Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine

OBJECTIVE: Pregabalin has demonstrated robust, rapid efficacy in reducing symptoms of generalized anxiety disorder (GAD) in 4 placebo-controlled clinical trials. The current study compared the efficacy and safety of pregabalin and venlafaxine in patients diagnosed with moderate to severe GAD. METHOD: The study was conducted from December 21, 1999, to July 31, 2001. Outpatients (N = 421) in primary care or psychiatry settings meeting DSM-IV criteria for GAD were randomly assigned to 6 weeks of double-blind treatment with pregabalin 400 or 600 mg/day, venlafaxine 75 mg/day, or placebo. The primary analysis was change in Hamilton Rating Scale for Anxiety (HAM-A) total score from baseline to last-observation-carried-forward (LOCF) endpoint. Secondary analyses included the change in HAM-A psychic (emotional) and somatic (physical) factor scores, significant improvement at week 1, and week 1 improvement sustained at every visit through endpoint. RESULTS: Pregabalin at both dosages (400 mg/day, p = .008; 600 mg/day, p = .03) and venlafaxine (p = .03) produced significantly-greater improvement in HAM-A total score at LOCF endpoint than did placebo. Only the pregabalin 400-mg/day treatment group experienced significant improvement in all a priori primary and secondary efficacy measures. Pregabalin in both dosage treatment groups (400 mg/day, p < .01; 600 mg/day, p < .001) significantly improved HAM-A total score at week 1, with significant improvement through LOCF endpoint. Statistically significant improvement began at week 2 for venlafaxine. Discontinuation rates due to associated adverse events were greatest in the venlafaxine treatment group: venlafaxine, 20.4%; pregabalin 400 mg/day, 6.2%; pregabalin 600 mg/day, 13.6%; placebo, 9.9%. CONCLUSION: Pregabalin was safe, well tolerated, and rapidly efficacious across the physical-somatic as well as the emotional symptoms of GAD in the majority of patients studied in primary care and psychiatric settings.     

Hematoma-Directed Ultrasound-Guided (HUG) Breast Lumpectomy

Background Needle localization breast biopsy (NLBB) is presently the primary means of localizing non-palpable lesions. Disadvantages of NLBB include vasovagal episodes, patient discomfort, and miss rates. Because hematomas naturally fill the cavity after vacuum-assisted breast biopsies (VABB), we hypothesized that ultrasound (US) could be used to find and accurately excise the actual biopsy site of non-palpable breast lesions without a needle. Methods This is a retrospective study from January 2000 to July 2005. Electronic chart review identified patients with non-palpable breast lesions detected by means of mammogram who then underwent lumpectomy via NLBB or the hematoma-directed ultrasound-guided technique (HUG). HUG involved localizing the hematoma with a 7.5-MHz US probe and using the “line of sight” technique straight down toward the chest wall. A block of tissue encompassing the hematoma was then excised. Results Localization procedures were performed in 186 patients—63 (34%) via needle localization and 123 (66%) via HUG. The previous VABB site in 100% of patients was successfully excised using HUG, 65 of 123 (53%) were benign and 58 of 123 (47%) were malignant; margins were positive in 13 of these 58 (22%). NLBB was successful in 100% of patients, 44 of 63 (70%) were benign and 19 of 63 (30%) were malignant; margins were positive in 14 of these 19 (73%). Margin positivity was significantly higher for NLBB than HUG (P = 0.0001, Fisher Exact). Conclusions This study suggests that HUG is more accurate in localizing non-palpable lesions than NLBB. By eliminating the additional procedure needed for NLBB, HUG may also be more time- and cost efficient. HUG makes VABB not only a less invasive diagnostic procedure, but also a localization procedure. Margaret Thompson: Supported by the Virginia Clinton Kelley/Fashion Footwear Association of New York Breast Cancer Research Fellowship Aaron Margulies: Supported by the Susan G. Komen Breast Cancer Clinical Fellowship     

Scientific Presentation Award: The impact of magnetic resonance imaging on surgical treatment of invasive breast cancer

Background

The purpose of this study was to examine the relationship between magnetic resonance imaging (MRI) and surgical treatment of invasive breast cancer (IBC).

