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.

Detection of DNA damage by the alkaline comet assay after exposure to low-dose gamma radiation.

The alkaline comet assay as described by Olive et al. (Exp. Cell Res. 198, 259-267, 1992) was used to detect DNA damage in cells exposed to low doses (0-5 cGy) of gamma radiation. Experiments were performed using lymphocytes isolated from whole blood of rats. The comet parameters, normalized comet moment and comet length, described by Kent et al. (Int. J. Radiat. Biol. 67, 655-660, 1995), were used as measurements of DNA damage. It was observed that the alkaline comet assay can detect DNA damage at doses as low as 0.6 cGy. The results of the experiments using low-dose gamma radiation are comparable with published results obtained using the alkaline comet assay according to the method of Singh et al. (Int. J. Radiat. Biol. 66, 23-28, 1994). Based on this observation and analysis of results published previously, we conclude that the version of the alkaline comet assay described by Olive et al. is as sensitive as other modifications of the comet assay reported in literature for the detection of DNA damage in cells exposed to low doses of ionizing radiation.

Measurement of DNA damage after exposure to 2450 MHz electromagnetic radiation.

Recent reports suggest that exposure to 2450 MHz electromagnetic radiation causes DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) in cells of rat brain irradiated in vivo (Lai and Singh, Bioelectromagnetics 16, 207-210, 1995; Int. J. Radiat. Biol. 69, 513-521, 1996). Therefore, we endeavored to determine if exposure of cultured mammalian cells in vitro to 2450 MHz radiation causes DNA damage. The alkaline comet assay (single-cell gel electrophoresis), which is reportedly the most sensitive method to assay DNA damage in individual cells, was used to measure DNA damage after in vitro 2450 MHz irradiation. Exponentially growing U87MG and C3H 10T1/2 cells were exposed to 2450 MHz continuous-wave (CW) radiation in specially designed radial transmission lines (RTLs) that provided relatively uniform microwave exposure. Specific absorption rates (SARs) were calculated to be 0.7 and 1.9 W/kg. Temperatures in the RTLs were measured in real time and were maintained at 37 +/- 0.3 degrees C. Every experiment included sham exposure(s) in an RTL. Cells were irradiated for 2 h, 2 h followed by a 4-h incubation at 37 degrees C in an incubator, 4 h and 24 h. After these treatments samples were subjected to the alkaline comet assay as described by Olive et al. (Exp. Cell Res. 198, 259-267, 1992). Images of comets were digitized and analyzed using a PC-based image analysis system, and the "normalized comet moment" and "comet length" were determined. No significant differences were observed between the test group and the controls after exposure to 2450 MHz CW irradiation. Thus 2450 MHz irradiation does not appear to cause DNA damage in cultured mammalian cells under these exposure conditions as measured by this assay.

Measurement of DNA damage after exposure to electromagnetic radiation in the cellular phone communication frequency band (835.62 and 847.74 MHz).

Mouse C3H 10T1/2 fibroblasts and human glioblastoma U87MG cells were exposed to cellular phone communication frequency radiations to investigate whether such exposure produces DNA damage in in vitro cultures. Two types of frequency modulations were studied: frequency-modulated continuous-wave (FMCW), with a carrier frequency of 835.62 MHz, and code-division multiple-access (CDMA) centered on 847.74 MHz. Exponentially growing (U87MG and C3H 10T1/2 cells) and plateau-phase (C3H 10T1/2 cells) cultures were exposed to either FMCW or CDMA radiation for varying periods up to 24 h in specially designed radial transmission lines (RTLs) that provided relatively uniform exposure with a specific absorption rate (SAR) of 0.6 W/kg. Temperatures in the RTLs were monitored continuously and maintained at 37 +/- 0.3 degrees C. Sham exposure of cultures in an RTL (negative control) and 137Cs gamma-irradiated samples (positive control) were included with every experiment. The alkaline comet assay as described by Olive et al. (Exp. Cell Res. 198, 259-269, 1992) was used to measure DNA damage. No significant differences were observed between the test group exposed to FMCW or CDMA radiation and the sham-treated negative controls. Our results indicate that exposure of cultured mammalian cells to cellular phone communication frequencies under these conditions at an SAR of 0.6 W/kg does not cause DNA damage as measured by the alkaline comet assay.

Neoplastic transformation in C3H 10T(1/2) cells after exposure to 835.62 MHz FDMA and 847.74 MHz CDMA radiations.

