Global Evaluation Of Efficacy Research Articles

Usage of Glimepiride and Metformin Combination in Type 2 Diabetes Patients with Established Complications in Indian Settings

Objective: To evaluate the usage pattern of glimepiride and metformin fixed-dose combinations (FDC) and to determine its efficacy and tolerability in Type 2 diabetes mellitus (T2DM) patients with established complications in Indian settings. Methods: This was a retrospective multi-centric (n = 156), cross-sectional study. Patients of either sex, age above 18 years, who had developed microvascular and/or macrovascular complications receiving any strength of glimepiride and metformin FDC for the treatment of T2DM were included. Demographics, clinical characteristics, laboratory assessments, and adverse event profiles were retrieved from medical records. Results: A total of 470 patients with a mean age of 53.6 years were included. The majority of patients was obese (68.1%). Hypertension (58.7%) was the most common comorbidity, followed by dyslipidemia (36.0%). Macrovascular and microvascular complications were observed in 21.5% and 86.8% of patients, respectively. Among the available strengths, glimepiride 2 mg and metformin 500 mg FDC was most widely used in 30.2% of patients. Dosage up-titration was observed in 44.3% of patients. A significant improvement in glycemic parameters was observed posttreatment with glimepiride and metformin FDC (P < 0.001). Physicians’ global evaluation of efficacy and tolerability showed a majority of patients on a good to excellent scale (96.0% and 93.1%). Conclusion: Glimepiride and metformin FDCs have been extensively studied and found to be safe and effective in improving glycemic control with minimal risk of hypoglycemic events and weight gain in T2DM patients with established complications in Indian settings.

Real-World Observational Study on Vildagliptin With Insulin (VIL-INS) or Vildagliptin and Metformin With Insulin (VIL-MET-INS) Therapy in Indian Patients With Type 2 Diabetes Mellitus.

The therapeutic use of vildagliptin and insulin (VIL-INS) or vildagliptin and metformin in combination with insulin (VIL-MET-INS) in the Indian scenario has yet to be explored by generating real-world evidence. Therefore, the present study aimed to evaluate the demographic, clinical characteristics, and treatment patterns of patients with type 2 diabetes mellitus (T2DM) in Indian settings in the above context. This observational study conducted at 600 healthcare centers in India retrospectively analyzed data of adult patients with T2DM who had been treated with either vildagliptin with insulin or a combination of vildagliptin and metformin with insulin. Data were collected from medical records and analyzed by appropriate statistical tests. A total of 12,603 patients with T2DM were included with a mean age of 53.4 years of which 63.8% were males. The majority of patients (n=6511; 51.7%) received a combination of vildagliptin and metformin on top of insulin. A significantly high proportion of patients in the age group of 18-40 years received this treatment compared to patients who were initiated on insulin treatment after vildagliptin and metformin combination (11.6% vs. 9.7%; P<0.001). Of all the patients, 70.0% were able to achieve target glycemic control with either VIS-INS or VIL-MET-INS. After treatment with VIL-INS or VIL-MET-INS, the mean glycated hemoglobin (HbA1c) levels significantly decreased with a mean change of 1.46%. Out of all patients, 13.5% experienced weight changes during treatment, with 67.4% of them showing weight loss. A total of 68 patients reported hypoglycemic events and among them, 49 patients had mild hypoglycemic events. Physician global evaluation of efficacy and tolerability showed a majority of patients rated their experience as good to excellent (86.3% and 86.0%, respectively). Both treatment regimens wereeffective in terms of reduced HbA1c to achieve glycemic control. Furthermore, it is well tolerated without an increase in the risk of hypoglycemia or weight gain. Hence, this therapy has favorable outcomes for T2DM management in Indian clinical settings.

