Morton Leibowitz

Treatment of advanced Parkinson disease with pergolide.

Pergolide mesylate, a semisynthetic ergoline and a potent, long-acting central dopamine agonist, was tested in 13 patients with advanced Parkinson disease and diurnal oscillations in performance (“wearing-off” or “on-off” phenomena or both) whose response to levodopa had diminished considerably. Among all nine patients who completed the initial clinical trial, pergolide alone (two patients) or combined with levodopa (seven patients) had a marked antiparkinsonian effect. There was a significant reduction (p < 0.05) in rigidity, bradykinesia, gait disorder, and total Parkinson disease disability score. Pergolide had a marked effect in all the patients with “wearing-off” or “on-off” phenomena or both, resulting in a significant increase (p <0.01) in the duration of the time patients were “on.” The number of hours in which patients were “on” increased from 3.8 ± 0.5 (SEM) to 11.4 ± 0.8 (SEM). The mean daily dose of pergolide was 2.4 mg (range, 2 to 5 mg). Ten months later, all nine patients are doing well. Pergolide is an effective drug in patients with advanced Parkinson disease and reduces “on-off” phenomena.

Long-Term Hypnotic Efficacy and Safety of Triazolam and Flurazepam

Both triazolam and flurazepam are effective hypnotics when administered nightly for 12 consecutive weeks. However, at the dosages tested, 0.6 mg triazolam had a significantly faster onset of activity than 30 mg flurazepam. Long-term administration of either treatment did not influence the patients capability to recognize the difference between active drug and placebo. This supports the conclusion that there was no tolerance development on either treatment. There were no deleterious effects attributable to either treatment as measured by the 35-Item Hopkins Symptom Checklist or by physical examinations, laboratory tests, ECGs, and ophthalmologic examinations. Side effects occurred more often on flurazepam than on triazolam, and the number of patients experiencing side effects was significantly higher in the flurazepam group. Drowsiness and grogginess were reported most frequently on both treatments, and the number of patients reporting drowsiness or grogginess was also significantly higher in the flurazepam group.

Comparison of dopa decarboxylase inhibitor (carbidopa) combined with levodopa and levodopa alone in Parkinson's disease

A double-blind study comparing the effects of carbidopa and levodopa combined in a single tablet with levodopa alone was undertaken in 50 patients with Parkinsons disease. After 6 months, there was a statistically significant improvement over baseline in total score, rigidity, and tremor only in the patients randomized to carbidopa/levodopa. In addition, 40 percent of the patients treated with carbidopa/levodopa showed obvious clinical improvement (a greater than 50 percent reduction in their total score) over treatment with levodopa alone. However, after 2 years, only 20 percent continued to show this improvement. Nausea, vomiting, and anorexia developed in 56 percent of patients on levodopa but in only 27 percent of patients on carbidopa/levodopa. However, abnormal involuntary movements, observed in 48 percent of patients on levodopa, were present in 77 percent of patients on carbidopa/levodopa. Despite the increase in abnormal involuntary movements, carbidopa/levodopa is more effective than levodopa.

Defining the Role of Medication Adherence in Poor Glycemic Control among a General Adult Population with Diabetes

Aims This study assesses the attributable impact of adherence to oral glucose medications as a risk factor for poor glycemic control in population subgroups of a large general population, using an objective medication adherence measure. Methods Using electronic health records data, adherence to diabetes medications over a two-year period was calculated by prescription-based Medication Possession Ratios for adults with diabetes diagnosed before January 1, 2010. Glycemic control was determined by the HbA1c test closest to the last drug prescription during 2010–2012. Poor control was defined as HbA1c>75 mmol/mol (9.0%). Medication adherence was categorized as “good” (>80%), “moderate” (50–80%), or “poor” (<50%). Logistic regression models assessed the role medication adherence plays in the association between disease duration, age, and poor glycemic control. We calculated the change in the attributable fraction of glucose control if the non-adherent diabetic medication population would become adherent by age-groups. Results Among 228,846 diabetes patients treated by oral antiglycemic medication, 46.4% had good, 28.8% had moderate, and 24.8% had poor adherence. Good adherence rates increased with increasing disease duration, while glycemic control became worse. There was a strong inverse association between adherence level and poor control (ORu200a=u200a2.50; CIu200a=u200a2.43–2.58), and adherence was a significant mediator between age and poor control. Conclusions A large portion of the diabetes population is reported to have poor adherence to oral diabetes medications, which is strongly associated with poor glycemic control in all disease durations. While poor adherence does not mediate the poorer glycemic control seen in patients with longer-standing disease, it is a significant mediator of poor glycemic control among younger diabetes patients. A greater fraction of poorly controlled younger patients, compared to older patients, could be prevented if at least 80% adherence to their medications was achieved. Therefore, our results suggest that interventions to improve adherence should focus on this younger sub-group.

Further studies with pergolide in Parkinson disease

Pergolide was administered to 56 patients with advanced Parkinson disease who were no longer satisfactorily reponding to levodopa. The group included 45 patients with on-off phenomena. Pergolide, when combined with levodopa, resulted in a 44% decrease in disability as assessed in the on period, a 15% decrease in disability as assessed in the off period, and a 148% increase in the number of hours in which patients were on (from 4.6 ± 0.3 hours to 11.4 ± 0.6 hours). All these changes were significant at 1%. Forty-one of the 56 patients (59%) improved when pergolide was added to levodopa. Mean dose of pergolide was 2.5 mg (range, 0.2 to 10.0 mg). Mean duration of the study was 13 months (range, 1 day to 34 months). Maximum improvement occurred within 2 months and began to decline, usually after 6 months. The major adverse effects necessitating discontinuing pergolide were the occurrence of an organic confusional syndrome (six patients), increased dyskinesias (four patients), and cardiovascular abnormalities (three patients). Nine patients discontinued pergolide because of a lack of effect or declining effect.

