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At least 379 records · Page 21Linked to original sources
PubMed1998

Impact of antiretroviral combination therapies on AIDS surveillance reports in Switzerland. Swiss HIV Cohort Study.

BACKGROUND: AIDS reporting in Switzerland is mandatory by law. For the first time since the beginning of the epidemic, health authorities observed a decline in AIDS surveillance reports, from 545 new cases in 1995 to 459 in 1996, a decrease of 86 cases. OBJECTIVE: To examine the extent to which this decline in AIDS surveillance reports is attributable to the introduction of antiretroviral combination therapy. PATIENTS AND SETTING: Swiss HIV Cohort Study, a multicentre cohort of adult HIV-infected patients with national coverage. Participants at risk of developing a first AIDS-defining event, defined as persons with a CD4 cell count below 200 x 10(6)/l or in clinical stage B, were studied. METHODS: A parametric statistical survival model was used to estimate the number of AIDS cases expected in the absence of combination therapies. Taking reporting delays into account, the effect of the introduction of combination therapies in the cohort on national AIDS reports was estimated from the difference between the number of expected and observed cases. RESULTS: A total of 4915 participants contributed 10755 person-years and 2366 initial AIDS events. Between 1990 and 1994, about 35% received antiretroviral therapy, predominantly monotherapy. In 1995 and 1996, the prevalence of antiretroviral therapy increased steadily due to the introduction of dual and triple combinations. The mid-year prevalence of use of combination therapies was 6% in 1994, 13% in 1995, and 48% in 1996. The difference between expected and observed cases per half-year increased from 12 in the first 6 months of 1994 to 69 in the second half of 1996. Taking reporting delays into account, we estimated that 43 (95% confidence interval, 17-69) of the deficit of 86 reports could be attributed to combination therapies. CONCLUSION: The introduction of antiretroviral combination therapies in a single cohort study explained 50% of the decline in national AIDS surveillance reports. Monitoring the use and effectiveness of antiretroviral therapy must become an important component of AIDS surveillance systems.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Doxazosin as combination therapy for patients with stage 1 and stage 2 hypertension.

The purpose of this paper is to review the role of doxazosin, a long-acting alpha(1)-blocker, as a component of combination therapy for patients with stage 1 and stage 2 hypertension and for patients with concomitant hypertension and hyperlipidemia or glucose intolerance. Recent studies that evaluated doxazosin as combination therapy in the treatment of patients with inadequately controlled hypertension and patients with concomitant hypertension and other disorders were reviewed. Data extraction was based on the tolerability and efficacy data of doxazosin in patients with hypertension. Compared with placebo, doxazosin combination therapy leads to significant improvements in sitting and standing blood pressure. Doxazosin is well tolerated, with only minor adverse effects (e.g., headache, dizziness) as the most commonly reported treatment-related complications. The studies described demonstrate that doxazosin is effective as combination therapy for patients with stage 1 and stage 2 hypertension. The positive effects of doxazosin on serum lipids make combination therapy with doxazosin an attractive treatment option for patients who have concomitant hyperlipidemia or glucose intolerance.

Antihypertensive Agents↗
PubMed2005

[Analysis of the scientific evidence of the combination therapy in benign prostatic hyperplasia].

OBJECTIVE: The analysis of the scientific evidence of the combination therapy in Benign Prostatic Hyperplasia (BPH). METHODS: 5 published studies about combination therapy in BPH were analysed following the criteria of the Evidence Based Medicine (EBM). Hypothesis, variables, internal validity, results relevance, and the external validity of every study were analysed. RESULTS: Symptoms changes and maximal flow rate (Qmax) improvement were evaluated in four studies and only one analysed the BPH progression. Inclusion and exclusion criteria were similar in the 5 studies. The main reasons of a poor internal validity in 3 studies were the short follow-up, the missing percentage, the absence of a placebo group and a dosage bias. External validity were decreased in the 5 studies by the exclusion criteria and in 3 of them because high doses of alpha-blocker were given to achieve a therapeutic effect. The study with the highest scientific evidence (MTOPS) is the only that offers confidence intervals and number needed to treat. CONCLUSIONS: The Qmax and the symptoms improvement found in all the studies has a moderate clinical relevance. MTOPS study shows that BPH progression has a low incidence that can be highly reduced by means of combination therapy.

