First report of natural Wolbachia infections in mosquitoes from Cuba.

Mosquitoes are extensively responsible for the transmission of pathogens. Novel strategies using Wolbachia could transform that scenario, since these bacteria manipulate mosquito reproduction, and can confer a pathogen transmission-blocking phenotype in culicids. Here, we screened the Wolbachia surface protein region by PCR in eight Cuban mosquito species. We confirmed the natural infections by sequencing and assessed the phylogenetic relationships among the Wolbachia strains detected. We identified four Wolbachia hosts: Aedes albopictus, Culex quinquefasciatus, Mansonia titillans, and Aedes mediovittatus (first report worldwide). Knowledge of Wolbachia strains and their natural hosts is essential for future operationalization of this vector control strategy in Cuba.

Characterization of Insecticide Resistance in Aedes aegypti from the Zoological Garden of Havana, Cuba.

Chemical control of Aedes aegypti continues to be an indispensable alternative to preventing dengue, Zika, and chikungunya outbreaks. The Havana Zoological Garden requires constant vigilance because its special characteristics help in the spread of the causal agents of diseases transmitted by mosquitoes, which put the health of visitors at risk. The goals of this study were to determine the level of susceptibility and insecticide resistance mechanisms in the Ae. aegypti population. Temephos susceptibility in larvae was evaluated with bioassays using the World Health Organization's methodology, and susceptibility of adult mosquitoes was determined by the impregnated bottle bioassay, recommended by the Centers for Disease Control and Prevention. Resistance mechanisms were determined with biochemical assays. Mosquito larvae from the Havana Zoo were found resistant to temephos, which was associated with the activity of the enzymes α- and ß-esterases and mixed function oxidases but not glutathione-S-transferase. Adult mosquitoes were susceptible to pyrethroid (lambda-cyhalothrin, deltamethrin, and cypermethrin), organophosphate (chlorpyrifos), and carbamate (bendiocarb). Temephos resistance detected in the mosquito population from the Havana Zoo is an alert for the Vector Control Program, which must take measures to manage their resistance, relying on the surveillance carried out by Cuba's medical entomology laboratories.

Addition of alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis: a randomized, controlled clinical trial.

Alendronate and estrogen are effective therapies for postmenopausal osteoporosis, but their efficacy and safety as combined therapy are unknown. The objective of this study was to evaluate the addition of alendronate to ongoing hormone replacement therapy (HRT) in the treatment of postmenopausal women with osteoporosis. A total of 428 postmenopausal women with osteoporosis, who had been receiving HRT for at least 1 yr, were randomized to receive either alendronate (10 mg/day) or placebo. HRT was continued in both groups. Changes in bone mineral density (BMD) and biochemical markers of bone turnover were assessed. Compared with HRT alone, at 12 months, alendronate plus HRT produced significantly greater increases in BMD of the lumbar spine (3.6% vs. 1.0%, P < 0.001) and hip trochanter (2.7% vs. 0.5%, P < 0.001); however, the between-group difference in BMD at the femoral neck was not significant (1.7% vs. 0.8%, P = 0.072). Biochemical markers of bone turnover (serum bone-specific alkaline phosphatase and urine N-telopeptide) decreased significantly at 6 and 12 months with alendronate plus HRT, and they remained within premenopausal levels. Addition of alendronate to ongoing HRT was generally well tolerated, with no significant between-group differences in upper gastrointestinal adverse events or fractures. This study demonstrated that, in postmenopausal women with low bone density despite ongoing treatment with estrogen, alendronate added to HRT significantly increased bone mass at both spine and hip trochanter and was generally well tolerated.

An open multicenter long-term treatment evaluation of Sinemet CR. Sinemet CR Multicenter Study Group.

The safety and efficacy of Sinemet CR were studied in an open-label, 52-week trial. The study was completed by 156 mildly to moderately ill Parkinson's patients (primarily Hoehn and Yahr stage II to III) at 10 sites. Patients had their treatment optimized on standard Sinemet prior to beginning Sinemet CR treatment. Following titration, there was a median reduction in dosing frequency of 25% (from 4.1 to 3.2 doses/day) relative to the standard Sinemet baseline. Total daily levodopa dosage increased from 623 to 808 mg/day (+33%), a factor consistent with the lower bioavailability of the controlled-release formulation. Mean efficacy scores on the New York University Parkinson's Disease Scale decreased from 7.4 at the end of baseline to 5.8 at 12 weeks, a decline of 20%. The scores remained at this level throughout 52 weeks of treatment. At the end of 1 year of treatment, 60% of patients rated themselves as improved, while physicians rated 64% of the patients as improved. Adverse experiences were similar to those reported by patients taking standard levodopa preparations. Two thirds of the reported adverse experiences occurred within the 1st 3 months of Sinemet CR therapy, indicating that increased length of exposure to Sinemet CR was not associated with an increasing incidence of adverse experiences.

