Patient-year Of Treatment Research Articles

Cost analysis of patiromer vs sodium zirconium cyclosilicate for the treatment of hyperkalemia in Spain and the UK

Background Hyperkalemia is an electrolyte abnormality with potentially life-threatening consequences. Published data have shown that potassium-binding polymer patiromer (Veltassa) is associated with reduced rates of severe edema and hospitalization for heart failure compared with sodium zirconium cyclosilicate (SZC, Lokelma) when treating hyperkalemia. The aim of this study was to evaluate the possible costs associated with these interventions in the Spanish and UK settings. Methods A cost-analysis model was developed in Microsoft Excel to compare the costs associated with patiromer and SZC for the management of hyperkalemia. Clinical event rates were taken from a published real-world comparative study, with the base case capturing the statistically significant reduction in severe edema with patiromer vs SZC and a sensitivity analysis also including the non-statistically significant reduction in hospitalization for heart failure. Country-specific costs, expressed in 2022 Euros (EUR) and British pounds sterling (GBP), were evaluated from a healthcare payer perspective and included pharmacy costs and costs of clinical events. Results Patiromer may be associated with cost savings of EUR 107 and GBP 630 per patient-year of treatment vs SZC in Spain and the UK, respectively. The majority of cost savings were due to the possible lower daily cost of patiromer compared with SZC. Including the difference in heart failure hospitalization rates in a sensitivity analysis led to greater cost savings with patiromer over SZC, increasing to EUR 460 and GBP 902 in Spain and the UK, respectively. Extrapolation of patient-level economic outcomes to a population level found that patiromer was associated with annual cost savings of EUR 30.6 million in Spain, and GBP 801.7 million in the UK vs SZC. Conclusions Patiromer has the potential to be cost saving vs SZC for the treatment of hyperkalemia in Spain and the UK based on the results of a real-world evidence analysis.

Cognitive and psychiatric adverse events during adjunctive cenobamate treatment in phase 2 and phase 3 clinical studies

ObjectiveCognitive and psychiatric adverse events in patients with epilepsy are important determinants of therapeutic outcomes and patient quality of life. We assessed the relationship between adjunctive cenobamate treatment and selected cognitive and psychiatric treatment-emergent adverse events (TEAEs) in adults with uncontrolled focal epilepsy. MethodsThis was a retrospective analysis of pooled populations of patients with focal epilepsy from two phase 2, randomized, double-blind clinical trials; two open-label extensions (OLEs) of those trials; and a long-term, open-label, phase 3 safety study. Occurrence of cognitive and psychiatric TEAEs in patients treated with adjunctive cenobamate or placebo during double-blind treatment were evaluated. Exposure-adjusted incidence rates of the cognitive and psychiatric TEAEs, defined as the number of TEAEs per patient-year of treatment, during up to 7 years of long-term adjunctive cenobamate treatment, were determined in the pooled OLE and phase 3 patient populations. ResultsThe pooled randomized trials resulted in a population of 442 patients treated with cenobamate (100 mg/day: n = 108; 200 mg/day: n = 223; 400 mg/day: n = 111) and 216 placebo-treated patients. The combined open-label studies resulted in pooled populations of cenobamate-treated patients ranging from n = 1690 during Year 1 to n = 103 during Year 7. Among cenobamate-treated (all doses) and placebo-treated patients during double-blind treatment, cognitive TEAEs were reported by ≤ 1.9 % (range, 0 %-1.9 %) and ≤ 0.5 % (range, 0 %-0.5 %), respectively, and psychiatric TEAEs by ≤ 3.6 % (range, 0 %-3.6 %) and ≤ 3.2 % (range, 0 %-3.2 %), respectively. During up to 7 years of open-label adjunctive cenobamate treatment, exposure-adjusted incidence rates of cognitive and psychiatric TEAEs were < 0.018 and < 0.038 events per patient-year, respectively. Discontinuation of adjunctive cenobamate due to cognitive or psychiatric TEAEs assessed in this study during double-blind or open-label treatment occurred in ≤ 0.3 % and ≤ 1.7 % of patients, respectively. ConclusionsCognitive and psychiatric TEAEs were reported by similar numbers of cenobamate- and placebo-treated patients during double-blind adjunctive cenobamate treatment (< 4 % of patients), and exposure-adjusted incidence rates of these TEAEs remained low during open-label cenobamate treatment for up to 7 years. Treatment discontinuations due to these TEAEs were rare. The results of this post-hoc analysis indicate that adjunctive cenobamate treatment exhibits a low incidence of cognitive or psychiatric TEAEs in patients with uncontrolled focal seizures.