Adrenergic alpha-Antagonists↗
PubMed2006

Combination therapy.

So far, off-label recommendation of a combination therapy is mainly based on phase II study evidence and on largely accepted expert opinions. Combination therapy represents a new, more global strategy, to increase the possible benefits with the combined use of already available disease-modifying therapies or with other new agents, having an acceptable theoretical rationale and a good safety and efficacy profile. The therapeutic strategies of the near future will try to select among different and individualised combinations of drugs, with distinct mechanisms of action, and possibly with synergistic activity, to maximise benefits and minimise risks. The combination approach is at present particularly recommended for more aggressive forms of multiple sclerosis (MS) and for non-responders to available drugs, although the theoretical rationale and accumulated experience would suggest its use in all MS patients right from the beginning of the disease.

Clinical Trials, Phase II as Topic↗
PubMed2005

[Beneficial effects of combination therapy with losartan and low-dose hydrochlorothiazide in the treatment of essential hypertension].

Although strict blood pressure control is essential for the prevention of cardiovascular disease, there are many hypertensive patients whose current hypertension treatments are inadequate. Therefore, we designed a clinical study to evaluate the efficacy achieving a blood pressure reduction by combination therapy with losartan and a low-dose diuretic. In the 10 hypertensive patients treated with candesartan at 8 mg/day for more than 2 months, combination therapy with losartan at 50 mg/day and hydrochlorothiazide (HCTZ) at 12.5 mg/day was conducted for 3 months after the cessation of treatment with candesartan. Either immediately before the onset of combination therapy or 3 months after the treatment, the 24 hour ambulatory blood pressure(ABP) and pulse rate were measured every 30 minutes. Pulse wave velocity(PWV) and homeostasis model assessment insulin resistance index(HOMA-R) with fasting blood were also measured after 3 months. In the treatment with candesartan, the ABP was 134.4 +/- 8.7/88.1 +/- 6.1 mmHg at 24 hours, 139.7 +/- 8.4/91.3 +/- 7.1 mmHg in the daytime, 123.8 +/- 11.6/81.6 +/- 5.9 mmHg in the nighttime, and 139.3 +/- 10.3/92.3 +/- 7.3 mmHg in the early morning(6 : 00-8 : 00). After the switch to the combination therapy with losartan and HCTZ, the blood pressure changed to 126.8 +/- 9.3/81.6 +/- 7.0 mmHg (p < 0.05/p < 0.05) at 24 hours, 130.6 +/- 12.0/84.2 +/- 8.5 mmHg (p < 0.05/p < 0.05) in the daytime, 119.3 +/- 8.7/76.6 +/- 6.5 mmHg (NS/NS) in the nighttime, and 129.7 +/- 11.7/84.0 +/- 9.2 mmHg(p < 0.05/p < 0.05) in the early morning. However, both the changes in heart rate and PWV, and the differences in blood glucose, lipid and HOMA-R were not significant. Nonetheless, the blood pressure control for 24 hours was better using the combination therapy with losartan at 50 mg/day and HCTZ of 12.5 mg/day than in the treatment with candesartan at 8 mg/day alone. Since losartan decreases uric acid unlike other angiotensin receptor blockers, the combination therapy of losartan and a diuretic can be expected to provide one of the best therapies for essential hypertensive patients.

Adult↗
PubMedDate not supplied

Efficacy of combination therapy with amlodipine besylate/benazepril hydrochloride for lowering systolic blood pressure in stage 2 hypertension.

The Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study compared daily treatment with combination amlodipine besylate/benazepril hydrochloride 5/20 mg, amlodipine besylate 5 mg, and benazepril hydrochloride 20 mg in 505 patients aged 55 years of age or older with stage 2 hypertension (systolic blood pressure [BP] > or =160 and < or =200 mm Hg and diastolic BP > or =60 and < or =100 mm Hg). BP and pulse pressure were assessed by conventional office BP measurements and 24-hour ambulatory BP monitoring. In this analysis, combination therapy was associated with significantly greater reductions in mean 24-hour BP, pulse pressure, and mean ambulatory BP during various time intervals compared with either monotherapy in the intent-to-treat population, in those with isolated and predominantly systolic hypertension, and in dippers and nondippers. Adverse event rates were low and similar in all treatment groups. This study demonstrated that combination therapy is superior to monotherapy in older patients with stage 2 systolic hypertension and is well tolerated.