The effect of radiofrequency (RF) radiation in the cellular phone communication range (835.62 MHz frequency division multiple access, FDMA; 847.74 MHz code division multiple access, CDMA) on neoplastic transformation frequency was measured using the in vitro C3H 10T(1/2) cell transformation assay system. To determine if 835.62 MHz FDMA or 847.74 MHz CDMA radiations have any genotoxic effects that induce neoplastic transformation, C3H 10T(1/2) cells were exposed at 37 degrees C to either of the above radiations [each at a specific absorption rate (SAR) of 0.6 W/kg] or sham-exposed at the same time for 7 days. After the culture medium was changed, the cultures were transferred to incubators and refed with fresh growth medium every 7 days. After 42 days, the cells were fixed and stained with Giemsa, and transformed foci were scored. To determine if exposure to 835.62 MHz FDMA or 847.74 MHz CDMA radiation has any epigenetic effects that can promote neoplastic transformation, cells were first exposed to 4.5 Gy of X rays to induce the transformation process and then exposed to the above radiations (SAR = 0.6 W/kg) in temperature-controlled irradiators with weekly refeeding for 42 days. After both the 7-day RF exposure and the 42-day RF exposure after X irradiation, no statistically significant differences in the transformation frequencies were observed between incubator controls, the sham-exposed (maintained in irradiators without power to the antenna), and the 835.62 MHz FDMA or 847.74 MHz CDMA-exposed groups.

DNA damage in rat brain cells after in vivo exposure to 2450 MHz electromagnetic radiation and various methods of euthanasia.

The present study was done to confirm the reported observation that low-intensity acute exposure to 2450 MHz radiation causes DNA single-strand breaks (Lai and Singh, Bioelectromagnetics 16, 207-210, 1995). Male Sprague-Dawley rats weighing approximately 250 g were irradiated with 2450 MHz continuous-wave (CW) microwaves for 2 h at a specific absorption rate of 1.2 W/kg in a cylindrical waveguide system (Guy et al., Radio Sci. 14, 63-74, 1979). There was no associated rise in the core body temperature of the rats. After the irradiation or sham treatments, rats were euthanized by either CO2 asphyxia or decapitation by guillotine (eight pairs of animals per euthanasia group). After euthanasia the brains were removed and immediately immersed in cold Ames medium and the cells of the cerebral cortex and the hippocampus were dissociated separately and subjected to the alkaline comet assay. Irrespective of whether the rats were euthanized by CO2 asphyxia or decapitated by guillotine, no significant differences were observed between either the comet length or the normalized comet moment of cells from either the cerebral cortex or the hippocampus of sham-treated rats and those from the irradiated rats. However, the data for the rats asphyxiated with CO2 showed more intrinsic DNA damage and more experiment-to-experiment variation than did the data for rats euthanized by guillotine. Therefore, the guillotine method of euthanasia is the most appropriate in studies relating to DNA damage. Furthermore, we did not confirm the observation that DNA damage is produced in cells of the rat cerebral cortex or the hippocampus after a 2-h exposure to 2450 MHz CW microwaves or at 4 h after the exposure.

Referrals of participants in an urban WIC program to health and welfare services.

The Special Supplemental Food Program for Women, Infants, and Children (WIC) provides supplemental food, nutrition education, and referrals to available health and welfare services. Recipients are income-eligible pregnant and postpartum women, their infants, and their children who are younger than 5 years of age. Although studies have documented the nutritional benefits of the program, the extent to which WIC nutritionists help eligible women to obtain available health and welfare services, and the degree to which this referral activity promotes health, is largely unknown. The researchers examined the referral activity at one urban WIC clinic, but did not evaluate the outcomes. Of 1,850 persons seen, there were 762 referrals by WIC nutritionists for 597 persons at the Lawrence, MA, clinic during a 2-month period. Of the 597 persons, 494 (83 percent) were WIC participants and 103 (17 percent) were nonparticipants. The rate of referrals for WIC participants was 27 percent. Multiple referrals were common, with 127 people receiving more than one referral. WIC nutritionists at this site offered a variety of referrals to their clients. The majority of referrals (61.7 percent) were for supplemented food. Non nutrition-related referrals were to medical and dental services (20.5 percent), developmental and educational services (12.5 percent), and social services (5.4 percent). Non nutrition-related referrals for women included referrals for family planning, substance abuse, job training, teenaged parenting, and high school equivalency programs. Infants and children were referred for dental care, growth failure, the Head Start Program, kindergarten enrollment, early intervention, and protective services. WIC nutritionists are in an ideal position to evaluate a broad spectrum of health issues and to refer participants to health and welfare services because clients return regularly for vouchers and nutrition counselling. The authors conclude that WIC nutritionists should be given formal training in the evaluation of, and referral for, non nutrition related issues in order to maximize their health advocacy role.