P482 Safety and efficacy of ustekinumab for Crohn’s disease in the elderly population

BackgroundThe rising incidence of inflammatory bowel disease (IBD) worldwide and an ageing population has led to a marked increase in elderly IBD patients. Anti-tumour necrosis factor (TNF) agents are associated with an increased risk of serious infections and treatment discontinuation among elderly IBD patients but little is known about non anti-TNF biologics in this cohort. We aimed to examine safety and efficacy of ustekinumab in elderly Crohn’s disease (CD) patients.MethodsPatients ≥60 years old commencing ustekinumab for CD were included in this retrospective multi-centre cohort study. We gathered data on adverse events, Harvey Bradshaw Index (HBI) and concomitant steroid therapy. The primary outcome was serious infections, defined as requiring hospitalisation. Efficacy was assessed by serial HBI measurement and treatment persistence.Results70 patients were included, with a median age of 68 years (range 60–87), a male:female ratio of 9:5 and a median Charlson co-morbidity index of 4 (range 2–9). 44 (62.9%) had prior anti-TNF exposure and 15 (21.4%) previous vedolizumab. Median treatment duration was 12 months (range 2–48), with a total of 84 patient years. 31 patients (41.3%) had steroids at initiation, and 33 (47.1%) required a course of steroids at a later date.Seven patients (10%) had a combined 9 serious infections, of which 1 was life threatening requiring organ support. Incidence of serious infections was 0.107 per patient year. A further 18 patients had a combined 22 non-severe infections (Table 1). The overall infection rate was 0.417 per patient year. Charlson co-morbidity index was numerically higher among those who developed severe infections (median 5, range 3–7 vs. median 4, range 2–9, P=NS). 3 patients developed a malignancy; non-Hodgkin’s lymphoma, melanoma and prostate cancer.Mean HBI improved from 8.13 at baseline to 4.64 at 6 months and 4.10 at last follow up (both P<0.0001). Treatment persistence rate was 61.4% (N=43) and 36 (51.4%) were steroid-free. Reasons for discontinuation were primary non-response (42%), adverse event (32%), secondary loss of response (10%), malignancy (10%) and lack of funding (5%).Table 1AetiologyNumber of patients (%)SeverePneumonia3 (4.3)Line infection2 (2.9)Covid-191 (1.4)Biliary sepsis1 (1.4)Epididymo-orchitis1 (1.4)Shingles1 (1.4)Non-severeLower respiratory tract9 (12.9)Urinary6 (8.6)Coryzal4 (5.7)Pneumonia1 (1.4)Diarrhoea1 (1.4)Line infection1 (1.4)Soft tissue1 (1.4)ConclusionUstekinumab was safe and effective in a cohort of elderly CD patients. Infections were mostly mild, not resulting in therapy discontinuation. The risk of serious infection was low at 0.107 per patient year of treatment.

Safety Profile of Thiopurines in Crohn Disease: Analysis of 893 Patient-Years Follow-Up in a Southern China Cohort.