Aged↗
PubMed1993

[Kasabach-Merritt syndrome. Intraoperative heparin therapy with follow-up combination therapy of heparin and ticlopidine for the control of intravascular coagulation].

A 39-year-old woman with Kasabach-Merritt syndrome (cavernous vascular malformations with disseminated intravascular coagulation) sustained a displaced fracture of the femoral shaft. Despite pronounced hypofibrinogenemia (< 0.1 g/l) there was no significant bleeding. The concentration of D dimer was raised to > 32 < 64 mg/l and that of prothrombin fragments F1 and F2 to > 10 nmol/l. The platelet count was 102,000/microliters and other coagulation parameters were normal or only slightly abnormal. The consumption coagulopathy was successfully controlled by continuous intravenous infusion of heparin (17,000 I.U./d) without need for clotting factor replacement, and was subsequently stabilized by combined treatment with low molecular weight heparin (5,000 I.U./d s.c.) and ticlopidine (250 mg twice daily by mouth). Oral therapy with acetylsalicylic acid alone or in combination with ticlopidine proved insufficient, being rapidly followed by a renewed fall in fibrinogen level and platelet count. The findings suggest that fibrin formation in the abnormal vascular territories was the principal pathogenetic factor in this case.

Abdominal Neoplasms↗
PubMed1989

Effect of combination therapy of radiation and local administration of OK-432 on a murine fibrosarcoma.

The effects of a combination therapy of radiation and local administration of OK-432, which is one of BRMs (biological response modifiers), were studied using a radioresistant murine fibrosarcoma with weak immunogenicity. Fifty percent tumor control doses were 83.5 (79.6-87.4) Gy in animals given radiation alone and 64.3 (57.9-71.0) Gy in animals given OK-432 immediately after radiation, indicating that this biological response modifier can enhance the radiation dose effectiveness by a factor of 83.5/64.3, that is, 1.30. Histological observations of treated tumors showed that the combination therapy induced a marked infiltration with lymphocytes and prominent degeneration and necrosis of the tumor cells. Examination of subsets of the infiltrating lymphocytes using the monoclonal antibodies showed that Lyt-2 positive lymphocytes were more abundant in the group given the combination therapy than in the radiation alone group on day 5 (p greater than 0.05). Two days later, Lyt-1, Lyt-2, and L3T4 positive lymphocytes increased in the group given the combination therapy, whereas these lymphocytes disappeared in the group given radiation alone.

Animals↗
PubMed1993

Combined therapy in human immunodeficiency virus-infected children--a 4-year experience.

From 1988 to 1991 the long-term efficacy of a combined therapy with a polyvalent immunoglobulin/cytomegalovirus (CMV) hyperimmunoglobulin, oral low dose zidovudine, oral cotrimoxazole or inhaled pentamidine was investigated in three groups of human immunodeficiency virus (HIV)-infected children. Group 1A consisted of three perinatally infected children with a CD4 cell decrease of > 400 cells/microliters per year. Group 1B were 17 perinatally infected children with a CD4 cell decrease of < 400 cells/microliters per year. Group 2 comprised eight haemophilic children infected by clotting factors. Despite combined therapy none of group 1A survived longer than 12 months showing a rapid loss of CD4 cell counts, progressive encephalopathy, wasting syndrome and severe bacterial, fungal and CMV reactivation. Under pure intravenous immunoglobulin (IVIG) therapy severe bacterial infections were seen in 1 of 12 children in group 1B. The majority of these patients showed increases or stabilisation of length and weight percentiles. In this group low dose zidovudine therapy was of benefit in HIV-associated neurological symptoms. Nevertheless combined therapy could not prevent further deterioration of CD4 cell counts. In group 2 severe bacterial infections were not seen under IVIG therapy. In this group a temporary increase (6 months) of CD4 cell counts under IVIG/zidovudine combined therapy occurred. Pneumocystis carinii pneumonia (PCP) prophylaxis with oral cotrimoxazole or inhaled pentamidine successfully prevented PCP in all three groups. Under CMV hyperimmunoglobulin (n = 22), ten out of ten patients did not acquire primary CMV infection, whereas CMV reactivations mainly located in the CNS could not be prevented in 5 of 12 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-Positive T-Lymphocytes↗
PubMed2003

Retreatment of hepatitis C non-responsive to interferon. A placebo controlled randomized trial of ribavirin monotherapy versus combination therapy with Ribavirin and Interferon in 121 patients in the Benelux [ISRCTN53821378].

