Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial.

BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

Accuracy of distributed multipoles and polarizabilities: comparison between the LoProp and MpProp models.

Localized multipole moments up to the fifth moment as well as localized dipole polarizabilities are calculated with the MpProp and the newly developed LoProp methods for a total of 20 molecules, predominantly derived from amino acids. A comparison of electrostatic potentials calculated from the multipole expansion obtained by the two methods with ab initio results shows that both methods reproduce the electrostatic interaction with an elementary charge with a mean absolute error of approximately 1.5 kJ/mol at contact distance and less than 0.1 kJ/mol at distances 2 A further out when terms up to the octupole moments are included. The polarizabilities are tested with homogenous electric fields and are found to have similar accuracy. The MpProp method gives better multipole moments unless diffuse basis sets are used, whereas LoProp gives better polarizabilities.

Retroperitoneal cystic papillary carcinoma of probable nephrogenic origin.

A case of primary retroperitoneal cystic papillary carcinoma of probable nephrogenic origin is presented. To our knowledge, this is the first such case reported in the literature.

Transurethral microwave thermotherapy for treatment of benign prostatic hyperplasia: results obtained with the Prostalund device.

The 6-month results of treatment with transurethral microwave thermotherapy (Prostalund) of 28 patients with lower urinary tract symptoms (LUTS) due to benign hyperplasia of the prostate are reported. The median International Prostate Symptom Score (I-PSS) fell from 16.5 (range 9-33) to 10.5 (range 3-30; P < 0.00005). Quality-of-life assessment improved from a median value of 4 (range 2-6) to 2 (range 1-5; P = 0.0001). In the Danish Prostate Symptom Score (DAN-PSS) the median total score fell from 20 (range 5-55) to 5 (range 0-43; P = 0.001). The median peak urinary flow increased from 10.6 to 11.5 ml/s (P = 0.20). Pressure-flow studies revealed no decrease in the median detrusor pressure at peak uroflow (PdetQmax) from 56 cmH2O preoperatively to 56 cmH2O after 6 months (P = 0.36). No change was found in postvoid residual urinary volume or in the calculated prostate volume. Complications included hematuria in most patients, urinary tract infections in 6 (21.4%) patients, and transient retention in 3 (10.7%) patients. In all, 20 (71.4%) patients responded to treatment with good symptomatic relief, but only minor changes were observed in urodynamic parameters.

[Vasectomy: who regrets it and why?]. / Vasektomi: hvem har fortrudt og hvorfor?

In order to determine the real percentage of sterilised men who regretted their sterilisation and for which reasons, a retrospective questionnaire survey was conducted in 1990-1991 on 244 men sterilised between 1980 and 1983. Information was also collected from their case records. 7.4% of the sterilised men regretted their decision. Of these, 39% were younger than 30, and 94% had started a relation with another woman. The lower age limit for sterilisation according to the law is 25 years, 37% found this age limit too low and 6% found it too high. We conclude that it should be considered whether the legal lower age limit for sterilisation is too low. It is important to thoroughly inform the patient about problems in sexual relations and alternative methods of contraception before he decides on sterilisation.

PIP: During January 1980-February 1983, a total of 421 men were referred to the urological department of Bispebjerg Hospital, Copenhagen, for vasectomy operations, of whom 19 opted out. In 1990, questionnaires were mailed out to 367 of these men. 246 (68%) returned them, but 2 were incomplete, thus a sample was left for analysis of 244 men who had been sterilized 8-10 years before. The inquiry concerned the percentage of regret among them and its causes. 18 (7.4%) regretted their decision, of whom 7 (39%) had been under 30 years of age at the time of operation. In contrast, of the remaining 226 who did not regret it, only 27 (12%) were under 30. A total of 61 (25%) established a new relationship after sterilization. 17 of those who regretted vasectomy had a new relationship, constituting 94% of all those regretting. 37% of the whole sample thought that the legal age limit for sterilization was low, 57% thought it was acceptable, and 6% thought it was too high. At the time of sterilization, 235 (96%) were in steady relationship and 9 were single. 50% of men who regretted their decision and subsequently underwent sterilization reversal operations were under 30 years of age with a median age of 29, compared to 39 years for those regretted it but did not attempt sterilization reversal. The average number of children before sterilization was 2.1, among those regretting it was 2.6, and among those not regretting 2.1. Among the causes of sterilization 210 (86%) cited the desire not to have more children, 120 (49%) cited their relationship, and some referred to the many side effects of oral contraceptives, previous miscarriage, complicated birth, and the desire to have a better sex life. The questions concerning changes in sex life was answered by 77 (32%) as better, 157 (64%) experienced no change, and 10 (4%) said it had become worse. 166 patients (68%) were satisfied with prior instruction from their physician, 161 (66%) from the department, and 217 (89%) had been counseled with at least one case illustration.

