Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D).

AIM: To present the pre-specified analyses of >5-years follow-up of the Phase III ALTTO trial. PATIENTS AND METHODS: 8381 patients with stage I-III HER2 positive breast cancer randomised to chemotherapy plus 1-year of trastuzumab (T), oral lapatinib (L; no longer evaluated), trastuzumab followed by lapatinib (T→L), and lapatinib + trastuzumab (L+T). The primary endpoint was disease-free survival (DFS). A secondary analysis examined DFS treatment effects by hormone receptor status, nodal status and chemotherapy timing; time to recurrence; overall survival (OS) and safety (overall and cardiac). RESULTS: At a median follow-up of 6.9 years, 705 DFS events for L+T versus T were observed. Hazard Ratio (HR) for DFS was 0.86 (95% CI, 0.74-1.00) for L+T versus T and 0.93 (95% CI, 0.81-1.08) for T→L versus T. The 6-year DFS were 85%, 84%, and 82% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70-1.06) for L+T versus T and 0.88 (95% CI, 0.71-1.08) for T→L versus T. The 6-year OS were 93%, 92%, and 91% for L+T, T→L, and T, respectively. Subset analyses showed a numerically better HR for DFS in favour of L+T versus T for the hormone-receptor-negative [HR 0.80 (95% CI, 0.64-1.00; 6-yr DFS% = 84% versus 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69-1.00; 6-yr DFS% = 83% versus79%)] subgroups. CONCLUSION: T+L did not significantly improve DFS and OS over T alone, both with chemotherapy, and, therefore, cannot be recommended for adjuvant treatment of early-stage HER2-positive breast cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00490139.

Difficulties arising in reimbursement recommendations on new medicines due to inadequate reporting of population adjustment indirect comparison methods.

Indirect treatment comparisons are useful to estimate relative treatment effects when head-to-head studies are not conducted. Statisticians at the National Centre for Pharmacoeconomics Ireland (NCPE) and Scottish Medicines Consortium (SMC) assess the clinical and cost-effectiveness of new medicines as part of multidisciplinary teams. We describe some shared observations on areas where reporting of population-adjustment indirect comparison methods is causing uncertainty in our recommendations to decision-making committees when assessing reimbursement of medicines.

Acquired transverse myelopathy in children in the United Kingdom--a 2 year prospective study.

AIMS: To define the incidence, describe presentation, management and outcome and identify prognostic factors in Acquired Transverse Myelopathy (ATM) in children under 16 years. METHODS: A prospective population-based surveillance study, involving all consultant paediatric neurologists in the United Kingdom from 1 July 2002 to 30 June 2004. RESULTS AND DISCUSSION: Response rate was 91%, and 60 children were reported, of whom 41 were included. Median age was 9 years. The incidence of ATM in children under 16 years in confirmed cases is at least 1.72 per million children per year. There was a previously unrecognised male predominance (M:F 25:16). Early evaluation of bladder function is sometimes omitted. MR imaging should include whole spine and brain to maximise diagnostic information. Despite the use of high dose steroids, 25% of cases were left with significant sequelae. Outcome data was available for 36 children in whom recovery was defined as 'complete' in 19, 'good' in 8, 'fair' in 3 and 'poor' in 6. Significant positive prognostic factors were preceding infection, start of recovery within a week of onset, age less than 10 years, and lumbosacral spinal level on clinical assessment. Significant negative predictors were flaccid legs at presentation, sphincter involvement and rapid progression from onset to nadir within 24h.

Evaluation of severe infection and survival after splenectomy.

PURPOSE: Splenectomized patients are known to be at risk of severe infection, but the extent of risk is unclear. We evaluated the incidence of severe infection and survival in 1648 splenectomized patients. METHODS: Patients who underwent splenectomy between 1988 and 1999 in Scotland were identified through the Scottish hospital discharge records (SMR01) and then linked to the death certificate data recorded by the General Register Office in Scotland to obtain clinical and demographical information. RESULTS: The overall rate of first severe infection was 7.0 per 100 person-years (95% confidence interval, 6.30-7.78). The overall rate for a second infection per 100 person-years was 44.9 and 109.3 for a third infection after the first episode of infection. Among the repeated episodes of severe infection, 42% to 76% and 61% to 84% of total episodes of second and third severe infection, respectively, occurred within 6 months after the first severe infection. The susceptibility to severe infection was greatest in older age groups (5.5 per 100 person-years in those aged > 50 years) and in patients splenectomized for hematologic malignancy (9.2), and iatrogenic splenectomy for malignancy disease (7.4). Between 50% and 80% of all severe infections or deaths occurred within 1 to 3 years after splenectomy. CONCLUSIONS: The risk of severe infection is an important health problem in splenectomized patients, especially in those who underwent surgery for malignancies. Antibiotic prophylaxis could offer the most benefits in the first 3 years postsplenectomy or the first 6 months after the occurrence of a first severe infection.

Influenza and pneumococcal vaccination in Scottish nursing homes: coverage, policies and reasons for receipt and non-receipt of vaccine.

A national survey was carried out to determine the coverage of influenza and pneumococcal vaccines, policies, reasons for receipt, non-receipt of vaccine and strategies to improve vaccine coverage in Scottish nursing homes. Of the 550 nursing homes, 72% (394) participated in the study. Overall coverage was 85% for influenza vaccine in 2001-2002 season and 11% for pneumococcal vaccine in the last 5-year period. Only 6% (23/394) of homes were reported to have a systematic immunization record. The most frequently stated reasons for improved coverage of both vaccines were clear immunization policies (76%), awareness and education for staff and residents (68%), and consent on behalf of the incompetent residents (66%). The presence of vaccination policies was higher for influenza vaccine than pneumococcal vaccine expressed as verbal agreement (27% versus 3%), written policies with set target (24% versus 5%) and written policies without set target (17% versus 2%). Advice from the members of the community health care team was the principal reason for the receipt of both vaccines. The predominant reasons for non-receipt of vaccine were refusal by residents and family members (both vaccines) and lack of advice from general practitioners (pneumococcal vaccine). The substantial disparity in coverage of influenza and pneumococcal vaccine reflects the lack of national recommendations and policies for reimbursements for pneumococcal vaccination. These data suggest that greater efforts are needed to improve prevention behaviors of health care professionals and the public, organized vaccine delivery strategies and systematic vaccination documents to increase influenza and pneumococcal vaccination rates in nursing homes and other long-term care facilities.