Thiopurines have been associated with both clinical improvement and mucosal healing in treating Crohn disease (CD). Unfortunately, the high rate of adverse events (AEs) leading to drug withdrawal represents a major limitation in the use of these drugs.To evaluate the safety of thiopurines in patients with CD. To identify predictive factors associated with the development of thiopurine-induced AEs and withdrawal.This longitudinal cohort study examined patients from a university-based IBD referral center. Time-to-event analysis was performed with the Kaplan–Meier curve. Cox regression analysis was performed to identify potential predictive factors of AEs.Two hundred sixty-seven CD patients on thiopurines were included. A total of 143 AEs occurred at a median of 7.4 months (interquartile range, 3.7–15.3 months) after starting treatment. The cumulative incidence of AEs was 26%, with an annual risk of 4.3% per patient-year of treatment. The most frequent was leucopenia (41/267, 15.36%), followed by infections (29/267, 10.86%). Independent factors predictive of leucopenia were lower baseline hemoglobin (hazard ratio (HR), 0.34; 95% confidence interval (CI) 0.18–0.67) and the concomitant use of 5-aminosalicylic acid (HR, 3.05; 95% CI 1.44–8.76). Of the 28.44% (76/267) CD patients discontinued therapy, 14.61% due to AEs. A lower body mass index, the presence of extraintestinal manifestation, and the incidence of leucopenia independently predicted thiopurine withdrawal. In total, 37.5% of these patients restarted thiopurines and 52.3% of them had AEs again.About a quarter of patients on thiopurine therapy had AEs during follow-up and 1 of 7 patients had to discontinue thiopurines due to AEs.

Long-Term Peritoneal Dialysis Experience: Quality Control Supports the use of Fluconazole to Prevent Fungal Peritonitis

Fungal peritonitis (FP) is rare, but it is associated with high morbidity and mortality. A prospective study was conducted based on the peritonitis episodes registry to evaluate FP rate, possible risk factors, and outcomes. The impact of prophylactic intervention with oral fluconazole was evaluated. Over 24 years of experience, 417 patients underwent peritoneal dialysis (PD), followed for 956 patient-years. By the end of the study, the peritonitis rate reached 0.47 episodes per patient-year of treatment (ep/pt-y). FP was detected in 24 patients. The global rate of FP was 0.03 ep/pt-y (4.8%). Candida species accounted for 92% of the FP. Risk factors identified: recent use of antibiotics in 63% (13 episodes of bacterial peritonitis and 2 exit-site infections (ESI)) and immunosuppressive therapy in 8%. While rare, the FP proportion was still observed to increase from the beginning of the program, reaching 7.8% (0.05 ep/pt-y). A strategy of antifungal prophylaxis with oral fluconazole during peritonitis or ESI antibiotic therapy was adopted, which allowed thereafter a 4.0% falling FP proportion (by study end, rate of 0.01 ep/pt-y). Catheter removal occurred in all patients. The mortality rate was 12.5%. Reinsertion of dialysis catheter was attempted in 4 patients and PD was successfully resumed in 3 patients. FP was associated with high mortality and required early removal of the catheter in all patients. Recent use of antibiotics was a predisposing factor to PF. The quality control process determined a prophylactic strategy and reduction of PF after introduction of oral fluconazole was implemented.

Safety of Thiopurine Therapy in Inflammatory Bowel Disease

To evaluate the safety of thiopurines in patients with inflammatory bowel disease. To identify predictive factors associated with the development of thiopurine-induced adverse events. Long-term incidence of adverse events was estimated in patients from a prospectively maintained Spanish nationwide database using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors of adverse events. Three thousand nine hundred and thirty-one patients were included. Ninety-five percent of patients were on azathioprine. The median follow-up with thiopurines was 44 months (range, 0-420). Adverse events occurred at a median of 1 month after starting treatment. The cumulative incidence of adverse events was 26%, with an annual risk of 7% per patient-year of treatment. Most frequent adverse events were nausea (8%), hepatotoxicity (4%), myelotoxicity (4%), and pancreatitis (4%). Four patients had lymphoma. Female and Crohn's disease increased the risk of having nausea. The risk of hepatotoxicity was lower in females and higher in Crohn's disease. The risk of myelotoxicity was significantly higher in patients treated with mercaptopurine and in females. The risk of pancreatitis was higher in Crohn's disease. Overall, 17% of patients discontinued thiopurine treatment due to adverse events. Thirty-seven percent of these patients started thiopurines again and 40% of them had adverse events again. As many as 1 of 4 patients on thiopurine therapy had adverse events during follow-up. A relatively high proportion of patients (17%) had to discontinue the treatment with thiopurines due to adverse events. However, more than half of patients that restarted thiopurine treatment after its discontinuation due to adverse events tolerated it. Several predictive factors for some adverse events have been identified.