Age as a prognostic variable in patients undergoing transurethral prostatectomy.

In a retrospective study the outcome of transurethral prostatectomy (TURP) for benign prostatic hyperplasia (BPH) in patients more than 80 years old was compared to a control group of patients with a mean age ten years younger. The elderly had significantly more tissue resected and presented with a higher rate of preoperative urinary tract infection. More urological complications were seen among the elderly but these were generally short lived and had no influence on the morbidity, mortality and symptomatic outcome. The perioperative mortality was 3.2% among elderly and 0% in the younger age group. A cardiorespiratory risk score could not predict patients at risk. In conclusion the age per se had no major influence on the outcome of TURP.

[Surgery of penile deviation by Ebbehøj's method]. / Operation for deviatio penis a.m. Ebbehøj.

A questionnaire investigation to evaluate the results of surgery for penile angulation by plicature of tunica albuginea by Ebbehøj's method is presented. In 31 patients with congenital penile angulation, 24 (77%) were satisfied with the functional result and 20 (65%) with the cosmetic result of the operation. In 14 patients with Peyronie's disease, eight (57%) were satisfied with the functional result and six (43%) with the cosmetic result of the operation. This is in accordance with previously published surveys of the results of surgery using this method. However, a high prevalence of late sequelae was observed, especially penile shortening and pain. In conclusion, the method yields acceptable functional and cosmetic results and is easy to perform. However, optimal surgical technique is imperative to reduce the prevalence of late sequelae which also necessitate detailed preoperative information and restrictive indications for surgery.

ABO and rhesus blood groups as prognostic factors in transitional cell carcinomas of the upper urinary tract.

In a study of 290 patients with transitional cell carcinoma of the upper urinary tract an excess of blood group A was found. Comparisons between blood group A versus O and rhesus-positive versus rhesus-negative in relation to tumor stages or grades of dysplasia showed no significant differences neither at presentation nor in actuarial survival rates. It is concluded that the blood group systems ABO and rhesus have no prognostic value in urothelial tumors of the upper urinary tract.

Long term complications of the intraprostatic spiral. Case report.

A 76-year-old man had an intraprostatic spiral inserted to relieve bladder outlet obstruction that was caused by benign prostatic hypertrophy. After 30 months numerous complications had arisen including severe encrustations, urethral stricture, and sclerosis of the bladder neck. Regular replacement of the spiral or close monitoring of the development of encrustations seem necessary. The distal tip and the plating of the spiral require improvement.

Prognostic variables in patients with prostate cancer: influence of blood group ABO (H), the Rhesus system, age, differentiation, tumour stage and metastases.

Among 279 patients with carcinoma of the prostate no relationship was observed in survival between blood groups ABO (H) or the rhesus system. Age at diagnosis is relevant for the outcome of the disease, but grade of differentiation, tumour stage and metastases are more important predictors of survival.

Topical anesthesia with eutetic mixture of local anesthetics cream in vasectomy: 2 randomized trials.

Two paired randomized trials testing topical anesthesia with a eutetic mixture of local anesthetics (EMLA cream*) in vasectomy were performed. In 1 trial EMLA cream was applied on 1 side of the scrotum, while infiltration anesthesia into the skin and subcutaneous tissue with mepivacaine was used on the contralateral side. All but 1 of the 13 patients (p less than 0.05) preferred infiltration anesthesia because of pain as the incision reached the subcutaneous tissue. In the other trial 29 patients received EMLA cream on 1 side of the scrotum before bilateral mepivacaine infiltration. There was significantly less pain on the sides with the anesthetic cream (p less than 0.001). Many patients would pay the price of the cream. In conclusion, EMLA cream cannot replace but it can supplement infiltration anesthesia during vasectomy.

