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Biomedical subjects

A I Goldberg

Publications and source records attributed to A I Goldberg.

At least 19 recordsLinked to original sources

Well being, work environment and work accidents.

We examine factors that influence accident proneness among employees. We agree that the determinants of accident proneness include organizational, emotional and personal factors. Using logistic regression we estimated three models, and their predictability for accident proneness among sample of 200 injured workers interviewed upon entering hospital emergency wards in Israel. Work injuries were not contingent on age, religion, nor education. The effects of gender were strong but non-significant. Subcontracted and higher-paid workers are more likely to get repeat injuries. Prior injury experience sensitized employees to stronger perceptions of risk associated with unsafe practices. Large family households, ameliorates stress feelings and lessens the likelihood of accident proneness while poor housing conditions have the opposite effect. The full model demonstrates considerable prediction of injuries when focusing on type of employment, personal income level, being involved in dangerous jobs, emotional distress and a poor housing environment. The model contains most of the significant results of interest and provides a high level of predictability for work injuries.

Accident Proneness↗

Physician assessments of patient compliance with medical treatment.

In a study of how physicians evaluate patient compliance, practitioner judgments were compared to the self-reports of 138 adult patients receiving treatment for pulmonary diseases at an outpatient clinic. The research found no significant relationship between physician evaluations of compliance and accounts given by the same patients. The conclusions of physicians regarding patient compliance proved to be influenced by their views on the seriousness of the condition and the effectiveness of treatments, but patient reports were different. Physicians clearly have difficulties in appraising the compliance behavior of their patients.

Adolescent↗

Comparative antihypertensive effects of losartan 50 mg and losartan 50 mg titrated to 100 mg in patients with essential hypertension.

The antihypertensive activity of losartan potassium (losartan, Cozaar), an angiotensin II receptor antagonist, was evaluated in a parallel 12-week, double-blind, placebo-controlled trial in hypertensive patients with mild-to-moderate hypertension. After a 4-week, single-blind, placebo lead-in period, which included monitoring of baseline variables, 366 patients with a group mean sitting diastolic blood pressure of 101 +/- 5 (s.d.) mmHg were assigned randomly to one of three treatment groups: placebo, losartan 50 mg, or losartan 50 mg with the option to titrate to 100 mg after the first 6 weeks if the target sitting diastolic blood pressure (< 90 mmHg) was not reached. To assess the potential blood pressure response associated with the act of titration, patients in the placebo and losartan 50 mg treatment groups with a sitting diastolic blood pressure of > or = 90 mmHg at week 6 were mock titrated (changed to a new tablet containing the same study medication and dose). Sitting diastolic blood pressure was also evaluated at the end of the trial during a 1-week off-drug period to assess for rebound hypertension. At week 6, patients in the active-drug-treatment arms experienced significantly greater peak (6 h post-dose) and trough (24 h post-dose) reduction in systolic and diastolic sitting blood pressures compared with placebo (p < or = 0.01). Based on trough blood pressures at week 12, active drug (both arms) was more effective than placebo in lowering sitting diastolic blood pressure, with a very small additional benefit associated with increasing the dose of losartan to 100 mg in patients who did not reach the target blood pressure after the first 6 weeks on losartan 50 mg. There was no evidence of rebound hypertension during 1 week after withdrawal of losartan. The correlation between baseline plasma renin activity and reduction in peak and trough blood pressure at week 12, although statistically significant, was generally poor in the active treatment groups. In this trial, losartan was efficacious and well tolerated, and was similar to placebo with regard to adverse-experience profile. Adverse experiences that could reasonably be related to excessive lowering of blood pressure were not common and there was no evidence of rebound hypertension.

Antihypertensive Agents↗

Losartan and low-dose hydrochlorothiazide in patients with essential hypertension. A double-blind, placebo-controlled trial of concomitant administration compared with individual components.