How frequently do tuberculosis screening tests convert in inflammatory bowel disease patients on anti-tumour necrosis factor-alpha? A pilot study

Tuberculosis reactivation can lead to severe complications in patients treated with anti-tumour necrosis factor-alpha. To assess the usefulness of repeat tuberculosis screening tests in inflammatory bowel disease patients on stable anti-TNF therapy. Cross-sectional study, in patients on prolonged anti-TNF treatment (≥ 12 months) and basal negative screening for latent tuberculosis. Quantiferon(®)-TB Gold In-tube test was performed and then, tuberculin skin test was administered. 74 patients were included, median duration of anti-TNF treatment was 30 months (IQR 19-54); 47 patients on infliximab and 27 on adalimumab; no patient was on glucocorticoids. Previous BCG vaccination was present in 5 cases. After anti-TNF was started, 4 patients suffered from potential tuberculosis exposure and two cases travelled to endemic areas. The cumulative incidence of tuberculin skin test conversion was 2.7% (95% CI 0.3-9.4%, 2/74), and the incidence rate of tuberculin skin test conversion was 0.83% (95% CI 0.1-2.9%) per patient-year of treatment with anti-TNF drugs. All Quantiferon tests but one (a patient with an indeterminate result and a negative tuberculin skin test) were negative. The incidence rate of conversion of tuberculosis screening tests among patients on anti-TNF treatment seems to be low and these conversions were diagnosed based on a positive tuberculin skin test and were discordant with Quantiferon testing.

Taking ART to Scale: Determinants of the Cost and Cost-Effectiveness of Antiretroviral Therapy in 45 Clinical Sites in Zambia

BackgroundWe estimated the unit costs and cost-effectiveness of a government ART program in 45 sites in Zambia supported by the Centre for Infectious Disease Research Zambia (CIDRZ).MethodsWe estimated per person-year costs at the facility level, and support costs incurred above the facility level and used multiple regression to estimate variation in these costs. To estimate ART effectiveness, we compared mortality in this Zambian population to that of a cohort of rural Ugandan HIV patients receiving co-trimoxazole (CTX) prophylaxis. We used micro-costing techniques to estimate incremental unit costs, and calculated cost-effectiveness ratios with a computer model which projected results to 10 years.ResultsThe program cost $69.7 million for 125,436 person-years of ART, or $556 per ART-year. Compared to CTX prophylaxis alone, the program averted 33.3 deaths or 244.5 disability adjusted life-years (DALYs) per 100 person-years of ART. In the base-case analysis, the net cost per DALY averted was $833 compared to CTX alone. More than two-thirds of the variation in average incremental total and on-site cost per patient-year of treatment is explained by eight determinants, including the complexity of the patient-case load, the degree of adherence among the patients, and institutional characteristics including, experience, scale, scope, setting and sector.Conclusions and SignificanceThe 45 sites exhibited substantial variation in unit costs and cost-effectiveness and are in the mid-range of cost-effectiveness when compared to other ART programs studied in southern Africa. Early treatment initiation, large scale, and hospital setting, are associated with statistically significantly lower costs, while others (rural location, private sector) are associated with shifting cost from on- to off-site. This study shows that ART programs can be significantly less costly or more cost-effective when they exploit economies of scale and scope, and initiate patients at higher CD4 counts.

Seasonal variation in peritoneal dialysis-associated peritonitis: a multi-centre registry study

The role of seasonal variation in peritoneal dialysis (PD)-related peritonitis has been limited to a few small single-centre studies. Using all 6610 Australian patients receiving PD between 1 October 2003 and 31 December 2008, we evaluated the influence of seasons on peritonitis rates (Poisson regression) and outcomes (multivariable logistic regression). The overall rate of peritonitis was 0.59 episodes per patient-year of treatment. Using winter as the reference season, the peritonitis incidence rate ratios (95% confidence interval) for summer, autumn and spring were 1.02 (0.95-1.09), 1.01 (0.94-1.08) and 0.99 (0.92-1.06), respectively. Significant seasonal variations were observed in the rates of peritonitis caused by coagulase-negative Staphylococci (spring and summer peaks), corynebacteria (winter peak) and Gram-negative organisms (summer and autumn peaks). There were trends to seasonal variations in fungal peritonitis (summer and autumn peaks) and pseudomonas peritonitis (summer peak). No significant seasonal variations were observed for other organisms. Peritonitis outcomes did not significantly vary according to season. Seasonal variation has no appreciable influence on overall PD peritonitis rates or clinical outcomes. Nevertheless, significant seasonal variations were observed in the rates of peritonitis due to specific microorganisms, which may allow institutions to more precisely target infection control strategies prior to higher risk seasons.

