Cost of patient follow-up after potentially curative lung cancer treatment.

The two objectives of this study were to determine the range of recommended follow-up strategies for patients with lung cancer treated with curative intent and to estimate the cost of such follow-up. Ten articles delineating eight specific follow-up strategies were identified from a Medline search of the literature for 1980 through 1995. An economic analysis was done of the costs associated with the identified strategies. Charge data obtained from the Part B Medicare Annual Data file and the Hospital Outpatient Bill file were used as a proxy for cost. Follow-up intensity varied widely across strategies for 5 years of posttreatment follow-up. Medicare-allowed charges for 5-year follow-up ranged from a low of $946 to a high of $5645. When Medicare-allowed charges were converted to a proxy for actual charges by a conversion ratio of 1.62, the range was $1533 to $9145, a fivefold difference in charges. There was no indication that more intensive, higher-cost strategies increased survival or quality of life. The published literature, including textbooks, holds few answers in this area.

Splenectomy as an adjuvant measure in the treatment of severe aplastic anaemia.

The role of splenectomy in aplastic anaemia (AA) is controversial. The hazards of operating on a severely pancytopenic patient, the fear of compromising the patient's immune function, and the improvement of non-surgical treatment have made splenectomy unpopular in this disease. We have evaluated positive and adverse effects of splenectomy in 80 patients with severe aplastic anaemia (SAA) treated with antilymphocyte globulin (ALG) (group A), using 52 nonsplenectomized ALG patients as controls (group B). All patients survived the operation. Nonfatal complications of surgery occurred in 10 (12.5%). Splenectomy induced a significant increase of peripheral blood neutrophils, reticulocytes and platelets within 2 weeks, followed by a continuous increase of all values over the following weeks. 28/132 patients (21%) developed a late clonal disorder of haemopoiesis, paroxysmal nocturnal haemoglobinuria (PNH) or myelodysplastic syndrome (MDS), or both. Their incidence was identical in groups A and B. 13/28 (59%) died, 10/17 (59%) in group A and 3/11 (27%) in group B (not significant (n.s.)). Overall probability of survival at 18 years after ALG was 51+/-6% for group A and 61+/-7% for group B (n.s.). We conclude that splenectomy in AA is safe. It induces an immediate increase of peripheral blood counts and, thereafter, a continuous improvement of haemopoiesis. It does not increase the incidence of late clonal complications but has a borderline effect on mortality from these disorders. Splenectomy should be reconsidered in selective nontransplanted patients who have prolonged transfusion requirements despite otherwise optimal treatment.

Clinical efficacy and safety of cefetamet pivoxil in toddlers.

The safety and efficacy of cefetamet pivoxil, an oral cephalosporin of the third generation, have been studied in open, prospective, randomized comparative, clinical trials including 301 toddlers (children aged 1 to 2 years) with upper and lower respiratory tract infections, and urinary tract infections. Cefetamet pivoxil (CAT) syrup formulation was given to 177 toddlers either in the standard dose of 10 mg/kg b.i.d. [n = 116] or 20 mg/kg b.i.d. [n = 61] and 124 toddlers have been treated with comparator drugs [cefaclor, n = 98; phenoxymethylpenicillin, n = 18; amoxicillin plus clavulanic acid; n = 8]. The treatment period was 7 days mainly, except for pharyngotonsillitis for which the treatment duration was 7 or 10 days. The assessment of treatment was based on clinical signs and symptoms primarily in infections of lower respiratory tract and acute otitis media, whereas in patients with pharyngotonsillitis and acute urinary tract infections the bacteriological findings were the main evaluation criteria. The overall therapeutic outcome was successful in 148 (95.4%) of the 155 toddlers to whom CAT was administered and in 87 (85.3%) out of 102 toddlers receiving standard drugs. Adverse events of mild to moderate severity, mainly of gastro-intestinal type (vomiting or diarrhoea) occurred in 14.7% in the patient group receiving CAT, 11.2% in the toddlers receiving the standard dose of CAT, and in 12.9% with the comparator drugs. From the data presented it is concluded that cefetamet pivoxil is efficient and safe in toddlers presenting with community-acquired respiratory and urinary infections mainly caused by S. pneumoniae, H. influenzae, Group A beta-haemolytic streptococci, M. catarrhalis, E. coli, Proteus spp. and K. pneumoniae.

