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.

The Impacts of Spirituality and Religious Participation on the Emotional Well-Being of Widowed Older Adults in Southeast Nigeria.

Background and Objectives: The population of older individuals in Africa is increasing, and at a rapid rate. Although the numbers of these individuals increase, many African countries, including Nigeria, are devoid of state-sponsored welfare systems that address their well-being. This situation has placed the bulk of support on the family members including spouses. Studies have shown that spouses are considered to be veritable sources of support in later life. However, spousal death tends to reduce the perceived support including emotional support, which usually occasions lower well-being, life dissatisfaction, and higher mortality rates. This study ascertains the impact of spirituality/religious participation on the emotional well-being of widowed older adults. Research Design and Methods: The study was conducted in Enugu State, southeast Nigeria. The study implemented a qualitative approach to collect data from 71 widowed older adults, aged 60 and older. The thematic analytical method was used to analyze the generated data. Results: Participating in spiritual/religious activities like prayers, church programs/activities reading, studying, and meditating on the word of God have enabled the widowed older adults to buffer some of the emotional challenges. Discussion and Implications: Older adults should be encouraged to participate in spiritual and religious activities. Religious leaders should also make every effort to organize activities that will address the emotional needs of these individuals.

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.

Cognitive-behaviour intervention for critical thinking disposition of religion and social science students.

BACKGROUND: The dispositions of students towards critical thinking (CT) no doubt improve their clinical practice and performance. Hence, efforts to explore ways to help students become aware and conscious of the need for CT are imperative for their self-actualization, development, and improved professional practice. It is worrisome that in spite of the limited intervention addressing CT disposition challenges, scholars are yet to study the problem, especially in developing countries. METHODS: In view of that, we assessed how CT disposition can be improved among students enrolled in cognitive-behavioral reflective training programme (CBRT-P) using a group-randomized control study with three months follow-up. To achieve this, 163 students were allocated to different groups. The recruited participants were exposed to CBRT-P. RESULTS: Repeated-measures analysis performed shows that at the posttest, the mean CT disposition scores of the participants enrolled in CBRT-programme (treatment group) were significantly greater compared to the counterpart group that is the comparison group. At the third assessment, the mean score of the dependent measure consistently remained higher in favor of the experimental group. CONCLUSION: Given the results, it is concluded that the treatment programme improves the CT disposition of students over time.

"They will only remember us during elections": The culture of government support to Nigerian older adults and policy implications.

Governments are obliged to ensure the healthy living, well-being, and life satisfaction of every citizen. This, however, has not been achieved in Nigeria, especially with regard to older adults. Despite the notable shift in the country's demographic stance, few studies have investigated the government's roles in addressing the support to Nigerian older adults given that inadequate support is a risk factor for general poor health conditions and high mortality rates. This study, therefore, sought to investigate views on available government support to older adults in Nnewi, South-East Nigeria. Focus Group Discussion and In-depth interviews were adopted to collect data from older adults. The generated data were subjected to a thematic method of analysis. Findings show that Nigerian older adults are usually remembered during political activities, such as electioneering and election. However, the support is not all-inclusive but reserved for those who could actively participate in these political activities. To achieve the African Union and the 2030 global agenda's commitment to "leave no one behind," the study recommends social policies that address all-inclusive support and care for Nigeria older adults. Social workers' intervention will also be crucial to facilitate the formulation and implementation of welfare policies and programmes for the support and well-being of older adults.

Mortality and AIDS-defining events among young people following transition from paediatric to adult HIV care in the UK.