Multicenter controlled study of Sinemet CR vs Sinemet (25/100) in advanced Parkinson's disease.

Controlled-release carbidopa/levodopa 50/200 (Sinemet CR) and standard carbidopa/levodopa (Sinemet 25/100) were compared in a multicenter double-blind trial involving 202 patients with advanced Parkinson's disease and motor response fluctuations. Treatment with Sinemet CR significantly reduced daily "off" time. According to both physician and patient global ratings, patients showed significant improvements with Sinemet CR compared to treatment with standard Sinemet. Patients preferred Sinemet CR treatment by a ratio of approximately 2 to 1. Daily dosing frequency was 33% less with Sinemet CR, while daily intake of levodopa required was increased by 25%. The safety profiles of the 2 formulations were similar. We conclude that Sinemet CR is superior to standard Sinemet for many patients with advanced Parkinson's disease, although it does not solve the problem of fluctuating motor performance.

Comparison of the effects on quality of life and of the efficacy and tolerability of lovastatin versus pravastatin. The Quality of Life Multicenter Group.

This multicenter study compared the effects of lovastatin (40 mg) and pravastatin (40 mg) on quality of life. Men, aged 20 to 65 years old, with primary hypercholesterolemia (types IIa and IIb) were eligible for enrollment if baseline low-density lipoprotein cholesterol met the first National Cholesterol Education Program adult treatment guidelines. Eligible patients were enrolled into a 6-week diet baseline period, followed by a 6-week diet-plus-placebo period. Patients whose low-density lipoprotein cholesterol still met National Cholesterol Education Program guidelines for drug therapy were randomized into the double-blind, active-treatment period to receive either lovastatin 40 mg or pravastatin 40 mg/day for 12 weeks. Clinic visits were scheduled every 4 weeks and included complete serum lipid profiles, monitoring of adverse experiences, and patient completion of health-related quality-of-life questionnaires. The primary end point of the study was the change in quality of life, as measured by the Nottingham Health Profile (part 1) after 12 weeks of treatment. Secondary end points included responses to a general health question from the National Health and Nutrition Examination Survey, sexual function questions from the Medical Outcomes Study, and stress/life event questions from the National Institutes of Health Post-Coronary Artery Bypass Grafting Study. No significant differences between the 2 groups were observed in tolerability, health-related quality-of-life measures, or changes in lipid profiles.

Use and efficacy of tuberculosis infection control practices at hospitals with previous outbreaks of multidrug-resistant tuberculosis.

OBJECTIVE: To evaluate the implementation and efficacy of selected Centers for Disease Control and Prevention guidelines for preventing spread of Mycobacterium tuberculosis. DESIGN: Analysis of prospective observational data. SETTING: Two medical centers where outbreaks of multidrug-resistant tuberculosis (TB) had occurred. PARTICIPANTS: All hospital inpatients who had active TB or who were placed in TB isolation and healthcare workers who were assigned to selected wards on which TB patients were treated. METHODS: During 1995 to 1997, study personnel prospectively recorded information on patients who had TB or were in TB isolation, performed observations of TB isolation rooms, and recorded tuberculin skin-test results of healthcare workers. Genetic typing of M tuberculosis isolates was performed by restriction fragment-length polymorphism analysis. RESULTS: We found that only 8.6% of patients placed in TB isolation proved to have TB; yet, 19% of patients with pulmonary TB were not isolated on the first day of hospital admission. Specimens were ordered for acid-fast bacillus smear and results received promptly, and most TB isolation rooms were under negative pressure. Among persons entering TB isolation rooms, 44.2% to 97.1% used an appropriate (particulate, high-efficiency particulate air or N95) respirator, depending on the hospital and year; others entering the rooms used a surgical mask or nothing. We did not find evidence of transmission of TB among healthcare workers (based on tuberculin skin-test results) or patients (based on epidemiological investigation and genetic typing). CONCLUSIONS: We found problems in implementation of some TB infection control measures, but no evidence of healthcare-associated transmission, possibly in part because of limitations in the number of patients and workers studied. Similar evaluations should be performed at hospitals treating TB patients to find inadequacies and guide improvements in infection control.

Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension.

The efficacy and tolerability of extended-release felodipine (felodipine-ER) and nifedipine gastrointestinal therapeutic system (nifedipine GITS) were compared in a multicenter, prospective, open-label clinical trial of 277 patients with mild-to-moderate uncomplicated essential hypertension (sitting diastolic blood pressure [SiDBP] > or = 95 and < or = 115 mm Hg). After a 3-week washout period, patients were randomized to receive felodipine-ER (5 mg once daily) or nifedipine GITS (30 mg once daily); during a subsequent 6-week titration phase, the once-daily felodipine-ER dose could be increased to 10 mg and the nifedipine GITS dose to 60 or 90 mg in an attempt to achieve adequate blood pressure response (SiDBP < or = 90 mm Hg, or < 100 mm Hg with a > 10-mm Hg reduction from baseline, as measured 24 hours after dosing [trough]). At the end of titration, the mean daily doses of felodipine-ER and nifedipine GITS were 8 and 50 mg, respectively. Mean changes in sitting systolic blood pressure (SiSBP)/SiDBP were -14/-12 and -16/-13 mm Hg, respectively. All reductions were significant when compared with baseline (P < 0.01), but there were no significant differences between treatment groups. Adequate blood pressure response occurred in 77% of the felodipine-ER group and 80% of the nifedipine GITS group; this difference was not significant. Blood pressure changes were similar among sex and race subgroups. A higher percentage of older patients (> 55 years of age) than younger patients (< or = 55 years of age) reached goal SiDBP with both drugs. Patients with adequate SiDBP response continued receiving their assigned medication for an additional 6-week maintenance period. Reductions in SiDBP and SiSBP from baseline continued to be significant in both treatment groups. No clinically important changes in heart rate were noted. A total of 28 patients (15 in the felodipine-ER group and 13 in the nifedipine GITS group) withdrew from the study because of inadequate blood pressure response. At least one adverse experience occurred in 55% of the felodipine-ER group and 63% of the nifedipine GITS group, prompting withdrawal of 14 patients (10%) and 16 patients (11%), respectively. Headache and edema were the most common adverse experiences. The incidence and pattern of adverse experiences did not differ significantly between treatments. The results of this study demonstrate that once-daily felodipine-ER and nifedipine GITS are similarly highly effective and generally well tolerated in patients with essential hypertension.

Efficacy and tolerability of losartan versus enalapril alone or in combination with hydrochlorothiazide in patients with essential hypertension.

The antihypertensive effects and the tolerability of losartan and enalapril given alone or in combination with hydrochlorothiazide (HCTZ) were compared in a multicenter, double-blind, randomized, parallel-group, 16-week clinical trial. The study consisted of a 4-week placebo washout phase and a 12-week active treatment phase. Patients with mild-to-moderate, uncomplicated essential hypertension were considered for participation in the study. To enter the treatment phase of the study, a mean sitting diastolic blood pressure (SiDBP) > or = 95 and < or = 115 mm Hg was required. Patients received either 50-mg losartan once daily or 5-mg enalapril once daily at randomization. The dose of enalapril could be titrated to 10 mg after 4 weeks and 25 mg of HCTZ could be added after 8 weeks, based on measurements of SiDBP at clinic visits. The dose of losartan remained at 50 mg; 12.5 mg of HCTZ could be added after 8 weeks. Changes in the treatment regimen at each step were required if SiDBP remained > or = mm Hg. Doses of the diuretic were chosen based on commercially available forms of the test agents in combination with HCTZ. Trough blood pressure, heart rate, and safety parameters were measured at 4-week intervals during the treatment phase of the study. Significant reductions in mean SiDBP and mean sitting systolic blood pressure (SiSBP) were achieved at all time points (4, 8, and 12 weeks) with both treatments. No significant differences between treatment groups for mean changes in SiDBP or SiSBP were observed overall. At study end, patients receiving the losartan regimen had a mean reduction in SiDBP of 10.3 mm Hg, whereas patients in the enalapril regimen had a mean reduction of 9.8 mm Hg. Likewise, the percentage of patients reaching goal blood pressure reduction was not significantly different between groups. The mean reduction in SiDBP-- but not SiSBP--in black patients was slightly greater in the losartan group than in the enalapril group (SiDBP, 10.0 mm Hg losartan vs 8.0 mm Hg enalapril; P = 0.02). Similarly, losartan patients aged 65 years and older had a slightly greater decrease in SiDBP than comparable enalapril patients (12.7 mm Hg vs 8.7 mm Hg; P = 0.03). The importance of these differences between subgroups must be clarified by additional studies. Overall, both treatments were well tolerated. A regimen of losartan alone or in combination with HCTZ was effective in treating patients with essential hypertension and was comparable to a regimen of enalapril alone or in combination with HCTZ. However, treatment with losartan was associated with a lower incidence of cough.