Cefetamet pivoxil in the treatment of uncomplicated gonorrhea.

We studied the efficacy and safety of cefetamet pivoxil (CAT), an oral aminothiazolyl cephalosporin, in a series of open, comparative multicenter studies in 207 women (four study centers) with uncomplicated gonorrhea, and summarized and pooled the results with those of earlier open dose-finding trials (360 men; six study centers). We compared single-dose treatment regimen of CAT--over the range of 400-1500 mg--with spectinomycin, thiamphenicol, ampicillin, or amoxicillin plus probenecid. The overall cure rates were 100% in 88 women treated with 1500 mg CAT and in 137 men treated with 1200 or 1500 mg CAT, 98% (114 of 116 men) in those treated with 800 or 1000 mg CAT, and 93% (42 of 45 men) in those treated with 400 or 500 mg CAT; the composite cure rate of the comparators was 97%. The tolerability of CAT (n = 428) compared favorably (1.8% adverse events) with that of the standard drugs (n = 139) (4.3% adverse events). Single-dose treatment with 1500 mg CAT is effective and safe in adults with uncomplicated gonorrhea.

Cefetamet pivoxil in otitis media.

In this multicentre, open, randomized, parallel-group study, 270 children with acute otitis media aged between 1 and 15 years were randomized to receive either cefetamet pivoxil 10 mg/kg b.i.d. for 7 days (n = 134) or cefaclor 13.5 mg/kg t.i.d. for 7 days (n = 136). At the end of treatment, bacteriological cure occurred in 44/44 (100%) patients receiving cefetamet pivoxil and 24/28 (86%) patients receiving cefaclor. Clinical cure or improvement was experienced by 117/121 (97%) of patients receiving cefetamet pivoxil and 104/115 (90%) patients in the cefaclor group. Adverse side effects, mainly gastrointestinal disorders, occurred in 11% of patients in the cefetamet pivoxil group compared with 15% of patients in the cefaclor group. All adverse events were of mild or moderate severity and subsided rapidly after treatment. Premature treatment withdrawals occurred in 0.7% of patients who received cefetamet pivoxil and in 2.2% of those who received cefaclor.

Literature survey on clinical efficacy and tolerability on cefetamet pivoxil: an analysis of 3,128 cases.

The oral third-generation cephalosporin cefetamet pivoxil has a broad spectrum of antibacterial activity and favorable pharmacokinetic properties which makes it particularly suitable for the treatment of upper and lower respiratory tract infections as well as of infections of the urinary tract. The clinical trial results of cefetamet pivoxil have been reviewed from the literature in 4,112 patients out of whom 3,128 patients were treated with cefetamet pivoxil. The standard doses of cefetamet pivoxil, 500 mg twice daily in adults and 10 mg/kg twice daily in children, were at least as effective and in many cases clinically superior to most currently recommended antibiotics for the treatment of complicated urinary tract infections including pyelonephritis. High efficacy has also been demonstrated in patients with pneumonia, in acute exacerbation of chronic bronchitis and infections of the ear, nose and throat. Clinical trial results have shown that a 7-day treatment period with cefetamet pivoxil is as effective as a 10-day course of phenoxymethylpenicillin in the treatment of pharyngotonsillitis due to group A beta-hemolytic streptococci. Cefetamet pivoxil was well tolerated: 226 patients (7.2%) out of 3,128 had adverse events which were mainly gastrointestinal, i.e. diarrhea, nausea and vomiting. An additional 53 (1.7%) patients had laboratory changes which were of no clinical relevance. Premature treatment withdrawals were reported in 13 (0.5%) out of 2,612 adults and in 11 (2.1%) out of 516 children. All adverse events subsided rapidly after treatment. Many current antibiotic treatment regimens require the administration of three daily doses. However, twice daily standard doses of cefetamet pivoxil of 500 mg in adults or 10 mg/kg in children provide unbound plasma concentrations of cefetamet which generally exceed the MIC90 for susceptible organisms between doses and are clinically effective, well tolerated and should result in good compliance.