Method

The IBC patients treated from January 2003-June 2008 were reviewed by a single institution.

Results

A total of 814 patients were treated, out of which 562 (69%) underwent breast conservation therapy (BCT), 151 (19%) chose mastectomy alone (M), and 101 (12%) chose mastectomy with reconstruction (M+ R). The mean age was comparatively low in M + R patients (P ≤ 0.001). The mean tumor size was the lowest in BCT patients (P ≤ 0.001). MRI use increased with no significant difference in type of surgery as noted by year. In multivariate analysis, type of surgery was significantly associated with tumor size, multifocality, age, and MRI use. The factors associated with MRI performance were: multifocality, younger age, tumor size, lobular histology, body mass index, and genetic testing.

Conclusions

The use of MRI in IBC patients has increased over the past 5 years, without any observable impact on surgical treatment. Similar factors are associated with mastectomy and MRI performance.     

Does magnetic resonance imaging accurately predict residual disease in breast cancer?

Background

The accuracy of magnetic resonance imaging (MRI) in identifying residual disease after breast conservation therapy (BCT) is unclear.

Method

Review of an institutional database identified patients with positive or close (≤2 mm) margins undergoing MRI before re-excision. Histopathologic correlation was performed.

Results

Forty-three women underwent MRI after BCT. MRI suggested residual disease in 29 patients, of whom 20 (69%) had residual carcinoma pathologically. Nine patients had false-positive MRI as seen by benign pathology findings. Fourteen MRIs indicated no residual disease, of which 6 had residual disease pathologically. The sensitivity and positive predictive value of MRI was 77% and 69%, respectively. MRI conducted within 28 days of the original surgery was 85% sensitive. MRI performed after 28 days was 69% sensitive.

Conclusions

MRI is able to detect residual disease among most patients undergoing re-excision. False-positive results may be caused by inflammatory processes that resemble residual disease.     

Home glucometer monitoring markedly improves diagnosis of post renal transplant diabetes mellitus in renal transplant recipients

BACKGROUND: Definitions of de novo posttransplant diabetes mellitus (PTDM) have varied widely in the renal transplant literature, and most have not used the American Diabetes Association (ADA) definition of diabetes (fasting plasma glucose [FPG] > or = 126 mg/dl on two occasions, or a casual plasma glucose level >200 mg/dl). Most patients are monitored for PTDM by 12-hour FPG levels drawn for clinic visits. In contrast, we describe the diagnosis of PTDM by home glucometer monitoring METHODS: We screened 89 consecutive nondiabetic renal transplant recipients for PTDM by ADA criteria and home glucometer monitoring during the first 3 months posttransplant RESULTS: Of 23 patients with impaired fasting glucose levels of 111-126 mg/dl, 14 (61%) met ADA criteria for diabetes mellitus of based on home glucometer monitoring. The incidence of de novo PTDM was 31% during this period. Predictors of PTDM in a Cox proportional hazards model were race and acute rejection, with a trend towards BMI. Clinic visit FPG levels did not differ between PTDM and non-PTDM patients. All diagnoses were made based on prelunch or supper FPG >200 mg/dl. CONCLUSIONS: Overnight FPG are inadequate for diagnosis of PTDM. All renal transplant recipients with impaired FPG should, at minimum, have home FPG testing.     

Ethical dilemmas in forensic psychiatry: two illustrative cases

One approach to the analysis of ethical dilemmas in medical practice uses the "four principles plus scope" approach. These principles are: respect for autonomy, beneficence, non-maleficence and justice, along with concern for their scope of application. However, conflicts between the different principles are commonplace in psychiatric practice, especially in forensic psychiatry, where duties to patients often conflict with duties to third parties such as the public. This article seeks to highlight some of the specific ethical dilemmas encountered in forensic psychiatry: the excessive use of segregation for the protection of others, the ethics of using mechanical restraint when clinically beneficial and the use of physical treatment without consent. We argue that justice, as a principle, should be paramount in forensic psychiatry, and that there is a need for a more specific code of ethics to cover specialised areas of medicine like forensic psychiatry. This code should specify that in cases of conflict between different principles, justice should gain precedence over the other principles.