Long-term durability of response to adalimumab in Crohnʼs disease

Adalimumab is an effective treatment for Crohn's disease (CD), but may also be associated with loss of response. Few reports provide insight into the durability of treatment of CD with adalimumab for periods longer than 12 months in clinical practice. To evaluate the long-term durability of adalimumab maintenance treatment and to identify predictive factors associated with loss of response. CD patients who initially responded to adalimumab were evaluated in a historical cohort study. Maintenance of long-term response was estimated using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors for loss of efficacy. In all, 380 CD patients were included (mean age, 38 years; 52% female). Of these, 43% had ileocolic CD, 50% inflammatory CD, and 41% perianal CD. Median follow-up with adalimumab was 8 months (range, 4-75 months). The annual risk of loss of response to adalimumab was 18% per patient-year of follow-up. Twenty-eight percent of patients were anti-TNF-naïve and 72% anti-TNF-experienced. The loss of efficacy was 8% per patient-year of follow-up in the anti-TNF-naïve patients and 22% in the anti-TNF-experienced group (P < 0.01). In the multivariate analysis, the presence of extraintestinal manifestations (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.02-2.9) and previous experience with other anti-TNF agents (HR = 2.5,95% CI = 1.2-5.3) were associated with higher risk of loss of efficacy. A relevant proportion of CD patients on long-term adalimumab lost response. The risk of loss of response was higher (more than 2-fold) in anti-TNF-experienced than in anti-TNF-naïve patients (22% vs. 8% per patient-year of treatment). Having extraintestinal manifestations seems to increase the risk of loss of efficacy.

Long-term Durability of Infliximab Treatment in Crohn's Disease and Efficacy of Dose “Escalation” in Patients Losing Response

The efficacy of infliximab therapy in patients with Crohn's disease (CD) is unknown beyond 12 months. For patients who lose their initial response, consideration can be given to dose "escalation" to regain therapeutic benefit. Our primary goal was to evaluate the long-term durability of maintenance infliximab treatment. The secondary goals were to identify potential predictors of loss of infliximab efficacy, to evaluate the response to infliximab escalation, and the safety of the treatment with infliximab with and without escalation of dose. CD patients treated with infliximab with response to an induction regimen were evaluated. Maintenance of long-term response was estimated using Kaplan-Meier analysis. The effect of specific variables was calculated using logistic regression analysis. Efficacy of dose escalation in patients who lose response to infliximab was analyzed. Three hundred and nine CD patients were included. The mean follow-up time with infliximab treatment was 41 months, and the majority (95%) were on concomitant immunosuppressive therapy. The annual risk of loss of response to infliximab was 12% per patient-year of treatment. After loss of response, 41% of patients were managed with infliximab therapy escalation. After the first intensified dose, 56% of patients achieved remission and 40% partial response. Concurrent immunomodulators enhanced and smoking decreased the proportion of patients who maintained response (P<0.05). A relevant proportion of CD patients on long-term infliximab treatment loss response. After loss of response, a high proportion of these patients initially respond to infliximab dose escalation. Concurrent immunomodulators may increase and smoking may decrease maintenance of response.

