The relationship between core stability and athletic performance in female university athletes.

Background: Questions remain as to whether core stability represents single or multiple components, how to assess core stability, and if a relationship exists with athletic performance in different sporting codes. Objectives: To investigate the relationship between core stability and athletic performance in female university athletes. Methods: Eighty-three female athletes (hockey, netball, running, soccer and tennis) participated in this quantitative, cross-sectional study. The isometric back extension (IBE), lateral flexion (LF) and abdominal flexion (AF) tests were used to measure core strength and endurance. The core stability grading system using a pressure biofeedback unit was applied to measure core neuromuscular control (NMC). Athletic performance was assessed using the 40 m sprint, T-test, vertical jump (VJ) and the medicine ball chest throw (MBCT). Correlations between the core stability tests and the athletic performance tests were determined overall and separately by sport. The effect of core stability on athletic performance was analysed using ANCOVA. Results: Overall for all sports, most correlations were weak (r=0.10-0.39), although there was a very strong correlation between LF (strength) and VJ (r=0.90). When the sports were considered separately, there were moderate correlations (r=0.40-0.69) between core strength, endurance and motor control with certain athletic performance tests in all five sport codes. In runners, strong correlations (r=0.70-0.89) were observed between AF (endurance) and VJ, and in tennis players between IBE (strength) and the sprint. Conclusion: Correlations were found between core stability and athletic performance, although most correlations were negligible or weak. Athletic performance in different sport codes is associated with different components of core stability.

Epidemiology of injuries among U18, U19, U21 and senior elite netball players.

Background: Despite a substantial body of literature on injuries among elite netball players in South Africa, no study reports on the timing and type of injuries and the reason for injuries. Objective: To determine the epidemiology of injuries in U18, U19, U21 and senior netball players in the Free State (FS), South Africa, over two consecutive netball seasons (2017/2018). Methods: An injury questionnaire was used to collect data on 96 eligible players. Results: A total of 48 injuries were reported. The profile of injuries revealed that 58% (n=28) of the injuries occurred during matches, 29% (n=14) during practice and 13% (n=6) during preseason training. Acute injuries accounted for 54% (n=26) of the total, while 46% (n=22) were overuse injuries. A third of all the injuries were re-injuries. The centre (C) position had the highest incidence of injuries in players (n=14; 29%). The ankle was the most frequently injured body part (n=18; 36%), followed by the lower leg and Achilles tendon (n=6; 13%) thus largely the ligaments and muscles. The overall incidence rate of injuries during match play was 33.9 injuries per 1 000 hours of match play. Conclusion: Preventative strategies should consist of ankle and lower leg strengthening and neuromuscular balance techniques. The focus should be on correct landing techniques, results of abrupt change of direction movements and short bursts of speed.

Physical and physiological profile of U18, U19, U21 and senior elite netball players.

Background: Physical and physiological profile data for elite netball players in South Africa and internationally are limited but are necessary for conditioning programme information. Objective: To determine the physical and physiological profiles of U18, U19, U21 and senior level elite netball players at provincial level in the Free State, South Africa. The information provided is by age group and playing position. The fitness of the players for South African and New Zealand netball is also given using the fitness normative data (norms). Methods: This cross-sectional, descriptive study consisted of 77 elite South African netball players. Anthropometric measurements were taken according to international standards. Fitness tests included the Star Execution Balance Test, standing broad jump, double- and single-leg vertical jump, Yo-Yo Intermittent Recovery Level 1(IR1) test, sprints over 5, 10 and 40 m, horizontal pull-ups and press-ups, the prone bridge test and anaerobic Octorepeater tests with 10 m and 20 m repeated shuttle sprints. In keeping with the descriptive nature of the study, descriptive statistics were calculated for numerical data by age group and playing position. Results: Players generally did not meet the accepted fitness standards in the following areas: press-ups (all age groups), horizontal pull-ups (senior and U21), standing broad jump (senior and U21), vertical squat jump (senior and U21), 5 m and 10 m sprints (senior and U21); anaerobic Octorepeater (senior players), and the aerobic Yo-Yo IR1 test (all age groups). Conclusion: Strength and conditioning coaches should develop training programmes to address fitness areas where players do not meet the international standards.