Patient preference, efficacy, and compliance with timolol maleate ophthalmic gel-forming solution versus timolol maleate ophthalmic solution in patients with ocular hypertension or open-angle glaucoma.

This study was designed to compare timolol maleate ophthalmic gel-forming solution 0.5% (timolol gel) once daily with timolol maleate ophthalmic solution 0.5% (timolol solution) twice daily with respect to patient preference, intraocular pressure (IOP)-lowering effect, and tolerability. A total of 202 patients with ocular hypertension or open-angle glaucoma and an IOP > or = 22 mm Hg were enrolled in this 12-week, randomized, observer-masked, two-period crossover study. Significantly more patients preferred timolol gel to timolol solution (P < 0.001). Ninety-two percent of patients preferring timolol gel strongly agreed or agreed that once-daily dosing was a reason for their preference. Those who preferred timolol solution did so because of fewer side effects. The mean IOP-lowering effects of the 2 treatments were similar at both morning trough and peak time points. The incidence of drug-related adverse experiences was similar (timolol gel 11.4% vs timolol solution 10.9%). Because both treatments were well tolerated and effective in lowering IOP, timolol gel, with its once-daily dosing regimen, should be considered in patients who are candidates for therapy with an ophthalmic beta-blocking agent.

Efficacy, tolerability, and quality of life of losartan, alone or with hydrochlorothiazide, versus nifedipine GITS in patients with essential hypertension.

A randomized, double-masked, parallel-group, multicenter clinical trial was conducted to compare the efficacy, tolerability, and effects on quality of life associated with the angiotensin II receptor antagonist losartan, alone or with hydrochlorothiazide (HCTZ), and the dihydropyridine calcium channel blocker nifedipine gastrointestinal therapeutic system (GITS) in patients whose sitting diastolic blood pressure measurements were between 95 and 115 mm Hg, inclusive, while receiving placebo. Patients were randomized to receive either losartan or nifedipine GITS in a double-masked, double-dummy fashion. A 4-week placebo washout period established baseline untreated blood pressure measurements and was followed by a 12-week active treatment period. Patients receiving losartan (n = 110) were initially given 50 mg once a day (QD) and could be titrated to losartan/HCTZ 50 mg/12.5 mg QD after 4 weeks followed by losartan/HCTZ 50 mg/25 mg QD after 8 weeks, as necessary. Patients in the nifedipine GITS group (n = 113) received 30 mg QD, which could titrated to 60 mg QD after 4 weeks followed by 90 mg QD after 8 weeks. Medication was titrated upward as necessary to achieve a sitting trough diastolic blood pressure < 90 mm Hg. Efficacy, tolerability, and quality-of-life scores were assessed after 12 weeks of each therapy. Trough sitting diastolic blood pressure reductions after 4, 8, and 12 weeks of therapy were clinically comparable: losartan, -8.9, -11.6, and -12.7 mm Hg, respectively, and nifedipine GITS, -9.3, -11.0, and -11.1 mm Hg, respectively, with the mean reduction in sitting diastolic blood pressure at 12 weeks in the losartan group 1.6 mm Hg lower (95% confidence interval, 3.4 mm Hg lower to 0.3 mm Hg Higher) than the mean reduction in sitting diastolic blood pressure in the nifedipine GITS group. Similarly, reductions in systolic blood pressure between the two treatment groups were comparable at all time points. The percentage of patients reaching the goal trough sitting diastolic blood pressure was comparable for the two treatment groups, with 74% of patients in the losartan regimen and 68% of patients in the nifedipine GITS regimen reaching the goal. Of patients reporting adverse events in the two groups (75 patients receiving losartan and 69 receiving nifedipine GITS), there was significantly more edema in the nifedipine GITS group (15% vs 4%; P = 0.005). Fourteen (12%) patients in the nifedipine GITS group were withdrawn due to an adverse event (eight of these were for edema). Six patients (5%) in the losartan group were withdrawn due to an adverse event (none of these patients had edema). There were significant differences in the patient-reported quality-of-life symptom bother inventory with respect to edema, with nifedipine GITS therapy causing significantly more bother due to edema in patients, regardless of whether that symptom was present at baseline (27% vs 9%; P = 0.0004). No statistically significant differences for bother due to the other symptoms in the inventory were noted. Of note, while the incidence of patient-reported symptom bother due to edema in the nifedipine GITS group was 27%, the incidence of physician-reported drug-related edema was 12%. This difference points to the need for improved physician-patient communication regarding adverse effects and their impact of patients' quality of life. In conclusion, a regimen of losartan, when compared with a regimen of nifedipine GITS, provides comparable efficacy, and with respect to edema, superior tolerability, less bother to patients, and fewer therapy dropouts.