BACKGROUND: Evidence based medicine depends on unbiased selection of completed randomized controlled trials. For completeness it is important to publish all trials. This report describes the first large randomised controlled trial where combination therapy was compared to placebo therapy and to ribavirin monotherapy, which has not been published until now. METHODS: One hundred and twenty one patients with chronic hepatitis C and elevated transaminases who did not respond to previous treatment with standard interferon monotherapy, were included from 16 centers in Belgium, the Netherlands and Luxembourg between 1992 and 1996. Patient poor-response characteristics were: genotype 1 (69%), HCV RNA above 2 x 10(6) copies/ml (55%) and cirrhosis (38%). Patients were randomized to 6 months combination therapy with interferon alpha-2b (3 MU tiw) and ribavirin (1000-1200 mg/day), 6 months ribavirin monotherapy (1000-1200 mg/day) or 6 months ribavirin placebo. The study was double blinded for the ribavirin/placebo component. One patient did not fit the entry criteria, and 3 did not start. All 117 patients who received at least one dose of treatment were included in the intention to treat analysis. RESULTS: At the end of treatment, HCV RNA was undetectable in 35% of patients on combination therapy and in none of the patients treated with ribavirin monotherapy or placebo. The sustained virological response rate at 6 months after therapy was 15% for patients treated with interferon and ribavirin. During the 6 months treatment period 13% of patients on interferon ribavirin combination therapy, 13% of patients on ribavirin monotherapy and 11% of patients on placebo withdrew due to side effects or noncompliance. At 24 weeks of treatment the mean Hb level was 85% of the baseline value, which means a mean decrease from 9.1 mmol/l to 7.8 mmol/l. The Hb levels at the end of treatment were not significantly different from patients treated with ribavirin monotherapy (p = 0.76). End of treatment WBC was significantly lower in patients treated with combination therapy, compared to ribavirin (p < 0.01) as well as for patients treated with ribavirin monotherapy compared to placebo (p < 0.01). DISCUSSION: This belated report on the only placebo controlled study of interferon ribavirin combination therapy in non responders to standard doses of interferon monotherapy documents the effectiveness, be it limited, of this approach as well as the dynamics of the effects on blood counts.

Adult↗
PubMed1998

Combination therapy for HIV: the effect on inpatient activity, morbidity and mortality of a cohort of patients.

We set out to quantify the changes in HIV-related morbidity and mortality associated with the clinical use of antiretroviral therapy via prospectively collected patient-related events (admissions, bed days, deaths, WHO stage 3 and 4 events and drug costs) on all HIV patients known to the Regional Infectious Disease Unit (RIDU) from 1 January 1987 to 31 December 1996. The introduction of zidovudine monotherapy in 1987 for those with AIDS was associated with a subsequent decline of inpatient activity for 2 years: in 1989 there was a 23% reduction in bed days but only a 6% reduction in admissions. A further dramatic decline of patient-related events in those with AIDS was noted during 1996 following the introduction of combination therapy, a 39% reduction in admissions, 44% reduction in bed days, 54% reduction in stage 4 events, 33% reduction in WHO stage 3 events and 40% reduction in the death rate. Reductions were also observed for patients without AIDS including a 42% reduction in the rate of patients developing AIDS. Similar reductions were noted when the patients were classified by immunological instead of clinical status although data for 1997 suggest an increase in patient-related activity for those with CD4 counts >200 cells/microl possibly as a result of low levels of anti-HIV therapy. The introduction of combination therapy for HIV has to date led to a minimum saving of one inpatient bed per 100 patient years which helped defray the cost of combination therapy. Although we cannot imply causality from an observational study, dramatic reductions in patient-related activity were associated with the introduction of combination therapy into clinical practice. The ultimate extent and duration of this effect cannot as yet be predicted and caution is required since similar reductions were noted with zidovudine therapy which were unfortunately time limited.