BACKGROUND: Angiotensin II acts at the cellular level through specific angiotensin II subtype I, AT-1 receptors. Losartan is the first of a new class of antihypertensive agents that specifically block angiotensin II at AT-1 receptors. By acting on complementary and different pharmacologic mechanisms, the concomitant use of low doses of hydrochlorothiazide with losartan may offer an additive antihypertensive activity with fewer adverse experiences. METHODS: This double-blind study evaluated losartan concomitantly administered with hydrochlorothiazide as initial therapy in 703 patients with essential hypertension. RESULTS: The greatest reduction in blood pressure was observed in the 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide group (17.2 mm Hg in sitting systolic blood pressure and 13.2 mm Hg in sitting diastolic blood pressure [P < or = .001]), and the effects of the two components appeared to be additive. Seventy-eight percent of the patients treated with 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide had an excellent or good antihypertensive response (sitting diastolic blood pressure < 90 mm Hg or > or = 90 mm Hg with a reduction of 10 mm Hg or more). Peak (6 hours after dosing) and trough placebo-adjusted ratios for the losartan-hydrochlorothiazide groups ranged from 62% to 85%, indicating that there was a smooth reduction in sitting diastolic blood pressure that was sustained over 24 hours. The most common clinical adverse experiences (> or = 4%) that occurred with an incidence slightly greater than that reported by the placebo-treated patients were headache, asthenia or fatigue, dizziness, sinusitis, and upper respiratory infection. CONCLUSION: The concomitant administration of losartan potassium, 50 mg, with 12.5 mg of hydrochlorothiazide once daily produced an additive reduction in trough sitting systolic and diastolic blood pressure and was well tolerated.

Adult↗

Comparative effects of combination drug therapy regimens commencing with either losartan potassium, an angiotensin II receptor antagonist, or enalapril maleate for the treatment of severe hypertension.

OBJECTIVE: To compare the efficacy and safety of a regimen of losartan potassium (losartan) and a regimen of enalapril maleate (enalapril) in a randomized trial of patients with severe hypertension in which the initial treatments were blinded. DESIGN AND METHODS: Seventy-five patients, 23-74 years of age, with sitting diastolic blood pressure of 115-130mmHg, were enrolled in a 12-site multicenter study. The primary efficacy parameters were the change in trough systolic and diastolic blood pressure, as well as response to treatment in terms of categories of hypertensive response. RESULTS: A gradual reduction in mean sitting diastolic blood pressure was observed in all patients treated from week 1 to 12 (10-29mmHg for the losartan regimen and 14-32 mmHg for the enalapril regimen). At week 4, a substantial number of patients remained on monotherapy at either the initial dose or double the dose of losartan (52%) or enalapril (72%). The blood pressure curves for each treatment were parallel over time. The enalapril-based regimen elicited a statistically significantly greater reduction in blood pressure than the losartan-based regimen, although the mean differences in the blood pressure response between the two treatment groups was small. Based on sitting diastolic blood pressure < 90 mmHg or a reduction in blood pressure of at least 10 mmHg, 98% of the patients assigned to the losartan regimen and 100% of the patients assigned to the enalapril regimen had a satisfactory response with a regimen of one to three antihypertensive drugs. Headache was the most common adverse experience in both treatment groups (occurring in 22% of patients assigned to the losartan regimen and 20% of patients assigned to the enalapril regimen). CONCLUSIONS: In this study, the losartan-based regimen effectively lowered blood pressure, was generally well tolerated, and was generally similar to the enalapril-based regimen in the treatment of patients with severe hypertension.

Adult↗

Controlled trial of losartan given concomitantly with different doses of hydrochlorothiazide in hypertensive patients.