Efficacy, tolerability, and effects on quality of life of losartan, alone or with hydrochlorothiazide, versus amlodipine, alone or with hydrochlorothiazide, in patients with essential hypertension.

A randomized, double-masked, parallel-group, multicenter clinical trial was conducted to compare the efficacy, tolerability, and effects on quality of life associated with treatment regimens including the angiotensin II receptor antagonist losartan, with hydrochlorothiazide (HCTZ) added as needed, with regimens including the dihydropyridine calcium channel blocker amlodipine with HCTZ added as needed. The trial included patients whose sitting diastolic blood pressure (SiDBP) measurements were between 95 and 114 mm Hg, inclusive, at placebo baseline. Patients were randomized to receive either losartan or amlodipine in a double-masked, double-dummy fashion. A 4-week placebo washout period was followed by a 12-week active treatment period. Patients in the losartan arm (n = 97) were initially given 50 mg of oral (PO) losartan once a day (QD); the medication could be titrated to 50-mg losartan/ 12.5-mg HCTZ PO QD after 4 weeks, followed by 50-mg losartan plus 25-mg HCTZ PO QD after 8 weeks as necessary. Patients in the amlodipine group (n = 93) received 5-mg amlodipine PO QD, which could be titrated to 10 mg PO QD after 4 weeks, followed by 10 mg plus 25-mg HCTZ PO QD after 8 weeks. Medication was titrated upward as necessary to achieve trough SiDBP < 90 mm Hg. Efficacy, tolerability, and quality-of-life scores were assessed after 12 weeks of therapy with each regimen. Trough SiDBP reductions after 4, 8, and 12 weeks of therapy were clinically comparable (losartan group: 7.3, 10.4, and 11.1 mm Hg, respectively; amlodipine group: 7.9, 11.2, and 11.8 mm Hg, respectively). Similar reductions in systolic blood pressure were also seen for both treatment groups. The percentage of patients reaching goal SiDBP (defined as trough SiDBP < 90 mm Hg or SiDBP > or = 90 mm Hg with a > or = 10 mm Hg drop from placebo baseline) was comparable for the two groups, with 68% of patients in the losartan group and 71% of patients in the amlodipine group reaching goal. Significantly more patients in the amlodipine group had drug-related adverse experiences (27% vs 13%). In particular, drug-related edema was more common in patients receiving the amlodipine regimen than in those receiving the losartan regimen (11% vs 1%). Patients in the amlodipine arm reported significantly more bother due to edema, regardless of whether edema was present at baseline, than did patients in the losartan arm (12% vs 2%), although overall quality of life was not different in the two treatment groups. This study demonstrates that a regimen of losartan with HCTZ added as needed, when compared with a regimen of amlodipine with HCTZ added as needed, provides comparable efficacy and superior tolerability and less bother to patients with respect to edema.

Efficacy and tolerability of finasteride in symptomatic benign prostatic hyperplasia: a primary care study. Primary Care Investigator Study Group.

