Late-life depression: a model for medical classification.

Geriatric psychiatric syndromes might serve as the starting point for a medical classification of psychiatric disorders, because their medical and neurological comorbidity and their clinical, neuropsychological, and neuroimaging features often reflect specific brain abnormalities. Geriatric syndromes, however, consist of complex behaviors that are unlikely to be caused by single lesions. We propose a model in which aging-related changes in specific brain structures increase the propensity for the development of certain psychiatric syndromes. The predisposing factors are distinct from the mechanisms mediating the expression of a syndromic state, much like hypertension is distinct from stroke, but constitutes a morbid vulnerability. We argue that research seeking to identify both brain abnormalities conferring vulnerability as well as the mediating mechanisms of symptomatology has the potential to lead to a medical classification of psychiatric disorders. In addition, a medical classification can guide the effort to improve treatment and prevention of psychiatric disorders as it can direct therapeutic efforts to the underlying predisposing abnormalities, the syndrome-mediating mechanisms, and to development of behavioral skills needed for coping with adversity and disability.     

Patterns of hearing loss and psychiatric morbidity in elderly patients attending a hearing clinic

This study examines the relationship between hearing loss and psychiatric diagnosis in a geriatric population attending a hearing clinic. Major depression was the most frequent psychiatric disorder and was diagnosed in 30% of subjects. A sensorineural type hearing loss was diagnosed in 85% of the depressed subjects. More hearing loss was seen in subjects with onset of depression after age 55 years, in comparison to geriatric patients with depression onset before age 55 years, subjects with other psychiatric disorders and subjects without a psychiatric diagnosis (p <0.001). The audiogram and speech audiometry suggest involvement of auditory nerve and central auditory pathways in late onset depression.     

The role of medical comorbidity in outcome of major depression in primary care: the PROSPECT study.

OBJECTIVE: The authors described the influence of specific medical conditions on clinical remission and response of major depression (MDD) in a clinical trial evaluating a care-management intervention among older primary-care patients. METHODS: Adults age 60 years and older were randomly selected and screened for depression. Participants were randomly assigned to Usual Care or to an Intervention with a depression care-manager offering algorithm-based care for MDD. In all, 324 adults meeting criteria for MDD were included in these analyses. Remission and response was defined by a score on the Hamilton Rating Scale for Depression <10 and by a decrease from baseline of > or =50%, respectively. Medical comorbidity was ascertained through self-report. Cognitive impairment was defined by a score <24 on the Mini-Mental State Exam (MMSE). RESULTS: In Usual Care, rates of remission were faster in persons who reported atrial fibrillation (AF) than in persons who did not report AF and slower in persons who reported chronic pulmonary disease than in persons who did not report chronic pulmonary disease; rates of response were less stable in persons with MMSE <24 than in those with MMSE > or =24. In the Intervention condition, none of the specific chronic medical conditions were significantly associated with outcomes for MDD. CONCLUSIONS: Because disease-specific findings were observed in persons who received Usual Care but not in persons who received more intensive treatment in the Intervention condition, our results suggest that the association of medical comorbidity and treatment outcomes for MDD may be determined by the intensity of treatment for depression.     

Longitudinal association of initiation/perseveration and severity of geriatric depression.

OBJECTIVE: Many older adults with major depression (MDD) present with impairment in initiation and perseveration (IP) tests. However, it remains unclear how these abnormalities change during the course of depression. METHODS: The authors studied the longitudinal covariation of depression severity and IP functioning in 157 depressed older adults with MDD. Patients with and without baseline IP impairment were studied on three occasions over 1 year. RESULTS: Depression severity was associated with concurrent IP scores; however, despite IP improvement, those with impaired baseline IP functioning did not reach the level of their non-impaired counterparts. CONCLUSION: The persistence of IP abnormalities suggests that these patients require careful treatment planning and follow-up, given that earlier studies noted an association of abnormal IP with disability and poor outcomes of depression treatment.     

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.     