The purpose of this trial was to evaluate the antihypertensive efficacy of the concomitant administration of selected doses of hydrochlorothiazide (HCTZ) on a background of losartan potassium (losartan) 50 mg, a selective angiotensin II receptor antagonist. Patients with essential hypertension ( > or = 95 mmHg inclusion criteria) with a mean sitting diastolic blood pressure (SiDBP) of 105 +/- 0.4 (S.E.) mmHg entered a 4-week, single-blind monotherapy period of losartan 50 mg once daily. At the end of the monotherapy period, patients whose blood pressure was adequately controlled were discontinued. Patients whose blood pressure was partially controlled based on a SiDBP > 92 mmHg entered a 12 week double-blind period and were randomly assigned to either receive placebo (n = 80), HCTZ 6.25 mg (n = 80), HCTZ 12.5 mg (n = 72) or HCTZ 25 mg (n = 80) in addition to losartan 50 mg. During the losartan monotherapy period, there was a 4 mmHg fall in SiDBP with a further fall of 5 mmHg after 12 weeks of double-blind therapy in the losartan/placebo control group. Based on the between group differences in BP change from the end of the losartan monotherapy period (baseline) to end of 12 weeks of double-blind, the concomitant administration of a very low dose of HCTZ (6.25 mg) with losartan did not significantly decrease SiDBP compared with the fall in blood pressure in the losartan/placebo control group (diff. between groups = -2 (95% C.I.[-4.1, +0.9] mmHg)). However, the concomitant administration of HCTZ 12.5 or 25 mg with losartan 50 mg resulted in significantly different (p < or = 0.05) reductions in diastolic blood pressure compared to the losartan/placebo group (diff. between groups = -4 (95% C.I. [-6.3, -1.1] mmHg) for 12.5mg combination group; -6 (95% C.I. [-8.3, -3.3]) mmHg for the HCTZ 25 mg combination group). The proportions of patients treated with losartan plus HCTZ 12.5 mg or 25 mg that achieved a trough SiDBP < 88 mmHg or a trough SiDBP > or = 88 mmHg but with a decrease of at least 5 mmHg were 71% and 83%, respectively. The percentage of clinical adverse experiences that were considered drug-related as assessed by the investigator were generally similar across all treatment groups. There were no reports of orthostatic hypotension in any of the treatment groups. Changes in serum glucose, potassium and uric acid were not appreciably different amongst the treatment groups. In summary, in patients with predominantly moderate to severe essential hypertension, the addition of HCTZ 12.5 mg or 25 mg to losartan 50 mg produced effective control of blood pressure in a substantial majority of patients who only partially responded to losartan monotherapy. There were no differences amongst the treatment groups with respect to drug-related adverse experiences in this trial.

Adult↗

Global efficacy and tolerability of losartan, an angiotensin II subtype 1-receptor antagonist, in the treatment of hypertension.

Losartan is the first drug of a new therapeutic class, the angiotensin II (A II)-receptor antagonists, to be clinically studied and become available for the management of hypertension. Clinical experience with losartan from worldwide, double-blind, controlled studies has been obtained in more than 2900 hypertensive patients treated with losartan alone or in combination with hydrochlorothiazide, with 1700 patients receiving treatment for more than a year. The efficacy of losartan was evaluated in the young and old, in different degrees of hypertension, in blacks and nonblacks, and in patients with renal impairment. Tolerability parameters were assessed by subgroup as well. In dose-ranging studies, 50 mg once daily has generally been shown to produce near maximum effects and a dose of 100 mg does not produce additional effects. The efficacy of losartan (50 to 100 mg once daily) has been compared to atenolol (50 to 100 mg once daily), felodipine ER (5 to 10 mg once daily), and enalapril (20 mg once daily). The blood pressure-lowering effect of losartan was comparable to felodipine, enalapril, and atenolol. The efficacy of losartan was demonstrated using ambulatory blood pressure monitoring, which showed that losartan 50 mg once daily produced gradual reduction in blood pressure, providing 24-h control without affecting the body's circadian rhythm. In subgroups of study populations, no differences in efficacy were noted with respect to age, gender and the severity of hypertension. No initial dosage adjustment is necessary in the elderly and patients with renal impairment (even those on dialysis). Among blacks, the mean response of losartan was lower, which is not surprising given the lesser activation of the renin-angiotensin system in this population. A subgroup safety and tolerability analysis confirmed that there were no important differences in adverse events when assessed by age, race, or gender. The data obtained from controlled clinical trials conducted with losartan, the first A II-receptor antagonist, has shown that a single daily 50-mg dose provides adequate 24-h control of blood pressure in most patients with comparable efficacy to other classes and is well tolerated.

