From the Bench to the Trench: A Comparison of Sertraline Treatment of Major Depression in Clinical and Research Patient Samples

BACKGROUND: New medications that enter the marketplace have been tested almost exclusively in controlled clinical trials conducted in specialty research settings. There is some concern that these carefully selected patient samples may not provide information generalizable to the "real world" clinical population. The purpose of this investigation was to compare results from a large, open-label study of sertraline in the treatment of major depression in the clinical practice setting with pooled results from 2 multicenter, double-blind, placebo-controlled studies conducted in specialty research settings. METHOD: Clinical practice patients (N = 1482), aged 21 to 65 years, from 228 psychiatric clinical practice sites across the United States participated in the open-label treatment study (Clinical Practice sample). Patients who met DSM-III-R criteria for moderate-to-severe unipolar major depression (i.e., had pretreatment Hamilton Rating Scale for Depression [HAM-D] scores >/= 18) were treated for 8 weeks with sertraline in a flexible dosing fashion (50-200 mg daily). Outcomes on the HAM-D and Clinical Global Impressions-Improvement scale (CGI-I) were compared with the pooled results from 2 previously published placebo-controlled, multicenter treatment studies of sertraline in outpatients with major depression (N = 280). The overall response to sertraline in the Clinical Practice sample was compared with the outcome from the research study patient sample (Clinical Research sample). Additionally, comparison of outcomes of patients with common depressive subtypes (double depression, anxious depression, and melancholic ["endogenous"] depression) were examined. RESULTS: The percentage of sertraline-treated patients rated as responders on the CGI-I was significantly higher in the Clinical Practice sample compared with the Clinical Research sample (87% vs. 73%; p <.001). Sertraline was also much better tolerated in the Clinical Practice sample than in the Clinical Research sample as evidenced by significantly lower overall reports of adverse events (9.4% vs. 13.2%; p <.05) and lower patient dropout rates (17.5% vs. 34.3%; p <.01). Among clinical practice patients, sertraline was found to be equally effective in treating endogenous/melancholic and anxious subtypes and only mildly less effective in achieving a response in patients with double depression (chronic low-grade depression with a superimposed major depression). A regression analysis identified older age and double depression as being predictors of a slower time to response. More than 70% of patients who reported nonresponse to previous treatment with fluoxetine or a tricyclic antidepressant responded to sertraline. CONCLUSION: The effectiveness and tolerability of sertraline treatment was found to be significantly better in the Clinical Practice sample, suggesting that the results from controlled studies in research settings may represent an underestimate of the benefits of a drug. More effectiveness research is needed to confirm and extend these findings.     

A novel view for the scintigraphic assessment of the elbow

Using any imaging modality, the elbow is a complex joint to evaluate. The use of scintigraphy in the evaluation of the effects of acute or chronic trauma has largely been confined to epicondylitis. We developed a skyline view of the elbow that minimized the effect of overlap and assessed its incremental value in the scintigraphic assessment of several pathological conditions. Thirty-four abnormalities were evaluated in 20 patients with a range of pathologies, including epicondylitis, ligamentous avulsion injury, articular injury, fractures and synovitis. The incremental value of addition of the skyline view to the standard views was assessed in addition to the overall accuracy of scintigraphy. Overall, scintigraphy detected 27 of 34 abnormalities, with the standard views of the elbow accurately identifying 15 and the skyline view 23 abnormalities. This gave the skyline view an incremental value of 24% over the standard views. In conclusion, scintigraphy has the potential to identify a greater range of pathologies in the elbow than previously reported, due to the addition of the skyline view to the standard views.     

Epidemiological features and diagnostic evaluation of intracranial aneurysms

Female gender and cigarette smoking appear to be risk factors for the development of multiple intracranial aneurysms. An acquired nature is likely in this form. The mechanism of aneurysm formation in patients with sickle cell anemia is apparently different. These patients also present multiple aneurysms that show propensity for vertebrobasilar territory and appear at a younger age. Familial cerebral aneurysms are diagnosed once heritable connective tissue disorders have been excluded. The age of patients tends to be lower and the size of aneurysm to be smaller at the time of rupture in the familial form. These aneurysms are less frequently found in the anterior communicating artery than the sporadic aneurysms. A high incidence of asymptomatic familial aneurysms was detected in people with family histories of intracranial aneurysms studied by means of magnetic resonance angiography. Furthermore, familial aneurysms are more likely to rupture in families having members with aneurysmal subarachnoid hemorrhage (SAH) than in those without. The results of an interesting study using color "power" transcranial Doppler ultrasound in patients with aneurysmal SAH suggest that as the intracranial pressure diminished, the size of the aneurysm increased, and there was relatively little change between maximum and minimum dimensions during the cardiac cycle, i.e., the pulsatility is reduced. The use of postoperative angiography after clipping is a matter of debate. The indication more widely accepted is in large aneurysms with a wide neck, in which incomplete clipping can be suspected. Taking into account the current low risk of angiography in centers of excellence, its routine use may be recommended. Aneurysm remnants, vessel occlusion, vasospasm, and newly identified aneurysms are the main findings that were reported.     