PIP: 2 types of randomized trials of a topical melting cream containing a mixture of local anesthetics (EMLA cream) alone or with infiltration with mepivacaine are reported in men having vasectomy. A sequential trial design was used so that the trial could be stopped when statistical significance was reached. EMLA cream was applied to a 20 square cm area and covered with occlusive tape for 30 minutes preoperatively. In the 1st trial 13 men received EMLA cream on one side and mepivacaine on the other. 12 of 13 preferred infiltration because they experienced pain when the incision reached the subcutaneous tissue. Subjects rated the procedure with EMLA cream as more painful than the one on the contralateral side, and 4 stated that they would have preferred the cream before infiltration. The procedure took on average 2 minutes longer to allow for another mepivacaine injection. In the 2nd trial 29 men had either infiltration anesthesia or both. All 15 men who had both anesthetics preferred the combined anesthesia, and 14 of the 15 stated that they would be willing to pay out-of pocket for the cream.

Transitional cell carcinoma of the upper urinary tract: prognostic variables and post-operative recurrences.

In a retrospective study of 198 patients with transitional cell carcinoma of the upper urinary tract, post-operative recurrences developed as contralateral tumours in 2.5%, in the ureteric stump after conservative resection in 19% and in the bladder in 36.4%. Upper tract recurrences resembled the primary tumours in terms of grade and stage; of the bladder tumours, 89% were similar in grade and 72% similar in stage to the primary tumours. Age, sex, grade and stage had no effect on the number of bladder recurrences, but ureteric tumours had significantly more recurrences than renal pelvicaliceal tumours. Sex, bladder recurrences and site of primary tumours did not influence survival. Thus grade and stage of the primary tumour were the only predictive variables of the final outcome.

Ureteritis cystica.

Six cases of ureteritis cystica are reported. Pathogenesis and diagnosis are discussed emphasizing the papillary tumour as an important differential diagnosis. A conservative attitude is recommended with a follow-up until the intravenous urography has normalized.

Long-term results of bladder neck incision in men.

A retrospective cohort of 163 male patients having either uni- (UI) or bilateral incision (BI) of the bladder neck to relieve infravesical obstruction was reviewed. Short-term results were excellent with significant improvement of flow rates. 82% (UI) and 87% (BI) of the incised patients were satisfied. Long-term results were assessed by a life-table analysis. 17% (UI) and 12% (BI) of the patients needed a reoperation during the observation period of 6 years. It is concluded that bladder neck incision is a method with few complications and favourable long-term results.

Long-term results of carbon dioxide laser treatment of meatal condylomata acuminata.

A group of 74 men who underwent carbon dioxide laser treatment of meatal condylomata were observed for an average of 18 months. The cure rate after 1 treatment of isolated meatal lesions was 78%; the presence of external lesions lowered the rate to 32% and additional external and urethral warts to 25%. Following multiple treatments all but 6 patients were cured; 83% of the recurrences developed within 3 months. One urethral and 6 meatal strictures occurred more than 3 months after treatment; 9 patients had a spraying stream many years after treatment and 2 complained of frequency.

Tetracycline sclerotherapy of hydroceles and epididymal cysts. Long-term results.

Fourty patients with 32 hydroceles and 11 epididymal cysts were treated by aspiration and instillation of tetracycline. After a follow up period of 24-39 months the cure rate was 77%. Most of the early recurrences were the results of chemical inflammation and vanished spontaneously. This group should therefore not be operated on until three months after their initial treatment. As aspiration of the fluid had allowed palpation of the testis and cytological examination, only a small proportion of patients with recurrences wanted further treatment. We therefore recommend tetracycline sclerotherapy because it is quick, easy, safe, and effective in the long as well as the short term.

[Emergency ultrasonic examinations]. / Akutte ultralydundersøgelser.

The employment and yields of emergency examinations carried out outside normal working hours in Bispebjerg Hospital, Copenhagen, in 1987 are illustrated. This facility is employed particularly by surgical departments for examination of patients with acute abdominal and retroperitoneal conditions and it is frequently supplemented by immediate ultrasonically guided drainage. The possibility of emergency examinations contributed to rapid, certain and gentle diagnosis in the treatment of patients.

Blood groups and urothelial tumours of the upper urinary tract. A study of 295 patients.

In 295 patients with transitional cell tumours of the upper urinary tract no significant relationship was found comparing blood groups A and O and the rhesus system to histological grade and invasive or non-invasive growth.

[Treatment principles in urethral stricture in Denmark. A questionnaire study]. / Behandlingsprincipper for urethrastrikturer i Danmark. En enquete.

A questionnaire presented to 79 danish surgical departments showed that about 2,000 urethral strictures are treated in Denmark per annum. These were mainly incised by Sachse's method. 8% of the patients do not have postoperative catheterisation, while the remainder have indwelling catheter from 1-28 days, mainly between 1-3 days. The reasons for the chosen regimes are presented.