A double-blind trial of "alternate-day" steroid therapy in adult nephrotics--a preliminary report.
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Adolescent↗
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[A comparison of different endotracheal tubes. Tracheal cuff seal, peak centering and the incidence of postoperative sore throat].
UNLABELLED: The study objective was to evaluate cuff seal, tube tip position and incidence of postoperative sore throat in three different endotracheal tubes: the reusable Rüsch "red rubber" tube (low-volume, high-pressure cuff) and the disposable Rüsch "Super Safety Clear" and Mallinckrodt "lo-pro" tubes (both high-volume, low-pressure cuffs). METHODS: In a prospective randomized trial, 150 consecutive patients scheduled for minor orthopaedic surgery under standardized general anaesthesia, including standardized cuff pressure control, were allocated to one of the three types of endotracheal tube. Leakage and intratracheal tube tip position were investigated by means of fiberoptic tracheoscopy via the endotracheal tube, preceded by pharyngeal instillation of indigocarmine. The semi-standardized interviews for the recording of postoperative sore throat were performed once a day under double-blind conditions from the day of operation to postoperative day 3. Statistical independence testing was based on the chi 2-test, significance was assumed at P < 0.05. MAIN RESULTS: A past-cuff leakage of the pharyngeally instilled dye was found in three patients with "red rubber" tubes. In all of these cases the tracheal cross section deviated markedly from circular. The tips of the "Super Safety Clear" tubes tended to be better centred (P = 0.099). Bad tip position, however, had little influence on postoperative throat complaints (P = 0.394). The differences in incidence of postoperative throat complaints between the "red rubber" (48.9%), "Super Safety Clear" (35.6%) and "lo-pro" tubes (34.1%) did not reach the 5% level (P = 0.288). Such complaints, however, were significantly more frequent in females and in obese patients who exceeded their Broca weights by more than 25%. By contrast, postoperative throat complaints did not vary statistically significantly by age group, tracheal cross-sectional shape, use of atropine or duration of intubation. CONCLUSION: Despite the economic (usable up to 100 times) and ecological (less PVC waste) advantages of the rubber tube, the disposable tubes with high-volume, low-pressure cuffs tended to be superior regarding cuff seal, tube tip position and incidence of postoperative throat complaints. Nevertheless, the continued use of "red rubber" type reusable tubes may be justified in cases where the tube has to stay in place for only a short time.
Adult↗
Effects of zolpidem on the architecture and cyclical structure of sleep in poor sleepers.
Effects of zolpidem, a short acting non benzodiazepine hypnotic, have been studied in eight female poor sleepers, aged 25 to 54 years, documented during two consecutive adaptation nights. Subjects were recorded according to a 22 day single blind study. Placebo was given orally at bedtime on nights 2-4, zolpidem on nights 5-20 and finally placebo on nights 21-22. Polygraphic recordings (conventional analysis) were performed on nights 1-6; 12, 13; 19-22. Parameters of sleep continuity, sleep architecture and cyclical structure of sleep were studied. Zolpidem 10 mg showed a hypnotic effect on poor sleepers. It reduced sleep latency, increased total sleep time and decreased the number of awakenings during all recorded nights. During the first post-drug night a rebound insomnia was observed in two subjects only. Zolpidem did not increase specifically stage 2 to the detriment of stages 3 and 4 but it restored them during the first nights of administration. Study of the rapid eye movements-non rapid eye movements (REM-NREM) sleep cycles structure showed that the increase of stages 3 and 4 occurred only during the first part of the night. Finally, zolpidem had no effect on REM sleep temporal distribution.
Adult↗
Efficacy and safety of tramadol HCl in breakthrough musculoskeletal pain attributed to osteoarthritis.