Clinical Utility of Glimepiride and Metformin Fixed-Dose Combination in Obese/Overweight Patients with Type 2 Diabetes Mellitus in Indian Settings

Background: In India, glimepiride has become a promising option for add-on therapy with metformin in patients with type-2 diabetes mellitus (T2DM) owing to its efficacy, safety, and cost-effectiveness. This study aimed to analyze the clinical utility of multiple strengths of glimepiride and metformin fixed-dose combination (FDC) in obese/overweight patients with T2DM. Methods: This case-based questionnaire survey was conducted between June 2020 and June 2021 and included health-care professionals across India to assess the usage pattern of glimepiride and metformin FDC. Results: Overall, data from 1345 patients taking multiple strengths of glimepiride and metformin FDC were analyzed, of which 64.7% were men. A total of 57.6% of patients were overweight, 29.4% were obese Class I, 9.6% were obese Class II, and 3.4% belonged to obese Class III. Sedentary lifestyle (60.3%), smoking (36.7%), and emotional stress (33.3%) were the most common risk factors. Among the available strengths, glimepiride 2 mg and metformin 500/850/1000 mg FDC was most widely used in 50.5% and 47.4% of patients from overweight and obese groups, respectively. A total of 90.3% and 89.1% of patients, respectively, from the overweight and obese groups did not observe weight gain. The majority of the patients from overweight and obese groups observed blood pressure within optimum levels (68.5% and 71.4%, respectively). The mean glycated hemoglobin, fasting plasma glucose, and postprandial plasma glucose levels were significantly reduced with posttreatment of glimepiride and metformin FDC with a mean change of 1.4%, 44.3 mg/dL, and 73.5 mg/dL, respectively (P &lt; 0.01). The physician global evaluation of efficacy (90.3%) and tolerability (91.1%) showed the majority of the patients on a good to excellent scale. Conclusion: The real-world evidence in the Indian clinical setting indicates that the glimepiride and metformin FDC was found to be effective in achieving glycemic control and it is observed to be safer in terms of weight gain and hypoglycemia.

Real-World Evidence of Generic Dapagliflozin

Objective: The objective was to evaluate the clinical experience and treatment patterns of generic dapagliflozin usage in different patient profiles in Indian settings. Materials and Methods: A retrospective, multicentric, real-world study included patients with type 2 diabetes mellitus (T2DM) (aged &gt;18 years), inadequately controlled by existing antidiabetic therapy and receiving generic dapagliflozin as an add-on to existing oral antidiabetic drug(s) with or without insulin or switch therapy. Baseline characteristics and treatment-related outcomes were retrieved from the medical records and analyzed. Results: A total of 1935 patients were included, of which 1279 (66.1%) were males. The mean age was 57.4 years, and around half of the patients (51.4%) were aged from 45 to 60 years. Hypertension (55.9%) and dyslipidemia (19.8%) were the common comorbidities. The majority (n = 1122; 60%) of patients received dapagliflozin in combination with one or two antihyperglycemic drugs. More than half of the patients received metformin (56.8%) or sulfonylurea (52.3%) in combination with dapagliflozin. A dose of 10 mg (93.4%) was the most commonly used dose of dapagliflozin. The mean levels of glycated hemoglobin, fasting plasma glucose, and postprandial plasma glucose were significantly reduced to 1.1% (1.0–1.1), 30.5 mg/dL (29.2–31.9), and 57.5 mg/dL (55.1–59.9), respectively, after the initiation of dapagliflozin. A total of 1935 patients experienced weight changes during the treatment, of which 90.5% of patients showed weight loss. Hypoglycemic events were reported in 12.5% of patients. Physician global evaluation of efficacy and tolerability showed a majority of patients on a good-to-excellent scale (97.3% and 97.1%). Conclusion: Generic dapagliflozin showed a significant improvement in glycemic parameters and reduced body weight with low hypoglycemic events. The administration of dapagliflozin provided a good-to-excellent efficacy and tolerability profile in patients with T2DM. To the best of our knowledge, this is the first study confirming the efficacy, safety, and usefulness of generic dapagliflozin in patients with T2DM.

Clinical data analysis of telmisartan for hypertension management in Indian population.