Sample size determination in bioequivalence studies using statistical assurance.

AIMS: Bioequivalence (BE) trials aim to demonstrate that the 90% confidence interval of the T/R-ratio of the pharmacokinetic metrics between two formulations (test [T] and reference [R]) of a drug is fully included in the acceptance interval [0.80, 1.25]. Traditionally, the sample size of BE trials is based on a power calculation based on the intrasubject variability coefficient of variation (CV) and the T/R-ratio of the metrics. Since the exact value of the T/R-ratio is not known prior to the trial, it is often assumed that the difference between the treatments does not exceed 5%. Hence, uncertainty about the T/R-ratio is expressed by using a fixed value for the sample size calculation. We propose to characterise the uncertainty about the T/R-ratio by a (normal) distribution for the log(T/R-ratio), with an assumed mean of  log Î¸ = 0.00 (i.e. θ = 1.00) and a standard deviation σu , which quantifies the uncertainty. Evaluating this distribution leads to the statistical assurance of the BE trial. METHODS: The assurance of a clinical trial can be derived by integrating the power over the distribution of the input parameters, in this case, the assumed distribution of the log(T/R)-ratio. Because it is an average power, the assurance can be interpreted as a measure of the probability of success that does not depend on a specific assumed value for the log(T/R)-ratio. The relationship between power and assurance will be analysed by comparing the numerical outcomes. RESULTS: Using the assurance concept, values of the standard deviation for the distribution of potential log(T/R)-ratios can be chosen to reflect the magnitude of uncertainty. For most practical cases (i.e. when 0.95 ≤ Î¸ ≤ 1.05), the sample size is not, or only slightly, changed when σ = |log(θ)|. CONCLUSION: The advantage of deriving the assurance for BE trials is that uncertainty is directly expressed as a parameter of variability.

Age of diagnosis, incidence and prevalence of recurrent respiratory papillomatosis-A South African perspective.

OBJECTIVES: To determine the distribution of the age of diagnosis of recurrent respiratory papillomatosis (RRP) and to determine the incidence and prevalence of RRP in both adults and children in the Free State province of South Africa in order to provide data from a population in sub-Saharan African. DESIGN: Retrospective record review. PARTICIPANTS: All patients with RRP in the Free State province of South Africa between 2011 and 2015. MAIN OUTCOME MEASURES: Distribution of the age of diagnosis of RRP and incidence and prevalence of RRP. RESULTS: The best fitting mixture distribution for the age of diagnosis of RRP was a two-component mixture of log-normal distributions. Within the first component (JoRRP), the age of diagnosis was significantly lower in patients with human papillomavirus (HPV)11 disease (median 3.2 year) than those with HPV6 disease (median 5.6 years) (P = .021), while in the second component (AoRRP), there was no significant difference in the age of diagnosis between HPV11 disease (30.7 year) and HPV6 disease (median 44.0 years) (P = .0696). The incidence and prevalence of JoRRP were 1.34/100000 population/year and 3.88/100000 population, respectively, while the incidence and prevalence of AoRRP were 0.18/100000 population/year and 0.38/100000 population, respectively. CONCLUSION: Recurrent respiratory papillomatosis in the Free State province of South Africa is a disease with a predominantly juvenile onset, with AoRRP having a lower prevalence than in Europe. This is probably reflective of the situation in sub-Saharan Africa.

A world-wide survey and field study in clinical haemostasis laboratories to evaluate FVIII:C activity assay variability of ADYNOVATE and OBIZUR in comparison with ADVATE.