Anti-HIV Agents↗
PubMed2006

Treatment considerations for inflammatory acne: clinical evidence for adapalene 0.1% in combination therapies.

Acne vulgaris is an exceptionally common, chronic, and recurring disease. It involves multiple etiological factors including follicular hyperkeratinization, increased sebum production, Propionibacterium acnes proliferation, and inflammation. Presently, oral isotretinoin is the only single agent that is effective against all 4 major pathophysiologic features. However, this drug is also responsible for several serious side effects, including teratogenicity. Therefore, it should be used in only the most severe cases and alternative treatment approaches for inflammatory acne, such as initial combination therapy, should be considered first. Combination therapy in inflammatory acne simultaneously targets multiple pathogenic factors. Current guidelines recommend early initiation of combination therapy with a topical retinoid and antimicrobials for mild to moderate inflammatory acne and topical retinoids with oral antibiotics (with or without the use of benzoyl peroxide) for moderate to severe cases of acne, followed by maintenance therapy with topical retinoids. This review evaluates the rationale and clinical evidence for the use of adapalene in combination therapy for inflammatory acne.

Acne Vulgaris↗
PubMed1998

Combination therapy in the treatment of persistent nocturnal enuresis.

OBJECTIVE: To evaluate, in a retrospective study, the response rate of older children to combination therapy using a sustained-release anticholinergic agent, hyoscyamine, and a synthetic analogue of antidiuretic hormone, desmopressin acetate. PATIENTS AND METHOD: Twenty-eight patients (20 males and eight females, aged 9-18 years) diagnosed with nocturnal enuresis were evaluated using a questionnaire, history and physical examination. None had success with single-agent pharmacological therapy. All were begun on 0.375 mg of hyoscyamine and 20 microg of desmopressin intranasally at bedtime. The response rate was monitored at 2 and 4 weeks, and then every 3 months by recording dry nights on a calendar. To improve efficacy, the dosage of medication was adjusted up to 0.750 mg of hyoscyamine and 60 microg of desmopressin. Upon achieving dryness and spontaneous awakening to void, medication doses were tapered. RESULTS: Within 6 months 16 (57%) patients were completely dry and six (21%) were dry at least 80% of nights. Nine patients relapsed during dose tapering and therapy was reinstituted. Presently, 17 (60%) patients are off medication (after a mean of 8 months of medication). Eight patients are still on medication and are dry at least 80% of nights. Combination therapy failed in three patients and they have transferred to a different regimen. None experienced untoward side-effects from the medications. CONCLUSION: Most older children with nocturnal enuresis responded to combination therapy. These children require long-term follow-up and may need medication for up to 6 months because the relapse rate is fairly high. Combination therapy appears safe and reliable in treating nocturnal enuresis in older children who have had no success with other treatment modalities.

Adolescent↗
PubMed1993

[Studies on combination therapy with TAE and percutaneous ethanol injection therapy for unresectable hepatocellular carcinoma].

We studied and analysed the effects of combination therapy with TAE and PEIT for unresectable HCC. The subjects were 28 patients (21 males, 7 females) with 31 tumors treated in the Department of Surgery, Osaka Teishin Hospital. The patients were divided into four groups on the basis of the tumor size (< 3 cm, 3-5 cm, 5-8 cm, > 8 cm). The therapeutic effect on the tumors was evaluated on the basis of the maximum reduction rate within 3 months after TAE and PEIT. The response rates after treatment were 87.5%, 60.0%, 25.0% and 0% for < 3 cm, 3-5 cm, 5-8 cm, and > 8 cm tumor size, respectively. The 50% survival period was 50.9 months. The 1-, 2-, 3- and 5-year survival rates were 92%, 76%, 52% and 32%, respectively. In the cases of over 8 cm, this combination therapy had no effects on the survival period. The findings of the present study suggest that the combination therapy was useful for the unresectable HCC of under 5 cm in diameter.

Carcinoma, Hepatocellular↗
PubMed2003

Effects of interleukin-2 therapy combined with highly active antiretroviral therapy on immune restoration in HIV-1 infection: a randomized controlled trial.

