Clinical and biochemical results of the metalloproteinase inhibition with subantimicrobial doses of doxycycline to prevent acute coronary syndromes (MIDAS) pilot trial.

BACKGROUND: Vulnerable plaque demonstrates intense inflammation in which macrophages secrete matrix metalloproteinases (MMPs) that degrade the fibrous cap, ultimately leading to rupture, in situ thrombosis, and an associated clinical event. Thus, inhibition of MMP activity or more general suppression of vascular inflammation are attractive targets for interventions intended to reduce plaque rupture. We hypothesized that subantimicrobial doses of doxycycline (SDD) (20 mg twice daily) would benefit patients with coronary artery disease by reducing inflammation and MMP activity and thus possibly prevent coronary plaque rupture events. METHODS AND RESULTS: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study of 6 months of SDD or placebo treatment to reduce inflammation and prevent plaque rupture events. A total of 50 patients were enrolled, of whom 24 were randomized to placebo and 26 to SDD. At 6 months, there was no difference in the composite endpoint of sudden death, fatal myocardial infarction (MI), non-fatal MI, or troponin-positive unstable angina in SDD compared with placebo-treated patients (8.4% versus 0%, P=0.491). Biochemical markers of inflammation were assessed in plasma at study entry and after 6 months of therapy in 30 patients. In SDD-treated patients, high-sensitivity C-reactive protein (CRP) was reduced by 46% from 4.8+/-0.6 microg/mL to 2.6+/-0.4 microg/mL (P=0.007), whereas CRP was not significantly reduced in placebo patients. Interleukin (IL)-6 decreased from 22.1+/-3.7 pg/mL at baseline to 14.7+/-1.8 pg/mL at 6 months in SDD-treated patients (P=0.025) but did not decrease significantly in placebo-treated patients. On zymography, pro-MMP-9 activity was reduced 50% by SDD therapy (P=0.011), whereas it was unchanged by placebo treatment. CONCLUSIONS: SDD appears to exert potentially beneficial effects on inflammation that could promote plaque stability. These findings should be investigated in a larger study.

The impact of a palliative medicine consultation service in medical oncology.

This prospective study of consecutive patients describes the palliative medicine consult service in a tertiary level cancer center and its impact on patient care. All inpatients/outpatients referred to the Palliative Medicine Program in a 4-month period were enrolled. Data were collected at the initial consultation using standardized forms with spaces for: reason for the consultation, referring service, demographics and history, ECOG performance status, symptoms, prognosis and diagnostic tests, treatment, and care plan. In all, 240 patients were seen: 79% were referred for symptom management; 53% were referred from medical oncology; and 50% were women. Median patient age was 67 years (range 18-96). Median performance status was 2 (1-4). Most (84%) of the patients had cancer. The cancer sites were: lung in 26% of cases, colorectal in 8%, and breast in 7%. Inpatients accounted for 53% and outpatients, for 47% of the study population. The median number of symptoms per patient was 13 (2-30). The estimated survival was <2 weeks in 15%, 2-8 weeks in 38%, 2-6 months in 37%, and >6 months in 10%. The patients' goals were: improve symptoms for 84%, return home for 55%, and no further admissions for 5%. The support systems named by patients were: family in 89%, friends in 13%, and the community in 5%. Hospice care was discussed at the consultation with 38% of the patients, would have been inappropriate for 31%, was not discussed with 22%, and had been discussed before with 9%. In response to questions about psychosocial care, a caregiver was identified by 78%, a spokesperson by 75%, and durable power of attorney was referred to by 21%. The DNR status was discussed on consult by 57%, had already been discussed with 30%, and was not discussed with 13%. Plan of care foresaw outpatient follow-up for 40%, inpatient follow-up for 32%, and transfer to palliative medicine for 27%. In 39% of cases the consults were considered late referrals. New medications suggested were opioids for 46% of patients, antiemetics for 28%, a bowel regimen for 24%, steroids for 15%, and others for 51%. (1) Palliative medicine consultation involves common complex medical, psychological, and social problems. (2) Complex symptomatology in this population is confirmed. (3) Multiple interventions were suggested even at the initial consultation. (4) Important issues such as DNR (do not resuscitate) status, support system, treatment goals, and eligibility for hospice care had often not been addressed.