Early diagnosis of Alzheimer dementia based on clinical and biological factors

Alzheimer’s disease (AD) is common in elderly individuals; it causes distress for the patients and their relatives as well as large costs for the society. With the advent of symptomatic treatment at present and probable etiology-based cures in the future, it will be possible to relieve and put an end to these negative effects. Therefore, it is necessary to diagnose the disease as early as possible. In this review, we briefly summarize the state-of-the-art concerning various available clinical and biochemical methods for identifying AD. Increasing age, heritage, and presence of ApoE e4 allele have been confirmed as risk factors for AD as well as some putative factors (e.g., low education, hypertension, hypotension) based on epidemiological recent research. Selective impairment of episodic memory has been found to be a preclinical marker for future development of AD based on convergent data from asymptomatic AD-related mutation carriers, longitudinal studies of patients with mild cognitive impairment (MCI), and epidemiological studies of incident AD cases. Neurophysiological methods are inexpensive and useful for the identification of changes in brain dysfunction in AD and new promising methods are under development. Using magnetic resonance imaging (MRT), structural measurements of brain atrophy and specific brain structures such as the hippocampus have been reported to detect dementia development early in the course of disease. Similarly, functional measurements of brain activity (e.g., blood flow) have revealed that hypometabolism in bilateral parietotemporal brain areas early in the disease course. Finally, biochemical studies have demonstrated that certain proteins (e.g., tau the Aβ_1-42/43 metabolite of the amyloid precursor protein) may be associated with the disease process in AD, although the specificity of these markers remains to be established. It is concluded that still no single marker of AD exists, which makes it necessary to rely on data from multiple sources in order to arrive at the best possible diagnosis of AD.     

Vascular depression: a new view of late-onset depression

We have suggested that cerebrovascular disease may predispose, precipitate, or perpetuate some late-life depressive syndromes. The mechanisms of "vascular depression" include disruption of cortico-striato-pallido-thalamo-cortical (CSPTC) pathways or their modulating systems. This view is supported by the presentation of vascular depression, which consists of depressive symptoms, cognitive abnormalities, as well as neuroimaging findings that may result from CSPTC impairment. Moreover, clinical and electrophysiological evidence of CSPTC impairment, an abnormality frequently found in patients with vascular depression, appears to be associated with poor response to antidepressant treatment and early relapse and recurrence. The vascular depression hypothesis provides the conceptual background for studies that may have clinical and theoretical impact. Agents influencing dopamine, acetylcholine, and opioid neurotransmitters may be studied in vascular depression, since these are essential neurotransmitters of the frontostriatal circuitry. Drugs used for prevention and treatment of cerebrovascular disease may be shown to reduce the risk for vascular depression or improve its outcomes. The choice of antidepressants in vascular depression may depend on their effect on neurological recovery from ischemic lesions. Finally, identification of specific relationships between specific symptoms, cognitive deficits, and disability may lead to interventions that target the patients' deficits as well as their interactions with psychosocial factors known to contribute to depression. Research can clarify the pathways to vascular depression by focusing on the site of lesion, the resultant brain dysfunction, the presentation of depression and time of onset, and the contribution of nonbiological factors.     

Designing an intervention to prevent suicide: PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial)

Suicide is a major public health problem with greatest risk in the very old. This paper describes an approach to reducing the risk of suicide by intervening on depression in elderly primary care patients. Depression is an appropriate target for an intervention as it is highly prevalent in primary care, is a strong risk factor for suicide, and is more often than not inadequately treated. PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial) is a National institute of Mental Health (NIMH)-funded collaborative study that is testing this approach to suicide risk prevention in 18 primary care practices in the United States. PROSPECT'S intervention of "guideline management" introduces a health specialist into the primary care setting to help physicians provide "on-time, on-target" treatment and long-term management of late-life depression following structured clinical guidelines. The effectiveness of the intervention in reducing suicidal risk and depression is evaluated by following a representative sample of older patients identified using a 2-stage design.     