OBJECTIVE: To evaluate the efficacy of tramadol as adjunctive therapy in patients with musculoskeletal pain attributed to osteoarthritis (OA) who experienced breakthrough pain while taking a nonsteroidal antiinflammatory drug (NSAID). METHODS: This single center, parallel, placebo controlled, 2 phase study was conducted in adults who experienced breakthrough OA pain while undergoing stable NSAID therapy. In a 24 h open label phase, patients took 100 mg of tramadol followed by 50 mg every 6 h (total 250 mg) in addition to their daily NSAID regimen. Supplemental analgesics were prohibited. Patients who met entry criteria and were willing to continue therapy were randomized to a 13 day double blind phase of adjunctive therapy with tramadol (50-100 mg every 4-6 h as needed for pain) or placebo; NSAID therapy was continued. The primary efficacy endpoint was the time to exit from the study because of therapeutic failure (i.e., insufficient pain relief or an inability to perform activities of daily living). RESULTS: The time to exit from the study because of insufficient pain relief tended to be longer in the tramadol group (250 mg/day) compared with the placebo group (p = 0.066). At the end of the double blind phase, pain at rest was significantly less severe in tramadol treated patients (p = 0.046). In addition, severity of pain on motion tended to be less severe in tramadol treated patients (p = 0.059). General severity of current pain and ability to perform activities of daily living were not significantly different with tramadol or placebo. Patients' overall assessment of therapy (p = 0.022) and investigator's rating of global improvement (p = 0.004) were significantly better with tramadol than with placebo. CONCLUSION: Tramadol may have a role as adjunctive treatment for breakthrough pain in patients receiving NSAID therapy for musculoskeletal pain attributed to OA.
Aged↗
[Karyometric studies on primary optic and hypothalamic nuclear regions in unilaterally blinded rats].
Six days after bilateral experimental ablation of the rat retina the nuclear diameter of the suprachiasmatic neurons decreased by 10.3% (Wenisch und Hartwig 1973). From these results it has been postulated that a direct retinohypothalamic connection exists between the eye and the suprachiasmatic nuclei. When unilateral retinal ablation was performed, a decrease in nuclear diameter was only observed in the contralateral suprachiasmatic nucleus (11.3% decrease, similar to that in bilaterally blinded rats). In the ipsilateral nucleus, as was the case in the sham-operated animals, no change in nuclear diameter occured. The nuclear diameter of the supraoptic nucleus, the medial geniculate nucleus and the ipsilateral geniculate nucleus 6 days after unilateral retinal ablation did not show any change, as was the case for these same nuclei in the sham-operated rats. However in the contralateral lateral geniculate nucleus an increase of 10.9% in nuclear diameter was observed. This apparent difference in the observed response of the lateral geniculate nucleus, as compared to the suprachiasmatic nucleus, could possibly be related to the greater distance of this area from the retina; the degeneration of the suprachiasmatic nucleus having been initiated earlier. From the silver-impregnation methods of Nauta-Fink-Heimer and Bodian-Ziemer applied to demonstrate degenerating nerve fibers and terminals 10 days after unilateral and bilateral ablation of the retina no definite conclusions could be drawn for the existence of a direct retinohypothalamic pathway.
Animals↗
Randomized double-blind study comparing 7- and 10-day regimens of faropenem medoxomil with a 10-day cefuroxime axetil regimen for treatment of acute bacterial sinusitis.
OBJECTIVE: To compare the efficacy and safety of faropenem medoxomil, 300 mg twice daily for seven or ten days, with cefuroxime axetil 250 mg twice daily for ten days in adults with acute bacterial sinusitis (ABS). STUDY DESIGN AND SETTING: Prospective, double-blinded, phase III trial with entry criteria consistent with FDA/IDSA guidelines for diagnosis of ABS. Primary efficacy parameter was clinical response at 7 to 21 days posttherapy. RESULTS: One thousand ninety-nine subjects were randomized and treated; 861 were efficacy valid. Clinical cure rates were 80.3% for seven days of faropenem, 81.8% for ten days of faropenem, and 74.5% for 10 days of cefuroxime axetil. The incidence of adverse events and premature discontinuations were similar for the three treatment regimens. CONCLUSIONS: Seven- and ten-day faropenem medoxomil regimens were similar (noninferior) to a ten-day cefuroxime axetil regimen based on clinical response in patients with ABS. SIGNIFICANCE: A seven-day course of faropenem medoxomil 300 mg twice-daily regimen is a promising alternative for treatment of ABS.