Lisuride in Parkinson disease Efficacy of lisuride compared to levodopa

Lisuride hydrogen maleate, a semisynthetic ergoline and potent central dopamine and serotonin agonist, was tested in 10 patients with moderate to marked Parkinson disease whose response to levodopa had diminished. In the group of 10 patients, there was a significant reduction (p =z 0.05) in bradykinesia, gait disorder, and total Parkinson disease disability score when levodopa was replaced with lisuride. The mean dose of lisuride was 3.6 mg per day. Among the 10 patients, 5 were better on lisuride than on levodopa, and 4 continue on lisuride 1 year later. A decline in efficacy was noted in all four after a mean of 45 months. Adverse effects necessitating discontinuing the drug were mental changes in three patients and nausea in one patient. Lisuride, when used alone, has definite antiparkinsonian activity and is a promising new drug.

Association Between Achieved Low-Density Lipoprotein Levels and Major Adverse Cardiac Events in Patients With Stable Ischemic Heart Disease Taking Statin Treatment

IMPORTANCEnInternational guidelines recommend treatment with statins for patients with preexisting ischemic heart disease to prevent additional cardiovascular events but differ regarding target levels of low-density lipoprotein cholesterol (LDL-C). Trial data on this question are inconclusive and observational data are lacking.nnnOBJECTIVEnTo assess the relationship between levels of LDL-C achieved with statin treatment and cardiovascular events in adherent patients with preexisting ischemic heart disease.nnnDESIGN, SETTING, AND PARTICIPANTSnPopulation-based observational cohort study from 2009 to 2013 using data from a health care organization in Israel covering more than 4.3 million members. Included patients had ischemic heart disease, were aged 30 to 84 years, were treated with statins, and were at least 80% adherent to treatment or, in a sensitivity analysis, at least 50% adherent. Patients with active cancer or metabolic abnormalities were excluded.nnnEXPOSURESnIndex LDL-C was defined as the first achieved serum LDL-C measure after at least 1 year of statin treatment, grouped as low (≤70.0 mg/dL), moderate (70.1-100.0 mg/dL), or high (100.1-130.0 mg/dL).nnnMAIN OUTCOMES AND MEASURESnMajor adverse cardiac events included acute myocardial infarction, unstable angina, stroke, angioplasty, bypass surgery, or all-cause mortality. The hazard ratio of adverse outcomes was estimated using 2 Cox proportional hazards models with low vs moderate and moderate vs high LDL-C, adjusted for confounders and further tested using propensity score matching analysis.nnnRESULTSnThe cohort with at least 80% adherence included 31u202f619 patients, for whom the mean (SD) age was 67.3 (9.8) years. Of this population, 27% were female and 29% had low, 53% moderate, and 18% high LDL-C when taking statin treatment. Overall, there were 9035 patients who had an adverse outcome during a mean 1.6 years of follow-up (6.7 per 1000 persons per year). The adjusted incidence of adverse outcomes was not different between low and moderate LDL-C (hazard ratio [HR], 1.02; 95% CI, 0.97-1.07; Pu2009=u2009.54), but it was lower with moderate vs high LDL-C (HR, 0.89; 95% CI, 0.84-0.94; Pu2009<u2009.001). Among 54u202f884 patients with at least 50% statin adherence, the adjusted HR was 1.06 (95% CI, 1.02-1.10; Pu2009=u2009.001) in the low vs moderate groups and 0.87 (95% CI, 0.84-0.91; Pu2009=u2009.001) in the moderate vs high groups.nnnCONCLUSIONS AND RELEVANCEnPatients with LDL-C levels of 70 to 100 mg/dL taking statins had lower risk of adverse cardiac outcomes compared with those with LDL-C levels between 100 and 130 mg/dL, but no additional benefit was gained by achieving LDL-C of 70 mg/dL or less. These population-based data do not support treatment guidelines recommending very low target LDL-C levels for all patients with preexisting heart disease.

Bilateral Cervical Carotid and Intracranial Vasospasm Causing Cerebral Ischemia in a Migrainous Patient: A Case of "Diplegic Migraine"

SYNOPSIS

Cardiac effects of pergolide

We examined the effect of pergolide, a semi synthetic ergot alkaloid, alone or combined with carbidopa and levodopa (Sinemet), on the cardiac rhythm of 12 patients with Parkinsons disease. The patients were selected on the basis of severe Parkinsons disease and stable cardiac rhythm as determined by I to 5 days of Hoher monitoring. Monitoring was then carried out for an additional period of between 2 and 10 wk while the patients were on pergolide. Seven of the 12 patients had repetitive ventricular rhythms (RVRs). These were isolated, infrequent, and not associated with increases in premature ventricular contractions. The dose at which the RVRs occurred may be a function of the presence or absence of heart disease, but the significance of RVRs remains to be determined.

Long‐term treatment with pergolide Decreased efficacy with time

We studied the effect of pergolide (combined with levodopa) in 17 patients with Parkinsons disease, including 15 with “wearing off” or on-off phenomena, who had been taking pergolide for at least 2 years. Mean duration of the study was 27.8 months. All 17 patients improved initially, but the improvement later faded. Mean disability score, which decreased initially by 60% (significant), was decreased only by 20% after 2 years (not significant). Wearing off and on-off phenomena, which improved initially, became prominent again. Four patients lost all the improvement, nine patients lost much of the improvement, and four maintained much of the improvement. Mean dose of pergolide was 2.2 mg (range, 0.8 to 5.0 mg).