Adult↗

Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension.

This report presents data on the safety and tolerability of losartan potassium (losartan), a selective antagonist of the angiotensin II AT-1 receptor, in approximately 2,900 hypertensive patients treated in double-blind clinical trials. In these studies, headache (14.1%), upper respiratory infection (6.5%), dizziness (14.1%), asthenia/fatigue (3.8%), and cough (3.1%) were the clinical adverse experiences most often reported in patients treated with losartan. These adverse experiences were also frequently reported in patients receiving placebo: 17.2%, 5.6%, 2.4%, 3.9%, and 2.6%, respectively. Dry cough as an adverse event was reported in 8.8% of patients treated with angiotensin-converting enzyme inhibitors, and in 3.1% and 2.6% of patients treated with losartan or placebo, respectively. Only dizziness was considered "drug-related" more often in losartan-treated (2.4%) than placebo-treated (1.3%) patients. In controlled clinical trials, losartan was better tolerated than other antihypertensive agents as determined by the incidence of patients reporting any drug-related adverse experiences. Rates of discontinuation due to clinical adverse experiences in patients who received losartan monotherapy or losartan+hydrochlorothiazide were 2.3% and 2.8%, respectively, compared with placebo (3.7%). No laboratory adverse experiences were unexpected or of clinical importance. First-dose hypotension rarely occurred with losartan or with losartan plus hydrochlorothiazide, and withdrawal effects such as rebound hypertension were not observed in clinical trials. There were no clinically important differences in the clinical or laboratory safety profiles in the demographic subgroups for age, gender, or race. In controlled clinical trials, losartan demonstrated an excellent tolerability profile.

Adult↗

Blood pressure effects of the angiotensin II receptor blocker, losartan.

BACKGROUND: Losartan potassium, the first nonpeptide selective blocker of angiotensin II at the AT1 receptor, has been shown to exhibit clinical antihypertensive effects. The aim of the present study was to characterize the efficacy and duration of action of losartan by ambulatory blood pressure monitoring. METHODS: The study was performed in nonblack hypertensive patients whose baseline untreated clinical diastolic blood pressures were 95 mm Hg or higher and whose average 24-hour ambulatory diastolic blood pressures were 85 mm Hg or higher. Patients were randomized, double-blind, into four treatment groups: placebo (n = 32) or losartan, 50 mg once daily (n = 29), 100 mg once daily (n = 30), or 50 mg twice daily (n = 31). Clinical and 24-hour ambulatory blood pressures were measured at baseline (off treatment for at least 4 weeks) and after 4 weeks of treatment. RESULTS: By clinical sphygmomanometer measurements at the end of the 24-hour or 12-hour dosing intervals (trough), all three losartan dosages were significantly more effective than placebo at decreasing systolic and diastolic blood pressures. By average 24-hour ambulatory systolic/diastolic blood pressure measurements, the decreases produced were 0.0/0.2 mm Hg for placebo and 9.2/6.9, 9.9/6.4, and 13.2/8.5 mm Hg, respectively, for losartan, 50 mg once daily, 100 mg once daily, and 50 mg twice daily. All drug effects were different from placebo (P < .01). The effects of losartan, 50 mg twice daily, were not significantly different from those of losartan, 100 mg once daily, but, as expected, the effects were greater than those of losartan, 50 mg once daily (P < .05). Addition of hydrochlorothiazide, 12.5 mg/d, during an additional 2-week treatment period in patients whose clinical diastolic blood pressure remained at 85 mm Hg or higher while receiving monotherapy produced additional and clinically meaningful blood pressure decrements that were similar in all four treatment groups. There was no clinically important difference in the incidence of adverse events among the losartan-treated and placebo groups [corrected]. CONCLUSION: Ambulatory blood pressure monitoring, which virtually eliminated antihypertensive placebo responses, demonstrated clear 24-hour efficacy for losartan, 50 mg once daily, as well as for higher doses of 100 mg once daily and 50 mg twice daily. This AT1 receptor blocker had antihypertensive effects that appeared additive when combined with low-dose diuretic therapy. Losartan was generally well tolerated.