Acute Disease↗
[Exercise tolerance in angina patients 3 and 24 hours after administration of a new delayed-action preparation of metoprolol].
To assess the duration of improved exercise tolerance by metoprolol given in a new sustained-release formulation, 40 in-patients affected by stable exercise-induced angina pectoris received single-blind placebo in day 1 and thereafter, in double-blind cross-over once daily administration, metoprolol RETARD 100 mg and 200 mg in days 3 and 5. Symptom-limited cycloergometric exercise tests were performed at 3 and 24 hours after placebo and after each of the two doses of metoprolol RETARD. Duration of exercise, maximal workload and total work performed did significantly increase at 3 and 24 hours after metoprolol RETARD 100 mg (P less than 0.01) and 200 mg (P less than 0.01), without any significant difference between the two doses. Peak systolic arterial pressure and heart rate were lowered by metoprolol RETARD 200 mg at 3 (P less than 0.01) and 24 (P less than 0.01) hours, whereas only the peak heart rate at 3 hours was lowered (P less than 0.05) by the 100 mg dose. It is concluded that in patients with stable exercise-induced angina pectoris, metoprolol RETARD 200 mg appears to be able to increase exercise tolerance and to reduce exercise-induced myocardial oxygen consumption throughout 24 hours period. This may justify a once daily dosing schedule of the 200 mg dose, aimed at improving patient compliance.
Adult↗
Symptom resolution assessed using a patient directed diary card during treatment of acute exacerbations of chronic bronchitis.
BACKGROUND: Acute exacerbations of chronic bronchitis are common and the presenting symptoms vary, although it is not clear how this should influence management. From a health care perspective, an understanding of the speed of symptom resolution is of importance to determine the success of treatment or when a change is indicated because of treatment failure. METHODS: The response of 63 patients treated at home for exacerbations of chronic bronchitis was assessed using a patient directed diary card incorporating sputum characteristics and symptoms. Treatment was given according to the nature of the sputum at presentation; patients with purulent sputum received an antibiotic for 5 or 10 days (randomised, double blind) whereas patients with mucoid sputum received high dose inhaled steroid or placebo for 14 days (randomised, double blind). RESULTS: The mean (SE) total diary card score at presentation was significantly higher in the purulent group than in the mucoid group (19.7 (0.9) v 16.3 (0.9); mean difference -3.4 (95% CI -6.1 to -0.7), p<0.05). In the purulent group sputum colour and volume improved rapidly and in both groups the mean (SE) total diary card score had improved by the fifth day of treatment to 13.0 (0.7) in the purulent group (mean difference -6.6 (95% CI -8.8 to -4.4), p<0.001) and 14.6 (0.8) in the mucoid group (mean difference -1.7 (95% CI -4.0 to 0.8), p<0.05), which was no longer significantly different from the stable state. Diary card scores did not differ significantly between patients who received antibiotics for 5 or 10 days in the purulent group or between patients who received inhaled fluticasone or placebo in the mucoid group. CONCLUSIONS: Exacerbations of chronic bronchitis associated with purulent sputum have significantly worse symptoms at presentation than those with mucoid sputum. In both groups these symptoms resolve rapidly so that by the fifth day of treatment they are no different from the stable state. No significant effect was found on symptom resolution of antibiotic duration (5 v 10 days) in the purulent group or of inhaled fluticasone in the mucoid group, which resolved without antibiotics. Larger numbers may be required to demonstrate a statistically (if not clinically) significant difference.
Acute Disease↗
A randomized, double-blind, placebo-controlled trial of TMC125 as 7-day monotherapy in antiretroviral naive, HIV-1 infected subjects.