Because increasing numbers of men are seeking treatment for benign prostatic hyperplasia (BPH) from primary care physicians, we sought to assess the efficacy and tolerability of finasteride in a primary care setting. In this randomized, double-masked study, 2,112 men with symptomatic BPH received either finasteride (n = 1,589) or placebo (n = 523) for 1 year. At 3, 6, 9, and 12 months, urinary symptoms were measured using the American Urological Association Symptom Index (AUASI). Quality of life was assessed using the BPH Impact Index (BII), which assessed bother, worry, physical discomfort, and restriction in activities. Both patients and investigators assessed overall urologic status. Investigators assessed the effect of the drug on plasma lipids in a subset of patients. Patients treated with finasteride had a statistically significant mean decrease in AUASI scores compared with patients treated with placebo beginning at month 6 and continuing throughout the study. At month 12, adjusted mean decreases in AUASI scores were -4.96 for finasteride versus -3.71 for placebo. Statistically significant differences in favor of finasteride were also noted on BII at months 9 and 12. Patient and investigator overall assessments showed greater improvement in the finasteride group beginning at month 6. The incidence of drug-related sexual adverse experiences was significantly greater in finasteride-treated patients but led to withdrawal in only 2.2% of these patients. Overall lipid profile was not significantly altered in either group. Based on improvement in symptoms and quality of life, and on its favorable tolerability profile, finasteride should be considered by primary care physicians for management of symptomatic BPH.

Efficacy, tolerability, and effect on health-related quality of life of finasteride versus placebo in men with symptomatic benign prostatic hyperplasia: a community based study. CUSP Investigators. Community based study of Proscar.

This study sought to assess the efficacy, tolerability, and effect of finasteride on health-related quality of life (HRQL) in a diverse population of men with moderate-to-severe symptomatic benign prostatic hyperplasia (BPH). This double-blind study evaluated finasteride and placebo for 12 months in 2342 men with BPH (16.2% black, 14.5% Hispanic, 69.3% Caucasian/other) in a community-based setting. At 3-month intervals, urinary symptoms were measured by use of the American Urologic Association symptom index. HRQL was assessed by use of the BPH impact index (BII), which evaluated degree of bother, worry, physical discomfort, and restriction in activities as a result of urinary symptoms. Additional questions regarding activities of living were administered, and global assessments of change in urologic status were performed by both patients and investigators. Compared with placebo, patients treated with finasteride had a statistically significant decrease in symptom scores when first measured at month 3. Symptom scores continued to improve in finasteride-treated patients throughout the study; at month 12, the mean decrease in symptom scores in the finasteride-treated patients was -4.8 compared with -3.4 for placebo patients ( P = 0.0001). Statistically significant differences in favor of finasteride also were noted at month 12 on the BII (P = 0.0465), and finasteride-treated patients experienced less interference with activities of living (P = 0.0518). Patient and investigator global assessments of urologic status showed that significantly more patients in the finasteride group considered themselves improved and were considered improved by investigators at month 12 (P = 0.000). Finasteride was generally well tolerated. The incidence of drug-related sexual adverse experiences was significantly higher in the finasteride group (P = 0.000), but led to withdrawal in only 1.5% of patients. The demonstrated efficacy and tolerability of finasteride in reducing symptoms and improving quality of life confirm observations of previous trials and make finasteride a highly desirable treatment option for many men with symptomatic BPH.

Comparison of dorzolamide and pilocarpine as adjunctive therapy in patients with open-angle glaucoma and ocular hypertension.