Effectiveness of cefetamet pivoxil in the treatment of pyelonephritis in children.

Cefetamet pivoxil was investigated in an open, randomized comparative study involving a total of 37 children with acute pyelonephritis, whose ages ranged from 2 to 14 years. The patients received either 10 mg/kg (n = 18) or 20 mg/kg (n = 8) cefetamet pivoxil twice daily, or 30-50 mg/kg amoxycillin/clavulanic acid three times daily (n = 11) for a period of 7-10 days. Escherichia coli was the main causative agent isolated in 28 (75.7%) of the patients; other pathogens included Proteus mirabilis (three patients). Proteus species (one patient), Klebsiella pneumoniae (two patients), Pseudomonas diminuta (one patient) and mixed infections (three patients). No differences in the overall treatment outcome could be observed between the treatment regimens used and, at the end of treatment, all pathogens were eradicated with neither relapse, nor persistence of the isolated pathogen, nor reinfection occurring. The clinical signs and symptoms had subsided in all patients at treatment end and the tolerability of the trial drugs was found to be satisfactory with no premature treatment withdrawal required. It is concluded that cefetamet pivoxil in the standard twice-daily dose of 10 mg/kg was equally effective and as well tolerated as 20 mg/kg cefetamet pivoxil given twice daily or 30-50 mg/kg amoxycillin/clavulanic acid given three times daily.

Cefetamet pivoxil in community-acquired pneumonia: an overview.

A total of 305 patients with community-acquired pneumonia have participated in comparative or non-comparative studies involving cefetamet pivoxil. Of these, 211 (55 adults and 156 children) were involved in a series of open, prospective, comparator-controlled, multi-centre studies. Adults were randomized to receive either cefetamet pivoxil 1000 mg twice daily or amoxycillin 750 mg 3-times daily for 10 days. Children received either cefetamet pivoxil 10 mg/kg twice daily, cefetamet pivoxil 20 mg/kg twice daily or cefaclor 10 mg/kg 3-times daily for 7 to 8 days. The remaining 94 patients were treated openly with cefetamet pivoxil, with most patients receiving cefetamet pivoxil 500 mg twice daily for an average of 10 days; an elderly sub-group of these patients aged 70 to 103 years received therapy for an average of 11 days. The main causative organisms isolated were Streptococcus pneumoniae and Haemophilus influenzae. In adult patients, a successful clinical outcome was achieved in 100% of assessable patients receiving cefetamet pivoxil 1000 mg twice daily, and about 90% in those receiving 500 mg twice daily. The success rate in children was 98% for both dose levels of cefetamet pivoxil and 90% for those receiving cefaclor. In elderly patients, the percentage was 78% for the 500 mg twice daily patients. Thus, the standard dose of cefetamet pivoxil (500 mg twice daily in adults, 10 mg/kg twice daily in children) was well tolerated and proved to be at least as effective as the comparator drugs which were given 3-times a day.

Cefetamet pivoxil: a review of its microbiology, toxicology, pharmacokinetics and clinical efficacy.