OBJECTIVE: To evaluate antiviral activity, tolerability, safety and pharmacokinetics of treatment with TMC125 (a non-nucleoside reverse transcriptase inhibitor), 900 mg twice daily for 7 days. DESIGN: Randomized, double-blind, placebo-controlled, phase IIA clinical trial. SETTING: Two hospital clinics in Moscow and St Petersburg, Russian Federation. PARTICIPANTS: Nineteen antiretroviral-naive, HIV-1-infected subjects. INTERVENTIONS: Randomization (2:1) was to twice daily treatment with either 900 mg TMC125 or matched placebo as monotherapy for 7 days. MAIN OUTCOME MEASURES: Change in plasma HIV-1 RNA from baseline values (primary); change in CD4 cell counts from baseline, and evaluation of safety, tolerability and pharmacokinetics of TMC125 treatment (secondary). RESULTS: A mean decrease from baseline in plasma HIV-1 RNA of 1.99 log10 copies/ml and 0.06 log10 copies/ml was achieved after 7 days in the TMC125 and placebo groups, respectively (P < 0.001). Plasma viral daily decay rates of 0.33 log10 copies/ml and 0.02 log10 copies/ml were observed in the TMC125 and placebo groups, respectively (P < 0.001). A steady-state plasma concentration of TMC125 was attained within 5 days of treatment with a mean minimum concentration of 246 ng/ml and a mean maximum concentration of 419 ng/ml. The majority of subjects did not report any adverse events. No abnormalities consistent with changes in blood chemistry, haematology, urinalysis, electrocardiograph or vital signs were observed. CONCLUSIONS: TMC125 administered as monotherapy for 7 days yielded a 1.99 log10 copies/ml reduction in HIV-1 RNA in antiretroviral-naive, HIV-1-infected subjects. TMC125 was well tolerated and represents a promising and highly potent, next generation non-nucleoside reverse transcriptase inhibitor candidate.
Adult↗
D-cycloserine for the treatment of ataxia in spinocerebellar degeneration.
We studied the effects of D-cycloserine, a partial NMDA receptor allosteric agonist, on ataxia in patients with spinocerebellar degeneration. Fifteen Japanese ataxic patients enrolled in a 14-day single-blind trial of D-cycloserine (daily oral dose of 50 mg) following a 14-day single-blind placebo phase. At the end of the D-cycloserine administration, there was a significant reduction in the posture, gait and total score of the international cooperative ataxia rating scale and in the time for walking and speech tasks. D-Cycloserine was well-tolerated and no adverse effect was observed. D-Cycloserine may have therapeutic efficacy for spinocerebellar ataxia.
Adult↗
Analgesia after day-case knee arthroscopy: double-blind study of intra-articular tenoxicam, intra-articular bupivacaine and placebo.
Arthroscopy of the knee is performed regularly on a day-case basis. Intra-articular bupivacaine produces transient analgesia and reports of analgesia using intra-articular morphine have produced conflicting results. Non-steroidal anti-inflammatory drugs given systemically can provide effective analgesia for this procedure. In this study we attempted to determine if intra-articular tenoxicam provided useful analgesia after day-case arthroscopy. Sixty three ASA I-II patients were allocated randomly to one of three groups to receive 40 ml of a solution containing 0.9% saline (group Pla), 0.25% bupivacaine (group Bup) or tenoxicam 20 mg (group Ten). The injection was made into the knee joint at the end of surgery, 10 min before tourniquet deflation. Verbal rating and visual analogue pain scores (at rest and on knee flexion), use of analgesia, mobilization and disturbance by pain at home were recorded for the next 48 h. There were no differences between pain scores in any of the three groups when tested at rest or on movement. Less analgesia was used in the first 24 h by patients in the tenoxicam group but the difference in time to first analgesia was not statistically significant. Side effects and disturbance by pain were similar in all groups. The use of intra-articular tenoxicam 20 mg at the end of arthroscopy reduced oral analgesic requirements during the first day after operation but did not alter patients' perception of pain.
Adolescent↗
Etodolac versus diclofenac: double-blind cross-over study in rheumatoid arthritis.