INTRODUCTION: Discrepancies have been previously reported for one-stage clotting and chromogenic assays for FVIII activity analysis. Inter-laboratory variations in instruments, method of clot detection, assay set-up, reference standard calibration, reagent source and reagent composition all contribute to assay variability. AIM: To characterise multilaboratory assay variability in measuring ADYNOVATE, OBIZUR and ADVATE FVIII activity in human plasma and survey multinational FVIII activity assay preferences. METHODS: As samples from patients treated with either of the FVIII products are not available in the quantities required for a systematic collaborative study, haemophilia A plasma was spiked in vitro with either ADYNOVATE (PEGylated rFVIII), OBIZUR [Porcine Sequence Antihaemophilic Factor (Recombinant)] or ADVATE at high (0.80 IU or U mL-1 ), medium (0.20 IU or U mL-1 ) and low (0.05 IU or U mL-1 ) FVIII concentrations, based on labelled potencies. Clinical laboratories used their routine FVIII activity assay to determine FVIII activity of each product. Thirty-five data sets using one-stage clotting assay and 11 sets using chromogenic assay were obtained. RESULTS: A vast majority of laboratories (98%) prefer and rely on the one-stage clotting assay. Mean recoveries across all concentrations were 113%, 120% and 127% for ADYNOVATE, OBIZUR and ADVATE respectively. Assay variation was comparable between ADVATE, ADYNOVATE and OBIZUR with inter-laboratory percent coefficients of variation (%CV) ranging from 11 to 22%. Mean chromogenic assay results were 116%, 51% and 113% for ADYNOVATE, OBIZUR and ADVATE respectively. Inter-laboratory CV's were similar for ADYNOVATE, OBIZUR and ADVATE. CONCLUSIONS: One-stage clotting assays can and will be used with sufficient accuracy and precision for the measurement of ADYNOVATE, OBIZUR and ADVATE in plasma samples from subjects with haemophilia A. Chromogenic assay underestimates OBIZUR potency, particularly at lower concentrations.

Indirect bioequivalence assessment using network meta-analyses.

AIMS: For market approval, new drug formulations (test) must demonstrate bioequivalence (BE) to at least one approved formulation (reference). If several formulations of a drug are already on the market, one might have to show BE to more than one reference formulation. Similarly, if several test formulations have shown BE to a reference formulation, it will be of interest whether the test formulations are bioequivalent to each other. METHODS: An enhanced statistical model to assess BE indirectly through a network meta-analysis is provided. Statistical properties of a parallel and a bridging approach are derived, in particular the relative statistical efficiency of the two approaches. The analysis is illustrated using individual subject data from two 3×3 crossover trials of metformin formulations, which have one of the formulations in common. RESULTS: The parallel estimate of relative bioavailability is confounded with between-trial differences, while the bridging estimate is not. The standard errors of the formulation differences using the bridging approach are smaller than the standard errors using the parallel approach if the within-subject correlation in each trial of the network is larger than 0.5. This is the condition for a crossover trial to be more efficient than a parallel trial, and thus is usually fulfilled in pharmacokinetic crossover trials. CONCLUSIONS: Indirect BE assessment offers the opportunity to efficiently determine the relative bioavailability of drug formulations that have not been studied in the same randomized BE trial. The methodology developed here allows estimating formulation differences across a larger network.

Assessment of combined symptom and medication scores for rhinoconjunctivitis immunotherapy clinical trials.

BACKGROUND: In randomized, double-blind, placebo-controlled clinical trials the efficacy of immunotherapy for allergic rhinoconjunctivitis is evaluated using the Average Rhinoconjunctivitis Total Symptom Score (ARTSS). Effective treatment is associated with lower ARTSS relative to placebo. For ethical reasons patients are provided with registered rescue medication, which may alleviate symptoms and thus reduce symptom scores. This effect biases the mean difference in ARTSS between effective treatment and placebo towards zero. Therefore, when rescue medication is taken by a patient, the ARTSS needs to be adjusted appropriately. METHODS: We considered five outcome measures: ARTSS, Average Rescue Medication Score (ARMS), and three combined symptom and RMSs. To assess the different outcome measures regarding their power to discriminate between effective treatment and placebo, we calculated their effect size when applied to data from a clinical trial of immunotherapy for allergic rhinoconjunctivitis. RESULTS: Of the five outcome measures considered, the average of the ARTSS and ARMS was associated with the largest effect size, and thus with the highest power to show treatment efficacy. Discriminant and multivariate analyses suggest that this average is approximately optimal among all weighted sums of ARTSS and ARMS. CONCLUSION: Our findings support recommendations made in a World Allergy Organisation document on methodological aspects of immunotherapy trials. The average of the ARTSS and ARMS should be considered as a primary efficacy variable in clinical trials of immunotherapy for allergic rhinoconjunctivitis.