Cefetamet pivoxil is an oral, third-generation cephalosporin whose broad spectrum of antibacterial activity and favorable pharmacokinetic profile make it particularly suitable for the treatment of a wide range of infectious diseases. Cefetamet has high in vitro activity against both gram-positive and gram-negative bacteria that cause a number of respiratory tract and urinary tract infections. These include penicillin-sensitive Streptococcus pneumoniae, Streptococcus spp, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Proteus spp., Klebsiella spp. and Neisseria gonorrhoeae. It is not active against staphylococci, enterococci, Pseudomonas spp. or Bacteroides fragilis but does inhibit most bile-sensitive (oral) Bacteroides spp. Animal toxicology studies indicate that neither cefetamet pivoxil nor the active compound cefetamet have significant teratogenic, mutagenic, photogenic or allergenic potential. Cefetamet is eliminated unchanged in the urine with a half-life of 2.2 h. Volume of distribution approximates the extracellular fluid space (0.3 1/kg), protein binding is minima (22%) and oral bioavailability of cefetamet pivoxil is approximately 50% when taken with food. No significant drug interactions have been noted to date. The efficacy and tolerability of cefetamet pivoxil have been evaluated in the treatment of gram-positive and gram-negative infections in almost 5,000 patients. In comparative studies, cefetamet pivoxil was at least as effective, and in many cases clinically superior, to most currently recommended antibiotics for the treatment of urinary tract infections including gonorrhea and complicated infections in high risk patients. Efficacy has also been demonstrated in acute exacerbations of chronic bronchitis, pneumonia and infections of the ear, nose and throat. Clinical trials have shown that a 7 day treatment period with cefetamet pivoxil is as effective as a 10 day course of phenoxymethylpenicillin in the treatment of pharyngotonsillitis. Cefetamet pivoxil has been well-tolerated in clinical trials with only 1.2% of patients on standard doses discontinuing therapy prematurely. The most common adverse effects are gastrointestinal (diarrhea, nausea, vomiting) which occur in less than 10% of patients. Many current antibiotic treatment regimens involve the administration of three or more daily doses. However, standard doses of cefetamet pivoxil 500 mg twice daily provide unbound plasma concentrations of cefetamet which generally exceed the MIC(90) for susceptible organisms throughout the dosing interval and have been demonstrated to be clinically effective. This should result in good compliance with therapy in out-patients. Dosing regimens for cefetamet pivoxil should be adjusted in patients with impaired renal function while standard doses can be given to elderly patients and those with liver disease. Standard doses in children are 10 mg/kg or alternatively, children may receive a dose reduced in proportion to the ratio of their body surface area to that of an adult.

Effect of fleroxacin and ciprofloxacin on the formation of human mature colonies of healthy donor versus transplanted hemopoietic progenitor cells.

The effect of fleroxacin and ciprofloxacin on hemopoietic progenitor cells was tested in vitro. Cryopreserved bone marrow samples from 5 patients with acute myeloid leukemia who underwent bone marrow transplantation as well as samples from the respective donors were investigated in parallel. Regarding burst and/or colony formation by erythroid, neutrophil and macrophage precursors, no significant differences were detected with donor and transplanted bone marrows between control cultures and cultures containing 100 mg/l fleroxacin, while 100 mg/l ciprofloxacin inhibited cell proliferation completely. At 50 and 10 mg/l ciprofloxacin had a 50% and no inhibitory effect, respectively.

Efficacy and tolerability of cefetamet pivoxil in diabetic patients with urinary tract infections: a case-control study.

Cefetamet pivoxil, an oral third generation cephalosporin, was evaluated in 218 hospitalized patients with complicated urinary tract infections. Among these patients, 28 (13.1%) were suffering from concomitant diabetes: 25 of these patients were matched with 25 non-diabetic patients and for each pair, the age +/- 2 years, sex, complicating factors, etc. had to be identical. All patients received 2000 mg cefetamet pivoxil daily for 10 days. The predominant pathogen was E. coli; 18 in the diabetic group, 15 among non-diabetics. Comparison of the therapeutic results showed that the bacteriological eradication rate was similar in diabetic and non-diabetic patients, 92% and 87.5%, respectively. There was a similar improvement in pyuria, and therapeutic response was equal in diabetic patients as in non-diabetic patients. No unwanted effects on renal function were observed in the high-risk diabetic group.

Cefetamet in the treatment of acute sinusitis in adult patients.