Adult↗

Efficacy and tolerability of losartan potassium and atenolol in patients with mild to moderate essential hypertension.

The objective of this study was to compare the antihypertensive efficacy and tolerability of losartan potassium (losartan) and atenolol in patients with mild-to-moderate essential hypertension. This was a multinational, prospective, randomized, 12-week double-blind parallel study with a follow-up of 4 to 10 days posttreatment to assess any adverse effects of abrupt therapy withdrawal. Two hundred two patients were randomized (2:1) to treatment with losartan or atenolol, 50 mg once daily. Patients were titrated after 6 weeks to 100 mg once daily if their blood pressure was uncontrolled (sitting diastolic blood pressure > or = 90 mm Hg). Trough sitting diastolic blood pressure reductions at weeks 6 and 12 were similar in both the losartan (-9.2 mm Hg and -8.3 mm Hg) and atenolol (-10.8 mm Hg and -10.1 mm Hg) groups and a similar percentage of patients responded to each drug. Both agents were generally well tolerated, although eight patients (two patients taking losartan, and six taking atenolol) were withdrawn because of clinical adverse events (P < or = .05). Reduction in pulse rate from baseline averaged 10 beats/min in the atenolol group with no pulse rate reduction observed in the losartan group (P < .01). No evidence of rebound hypertension was observed in either group. In conclusion, losartan was as efficacious as atenolol in blood pressure reduction, and was at least as well tolerated.

Adult↗

A randomized, placebo-controlled, double-blind, parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension.

The efficacy and safety of various doses of losartan potassium, a specific and selective angiotensin II receptor antagonist, were compared with those of placebo and enalapril maleate 20 mg in patients with mild to moderate essential hypertension in a randomized, double-blind, parallel study. We randomly allocated 576 patients at the end of a 4-week placebo baseline period to 8 weeks of once-daily double-blind treatment with losartan potassium 10, 25, 50, 100, or 150 mg, enalapril maleate 20 mg, or placebo. After 8 weeks of treatment, mean reductions from baseline in supine systolic/diastolic pressure 24 hours after dosing (trough) for losartan potassium 10, 25, 50, 100, and 150 mg, enalapril maleate 20 mg, and placebo were 7.6/7.9, 7.8/6.8, 13.0/10.1, 8.9/9.9, 10.5/9.7, 14.7/11.2, and 3.8/5.6 mm Hg, respectively. Compared with mean changes in supine diastolic pressure in the placebo group, losartan potassium 50 to 150 mg and enalapril maleate 20 mg produced clinically important and statistically significant reductions (P < or = .01) in blood pressure. At 24 hours after dosing, the blood pressure changes obtained with losartan potassium 50 mg were essentially identical to those obtained with enalapril maleate 20 mg. While there was a dose-related effect with losartan potassium from 10 to 50 mg at peak (6 hours after dosing), doses of 10 and 25 mg were not consistently different from placebo 24 hours after dosing. To assess the once-daily effect of losartan potassium, trough-to-peak ratios of the mean changes in supine diastolic pressure after 8 weeks of treatment were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of losartan on a background of hydrochlorothiazide in patients with hypertension.