BACKGROUND: Intermittent interleukin-2 (IL-2) therapy leads to a sustained increase of CD4 T cells in HIV-1-infected patients. METHODS: Symptom-free HIV-1-infected patients who were naive to all antiretroviral drugs (n = 68) and/or to protease inhibitors (n = 50) and had a CD4 cell count of 200-550 x 10(6) cells/l were randomly assigned to start lamivudine/stavudine/indinavir alone (controls) or combined from week 4 with subcutaneous IL-2 (5 x 10(6) IU twice daily for 5 days: every 4 weeks for three cycles, then every 8 weeks for seven cycles). Immunological and virological results were monitored until week 74. RESULTS: CD4 T cell counts increased more in the IL-2 group than in the controls (median increases 865 and 262 x 10(6) cells/l, respectively; P < 0.0001); an 80% increase in CD4 T cells was achieving by 89% of the IL-2 group and by 47% of the controls (P < 0.0001). Decrease of plasma viral loads was similar in both groups. Compared with controls, IL-2 induced a greater increase of naive and memory CD4 T cells, lymphocyte expression of CD28 and CD25 (P < 0.0001) and natural killer cells (P < 0.001). In a logistic regression analysis, odds of being responders to recall antigens was 8.5-fold higher in IL-2 recipients (P = 0.002) than in controls. The former experienced a higher level of antibody response to tetanus vaccination at week 64 than controls (32 and 8 haemagglutinating units/ml, respectively; P = 0.01). CONCLUSIONS: The combination of antiviral drugs and IL-2 induced a greater expansion and function of CD4 T cells than antiretroviral drugs alone.

Adjuvants, Immunologic↗
PubMed2000

[Electrophysiological mechanism of combination therapy with disopyramide and propranolol for paroxysmal atrial fibrillation].

OBJECTIVES: Combined administration of propranolol and disopyramide treatment often leads to better results in patients with atrial fibrillation refractory to only disopyramide administration. The electrophysiological mechanism of this combination therapy was investigated. METHODS: Nineteen patients with paroxysmal atrial fibrillation without organic heart disease were studied. The indices for atrial vulnerability were compared in the control state, 10 min after injection of disopyramide (2 mg/kg) and 10 min after additional administration of propranolol (0.2 mg/kg). RESULTS: Administration of both drugs did not significantly change the percentage fragmented atrial activity and the interatrial conduction delay. Disopyramide increased the atrial effective refractory period and the wavelength index, defined as the ratio of the atrial effective refractory period to the interatrial conduction delay and represented the length of the reentry circuit. Additional injection of propranolol caused further increases in both values. CONCLUSIONS: Combination therapy with disopyramide and propranolol improves atrial vulnerability by increasing the wavelength.

Adult↗
PubMed1994

Pentoxifylline and intravenous gamma globulin combination therapy for acute Kawasaki disease.

We compared the efficacy of oral administration of pentoxifylline (PTX) and intravenous infusions of gamma globulin (IVGG) combination therapy with that of IVGG in reducing the frequency of coronary-artery lesions (CAL) in children with Kawasaki disease (KD), in a randomized trial. All patients with KD received acetylsalicylic acid (30 mg/kg per day), until the 30th day, after the onset of fever, followed by daily acetylsalicylic acid at a dose of 3-5 mg/kg per day there-after, and intravenous IVGG, 200 mg/kg per day, for 5 consecutive days. In addition, patients randomly assigned to PTX and IVGG combination therapy groups received oral PTX at a dosage of 10 mg/kg per day (low-dose) or 20 mg/kg per day (high-dose), in three divided doses until the 30th day. Patients with KD were all free from CAL prior to treatment. We assessed the presence of CAL by two-dimensional echocardiography which was also done prior to treatment and then twice a week after hospital admission. We detected CAL in 3 of 18 patients (16.7%) in the IVGG therapy group, as compared with 2 of 18 patients (11.1%) in the low-dose PTX and IVGG combination therapy group. There were no significant difference between the two groups. In the next study, we detected CAL in 3 of 21 patients (14.3%) in the IVGG therapy group, as compared with none of 22 patients (0%) in the high-dose PTX and IVGG combination therapy group (chi 2 = 6.4, P < 0.02). No adverse side-effects were observed in 79 patients with KD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