Cefetamet, an oral third-generation cephalosporin, was investigated in a prospective, randomized, open, comparative trial in 41 outpatients with acute sinusitis. The efficacy of 500 mg cefetamet given orally twice daily for 7 days to 22 patients was compared with that of 500 mg cefaclor given orally three times daily for 7 days to 19 patients. Sinus punctures were performed before antimicrobial therapy in 10 patients from each treatment group. A successful bacteriological response was obtained in all the 21 assessable patients treated with cefetamet and in the cefaclor-treated group 18 assessable patients were cured and two were improved, but one failed to respond to therapy. The tolerability of both drugs was good and no withdrawals from treatment were necessary.

Cefetamet pivoxil in acute pyelonephritis: an open study.

Fifty-five adult patients with acute uncomplicated pyelonephritis were investigated in an open, prospective, randomized comparative study in which 31 patients were allocated to receive 1000 mg cefetamet pivoxil twice daily (or 2000 mg once daily) and 24 to receive 1000 mg cefadroxil twice daily, given orally for 10 to 15 days. Both groups were comparable for age, sex and body weight. Clinical signs and symptoms, i.e. flank tenderness, dysuria, urgency and pyuria, subsided somewhat more rapidly with cefetamet pivoxil, while defervescence was obtained by Day 3 +/- 1 in both groups. Twenty-nine of the cefetamet pivoxil patients were assessed bacteriologically. The pathogens isolated prior to treatment were E. coli (22), Proteus mirabilis (5), P. vulgaris (1) and P. stuartii (1). All 29 patients had sterile urine at treatment end. In the 22 assessable patients in the cefadroxil group, the pathogens isolated before treatment were E. coli (17), P. mirabilis (3), and K. pneumoniae (2). Six patients had relapsed at treatment end (5 E. coli and 1 P. mirabilis). Patients were re-assessed at follow-up, usually 2 to 4 weeks after the end of treatment. Four of the 29 patients in the cefetamet pivoxil group showed relapse (3 E. coli and 1 P. mirabilis) as did a further 3 in the cefadroxil group (2 E. coli and 1 P. mirabilis). The overall therapeutic outcome was considered as successful, i.e. cure or improvement, in 89.7% of the cefetamet pivoxil patients and 72.7% of those who had received cefadroxil. Tolerability was satisfactory for both trial drugs and there were only a few mild to moderately severe adverse events reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefetamet pivoxil in paediatric patients suffering from lower respiratory tract infections.

A prospective, randomized comparative trial was carried out in 31 children suffering from lower respiratory tract infections, mainly bronchopneumonia or pneumonia. Twenty-one children received oral cefetamet pivoxil in a dose of 20 mg/kg/day (10 children) or 40 mg/kg/day (11 children), and 10 children 30 mg cefaclor/kg/day for 7 days. Clinical signs and symptoms, i.e. fever, dyspnoea, altered breath sounds and cough, subsided during treatment with both cefetamet pivoxil treatment doses in all patients. All X-ray findings and blood leucocytosis normalized, while 1 out of the 10 children to whom 30 mg cefaclor/kg/day was administered deteriorated from bronchopneumonia to pneumonitis during treatment. Treatment was stopped due to vomiting in 1 patient receiving the 40 mg cefetamet pivoxil/kg/day dose.

Cefetamet pivoxil a new oral cephalosporin: clinical evaluation.

Cefetamet pivoxil, an oral cephalosporin, was given to 683 patients; 414 received standard antibiotics. 1.5 and 1.2 g of cefetamet pivoxil were fully effective in gonorrhea. In two trials in uncomplicated urinary tract infections (UTI) 2 g cefetamet as a single dose was significantly superior (93.3% cure) to 2 g cefadroxil (74.4% cure) and 90.8% vs. 74.7% cure. Results in complicated UTI with 2 g cefetamet for 10 days were 87.9% cure and 71.4% cure with cefadroxil. In acute exacerbation of chronic bronchitis 88% were cured with cefetamet (101 patients) and 80% with cefaclor (n = 94). In acute ear-nose-throat infections, the response rate was 89% and 93% with 1 or 2 g cefetamet per day, respectively. Adverse events were noticed in 6% of the 683 cefetamet-treated patients; they were rapidly reversible.

Influence of stored aqueous ceftriaxone solutions on colony formation by neutrophil and macrophage precursor cells.