Old antihypertensives and new diabetes.

Diuretic antihypertensive therapy is recommended as first choice by many guidelines, often in combination with beta-blockers. However, such recommendations are based on relatively short-term trials, whereas treatment for hypertension is often a lifetime process. A meta-analysis of seven studies in 58,010 individuals, showed that the 'new' therapies, namely angiotensin-converting enzyme (ACE) inhibitors, angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) provoke less new diabetes than the conventional 'old' therapies (diuretics and beta-blockers). ACE inhibitors/ARBs decreased new diabetes by 20% (P < 0.001), whereas CCBs decreased new diabetes by 16% (P < 0.001). The number needed to treat for approximately 4 years by new rather than old conventional therapy to avoid one case of new diabetes is about 60-70. Other factors contributing to increased coronary risk are increased metabolic syndrome, blood lipid changes and hypokalaemia. It is not certain whether it is the new therapy that provides protection against new diabetes or the conventional therapy that precipitates new diabetes. However, when compared with placebo, ACE inhibition by ramipril or by the ARB, candesartan, both decrease the incidence of new diabetes, raising the hypothesis that these agents actually prevent the changes leading to insulin resistance, possibly by lessening the adverse effects of angiotensin II on the endothelium. Conversely, lipid abnormalities with conventional treatment could exert adverse effects on the endothelium. Therefore endothelial changes could help to explain the benefits of 'modern' treatment compared with the defects of conventional therapy.

Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer.

OBJECTIVE: To compare the efficacy of monthly administrations of the luteinizing hormone-releasing hormone agonists triptorelin pamoate and leuprolide acetate to induce and maintain castrate levels of serum testosterone in men with advanced prostate cancer. PATIENTS AND METHODS: Men with advanced prostate cancer were randomly assigned to receive triptorelin 3.75 mg or leuprolide 7.5 mg. The agent was injected intramuscularly every 28 days for nine injections. Primary endpoints were the percentages of men whose serum testosterone concentrations declined to and were maintained at or below castrate levels (

The effect of food on the pharmacokinetics of nifedipine in two slow release formulations: pronounced lag-time after a high fat breakfast.