It is of interest to evaluate the clinical characteristics, treatment patterns, clinical effectiveness, and safety of telmisartan as a monotherapy or as part of combination therapy in Indian adults (>18 years old) with hypertension. All patients were receiving telmisartan as monotherapy, or as a combination therapy for hypertension management. Demographics, risk factors, existing comorbidity, and ongoing medical therapies were retrieved from the patients’ medical records. A total of 8607 patients with hypertension (median age, 51.0 years) were part of the study. The gender distribution suggested, 5534(64.3%) patients were male, and 3073 (35.7%) were female patients. The excess salt intake (39.0%) was the most common risk factor according to the results. The analysis revealed telmisartan dual therapy (57.9%) as the most prescribed therapy, followed by monotherapy (32.5%), and triple therapy (9.6%). Further, telmisartan 40mg (21.3%) and telmisartan 40mg plus amlodipine 5mg (17.6%) were the most commonly prescribed therapies. The data suggested that only 17.2% of patients required dose titration. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHg) were significantly decreased with monotherapy (mean change: 19.8 [15.1] mmHg and 8.8[8.2] mmHg), dual therapy (mean change: 23.7 [16.6] mmHg and 10.3[8.5] mmHg), and triple therapy (mean change: 28.6 [19.0] mmHg and 12.1[10.8] mmHg) after the treatment (P<0.001). A total of 98.4% of the patients were compliant, and 97.6% achieved the target blood pressure goal with telmisartan-based therapy. There were 157 adverse events reported altogether. The Physicians' global evaluation of efficacy and tolerability showed the majority of the patients receiving telmisartan-based therapy on a good to excellent scale. Telmisartan used as a monotherapeutic agent or as a part of combination therapy was successful and effective in reducing blood pressure and achieving the blood pressure target. Irrespective of the patient’s age, duration, and stages of hypertension, the study resulted in a good to excellent scale in efficacy and tolerability in the Indian patients having hypertension.

Data on vildagliptin and vildagliptin plus metformin combination in type-2 diabetes mellitus management

It is of interest to evaluate the clinical effectiveness and safety of vildagliptin as monotherapy and combination therapy of vildagliptin and metformin for the management of type 2 diabetes mellitus (T2DM) patients in Indian settings. The study included patients with T2DM (aged &gt;18 years) receiving vildagliptin monotherapy and vildagliptin in combination with metformin therapy of various strengths. Data related to demographics, risk factors, medical history, glycated hemoglobin (HbA1c) levels, and medical therapies were retrieved from medical records. Out of 9678 patients (median age, 52.0 years), 59.1% were men. A combination of vildagliptin and metformin (50/500 mg) was the most commonly used therapy (54.8%), and the median duration of therapy was 24.0 months. The predominant reason for selecting vildagliptin therapy was to improve HbA1c levels (87.8%). A total of 87.5% of patients required dosage up-titration. Vildagliptin therapy was used in patients with T2DM and associated complications (peripheral neuropathy, CAD, nephropathy, retinopathy, autonomous neuropathy, stroke/TIA, and peripheral artery disease). Among 5175 patients who experienced body weight changes, a majority of patients had lost weight (68.6%). The target glycemic control was achieved in 95.3% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.34%; p&lt;0.001). Adverse events were reported in 0.4% of patients. Physicians rated the majority of patients as good to excellent on the global evaluation of efficacy and tolerability scale (98.9%, each). Vildagliptin with or without metformin was an effective therapy in reducing HbA1c helps in achieving target glycemic control, and was well-tolerated in Indian patients with T2DM continuum.

Data on vildagliptin and vildagliptin plus metformin combination in type-2 diabetes mellitus management.