Many patients with glaucoma or ocular hypertension initially receive beta-blocker monotherapy to control intraocular pressure (IOP), but some of these patients will require an additional IOP-lowering agent within 1 year. This active-controlled, double-masked, randomized, multicenter, 12-week study compared the effectiveness and tolerability of dorzolamide hydrochloride ophthalmic solution 2% TID with those of pilocarpine hydrochloride 2% QID as adjunctive therapy to timolol maleate ophthalmic gel-forming solution (TG) 0.5% QD as measured by changes in IOP and occurrence of adverse events. One hundred ninety-four patients with open-angle glaucoma or ocular hypertension participated in this study. Their mean age was approximately 63 years. Slightly more than one half were white, and approximately one third were black. After a 3-week run-in period during which all patients received TG 0.5% QD, patients with an IOP of > or = 22 mm Hg at the morning trough measurement were randomly assigned to receive additional double-masked therapy with either dorzolamide or pilocarpine. The primary outcome measure was the mean change in IOP at the morning trough measurement from baseline to week 12. The secondary outcome measure was the mean change in IOP at the morning peak measurement from baseline to week 12. There was no significant difference in IOP-lowering effect between the 2 drugs at either morning trough or morning peak. The mean change in IOP at morning trough was -3.17 mm Hg (-12%) in patients receiving dorzolamide; it was -3.45 mm Hg (-13%) in patients receiving pilocarpine. The mean change in IOP at morning peak was -2.25 mm Hg (-10%) for patients who received dorzolamide and -2.51 mm Hg (-11%) for those who received pilocarpine. In the pilocarpine group, 62 (63%) patients experienced > or =1 adverse event compared with 35 (36%) patients in the dorzolamide group (P < 0.001). Twenty-one (21%) patients in the pilocarpine group discontinued treatment because of an adverse event compared with 2 (2%) patients in the dorzolamide group (P < 0.001). These results demonstrate that dorzolamide and pilocarpine were equally effective as adjunctive therapy in lowering IOP but that dorzolamide was better tolerated.

Efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution QD compared with 0.5% levobunolol hydrochloride BID in patients with open-angle glaucoma or ocular hypertension.

We compared the efficacy of timolol maleate ophthalmic gel-forming solution 0.5% QD with that of levobunolol hydrochloride 0.5% BID, as measured by change in intraocular pressure (IOP), effect on heart rate, and ocular tolerability. The study had a positive-controlled, double-masked, randomized, multicenter, 12-week, two-period (6 weeks each), crossover design. One hundred fifty-two patients with open-angle glaucoma or ocular hypertension were randomized to receive either timolol maleate gel-forming solution QD or levobunolol BID for 6 weeks, followed by a crossover to the alternate treatment. IOP and heart rate were measured at morning trough and peak during weeks 3, 6, 9, and 12. Timolol maleate gel-forming solution QD was comparable to levobunolol BID in reducing IOP at peak and trough. Although the effects on peak heart rate were similar between the two medications, the effect on trough heart rate of timolol maleate gel-forming solution QD was significantly less than that of levobunolol BID (P = 0.001). The incidence of ocular burning and stinging was comparable between the two treatments. Patients experienced significantly more blurred vision when using timolol maleate gel-forming solution than when using levobunolol (P = 0.013). Overall, more patients experienced at least one adverse event when using timolol maleate gel-forming solution. Timolol maleate gel-forming solution QD is as efficacious in reducing IOP as levobunolol BID.

A study of losartan, alone or with hydrochlorothiazide vs nifedipine GITS in elderly patients with diastolic hypertension.

We conducted a randomised, double-blind, parallel design study comparing the efficacy and tolerability of the angiotensin II receptor antagonist, losartan, alone or with low-dose hydrochlorothiazide (HCTZ) to the dihydropyridine calcium channel blocker, nifedipine GITS (gastro-intestinal therapeutic system), in elderly patients (> or =65 years old) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg. After a placebo wash out period, 140 patients were randomly assigned to receive either losartan 50 mg or nifedipine GITS 30 mg. Patients were evaluated at 4-week intervals during a 12-week treatment period. Patients receiving losartan had HCTZ 12.5 mg added and increased to 25 mg to reduce DBP <90 mm Hg. Patients receiving nifedipine GITS had their dose increased to 60 mg and 90 mg to reduce DBP <90 mm Hg. Efficacy, tolerability and quality of life were assessed during the 12 weeks on each regimen. Patients treated with the losartan regimen (n = 73) had reductions in trough sitting DBP of -10, -13, and -13 mm Hg after 4, 8, and 12 weeks of therapy, respectively. Patients receiving the nifedipine GITS regimen (n = 67) had DBP reductions of -14, -15, and -15 mm Hg, respectively. There were no significant differences in the DBP response between the treatment groups except at week 4 (P < 0.05). Similar reductions in systolic BP (SBP) between the two treatment groups were observed at all time points. The percentages of patients in the two treatment groups reaching goal DBP (<90 mm Hg or DBP > or =90 mm Hg with a reduction from a baseline of > or =10 mm Hg) were comparable (81% on the losartan regimen and 90% on the nifedipine GITS regimen). There were significantly more adverse events reported in patients receiving nifedipine GITS when compared to the losartan regimen (54% vs 36%, P < 0.05). A patient-reported symptom inventory also showed that swollen ankles was bothersome in significantly more patients treated with the nifedipine GITS regimen when compared to the losartan regimen (24% vs 5%, P = 0.001). Thus, in elderly patients with diastolic hypertension, a regimen of losartan alone or with HCTZ has similar efficacy to a regimen of nifedipine GITS with greater tolerability and less symptom bother due to swollen ankles.

