses, omitting covariates from the analysis of randomized trials leads to a loss of efficiency as well as a change in the treatment effect being estimated. We recommend that the primary analyses adjust for important prognostic covariates in order to come as close as possible to the clinically most relevant subject-specific measure of treatment effect. Additional benefits would be an increase in efficiency of tests for no treatment effect and improved external validity. The latter is particularly relevant to meta-analyses.