It is of interest to evaluate the clinical effectiveness and safety of vildagliptin as monotherapy and combination therapy of vildagliptin and metformin for the management of type 2 diabetes mellitus (T2DM) patients in Indian settings. The study included patients with T2DM (aged >18 years) receiving vildagliptin monotherapy and vildagliptin in combination with metformin therapy of various strengths. Data related to demographics, risk factors, medical history, glycated hemoglobin (HbA1c) levels, and medical therapies were retrieved from medical records. Out of 9678 patients (median age, 52.0 years), 59.1% were men. A combination of vildagliptin and metformin (50/500 mg) was the most commonly used therapy (54.8%), and the median duration of therapy was 24.0 months. The predominant reason for selecting vildagliptin therapy was to improve HbA1c levels (87.8%). A total of 87.5% of patients required dosage up-titration. Vildagliptin therapy was used in patients with T2DM and associated complications (peripheral neuropathy, CAD, nephropathy, retinopathy, autonomous neuropathy, stroke/TIA, and peripheral artery disease). Among 5175 patients who experienced body weight changes, a majority of patients showed a loss of weight (68.6%). The target glycemic control was achieved in 95.3% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.34%; p<0.001). Adverse events were reported in 0.4% of patients. Physicians rated the majority of patients as good to excellent on the global evaluation of efficacy and tolerability scale (98.9%, each). Vildagliptin as monotherapy and combination therapy of vildagliptin and metformin was an effective therapy in reducing HbA1c helps in achieving target glycemic control, and was well tolerated in Indian patients with T2DM continuum.

Real-World Observational Study of Glimepiride and Metformin Fixed-Dose Combination Along With Insulin in the Management of Type 2 Diabetes Mellitus: Indian Experience.

BackgroundType 2 diabetes mellitus (T2DM) is associated with a significant burden on both patients and the healthcare system. This study aimed to evaluate the demographics of patients with T2DM receiving different strengths of glimepiride and metformin combination along with insulin. This study also examined the concomitant conditions and therapies, duration of therapies, dosage titration, glycated hemoglobin (HbA1c) levels, hypoglycemic events, and weight changes during the course of therapy.MethodsThis retrospective, multicenter (347), observational study included adult patients with T2DM who received glimepiride and metformin combination along with insulin. Data related to demographic characteristics, duration of disease, co-morbidities, concomitant medications, and dosage pattern was collected from medical records authenticated by physicians during routine care.ResultsA total of 7058 patients were included in the study. The median age of included patients was 55 years and around 29% were aged >60 years and 60% were men. The majority of patients (83.3%) had insulin treatment initiation after glimepiride and metformin combination while other patients (16.7%) received glimepiride and metformin combination after insulin initiation. The mean HbA1c levels significantly decreased with a mean change of 1.33%. In one-third of the patients, down-titration of the insulin dose was done, indicating the insulin-sparing effect with the addition of the glimepiride and metformin combination. The most common comorbid condition was hypertension (64.7%). Of 3705 patients, 33.2% patients had weight loss and 66.8% had weight gain. A total of 432 patients reported hypoglycemic events. Physician global evaluation of efficacy and tolerability showed a good to excellent on the scale (97.3% and 96.6%).ConclusionThis study presented good HbA1c lowering with glimepiride and metformin combination with insulin, ensuring a positive clinical outcome. Good to excellent efficacy and tolerability were observed in patients with T2DM across the age groups, in early as well as long-standing disease.

Real-World Clinical Experience on the Usage of High-Dose Metformin (1500-2500 mg/day) in Type 2 Diabetes Management.

Background:To evaluate the clinical characteristics, treatment patterns, and clinical effectiveness and safety of high doses of metformin (1500-2500 mg/day) in Indian adults with type 2 diabetes mellitus (T2DM).Materials and methods:A retrospective, multicentric (n = 241), real-world study included patients with T2DM (aged >18 years) receiving high doses of metformin. Details were retrieved from patient’s medical records.Results:Out of 5695 patients, 62.7% were men with median age was 50.0 years. Hypertension (67.5%) and dyslipidemia (48.7%) were the prevalent comorbidities. Doses of 2000 mg (57.4%) and 1500 mg (29.1%) were the most commonly used doses of metformin and median duration of high-dose metformin therapy was 24.0 months. Metformin twice daily was the most frequently used dosage pattern (94.2%). Up-titration of doses was done in 96.8% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.08%; P < .001). The target glycemic control was achieved in 91.2% patients. A total of 83.0% had decreased weight. Adverse events were reported in 156 patients. Physician global evaluation of efficacy and tolerability showed majority of patients on a good to excellent scale (98.2% and 97.7%).Conclusion:Clinical effectiveness and safety of a high-dose metformin was demonstrated through significant improvement in HbA1c levels and weight reduction.