A 14-day double-blind clinical study was conducted on 16 patients with clinically active rheumatoid arthritis to compare the effects of etodolac (600 mg daily) and diclofenac (150 mg daily). Admission criteria were: functional impairment between Steinbrocker's classes I to III, Ritchie's index greater than 10 and erythrocyte sedimentation rate greater than 25 mm/h, and finally active involvement of the small joints of the hands. Following a wash-out period of at least two days from their previous non-steroidal anti-inflammatory drugs, trial patients received etodolac or diclofenac for five consecutive days by random allocation; after that, and after another two day wash-out period, all patients were crossed-over to the alternate drug for another five consecutive days. One day before intake and on the last day of each treatment lap, each patient was examined in regard to the circadian grip strength (of the more severely affected hand), Ritchie's index and acute phase reactants; at the end of the second treatment period, subjective drug preference was explored. Grip strength was assessed by the patients themselves with a dynamometer at 08h00 and every two hours thereafter until 20h00. The overall daily value was calculated by measuring the area under curve (AUC) depicting the grip strength profile. Both groups of patients showed significant improvement of the Ritchie's index (p less than 0.01) and grip strength AUC (p less than 0.05), while taking medication, whereas no significant variations were noted in regard to the values of the acute phase parameters both between the two treatment groups, and within each treatment group. At termination, four patients expressed preference for etodolac, eight were in favour of diclofenac, and four gave an indifferent judgement. No statistically significant differences were detected between the two treatment groups; also no adverse events were seen in this short-term study. The results confirm the effectiveness and tolerability of etodolac in the acute stage of rheumatoid arthritis.
Adult↗
Albendazole therapy for neurocysticercosis: a prospective double-blind trial comparing 7 versus 14 days of treatment. Cysticercosis Working Group in Peru.
OBJECTIVE: To compare the effectiveness of two regimens of albendazole therapy for neurocysticercosis. DESIGN: Randomized, double-blind clinical trial. SETTINGS: Patients admitted to neurologic wards in Lima, Peru. PATIENTS: Adult patients with active neurocysticercosis demonstrated by CT and Western blot (immunoblot). INTERVENTION: One week (n = 25) versus 2 weeks (n = 25) of albendazole therapy. MEASUREMENTS: Decrease in the number of cysts on CT. RESULTS: Effectiveness of albendazole was 78%, with no difference between the groups when compared 3 months after therapy. Complete cure was obtained in only 38% of patients. Patients with more than 20 cysts had poorer responses to therapy. The clinical course and EEG evolution improved in most patients. Side effects were present in 38% of patients, mainly mild, transient gastrointestinal symptoms. Therapy was also associated with exacerbation of neurologic symptoms. Two patients died in the first year after therapy, both because of aggregated infections of ventricle-peritoneal shunts. One-year follow-up CT showed lesions in three of 10 patients presumed to be cured 3 months after therapy. CONCLUSIONS: Extension of albendazole therapy for more than 7 days adds no benefits for the patients.
Adult↗
A pilot study examining topical amitriptyline, ketamine, and a combination of both in the treatment of neuropathic pain.
OBJECTIVE: The involvement of ongoing peripheral activity in the generation of nociceptive input in neuropathic pain suggests that topical drug delivery may be useful as a treatment strategy. This is a pilot study providing initial information regarding the use of novel topical preparations containing amitriptyline (AMI), ketamine (KET), and a combination of both in the treatment of neuropathic pain. METHODS: The study design included a 2 day randomized, double blind, placebo controlled, 4 way cross-over trial of all treatments, followed by an open label treatment phase using the combination cream for 7 days. Twenty volunteers with chronic neuropathic pain were randomly assigned to treatment order and applied 5 mls of each topical treatment (1% AMI, 0.5% KET, combination AMI 1%/KET 0.5%, and placebo) for 2 days. Measures of pain at the end of each block included the short form McGill Pain Questionnaire (MPQ) and visual analog scales (VAS) for present pain intensity and pain relief. Eleven subjects who judged subjective improvement from any treatment in the initial trial entered the open-label trial and used the combination cream for 7 days. Pain levels were recorded daily using the same measures. Blood levels for amitriptyline and ketamine were performed at 7 days to determine whether systemic absorption had occurred. RESULTS: There was no statistically significant difference from placebo after 2 days for any treatment during the double blind component of the trial. In the 11 subjects who used the combination cream, there was a statistically significant effect, with subjects reporting significantly greater analgesia by days 3 to 7 according to measures of pain and pain relief. Blood levels revealed that there was no significant systemic absorption of amitriptyline or ketamine. Only 2 subjects experienced side effects; these were minor and did not lead to discontinuation of the cream. CONCLUSION: This pilot study demonstrated a lack of effect for all treatments in the 2 day double blind placebo controlled trial, followed by analgesia in an open label trial in a subgroup of subjects who chose to use the combination cream for 7 days. Blood analysis revealed no significant systemic absorption of either agent after 7 days of treatment, and creams were well tolerated. A larger scale randomized trial over a longer interval is warranted to examine further effects observed in the open label trial.
