Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM).

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

Trends in hip fracture care in the Republic of Ireland from 2013 to 2018: results from the Irish Hip Fracture Database.

Hip fractures continue to be one of the most serious and costly injuries suffered by older people globally. This paper describes the development of a national hip fracture audit and summarises the first 6 years of data from the Republic of Ireland. This can help inform care, standards and outcomes of hip fracture patients. INTRODUCTION: Ireland has one of the highest standardised rates of hip fracture in the world behind northern European countries. The Irish Hip Fracture Database (IHFD) was established in 2012 to drive clinical and organisational improvements in quality and effectiveness of hip fracture care. This paper describes the progression of the IHFD between 2013 and 2018 and identifies trends and areas for improvement. METHODS: The IHFD is a clinically led, web-based audit, with data collected through the national Hospital Inpatient Enquiry (HIPE) electronic system, the principal source of information from publicly funded acute hospitals in Ireland. Eligible cases are aged ≥ 60 years with hip fracture as defined by IHFD or with other specified hip fracture excluding periprosthetic fractures. As of 2015, all 16 trauma-receiving hospitals within Ireland submitted data. Demographics and adherence to six national quality standards are described. RESULTS: A total of 17,983 cases were included in the analysis. National coverage has increased from 63% in 2013 to 99% in 2018. Demographic characteristics are unchanged, but higher levels of comorbidity are seen. Internal fixation and hemiarthroplasty are the most common modes of surgical repair with two-thirds of cases receiving spinal rather than general anaesthesia. Increasingly patients are being assessed by a geriatrician (11% in 2013 to 69% in 2018) and receive a bone health assessment (65% in 2013 to 84% in 2018). CONCLUSION: While some hip fracture standards have improved, further improvements are required to compare favourably internationally. Reduction of surgical delay and ensuring early mobilisation post-operatively are immediate priorities for the IHFD.

Menstrual psychosis.

In this report, we explore a case of symptoms consistent with menstrual psychosis. In order to do this, a review of the literature relating to this topic was conducted and a report was written. This is a case of a previously well adolescent female who experienced psychotic symptoms in the pre-menstrual phase of her cycle and became well soon after her menstrual period began. These episodes were prevented by aripiprazole, but recurred once medication was withdrawn. We conclude that psychosis in some women may have a relationship with the menstrual cycle. In women presenting with psychosis, it may be appropriate to note menstrual variation in symptoms. This could have a potential role in individualisation of treatment for women with psychotic disorders.

Discharge destination after hip fracture: findings from the Irish hip fracture database.

PURPOSE: Although home continues to be the place from which the majority of patients are admitted, less than one third of patients are Discharged Directly Home (DDH) following hip fracture. Once ready for discharge, DDH as opposed to Discharge to an Alternative Location (DAL), i.e., community care, rehabilitation facility or long-term care, is a high priority for patients and clinicians alike. Not only is DDH integral to the quality of life of patients, it is also an essential driver of the socioeconomic cost of hip fracture care. METHODS: We analysed 21,819 cases in the Irish Hip Fracture Database from 2013 to 2019. Descriptive and analytical statistics were conducted. RESULTS: 29% (n = 6476) of patients were DDH during the study period. On multivariate analysis, the odds of DDH decreased as age increased (OR 0.28, p < 0.01, 95% CI 0.24-0.34). Patients who were independently mobile prior to fracture were 47% more likely to be DDH (OR 1.47, p < 0.01, 95% CI 1.29-1.68). Those mobilised early post operatively were 24% more likely to be DDH (OR 1.24, p < 0.01, 95% CI 1.06-1.45). Patients who waited > 72 h prior to surgery were 30% less likely to be DDH (OR 0.70, p < 0.01, 95% CI 0.56-0.88). CONCLUSION: The authors identified patient characteristics that increased the likelihood of DDH, i.e., younger patients independently mobile prior to fracture, who received timely surgery and early post-operative mobilisation. The Irish Hip Fracture Standards (IHFS) incorporate 2 out the 3 modifiable factors identified, which reinforces the importance of the IHFS in improving patient outcomes.

Haemoglobin F Victoria Jubilee (alpha 2 A gamma 2 80 Asp-Try).

A new A gamma chain haemoglobin variant, haemoglobin F Victoria Jubilee, with an electrophoretic mobility slightly anodal to haemoglobin F Port Royal, was found in a Jamaican infant. The amino acid residue substitution of 80 Aspartic Acid leads to Tyrosine was associated with alanine in position 136. Haemoglobin F Victoria Jubilee constituted about 7.0 percent of the total haemoglobin F.