Studentschool bonding and adolescent problem behavior

Adolescent problem behavior, including substance use, schoolmisconduct and delinquency, is a national concern. Implicitin the concept of middle school is the recognition that studentswho develop positive social bonds with their school are morelikely to perform well academically, and refrain from misconductand other antisocial behavior. However, little scientific attentionhas been given to the complex interactions between middle schoolstudents and the school environment. Prior to implementing amiddle school problem behavior prevention program we conducteda survey in the seven middle schools in one US school district.Out of 4668 grade 6–8 students enrolled, 4263 (91.3%)completed the survey. Student–school bonding was positivelycorrelated with school adjustment (r = 0.49) and perceived schoolclimate (r = 0.77), but inversely correlated with problem behavior(r = –0.39 to –0.43). Problem behavior was significantlyhigher (P < 0.001) among males than females and among studentsin higher grades. Conversely, school bonding, climate and adjustmentwere significantly higher (P < 0.001) among females thanmales, but declined significantly from one grade to the next.The data support the conclusion that school bonding is associatedwith problem behavior. We describe the development of a multiple-componentintervention in middle schools designed to increase student–schoolbonding and prevent problem behavior.     

Intraoperative laparoscopic complications

PURPOSE: The aim of this study was to assess various intraoperative and postoperative complications associated with laparoscopic colorectal surgery. Specifically, the impact of surgical experience and procedure type on complications was analyzed. METHODS: All patients who underwent laparoscopic surgery were analyzed by age, sex, surgical indications, procedure performed, procedure length, intraoperative and postoperative complications, incidence and causes for conversion, duration of postoperative ileus, and length of hospital stay. Patients were classified for type of procedure and chronologically into four consecutive groups. Procedures were also categorized into four different groups: GI, total abdominal colectomies; GII, segmental resections; GIII, diverting procedures; GIV, others (abdominoperineal resection, Hartmann's creation or closure, anterior resection, and rectopexy). RESULTS: Between August 1991 and October 1995, 167 patients of a mean age of 49.6 (15–88) years underwent laparoscopic colorectal procedures. All procedures were electively performed. Common indications for surgery included inflammatory disease in 70 (42 percent), neoplasia in 56 (33 percent), functional bowel disorders in 30 (18 percent), and other forms of colorectal disorders in 11 (7 percent) patients. The most significant variable affecting intraoperative laparoscopic complication rate was surgical experience measured as the time interval during which surgery was performed (P=0.02). Total complication rate decreased from 29 percent during the first period to 11 percent by the second period (P<0.04) and 7 percent during the third period (P<0.005). Thus, the learning curve appeared to have required more than 50 cases to achieve. Moreover, even after performance of 94 (1991–1993) procedures in GI and GIV, these procedures were associated with higher complication rates than were those procedures in GII and GIII (P=0.04). CONCLUSION: Surgical experience and case selection are the most critical variables by which the surgeon can decrease the intraoperative laparoscopic complication rate.     

Prospective comparison of open<Emphasis Type="Italic">vs</Emphasis>. laparoscopic colon surgery for carcinoma

Laparoscopy for colonic diseases began in 1990 and has established a role in benign disease. Early observations and experiences demonstrated feasibility of laparoscopic surgery for a variety of colonic disease processes, but the applicability to colonic carcinoma was unclear. METHODS: In 1990, we began a comparative study of open (OCR)vs.laparoscopic (LCR) approach to colon cancer. The study progressed 65 months, with 224 patients in OCR group and 191 patients in LCR group. Parameters studied are stage, location, length of specimen, number of lymph nodes resected, margins, postoperative course, wound complications, recurrence rates, and immediate and long-term survival. OCR were standardized by one group, and LCR were standardized by a second group. All patients undergoing LCR were given freedom to choose either OCR or LCR, and informed consent was obtained. RESULTS: Equal or greater lymph node retrieval, resections, and distal margins were evident with LCR. Benefits with LCR were shown with shorter hospitalization (5.7vs.9.7 days), less blood loss, less wound problems (1vs.14), and quicker return of bowel function. Survival, recurrence, and death rates were essentially the same. There were no trocar implants in the LCR group. CONCLUSION: After five years, this study shows that laparoscopy does no harm to the patient, offers comparable oncologic resections, and seems to be patient-friendly, with less pain, quicker return of bowel functions, shortened hospitalization, and quicker return to full activity.