Randomized equivalence trial: A novel multidose dry powder inhaler and originator device in adult and adolescent asthma.

Guideline-defined asthma control can be achieved and maintained in patients by treatment with fluticasone propionate-salmeterol (FP-Sal). To compare the efficacy and safety of FP-Sal delivered via a novel multidose dry powder inhaler (mDPI) versus an originator device in adolescent and adult patients with moderate-to-severe persistent asthma. Patients ages 12-65 years (N = 555) were randomized to treatment with FP-Sal novel mDPI 100 μg-50 μg or 500 μg-50 μg, or originator device 100 μg-50 μg or 500 μg-50 μg in a double-blind, double-dummy, parallel-group, multicenter study. Primary efficacy measures were absolute change in forced expiratory volume in 1 second (FEV1) from baseline and the area under the 12-hour serial FEV1 curve at the end of 12 weeks of treatment. Secondary end points included mean changes in FEV1; FEV1 % predicted; morning predose peak expiratory flow; daytime, nighttime, total asthma symptom scores; rescue medication use; percentage of patients with guideline-defined controlled asthma; global efficacy evaluation; patients' device preference; and safety. FP-Sal mDPI and originator device-mediated increases in FEV1 from baseline to the end of treatment were not significantly different, difference in least squares mean, -0.065 L (95% confidence interval, -0.154 to 0.024 L) at 100 μg-50 μg, and -0.032 L (95% confidence interval, -0.121 to 0.057 L) at 500 μg-50 μg). Both doses of FP-Sal mDPI improved FEV1 area under the 12-hour serial FEV1 curve from baseline and all secondary efficacy measures with no significant differences from the originator device at equivalent doses, with similar safety profiles. FP-Sal mDPI demonstrated equivalent efficacy and safety profile to the originator device and is an alternative in this patient group.

Efficacy and safety of lornoxicam vs ibuprofen in primary dysmenorrhea: a randomized, double-blind, double dummy, active-controlled, cross over study

ObjectivesStudy was planned to evaluate the efficacy and safety of lornoxicam in moderate to severe menstrual pain due to primary dysmenorrhea. Study designThis doubled blind, double dummy, randomized, comparable study of lornoxciam versus ibuprofen was conducted at Sir Takhtsinghji General Hospital, Bhavnagar, Gujarat, India. Total 57 primary dysmenorrhea participants having mean age±standard deviation (SD) of 19.2±2.08 were analyzed. The participants were randomly allocated to either lornoxicam 8mg or ibuprofen 400mg two times a day for maximum of three days on two consecutive menstrual periods. The different medication was taken on each cycle. The analgesic efficacy was compared by a total area under pain relief score to 4 and 8h, pain intensity difference, sum of pain intensity difference to 4 and 8h, peak pain intensity difference to 4 and 8h, peak pain relief to 4 and 8h, total medication consumption, rescue medication and participant global evaluation. Adverse effects were recorded in both groups. ResultsIn both treatments, efficacy parameters were significantly reduced at measured time points as compared to baseline. No significant difference was observed between lornoxicam and ibuprofen in terms of efficacy parameters: total area under pain relief to 4h (8.0±2.6 vs 8.3±2.7), total area under pain relief to 8h (22.4±4.6 vs 23.0±4.4), sum of pain intensity difference to 4h (−5.7±1.9 vs −6.0±2.0), sum of pain intensity difference to 8h (−17.5±3.3 vs −17.8±3.5), peak pain relief to 4h (3.4±0.8 vs 3.5±0.8), peak pain relief to 8h (3.9±0.5 vs 3.9±0.4), peak pain intensity difference to 4h (−2.6±0.7 vs −2.7±0.7), peak pain intensity difference to 8h (−3.3±0.6 vs −3.3±0.6). Total medication consumption, a requirement of rescue medication and global evaluation of efficacy were comparable in both groups. The incidence of adverse effect was also similar in both groups. ConclusionsLornoxicam appears to be a new therapeutic agent for the treatment of primary dysmenorrhea.

