Tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: long-term safety and efficacy in an open-label extension study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. Final safety and efficacy data from an open-label extension study of tofacitinib in psoriasis are reported. OBJECTIVES: To evaluate the long-term safety and durability of efficacy of tofacitinib in adults with moderate-to-severe chronic plaque psoriasis. METHODS: Eligible patients who completed qualifying phase II/III tofacitinib studies received tofacitinib 10 mg twice daily (q12h) until month 3; subsequently, the dose could be adjusted by investigators to either 5 or 10 mg q12h. Adverse events (AEs) are reported up to month 66 and laboratory data up to month 54. Efficacy end points up to month 54 included Physician's Global Assessment of 'clear' or 'almost clear' (PGA response) and 75% improvement in Psoriasis Area and Severity Index (PASI 75). RESULTS: Overall, 2867 patients received tofacitinib, with a median treatment duration of 35·6 months. Adverse events (AEs) and serious AEs were reported in 82·5% and 13·7% of patients, respectively; 13·9% of patients discontinued owing to AEs; and 29 patients died. Incidence rates (patients with event/100 patient-years) were 1·16 for serious infections, 0·67 for malignancies and 0·26 for major adverse cardiovascular events. After initial changes in qualifying studies, most laboratory parameters were generally stable over 54 months. PGA response was achieved by 52-62% of patients and PASI 75 by 56-74% of patients at each study visit through month 54. CONCLUSIONS: In patients with psoriasis, the safety profile of tofacitinib over 66 months was similar to previous reports in phase III studies and efficacy was sustained through 54 months (NCT01163253).

The role of colostrum in glomerulonephritis of Finnish Landrace lambs: effect of cross-fostering newly born Finnish Landrace and Cheviot lambs.

Newly-born Finnish Landrace and Cheviot lambs were cross-fostered to determine the role of colostrum in the development of mesangiocapillary glomerulonephritis of the Finnish Landrace breed. Severe glomerulonephritis occurred in four Finnish Landrace lambs reared by their own dams. One of six siblings of affected lambs, all reared by Cheviot foster mothers, developed a milder focal form of the disease. No glomerulonephritis occurred in three Cheviot lambs reared by Finnish Landrace foster mothers whose own naturally reared lambs died of the disease. An artificially reared colostrum-free Finnish Landrace lamb became severely affected, though its naturally reared sibling had no renal disease in sequential biopsies. It is concluded that colostrum has no primary role in the development of the disease.

The surgical management of spinal deformity in children with a Fontan circulation: The development of an algorithm for treatment.

The management of spinal deformity in children with univentricular cardiac pathology poses significant challenges to the surgical and anaesthetic teams. To date, only posterior instrumented fusion techniques have been used in these children and these are associated with a high rate of complications. We reviewed our experience of both growing rod instrumentation and posterior instrumented fusion in children with a univentricular circulation. Six children underwent spinal corrective surgery, two with cavopulmonary shunts and four following completion of a Fontan procedure. Three underwent growing rod instrumentation, two had a posterior fusion and one had spinal growth arrest. There were no complications following surgery, and the children undergoing growing rod instrumentation were successfully lengthened. We noted a trend for greater blood loss and haemodynamic instability in those whose surgery was undertaken following completion of a Fontan procedure. At a median follow-up of 87.6 months (interquartile range (IQR) 62.9 to 96.5) the median correction of deformity was 24.2% (64.5° (IQR 46° to 80°) vs 50.5° (IQR 36° to 63°)). We believe that early surgical intervention with growing rod instrumentation systems allows staged correction of the spinal deformity and reduces the haemodynamic insult to these physiologically compromised children. Due to the haemodynamic changes that occur with the completed Fontan circulation, the initial scoliosis surgery should ideally be undertaken when in the cavopulmonary shunt stage.

A survey of the treatment of displaced intracapsular femoral neck fractures in the UK.

A survey was undertaken to investigate the treatment of displaced intracapsular femoral neck fractures across the UK. The usual practice at 223 hospitals was recorded for two groups of patients, active and frail. Management of stereotyped fractures, in similar patients, varied between hospitals. There was also variation between specialists within some hospitals: two or more of the alternative methods of treatment were in routine use for active patients at 22% of hospitals and for frail patients at 27%. Overall, for active patients, bipolar hemiarthroplasty was undertaken at 41% of hospitals, internal fixation at 37%, unipolar hemiarthroplasty at 32% and total hip replacement at 16%. Cemented prostheses were used in 74% of arthroplasties for active patients. For frail patients, hemiarthroplasty with an Austin Moore or Thompson prostheses was undertaken at 94% of hospitals; bipolar prostheses were used at 8%; internal fixation was undertaken at 1%. Cement was used in 46% of hemiarthroplasties. These findings indicate a lack of consensus in aspects of the treatment of displaced intracapsular femoral neck fractures and are likely to reflect difficulties in determining "best practice."