Administration, Topical↗
The effects of steady-state erythromycin and azithromycin on the pharmacokinetics of sildenafil in healthy volunteers.
AIMS: Sildenafil, an effective oral treatment for erectile dysfunction, is predominantly metabolized by the cytochrome P450 isozyme 3A4, which is inhibited by a number of the macrolide antibiotics. Therefore, two placebo-controlled, parallel-group studies were conducted to evaluate the effects of multiple doses of erythromycin and azithromycin on the pharmacokinetics, safety and tolerability of a single oral 100-mg dose of sildenafil. METHODS: In the erythromycin interaction study, 26 male volunteers (18--45 years of age) received open-label sildenafil 100 mg on day 1. Half received blinded erythromycin (500 mg) twice daily on days 2--6, and the other half received placebo. On day 6, all subjects received a second 100-mg dose of sildenafil. In the azithromycin interaction study, 24 male volunteers (19--33 years of age) received open-label 100 mg sildenafil on day 1. Half then received blinded azithromycin (500 mg) once daily on days 2--4, and the other half received placebo. On day 4, all subjects received another 100-mg dose of sildenafil. In both studies, blood samples were collected on the first and last study day for the analysis of plasma concentrations of sildenafil and its primary metabolite, UK-103,320. RESULTS: Repeated dosing with erythromycin caused statistically significant increases in the AUC and Cmax of sildenafil (2.8-fold and 2.6-fold, respectively) but had no effect on Tmax, kel or t1/2. A statistically significant 1.4-fold increase in the AUC of UK-103,320 was also observed, as well as a significant decrease in kel, resulting in an increase of about 1 h in t1/2. In contrast, repeated dosing with azithromycin caused no significant change in any pharmacokinetic parameter of either sildenafil or UK-103,320. Erythromycin, azithromycin and sildenafil were well tolerated; adverse events were mild and transient. No subject withdrew from either trial for any reason related to study drug. CONCLUSIONS: These results indicate that erythromycin modifies the pharmacokinetics of sildenafil by inhibiting its CYP3A4-mediated first-pass metabolism. Given these data, a lower starting dose of sildenafil (25 mg) may be considered for patients receiving erythromycin or other potent CYP3A4 inhibitors. Azithromycin did not affect the pharmacokinetics of sildenafil; therefore, no adjustment in dosage is necessary for patients receiving these drugs concomitantly.
Adult↗
Pineal gland: influence on gonads of male rats treated with androgen 3 days after birth.
Either blinding or the injection of 1 milligram of testosterone propionate into male Sprague-Dawley rats, 3 days old, results in testes and accessory organs (seminal vesicles and coagulating glands) that are smaller than normal when the rats are 72 days old. The response to blinding is prevented by removal of the pineal gland, whereas the response to treatment with testosterone is unaffected by pinealectomy. Combination of the two treatments in 3-day- old rats causes testes to be less than one-third their normal size at 72 days of age; pinealectomy in these rats permits the reproductive organs to grow to the same size as those in the androgen-treated animals.
Animals↗
A multicenter, randomized, investigator-blinded study of 5- and 10-day gatifloxacin versus 10-day amoxicillin/clavulanate in patients with acute bacterial sinusitis.