A randomized, double-blind, placebo-controlled trial of paracetamol and ketoprofren lysine salt for pain control in children with pharyngotonsillitis cared by family pediatricians

BackgroundTo evaluate the analgesic effect and tolerability of paracetamol syrup compared to placebo and ketoprofen lysine salt in children with pharyngotonsillitis cared by family pediatricians.MethodsA double-blind, randomized, placebo-controlled trial of a 12 mg/kg single dose of paracetamol paralleled by open-label ketoprofren lysine salt sachet 40 mg. Six to 12 years old children with diagnosis of pharyngo-tonsillitis and a Children's Sore Throat Pain (CSTP) Thermometer score > 120 mm were enrolled. Primary endpoint was the Sum of Pain Intensity Differences (SPID) of the CSTP Intensity scale by the child.Results97 children were equally randomized to paracetamol, placebo or ketoprofen. Paracetamol was significantly more effective than placebo in the SPID of children and parents (P < 0.05) but not in the SPID reported by investigators, 1 hour after drug administration. Global evaluation of efficacy showed a statistically significant advantage of paracetamol over placebo after 1 hour either for children, parents or investigators. Patients treated in open fashion with ketoprofen lysine salt, showed similar improvement in pain over time. All treatments were well-tolerated.ConclusionsA single oral dose of paracetamol or ketoprofen lysine salt are safe and effective analgesic treatments for children with sore throat in daily pediatric ambulatory care.

Dr. McMain Replies

Back to table of contents Previous article Next article Letter to the EditorFull AccessDr. McMain RepliesShelley F. McMain, Ph.D.Shelley F. McMainSearch for more papers by this author, Ph.D.Published Online:1 Apr 2010https://doi.org/10.1176/appi.ajp.2009.09101532rAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We disagree with Dr. Case's view that when no difference is found between two potentially active treatments, confidence intervals would inform the question of whether a study demonstrates that the treatments are equivalent. Confidence intervals could not be used to answer the question of equivalence because our investigation was not designed or powered for an equivalence study. The lack of statistical significance, even with narrow confidence intervals, should not be used to conclude equivalence. It should be used only to conclude lack of difference. We agree that additional information, particularly confidence intervals, would have been helpful within our original report. Because of space limitations, we omitted this information. However, we have now provided the confidence intervals as a data supplement. Finally, upon examining our results, even if the study were much larger and had sufficient power to detect a difference, that difference would not have been clinically important.With respect to Dr. Case's question about group differences on baseline characteristics, our outcome analyses were based on global evaluation of efficacy and growth curve analyses and modeled for the possibility of between-group differences. No between-group differences at baseline were found on any variables.Toronto, Ont., CanadaThe author's disclosures accompany the original article. FiguresReferencesCited byDetailsCited ByJournal of Personality Disorders, Vol. 30, No. 1 Volume 167Issue 4 April 2010Pages 475-476 Metrics PDF download History Accepted 1 February 2010 Published online 1 April 2010 Published in print 1 April 2010

Therapeutic effect of 1,5-pentanediol for herpes simplex labialis: a randomized, double-blind, placebo-controlled clinical trial