AIMS: The aim of this study was to investigate the effect of concomitant food intake on the bioavailability of two nifedipine containing modified release dosage forms for once daily administration. The clinical study was performed to investigate the in vivo relevance of pH-dependent differences in the in vitro release properties of the two dosage forms. METHODS: This was a randomized, open, 4-way crossover study in 24 healthy, male subjects. Following an overnight fast of 12 h single doses of Adalat OROS or Slofedipine XL were administered either in the fasted state or immediately after a high fat American breakfast. Nifedipine plasma concentrations in samples obtained until 48 h after drug administration were determined using a validated LC-MS/MS method. Calculation of pharmacokinetic parameters was conducted model-independently. The two dosage forms as well as the two administration conditions were compared by calculating point estimates and 90% confidence intervals for the relevant pharmacokinetic parameters. In vitro dissolution tests were performed using a paddle apparatus 3 acc. USP, a pharmacopoeial dissolution system consisting of reciprocating cylinders in flat-bottomed glass vessels, with various buffer systems covering the entire physiological pH-range of the gastrointestinal tract. RESULTS: After fasted administration the extent of bioavailability of nifedipine as characterized by AUC(0,infinity) was slightly lower for Slofedipine XL compared with Adalat OROS with a point estimate of 82.3% primarily resulting from pronounced differences in nifedipine concentrations during the first 15 h after administration. Accordingly, maximum plasma concentrations were lower after administration of Slofedipine XL compared with Adalat OROS (point estimate: 84.3%). Under fed conditions the differences in bioavailability between the two products as characterized by the pharmacokinetic parameters AUC(0,tn) and Cmax were greater than after fasting conditions with point estimates of 69.6% and 81.0%, respectively. However, most striking was a pronounced delay in nifedipine absorption observed under fed conditions after administration of Slofedipine XL which resulted in lag-times of more than 15 h in 15 out of 24 subjects. Owing to this lag-time under fed conditions the relative bioavailability of nifedipine from Slofedipine XL compared with Adalat OROS was only 28% over the intended dosing interval of 24 h. CONCLUSIONS: In this study a dosage form-dependent food interaction was observed which, under fed conditions, resulted in pronounced differences in the relative bioavailability of nifedipine between Slofedipine XL and Adalat OROS over the intended dosing interval of 24 h. The delay in nifedipine absorption when Slofedipine XL is administered after a high-fat breakfast may be explained by the formulation properties. Slofedipine XL is an erosive tablet with an acid resistant coating whereas Adalat OROS is designed with an osmotic push-pull system. Under fed conditions drug from the single unit enteric coated dosage form exhibits a delayed absorption probably due to an extensively prolonged gastric residence time which does not allow drug release, on the other hand the osmotically driven push-pull system is not sensitive to concomitant food intake. The observed phenomenon might be of therapeutic relevance. For example a change from taking Slofedipine XL in the fed to the fasted state might result in increased systemic concentrations of nifedipine.

Comparison of the pharmacokinetic profiles of soluble aspirin and solid paracetamol tablets in fed and fasted volunteers.

The aim of this study was to investigate the absorption of popular preparations of two common analgesics--soluble aspirin and solid paracetamol tablets. An open, randomised, crossover study design was used to compare the pharmacokinetic parameters of soluble aspirin and solid paracetamol tablets in 16 healthy, male volunteers from the University of the Witwatersrand, South Africa, in both fed and fasted states. Plasma concentrations of paracetamol, aspirin and salicylic acid were measured. It was found that the rate of absorption was significantly faster for soluble aspirin than for solid paracetamol, regardless of fed or fasting state, considering time to maximum concentration (p < 0.01), time to first quantifiable concentrations (p < 0.05) and absorption rate (p < 0.01). Absorption rate was significantly affected by food for both soluble aspirin (p = 0.028) and for solid paracetamol (p = 0.0003). Time to maximum concentration was not significantly affected by food for soluble aspirin (p = 0.17) but significantly lengthened for solid paracetamol (p = 0.0003). The extent of absorption was affected by food in terms of maximum concentration for both drugs (p = 0.0001), with a reduction of 49% in the fed state for solid paracetamol compared to 18% for soluble aspirin, the difference between the drugs being statistically significant (p = 0.0024). The overall bioavailability of soluble aspirin was unaffected by food and the bioavailability of salicylic acid was increased in the fed state, whereas that of solid paracetamol was lowered in the fed state. Greater inter-individual variation was seen in paracetamol concentrations compared with aspirin or salicylic acid levels. In conclusion, these results show that the absorption of soluble aspirin is largely unaffected by food, whereas, in the same volunteers, the absorption of solid paracetamol tablets is greatly affected. In some volunteers, maximum plasma concentrations of paracetamol following food did not reach levels previously reported to be required for effective analgesia, and this may have implications for pain relief in some individuals. The practice in some individuals of taking aspirin tablets after food to minimise potential gastric disturbance should not affect the level of analgesia.

[GSG (Structured Health Regulation)-conforming documentation of surgical interventions in a university clinic--3 years clinical experiences 1994-1996]. / GSG-konforme Dokumentation operativer Eingriffe an einer Universitätsklinik--3 Jahre klinische Erfahrung 1994-1996.