The purpose of this multicenter trial was to compare the antihypertensive efficacy and safety of losartan potassium (losartan), a selective angiotensin II receptor antagonist, when added to hydrochlorothiazide in hypertensive patients whose blood pressure was not adequately controlled by 25 mg hydrochlorothiazide monotherapy. After a 4-week monotherapy period of 25 mg hydrochlorothiazide, 304 patients with trough (22 to 26 hours postdose) sitting diastolic pressure between 93 and 120 mm Hg were maintained on 25 mg hydrochlorothiazide and randomized double-blind into treatment arms consisting of either 25, 50, or 100 mg losartan or placebo once daily for 12 weeks. The reductions in sitting diastolic pressure for patients treated with 25, 50, or 100 mg losartan concomitantly administered with 25 mg hydrochlorothiazide were significantly greater (P < or = .05) than the reductions observed in the 25 mg hydrochlorothiazide plus placebo group beginning 1 week after randomization. The antihypertensive response in all groups was greater at week 3 than week 1, with some additional decrease in blood pressure in some groups at later times. Sitting systolic pressures were also significantly reduced in each group over time. Standing blood pressures at week 12 were similar to sitting blood pressures. A dose-response relationship to losartan was observed in this patient population. The percentages of the total drug-related clinical adverse experiences as assessed by the investigator were generally similar in the 25, 50, and 100 mg losartan plus 25 mg hydrochlorothiazide groups (10.3%, 24.4%, and 20.0%, respectively) compared with the placebo plus 25 mg hydrochlorothiazide group (24.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Randomised, double-blind, parallel study of the anti-hypertensive efficacy and safety of losartan potassium compared with felodipine ER in elderly patients with mild to moderate hypertension.

This study investigated the anti-hypertensive efficacy and tolerability of once-daily losartan potassium (50 mg titrated to 100 mg), an angiotensin II receptor antagonist, compared with once daily felodipine extended release (ER) (5 mg titrated to 10 mg), a calcium channel blocker, after 12 weeks of therapy in elderly hypertensive patients. Following a 4-week, single-blind, placebo baseline period, qualifying patients were randomly allocated to 12 weeks of double-blind treatment with losartan potassium or felodipine ER. After 6 weeks, patients with a 24 h post-dose sitting diastolic blood pressure > or = 90 mm Hg had their dose doubled for the remaining 6 weeks. At 6 weeks, there was a greater BP response for felodipine ER than losartan potassium in elderly patients with mild to moderate hypertension. However, after 12 weeks of therapy, losartan potassium reduced BP as effectively as felodipine ER with no differences in mean BP reduction or anti-hypertensive response category between treatment groups. In this study, both treatments were well tolerated; felodipine ER was associated with a numerically higher incidence of headache and oedema while the incidence of asthenia was numerically higher in losartan-treated patients.

Aged↗

Losartan potassium as initial therapy in patients with severe hypertension.

This 12-week, open-label study was conducted to gain experience with losartan potassium, an angiotensin II receptor antagonist, in patients with severe hypertension. Patients were either untreated or withdrawn from current therapy for at least 48 h before initiation of losartan 50 mg once daily. Patients were titrated to 100 mg as needed to achieve a goal of sitting diastolic blood pressure (SiDBP) 90 or 95 mm Hg. Hydrochlorothiazide (12.5 mg once daily titrated to 25 mg) was added and followed by either a dihydropyridine calcium channel blocker (CCB) and/or atenolol, if BP was not controlled. A total of 179 patients with a pretreatment mean baseline BP of 172 +/- 17/112 +/- 18 mm Hg enrolled in the trial and BP was recorded 24 h after dosing at baseline and weeks 2, 4, 8 and the final week (10-12 weeks). The mean reductions in SiDBP from baseline were 7.3, 9.3, 15.9 and 18.9 mm Hg, respectively, and these changes from baseline were statistically significant, P < 0.001. At the end of the trial, 22% of patients remained on losartan monotherapy, 30% required the addition of hydrochlorothiazide (HCTZ) and 31% required both HCTZ and a CCB; 11% required HCTZ and atenolol while 4% required HCTZ, a CCB and atenolol; 2% of patients were on regimens not specified by the protocol. SiDBP < 90 mm Hg was achieved in 68 patients by the final visit; 24% of these patients were treated with losartan monotherapy (50 or 100 mg), 41% achieved control with the addition of HCTZ (12.5 or 25 mg) and 24% required triple therapy which included losartan, HCTZ and a CCB. As assessed by the investigator, 25% of the patients in the study had drug-related clinical adverse experiences. Headache was the most frequently reported clinical adverse event (26% of patients). No clinically significant changes in laboratory parameters were observed. It is concluded that losartan potassium can be used as initial therapy for patients with severe hypertension and can be administered concurrently with hydrochlorothiazide, calcium channel blockers and atenolol.

Adolescent↗