Retrospective cost analysis of breast cancer patients treated in a Brazilian outpatient cancer center (OCC).

e11026 Background: Public health data indicate that the global burden of breast cancer in women, measured by incidence and mortality, is substantial. The associated treatment costs increase steadly above economic growth, leading to substantial financial, equity and access problems. However, the economic impact of management costs in Brazilian clinical practice has not been documented yet. Information about patients' quality of life associated with the introduction of new drugs and procedures is also lacking. Methods: This is a retrospective study of women with breast cancer treated at a private practice OCC in Rio de Janeiro, Brazil. All the patients were covered by Amil, a Brazilian HMO. Direct costs (DC) of 199 patients diagnosed since 2002 and followed to the end of 2009 were analyzed and correlated to clinical stage. Results: 48% of women were diagnosed in stage I, 34% patients in stage II, and only 2.5% were diagnosed in stage IV, similar numbers to those seen in developed countries. The average DC of their medical care per patient was US$21,658.94 (mean 2.48 yrs ± SD 1.66) for stage I compared to US$48,295.29 (mean 2.76 yrs ± SD 1.67) for stage II, and were US$63,662.06 (mean 2.34 yrs ± SD 1.56) for stage III and US$63,697.33 (mean 1.77 yrs ± SD 0.80) for stage IV. We also observed that DC per patient-year increased according to clinical stage. In the first year, average cost was US$15,183.85 for stage I, while it was US$ 44,160.74 for stage IV. Those DC decreased along the years in all stages. For example, in the seventh year of follow-up, the average DC was only US$ 467.27 for stage I (2005 purchasing power parity index 1 USD = 1.4 BRL). Conclusions: Breast cancer accounts for a significant part of the health insurance budget. Later stage at diagnosis is associated with higher DC per patient-year of treatment, and known lower probability of 5-year survival. No significant financial relationships to disclose.

P209 - A randomised controlled trial with Probio-Tec AB-25 for maintenance of remission in ulcerative colitis

P209 - A randomised controlled trial with Probio-Tec AB-25 for maintenance of remission in ulcerative colitis

El costo de la atención médica del cáncer mamario: el caso del Instituto Mexicano del Seguro Social

We studied the cost of health care for women with breast cancer treated at the Mexican Social Security Institute (IMSS, per its abbreviation in Spanish). Using the Medical and Operative Information Systems of the IMSS, we constructed a cohort of patients diagnosed in 2002 and followed these patients to the end of 2006, identifying the use of resources and imputing the IMSS-specific cost structure. Only 14% of women were diagnosed in stage 1 and 48% were diagnosed in stages III-IV. The average cost of their medical care per patient-year was $MX110,459. Costs for stage 1 were $MX74,522 compared to $102,042 for stage II, and were $MX154,018 for stage III and $MX199,274 for stage IV. Breast cancer accounts for a significant part of the IMSS health budget. Later stage at diagnosis is associated with higher economic costs per patient-year of treatment and lower probability of five-year survival.

Thirty‐five months experience of risperidone long‐acting injection in a UK psychiatric service including a mirror‐image analysis of in‐patient care

To report the use of risperidone long-acting injection (RLAI) in a UK psychiatric service. Retrospective case note review of all patients prescribed RLAI over a 35-month period. In the mirror-image analysis patients initiated on RLAI as in-patients had the index admission attributed to previous treatment. Patients prescribed RLAI had significantly higher baseline rates of drug misuse, alcohol misuse, unemployment and forensic markers than control patients prescribed oral antipsychotics. Most patients started RLAI because of poor compliance with oral antipsychotics. Inefficacy accounted for more discontinuations than intolerability. Fifty-eight percent (39/67) of patients were continuing RLAI 12 months after initiation. Mirror-image analysis (n = 74) showed that RLAI was associated with a reduction in the number of admissions (65 vs. 33, P < 0.005) and in total in-patient days (4550 vs. 2188 days, P < 0.005). The mean reduction in in-patient care was 29 days per patient-year of treatment, equivalent to a net financial saving over the acquisition and administration costs of RLAI of pound1172. Risperidone long-acting injection was associated with reduced in-patient care and was cost-effective.