The cost increase in the public health sector is steadily mounting and hence politicians are forced to redefine the economic conditions for regulations. As a new quality in the area of inpatient hospital care the new German law of structural health care (GSG), valid as of January 1, 1993 replaces the principle of covering full costs. The GSG law required in our hospital an adjustment of existing EDP structures with integrated automatic remuneration estimate and the installation of a medical structure of the organisation for complete and correct documentation. Weakpoints of the prescribed obligatory ICPM codes and inadequate legal regulations result in a lack of separation or wrong integration of the lump sum payment in individual cases (FP) and special compensation (SE). The summary analysis of the compensation system with a subsequent medical control system showed a primarily inaccurate classification by 12%. There is as yet no proof for the usefulness of a lump sum payment system resulting in a selection of risks.

Cost Effectiveness of G:CSF in Chemotherapy and Transplant-related Neutropenia.

Sustained fever over 38°C is potentially lethal when neutrophil counts remain below 0.1 × 10(9)/L. To determine whether the addition of a haematopoietic stimulatory peptide to conventional supportive care and antibiotic management was cost-effective, 74 such episodes were analysed. Group I (5µg/kg G: CSF: n = 41); Group II (10 µg/kg: n = 19) and Group III (controls: n = 14): these were similar in respect of race, gender, age and body weight. The median days and range of neutrophil count below 0.1 × 10(9)/Lw as 6 (0-12), 7 (0-20) and 8 (0-20) and the corresponding figures for 0.5 × 10(9)/L were 8 (0-19), 8 (1-23) and 13.5 (3-30) days respectively, while the median hospital period was 26 (18-49), 30 (9-86) and 35 (13-44). Mean, standard deviation and range for bed costs in Group I was R9,528 (2125:6120-1660), the corresponding figures for Group II were Rll,453 (5570:3060-2924), and for Group III Rll,366 (2755: 4420-1496). The approximate fate of exchange is: Rl = US$5.87. When expenditure for growth factor was integrated these figures were approximately R26,071, R37,787 and R27,376. There were no advantages in 10 over 5 µg/kg G: CSF. More red cell transfusions were needed in Group III. The days requiring antimicrobial therapy were 14, 16 and 20 respectively. It is concluded from this study, carried out in reverse isolation at a University Teaching Hospital, that duration of neutropenic fever was significantly shortened on G: CSF but there was no benefit in using the higher dose. Additionally, at equivalent cost, there was a shorter period of hospitalisation thereby reducing risk of acquiring nosocomial infections. Finally, there was concurrently a decreased exposure to potentially nephrotoxic antibiotics. Accordingly, this regimen can be justified in the routine management of this category of patient.

[Analysis of the acceptance of the internet presentation of the 115th Congress of the German Society of Surgery]. / Akzeptanzanalyse der Inernetpräsentation des 115. Kongresses der Deutschen Gesellschaft für Chirurgie.

The World Wide Web presentation of the 115th Annual Meeting of the German Society of Surgery was examined with regard to the frequency of hits per day and the use made of the online offers. The high frequency of the hits clearly shows the high acceptance of this medium. The temporal distribution of the hits imply that the group that was aimed at, namely "surgeons", have indeed been reached.

Pharmacokinetics of triptorelin after intravenous bolus administration in healthy males and in males with renal or hepatic insufficiency.