Aqueous solutions of ceftriaxone in concentrations similar to those achieved in man and stored at temperatures of 4 degrees C, 22 degrees C and 37 degrees C for up to four weeks were tested in methylcellulose cultures of normal bone marrow from ten donors. No significant differences were detected between the colony formation by neutrophil and macrophage precursors in control cultures and in cultures containing stored ceftriaxone. It is concluded that aqueous ceftriaxone solutions stored for up to four weeks at temperatures up to 37 degrees C are not altered to such an extent that they adversely affect colony formation by bone marrow progenitor cells from healthy donors.

Parenteral rifampicin in tuberculous and severe non-mycobacterial infections. Clinical data on 237 patients.

A parenteral formulation of rifampicin (Rimactan i.v., Ciba-Geigy, Basel, Switzerland) was administered to 237 critically ill or comatose patients, or patients with gastro-intestinal or absorption problems. There were 160 patients suffering from tuberculosis, 77 suffering from non-tuberculous (non-tb) infections including 30 cases of sepsis, 8 cases of bacterial meningitis and/or cerebral abscess and 9 patients with Legionnaires' disease. The usual daily dose of rifampicin was 450-600 mg, administered in most cases by i.v. bolus (122 cases) or i.v. drip infusion (79 cases) for a period of 1-113 days. Rifampicin was in all cases combined with one or more antimicrobial drug(s). The physicians considered the therapy as successful when the treatment with oral rifampicin could be instituted soon after parenteral administration or when the patients markedly improved their clinical condition. Of a total of 123 tuberculous patients for whom assessment of efficacy was possible, 100 (81.3%) showed favourable clinical results. Of 40 non-tb patients who could be analysed for clinical progress, 32 (80.0%) had a favourable outcome. Special attention should be drawn to the 11 patients with proven staphylococcal infections, of whom 10 were cured clinically and/or bacteriologically. Thrombophlebitis occurred in 10 out of the 237 (4.2%) patients, almost always in patients who were treated for more than 30 days. Systemic unwanted effects occurred in 14 (5.9%); the relationship to the treatment was not always established. Treatment was withdrawn due to unwanted effects in 5 (2.1%) of the 237 patients. Taking into account the severe, life-threatening infections reported, the results suggest that i.v. rifampicin is useful and in some critically ill patients even life-saving. Tolerability was good, even in long-term i.v. administration, although there seems to be the possibility that thrombophlebitis might develop if treatment is continued over 30 days.

Rifampicin in free combination with other antimicrobial drugs in non-Tb infections. Clinical data on 650 patients (a review).

A review of the published literature has allowed the identification of a number of non-tubercular indications where rifampicin (trade mark Ciba-Geigy: Rimactane) has been successfully used in combination with other chemotherapeutic agents. The cases reviewed with regard to effectiveness sum 562. The most frequently combined drugs were aminoglycosides (mainly gentamicin), cotrimoxazole, colistine, vancomycin and fusidic acid, these two latter in cases due to Staphylococcus spp. The main indications where combined rifampicin treatment led to favourable results were UTI (success rate 64.9%), bone infections (86.9%), staphylococcal endocarditis (85.0%), respiratory tract infections often due to gram-negative rods (97.7%) as well as skin and soft tissue infections (83.3%), and bacterial meningitis (100%). Very favourable results were obtained in a non-life-threatening though epidemiologically important condition, i.e. salmonella carriers, where a 100% conversion rate was reached in an average period of 6 weeks. Special attention may deserve the combined treatment of fungal infections with rifampicin and amphotericin B. Tolerability was evaluated on a total of 650 cases. It appears to be good for daily doses up to 1,200 mg/day, even on long-term treatment; less so for the highest doses used (1,800 or 30 mg/kg a day). The clinical results, which are in good agreement with the results of the in vitro tests, indicate that rifampicin may have an important role in the combined treatment of severe non-mycobacterial infections. Further prospective, whenever possible, comparative studies are warranted for a thorough appraisal of its possible usefulness.