Most episodes of recurrent herpes labialis are self-limited and mild, but can be troublesome when they occur frequently with painful and unsightly lesions. Therefore, there has been much interest in developing agents that can suppress outbreaks in addition to being therapeutically effective. The objective of the present study was to examine the prophylactic and therapeutic efficacy of 1,5-pentanediol (PD) gel in patients with recurrent episodes of herpes labialis. In this placebo-controlled, randomized, double-blind clinical trial, a total of 105 patients with frequent episodes of recurrent herpes were randomized to either PD or placebo. During the 26-week prophylactic phase of the study, the patients applied PD gel or placebo gel twice daily to both lips. Upon recurrence of an episode, a 5-day therapy phase started during which the gel was to be applied eight times daily. After the therapy phase, the patient resumed prophylactic treatment twice daily until the next herpes episode. The main outcome measures were number of herpes episodes during the prophylactic phase of 26 weeks, and successful therapy of occurring herpes episodes with a 5-day treatment. There was no significant difference in recurrence rate between the two groups (P>0.05). During recurrence there was a statistically significant improvement regarding the therapeutic effect of the symptoms "blistering," "swelling," and "pain" in the PD group. The global evaluation of efficacy by the investigators and patients showed a statistically significant superiority for PD as opposed to placebo (P<0.001). Under the conditions used in the present study, PD did not show any prophylactic effect against recurrence of herpes episodes. A significantly better therapeutic effect of PD over placebo could be demonstrated on the symptoms "blistering," "swelling," and "pain." PD was very safe as no side effects were observed during the course of the study.

Clinical Relevance of Efficacy Endpoints in OTC Headache Trials

This analysis evaluates and ranks efficacy endpoints often used in headache trials concerning their clinical relevance in relation to the patient-related criterion "global assessment of overall efficacy" based on data gained in a large trial investigating different over-the-counter drugs in the treatment of headache. The original study showed a significant superiority of the fixed combination of acetylsalicylic acid+paracetamol+caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache. For 1734 patients included in the efficacy analysis we investigated the correlation of patient's global efficacy assessment with the endpoints "time to 50% pain relief" (primary endpoint), "time to be pain-free," pain intensity difference, sum of pain intensity difference, and extent of impairment of daily activities. Patients recorded pain intensity on a visual analog scale. Efficacy, tolerability, and extent of impairment of daily activity were assessed on verbal rating scales.A logistic regression, proportional odds model was adapted to the time to event data. The highest correlation with patient's global efficacy assessment was demonstrated for the primary endpoint time to 50% pain relief (r = 0.6727) and the sum of pain intensity difference (r = 0.7037). The frequency distribution of patient's global efficacy assessment depended primarily on the time to 50% pain relief and similarly, but to a somewhat lesser extent, on the reduction of pain intensity to 10 mm as assessed on the visual analog scale. More than 86% of the patients assessed efficacy as very good or good when their pain was reduced by 50% at least within 1 hour after drug intake. The patients accept a longer time span than 2 hours for reaching no pain to give a positive global evaluation of efficacy.

Investigator global evaluations of efficacy with injectable poly-L-lactic acid versus human collagen in the correction of nasolabial fold wrinkles

Investigator global evaluations of efficacy with injectable poly-L-lactic acid versus human collagen in the correction of nasolabial fold wrinkles

Efficacy and Safety of Sodium Hyaluronate in the Treatment of Wilkes Stage II Disease

To show whether an intra-articular (IA) infiltration of 1 mL sodium hyaluronate (SH) into the temporomandibular joint (TMJ) would significantly reduce pain and improve joint function in Wilkes stage II disease, compared with the oral administration of a combination of methocarbamol and paracetamol. Forty-one patients with Wilkes stage II disease were selected and randomly assigned to 2 groups. The experimental group received 1 IA infiltration of SH with assessments at days 14, 28, 56, and 84. The control group was given 2 tablets of a combination of methocarbamol 380 mg and paracetamol 300 mg every 6 hours for 4 weeks, with assessments at days 14 and 28. Forty-one patients were randomized into the study (SH: 20 patients, control drug: 21 patients). A statistically significant difference (P < . 05) was detected in favor of the SH group from day 56 onward for TMJ pain at rest, from day 14 onward for pain on jaw opening, and at days 28 and 56 for pain on mastication. The TMJ function was statistically significantly (P < .05) better in the test group at all follow-up visits. The global evaluation of efficacy by both, the patients and investigators, was better for the test group. No adverse reactions were detected with SH. An IA infiltration of SH showed better efficacy in reducing pain and improving joint function in Wilkes stage II disease, compared with the oral administration of methocarbamol-paracetamol tablets.