AIMS: Triptorelin is a gonadotropin-releasing hormone (GnRH) analogue with enhanced affinity for GnRH receptors and a prolonged half-life due to its resistance to enzymatic degradation. The sustained-release formulation of this molecule is advantageous in conditions requiring chronic hormone suppression. METHODS: This was an open study to determine the pharmacokinetics of a single i.v. bolus dose of 0.5 mg triptorelin acetate in four groups of six male subjects; namely in healthy subjects (Group I), in patients with varying degrees of renal insufficiency (Groups II and III), and in patients with hepatic insufficiency (Group IV). RESULTS: The maximum concentrations of triptorelin were found to be similar for all four study groups (geometric mean Cmax between 41.6 mg ml(-1) and 53.9 mg ml(-1)). The total clearance of triptorelin decreased with increasing renal impairment, and was even lower in patients with hepatic insufficiency (geometric mean CLtot: 210 ml min(-1), 113 ml min(-1), 86.8 ml min(-1) and 57.3 ml min(-1) for Groups I, II, III and IV, respectively). Serum triptorelin concentrations in all four groups were adequately described by a three-compartment model. The elimination half-life for patients with hepatic impairment was similar to that of patients with renal impairment (geometric mean t(1/2, z): 6.6 h, 7.7 h and 7.6 h for Groups II, III and IV, respectively), but significantly longer than in healthy volunteers (2.8 h for Group I). The first and second distribution half-lives were similar for the four groups studied, with geometric mean distribution half-lives of about 0.1 h (6 min) and 0.75 h (45 min), respectively. CONCLUSIONS: Although both renal and hepatic function are important for the clearance of triptorelin, the liver plays the predominant role in subjects suffering from some degree of renal impairment.

An evaluation of the interaction of meloxicam with frusemide in patients with compensated chronic cardiac failure.

AIMS: To evaluate the interaction of meloxicam with frusemide in patients with compensated cardiac failure. METHODS: Nineteen patients with Grade II or III compensated chronic cardiac failure completed this randomized, double-blind, cross-over study. The patients received 40 mg frusemide day(-1) for 7 days. Thereafter, patients received either 15 mg meloxicam plus 40 mg frusemide day(-1), or one placebo tablet plus 40 mg frusemide day(-1) for 7 days. After a washout period of 7 days during which patients received 40 mg frusemide day(-1) for 7 days, the patients were crossed over to the alternate treatment. The effect of concomitant ingestion of meloxicam and frusemide on frusemide-induced diuresis, urine and serum electrolytes, urinary frusemide excretion, and plasma frusemide pharmacokinetics was also determined. RESULTS: The estimate (90% confidence interval) of the '(frusemide + meloxicam)/(frusemide alone)' mean ratio of the variables Cmax, AUC(SS) and Cmax/AUC(SS) for plasma frusemide were 121% (101% to 145%), 106% (96.4% to 117%), and 114% (98.3% to 132%), respectively. Similarly, the estimate (90% confidence interval) of the '(frusemide + meloxicam)/(frusemide alone)' of the mean ratio of the variable cumulative urinary frusemide excretion after multiple doses of frusemide were 123% (101% to 150%) for the period 0-8 h, and 122% (105% to 142%) for the period 0-24 h after drug administration on day 7. The estimate (90% confidence interval) of the '(frusemide + meloxicam)/(frusemide alone)' mean ratio of the pharmacodynamic variables cumulative sodium excretion was 105% (95.2% to 116%) for the period 0-8 h and 108% (96.5% to 121%) for the period 0-24 h after drug administration on day 7. CONCLUSIONS: Meloxicam may lead to slightly increased maximum concentrations of frusemide in plasma, as well as to slightly increased urinary excretion of frusemide, without affecting the pharmacodynamics of frusemide. Thus there is no clinically significant pharmacokinetic or pharmacodynamic interaction of meloxicam with frusemide following repeated co-administration of meloxicam and frusemide to patients with compensated chronic cardiac failure.

The early bactericidal activity of ciprofloxacin in patients with pulmonary tuberculosis.

The early bactericidal activity (EBA) of ciprofloxacin (CIP) was measured in 80 patients with previously untreated, smear-positive pulmonary tuberculosis by counting viable bacilli in sputum collections during the first 2 d of treatment. Groups of about 10 patients were treated daily with graded doses of CIP or with 300 mg isoniazid or with no drug. The mean EBA, defined as the fall in log CFU/ ml sputum/d, increased from -0.011 in the no drug group to 0.046, 0.092, 0.121, and 0.205 in the groups receiving 250, 500, 1,000, or 1,500 mg CIP, respectively, a highly significant trend. These results demonstrate the antimycobacterial activity of CIP in high dosage, though the mean EBAs of 0.55 and 0.66 in two groups receiving isoniazid were much higher.