Docetaxel and granulocyte colony-stimulating factor in patients with advanced non-small-cell lung cancer previously treated with platinum-based chemotherapy: a multicenter phase II trial

Purpose: To investigate the activity of docetaxel and granulocyte colony-stimulating factor support (G-CSF) in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with cisplatin. Patients and methods: A total of 60 patients with locoregional and metastatic NSCLC who had relapsed or progressed after first-line treatment with cisplatin-based regimens were enrolled into the trial. Docetaxel at 100 mg/m² was given as a 1-h infusion with G-CSF (rhG-CSF given s.c. at 150 μg/m²) support from day 2 to day 8 every 3 weeks; all patients received premedication with corticosteroids. Results: In all, 1 (1.6%) and 14 (23.3%) patients achieved a complete response (CR) and a partial response (PR), respectively, for an overall response rate of 25% (95% CI 14.0–35.9%); stable disease (SD) and progressive disease (PD) were documented in 18 (30%) and 27 (45%) patients, respectively. The median duration of response was 20 weeks and the median time to tumor progression was 28 weeks. The median overall survival was 32 weeks and the 1-year survival rate was 23%. A total of 263 courses were given at a median of 3 cycles/patient. Grade 3 and 4 neutropenia occurred in 11 (18%) and 14 (23%) patients, respectively, with 18 (30%) patients requiring hospitalization for neutropenic fever; 1 patient died of sepsis. Grade 2 peripheral neuropathy occurred in 9 patients (15%) and grade 3 asthenia, in 4 (7%). Other toxicities were mild. Conclusions: Docetaxel has considerable single-agent activity in patients with NSCLC who have relapsed or progressed after first-line chemotherapy with cisplatin-based regimens. Received: 17 June 1998 / Accepted: 17 August 1998     

Wide range of point prevalences of healthcare-associated infections in Western Greece

The purpose of this study was to estimate the prevalence of healthcare-associated infections (HAIs) in the region of Western Greece and its relationship with possible predisposing factors. Two 1-day prevalence studies were performed in all hospitals of the region. The average HAI prevalence was 2·9% (range 0-6·8%) in the hospitals and 0-22·7% between different medical wards. Overall, 90% of HAI patients had predisposing factors. The most frequently isolated microorganism was Escherichia coli (14·3%). The study revealed a relatively low overall point prevalence of HAI, but remarkable discrepancies between the hospitals and wards. This may be due to the presence of confounding medical conditions and/or underreporting of HAIs from certain hospital wards. Local point-prevalence surveys may increase the awareness of HAIs in hospital staff and contribute to the establishment of effective infection control.     

Gemcitabine and docetaxel as first-line treatment for advanced urothelial carcinoma: a phase II study

The purpose of the study was to investigate the toxicity and efficacy of the combination of gemcitabine and docetaxel in untreated advanced urothelial carcinoma. Patients with previously untreated, locally advanced/recurrent or metastatic urothelial carcinoma stage-IV disease were eligible. Patients with Performance status: PS ECOG >3 or age >75 years or creatinine clearance <50 ml min(-1) were excluded. Study treatment consisted of docetaxel 75 mg m(-2) (day 8) and gemcitabine 1000 mg m(-2) (days 1+8), every 21 days for a total of six to nine cycles. A total of 31 patients with urothelial bladder cancer, 25 men and six women, aged 42-74 (median 64) years were enrolled. The majority of patients had a good PS (51.6%; PS 0). In all, 15 (48.3%) patients had locally advanced or recurrent disease only and 16 (54.8%) presented with distant metastatic spread, with multiple site involvement in 22.5%. Toxicity was primarily haematologic, and the most frequent grade 3-4 toxicities were anaemia 11 (6.7%) thrombocytopenia eight (4.9%), and neutropenia 45 (27.6%), with 10 (6.1%) episodes of febrile neutropenia. No toxic deaths occurred. A number of patients had some cardiovascular morbidity (38.7%). Nonhaematological toxicities except alopecia (29 patients) were mild. Overall response rate was 51.6%, including four complete responses (12.9%) and 12 partial responses (38.7%), while a further five patients had disease stabilisation (s.d. 16.1%). The median time to progression was 8 months (95% CI 5.1-9.2 months) and the median overall survival was 15 months (95% CI 11.2-18.5 months), with 1-year survival rate of 60%. In conclusion, this schedule of gemcitabine and docetaxel is very active and well tolerated as a first-line treatment for advanced/relapsing or metastatic urothelial carcinoma. Although its relative efficacy and tolerance as compared to classic MVAC should be assessed in a phase III setting, the favourable toxicity profile of this regimen may offer an interesting alternative, particularly in patients with compromised renal function or cardiovascular disease.