Open-Label, Long-Term Safety Study of Cevimeline in the Treatment of Postirradiation Xerostomia

To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness on a scale of 0 (none) to 3 (severe). Overall, 175 subjects (68.6%) experienced expected treatment-related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001). Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region.

Efficacy, cost-effectiveness, and tolerability of mometasone furoate, levocabastine, and disodium cromoglycate nasal sprays in the treatment of seasonal allergic rhinitis

Current guidelines recommend intranasal glucocorticosteroids as first-line therapy for seasonal allergic rhinitis. To compare the efficacy, cost-effectiveness, and tolerability of the topical glucocorticosteroid mometasone furoate, the topical antihistamine levocabastine hydrochloride, and the cromone disodium cromoglycate in seasonal allergic rhinitis. This study was performed during the 2003 grass pollen season as an open, randomized, parallel-group, single-center study of 123 patients assigned to receive mometasone furoate (200 microg once daily), levocabastine hydrochloride (200 microg twice daily), or disodium cromoglycate (5.6 mg 4 times daily). Symptom scores and nasal inspiratory peak flow measurements were recorded in a patient diary. The global efficacy of the study medication was evaluated by patients after treatment. Eosinophil cationic protein concentrations were measured in nasal secretions before and after treatment. Cost-effectiveness was evaluated as medication cost per treatment success. Mometasone furoate therapy was significantly superior to the use of levocabastine or disodium cromoglycate with respect to all nasal symptoms, the global evaluation of efficacy, and eosinophil cationic protein concentration. Furthermore, mometasone furoate therapy was significantly superior to disodium cromoglycate therapy with respect to nasal inspiratory peak flow. Medication cost per treatment success was lowest with mometasone furoate use and highest with levocabastine use. This is the first study to compare mometasone furoate nasal spray with nonsteroidal topical treatments for seasonal allergic rhinitis. Mometasone furoate nasal spray was confirmed as a first-choice topical treatment option for seasonal allergic rhinitis.

Efficacy of a Comfrey root extract ointment in comparison to a Diclo-fenac gel in the treatment of ankle distortions: Results of an observer-blind, randomized, multicenter study

In the treatment of minor blunt injuries several topical drugs are known to have anti-inflammatory and analgesic properties. They represent, however, two fundamentally different major pharmacological therapy approaches: the "chemical-synthetical" and the "phytotherapeutical" approach. The main objective of this trial (CODEC_2004) was to compare the efficacy and tolerability of an ointment of Comfrey extract (Extr. Rad. Symphyti) with that of a Diclofenac gel in the treatment of acute unilateral ankle sprain (distortion). In a single-blind, controlled, randomized, parallel-group, multicenter and confirmatory clinical trial outpatients with acute unilateral ankle sprains (n=164, mean age 29.0 years, 47.6% female) received either a 6 cm long ointment layer of Kytta-Salbe f (Comfrey extract) (n=82) or of Diclofenac gel containing 1.16 g of diclofenac diethylamine salt (n=82) for 7 +/- 1 days, four times a day. Primary variable was the area-under-the-curve (AUC) of the pain reaction to pressure on the injured area measured by a calibrated caliper (tonometer). Secondary variables were the circumference of the joint (swelling; figure-of-eight method), the individual spontaneous pain sensation at rest and at movement according to a Visual Analogue Scale (VAS), the judgment of impaired movements of the injured joint by the method of "neutral-zero", consumption of rescue medication (paracetamol), as well as the global efficacy evaluation and the global assessment of tolerability (both by physician and patient, 4 ranks). In this study the primary variable was also to be validated prospectively. It was confirmatorily shown that Comfrey extract is non-inferior to diclofenac. The 95% confidence interval for the AUC (Comfrey extract minus Diclofenac gel) was 19.01-103.09h*N/cm2 and was completely above the margin of non-inferiority. Moreover, the results of the primary and secondary variables indicate that Comfrey extract may be superior to Diclofenac gel.