Risk of Cardiovascular Events in Patients Receiving Celecoxib: A Meta-Analysis of Randomized Clinical Trials

Some nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 selective inhibitors, have been associated with increased cardiovascular (CV) events in recent clinical trials or observational studies. To determine whether the cyclooxygenase-2 selective inhibitor celecoxib affects CV risk, the incidence of CV events was analyzed in patients treated with celecoxib, placebo, or nonselective NSAIDs in the clinical trial database for celecoxib using defined Antiplatelet Trialists' Collaboration end points of nonfatal myocardial infarction, nonfatal stroke, and CV death. Patient data were derived from studies in osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, low back pain, and Alzheimer's disease. This meta-analysis included (1) 7,462 patients exposed to celecoxib 200 to 800 mg/day for 1,268 patient-years compared with 4,057 patients treated with placebo for 585 patient-years, and (2) 19,773 patients treated with celecoxib 200 to 800 mg/day for 5,651 patient-years compared with 13,990 patients treated with nonselective NSAIDs (diclofenac, ibuprofen, naproxen, ketoprofen, and loxoprofen) for 4,386 patient-years. CV events were adjudicated by a 3-member expert end point committee (WBW, JSB, PBG) blinded to treatment group and study. The incidence rates of the combined CV events were not significantly different between patients treated with celecoxib and placebo or between those treated with celecoxib and nonselective NSAIDs. Event rates were similar for adjudicated and nonadjudicated data. Dose of celecoxib, the use of aspirin, or the presence of CV risk factors did not alter these results. In conclusion, these analyses failed to demonstrate an increased CV risk with celecoxib relative to placebo and demonstrated a comparable rate of CV events with celecoxib treatment compared with nonselective NSAIDs.

Nocardia peritonitis and abdominal abscess complicating continuous ambulatory peritoneal dialysis

SUMMARY:Peritonitis is a common problem in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and represents the most frequent cause of peritoneal catheter loss and discontinuation of CAPD. The incidence of peritonitis remains less than one episode per patient year of treatment. Common bacteria, particularly staphyloccal species, are the usual causative agents. Fungi and higher bacteria such as Nocardia as aetiological agents have been infrequent in patients undergoing CAPD. We report a case of Nocardia nova peritonitis complicated by an intra‐abdominal abscess requiring surgical drainage and a protracted course of antibiotics.

Anticoagulation clinics and the monitoring of anticoagulant therapy

Patients attending an anticoagulation clinic were studied to delineate predisposing risk factors for bleeding and thromboembolic episodes. Seventy-three patients were observed for a total of 921.8 patient-treatment months. The mean duration of treatment was 12.6 months (range 3–36 months). No major bleed occurred (a bleed which caused discontinuation of therapy, hospitalization or death). Thirty-two patients had minor bleeding episodes (0.42 bleeds per patient-year of treatment). The average prothrombin time ratio during the third to the sixth month of therapy was predictive of the bleeding risk. There was no association between bleeding and age, sex, indication for anticoagulation therapy or associated illnesses. Four thromboembolic episodes occurred (0.05 per patient-year of treatment), 3 arterial and 1 venous. At the time of the one venous thromboembolic event the prothrombin time ratio was subtherapeutic. In all 3 patients with arterial thromboembolism the mean 3- to 6-month prothrombin time ratio was less than or equal to the lower limit of the recommended range of 1.6–2.5. In our study prothrombin time ratios of 1.3–1.5 for venous thromboembolic disease and 1.6–2.5 for arterial thromboembolic disease were not associated with thromboembolism or major bleeding. Anticoagulation clinics facilitate the close monitoring of patients on oral anticoagulant therapy.

Spontaneous Retroperitoneal Hemorrhage During Oral Anticoagulant Therapy-Reply

We would like to thank Palleja et al for their comments regarding their experience with outpatient anticoagulant therapy in relation to our experiences, and for their brief, but useful, review of the unusual complication of spontaneous retroperitoneal hemorrhage seen in patients receiving oral anticoagulants. We would like to comment, however, on a few of their remarks in regards to the incidence of complications with anticoagulant therapy. Palleja et al made an error that many others have made when discussing the incidence of anticoagulant complications. They quote our 5% incidence of major complications per treatment course, and compare it with their 3.1% incidence per patient year of treatment. These statistics are not comparable. Because of variations in reporting complication rates, reports in the literature are equally difficult to compare. We think that the most appropriate unit of time for assessing complication rates is a month of treatment, since duration of therapy