An open multicenter trial of Sinemet CR in levodopa-naive Parkinson's disease patients.

It has been proposed that initiation of anti-Parkinson therapy with continuous release formulations of Sinemet might prevent or delay the development of adverse effects associated with chronic levodopa therapy employed in standard formulations. In anticipation of a prospective study comparing Sinemet to Sinemet CR in previously untreated Parkinson's disease patients, we evaluated Sinemet CR as primary therapy in 45 levodopa-naive Parkinson's disease patients in a 12 week, open-label, multi-center study. At the conclusion of the study, optimal results were obtained with levodopa administered as Sinemet CR in a total daily dose of 497 mg divided into 2.4 doses per day. Statistically significant improvement compared to baseline was observed for total Parkinson's score as well as each of rigidity, tremor, bradykinesia, gait and postural stability. Statistically significant improvement was also noted in total disability as well as in each of its components. Adverse experiences were mild and transient and no significant laboratory abnormalities were encountered. We conclude that a daily dose of 1 to 1.5 tablets b.i.d. of Sinemet CR as primary therapy for patients with Parkinson's disease is well tolerated and provides effective therapy.

Effect of MK-458 (HPMC) in Parkinson's disease previously untreated with dopaminergic drugs. A double-blind, placebo-controlled multicenter study.

Ninety-four patients with early Parkinson's disease were investigated in a double-blind, placebo-controlled evaluation of MK-458 [hydroxypropyl methylcellulose/lactose matrix (HPMC)], a sustained release formulation of a novel naphthoxazine compound with selective D-2 dopamine receptor agonism. Patients were previously untreated with dopaminergic drugs. Efficacy was assessed by clinical rating scales and by patient self-evaluation. MK-458 (HPMC) caused a significant decrease in most parkinsonian symptoms. Though disability rating scores were lowered by the drug, the scores did not differ significantly from placebo. However, statistically significant improvement occurred with MK-458 (HPMC) on both the physician and the patient global assessments. Adverse reactions such as nausea and vomiting, sedation, confusion, and hallucinations occurred more with MK-458 (HPMC) than with placebo. MK-458 (HPMC) possesses antiparkinsonian efficacy in early Parkinson's disease; however, side-effects are frequently associated with its use. Selective D-2 receptor agonists, such as MK-458 (HPMC), may not be the ideal treatment as monotherapy for Parkinson's disease.

Omeprazole or ranitidine plus metoclopramide for patients with severe erosive oesophagitis. A cost-effectiveness analysis.

The objective of this study was to evaluate the clinical and economic effects of 2 clinical strategies for treating severe (grade II and above) erosive oesophagitis or poorly responsive gastro-oesophageal reflux disease. A single-blind, randomised controlled trial of up to 8 weeks' duration was undertaken comparing omeprazole with ranitidine plus metoclopramide in patients with severe and symptomatic erosive oesophagitis (endoscopic grade II and above). Two cost-effectiveness ratios were calculated: cost per healed patient and cost per symptom-free day. The study perspective was that of the payer or insurer of medical care. Healing rates were significantly higher among omeprazole-treated patients than among those who received ranitidine/metoclopramide at 4 weeks (68.5% vs 30.4%; p < 0.01) and overall (81.5% vs 45.7%; p < 0.01). Overall, mean gastrointestinal-related direct medical costs per healed patient were lower for the omeprazole group ($US189.60) than for the ranitidine/metoclopramide group ($US319.28). The incremental cost of an additional cure with omeprazole compared with ranitidine/metoclopramide was $US24.05. The overall average cost per symptom-free day was lower in the omeprazole group ($US7.88) than in the ranitidine/metoclopramide group ($US10.81). The incremental cost to obtain an additional symptom-free day with omeprazole, compared with ranitidine/metoclopramide, was $US1.41. In conclusion, superior efficacy at comparable cost is achieved by omeprazole compared with ranitidine/metoclopramide in the treatment of patients with severe erosive oesophagitis.