BACKGROUND: Treatment guidelines for acute bacterial sinusitis recommend 10 to 14 days of therapy with amoxicillin/clavulanate, high-dose amoxicillin, cefpodoxime, cefuroxime, or a newer fluoroquinolone. OBJECTIVE: This study compared the clinical efficacy of short-course (5-day) gatifloxacin with standard 10-day regimens of amoxicillin/clavulanate or gatifloxacin in patients with a diagnosis of acute, uncomplicated maxillary sinusitis. METHODS: This was a multicenter, investigator-blinded study in adult patients (age >18 years) with physical findings, signs and symptoms (for at least 7 days), and radiographic findings indicating acute, uncomplicated maxillary sinusitis. Patients were randomized to receive gatifloxacin 400 mg once daily for 5 days, gatifloxacin 400 mg once daily for 10 days, or amoxicillin/clavulanate 875 mg twice daily for 10 days. Clinical response was assessed once between days 3 and 5 of treatment, once I to 3 days after the completion of study treatment, once 7 to 14 days posttreatment (test-of-cure visit), and once 21 to 28 days posttreatment. Safety was assessed throughout the study. RESULTS: The study enrolled 445 patients. The treatment groups were similar in terms of history of sinusitis, presenting signs and symptoms, and radiographic findings. The most common presenting symptoms were nasal congestion, sinus tenderness, and purulent nasal discharge (>90% of patients); 99% of patients had abnormal radiographic findings. At the test-of-cure visit, clinical cure rates for clinically evaluable patients in the 3 treatment groups were 74% (102/137) for 5-day gatifloxacin, 80% (101/127) for 10-day gatifloxacin, and 72% (101/ 141) for 10-day amoxicillin/clavulanate (95% CI for the difference in cure rates: 5-day gatifloxacin vs amoxicillin/clavulanate, -7.6 to 13.2; 5- vs 10-day gatifloxacin, -15.2 to 5.1; 10-day gatifloxacin vs amoxicillin/clavulanate, -2.3 to 18.1). The distribution and incidence of drug-related adverse events (AEs) were comparable between treatment groups, and the majority (>95%) were mild or moderate in severity. The most common drug-related AEs included vaginitis, diarrhea, and nausea. CONCLUSION: In this population of patients with acute, uncomplicated sinusitis of presumed bacterial origin, a short course (5 days) of gatifloxacin therapy was associated with comparable clinical cure rates and tolerability to those of standard 10-day therapy with gatifloxacin or amoxicillin/clavulanate.
Adult↗
Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial.
BACKGROUND: Many countries in Africa are considering a change to combination treatment for falciparum malaria because of the increase in drug resistance. However, there are few effectiveness data for these combinations. Our aim was to study the effectiveness of three drug combinations that have proven efficacious in east Africa compared with amodiaquine monotherapy. METHODS: We undertook a randomised trial of antimalarial drug combinations for children (aged 4-59 months) with uncomplicated malaria in Muheza, Tanzania, an area with a high prevalence of resistance to sulfadoxine-pyrimethamine and chloroquine. Children were randomly allocated 3 days of amodiaquine (n=270), amodiaquine +sulfadoxine-pyrimethamine (n=507), or amodiaquine+artesunate (n=515), or a 3-day six-dose regimen of artemether-lumefantrine (n=519). Drugs were taken orally, at home, unobserved by medical staff. The primary endpoint was parasitological failure by day 14 assessed blind to treatment allocation. Secondary endpoints included day 28 follow-up and gametocyte carriage. Analysis was by intention to treat. FINDINGS: Of 3158 children screened, 1811 were randomly assigned treatment and 1717 (95%) reached the 14-day follow-up. The amodiaquine group was stopped early by the data and safety monitoring board. By day 14, the parasitological failure rates were 103 of 248 (42%) for amodiaquine, 97 of 476 (20%) for amodiaquine+sulfadoxine-pyrimethamine, 54 of 491 (11%) for amodiaquine+artesunate, and seven of 502 (1%) for artemether-lumefantrine. By day 28, the parasitological failure rates were 182 of 239 (76%), 282 of 476 (61%), 193 of 472 (40%), and 103 of 485 (21%), respectively. The difference between individual treatment groups and the next best treatment combination was significant (p<0.001) in every case. Recrudescence rates by day 28, after correction by genotyping, were 48.4%, 34.5%, 11.2%, and 2.8%, respectively. INTERPRETATION: The study shows how few the options are for treating malaria where there is already a high level of resistance to sulfadoxine-pyrimethamine and amodiaquine. The WHO-packaged six-dose regimen of artemether-lumefantrine is effective taken unsupervised, although cost is a major limitation.
Amodiaquine↗