OBJECTIVES: To investigate risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV. METHODS: Records of people aged ≥ 13 years on 31 December 2015 in the UK paediatric HIV cohort (Collaborative HIV Paediatric Study) were linked to those of adults in the UK Collaborative HIV Cohort (CHIC) cohort. We calculated time from transition to a new AIDS event/death, with follow-up censored at the last visit or 31 December 2015, whichever was the earliest. Cumulative incidence of and risk factors for AIDS/mortality were assessed using Kaplan-Meier and Cox regression. RESULTS: At the final paediatric visit, the 474 participants [51% female, 80% black, 60% born outside the UK, median (interquartile range) age at antiretroviral therapy (ART) initiation = 9 (5-13) years] had a median age of 18 (17-19) years and CD4 count of 471 (280-663) cell/µL; 89% were prescribed ART and 60% overall had a viral load ≤ 400 copies/mL. Over median follow-up in adult care of 3 (2-6) years, 35 (8%) experienced a new AIDS event (n = 25) or death (n = 14) (incidence = 1.8/100 person-years). In multivariable analyses, lower CD4 count at the last paediatric visit [adjusted hazard ratio = 0.8 (95% confidence interval: 0.7-1.0)/100 cells/µL increment] and AIDS diagnosis in paediatric care [2.7 (1.4-5.5)] were associated with a new AIDS event/mortality in adult care. CONCLUSIONS: Young people with perinatally acquired HIV transitioning to adult care with markers of disease progression in paediatric care experienced poorer outcomes in adult care. Increased investment in multidisciplinary specialized services is required to support this population at high risk of morbidity and mortality.

Reactions of aryl dimethylphosphinothioate esters with anionic oxygen nucleophiles: transition state structure in 70% water-30% ethanol.

Aryl dimethylphosphinates, 2, react with anionic oxygen nucleophiles in water via a concerted (ANDN) mechanism. With EtO- in anhydrous ethanol, the mechanism is associative (AN + DN), with rate-limiting pentacoordinate intermediate formation. This change in mechanism with solvent change has been ascribed to changes in the nucleophile and leaving group basicities accompanying solvent change. This paper reports on a kinetic analysis of the reactions of the aryl dimethylphosphinothioates, 3a-g, with oxygen nucleophiles in 70% water-30% ethanol (v/v) solvent at 25 °C, reactions known to proceed by a concerted mechanism in water, to test the rationalization stated above, since the nucleophiles and LGs of interest are more basic in aqueous ethanol than in water. The change in solvent causes an ca. 14 to 320-fold decrease in rate. Hammett and Brønsted-type correlations characterize a concerted TS with less P-LG bonding in aqueous ethanol than in water. Two opposing consequences are associated with the solvent change: (a) increased basicity of nucleophiles and LGs, which lead to a modest tightening of the TS; and (b) better stabilization of the IS relative to the TS in aqueous ethanol, which results in a slower reaction with a more product-like TS. Hammond and anti-Hammond effects on the TS arising from better stabilization of the IS over the TS dominate over the effects of increased nucleophile and LG basicity in determining the looser TS structure in aqueous ethanol. An altered TS structure is consistent with an altered reaction potential energy surface, in this case caused by a change in solvent polarity.

Measuring the quality of cancer care in the Barwon South Western region, Victoria, Australia.

OBJECTIVE: The implementation of clinical quality indicators for monitoring cancer care in regional, rural and remote areas. DESIGN: Retrospective data from a population-based Clinical Quality Registry for lung, colorectal and breast cancers. SETTING: All major health services in the Barwon South Western region, Victoria, Australia. PARTICIPANTS: All patients who were diagnosed with cancer and who presented to a health service. INTERVENTION(S): Clinical subgroups to review variations. MAIN OUTCOME MEASURES(S): Clinical quality indicators for lung, colorectal and breast cancers. RESULTS: Clinical indicators included the following: discussion at multidisciplinary meetings, the timeliness of care provided and the type of care for different stages of the disease and survival outcomes. Many of the derived clinical indicator targets were reached. However, variations led to an improvement in the tumour stage being recorded in the medical record; an improved awareness of the need for adjuvant chemotherapy for colorectal cancer; a reduction in time to treatment for lung cancer and a reduced time to surgery for breast cancer, and the 30-day mortality post-treatment for all of the tumour streams was highlighted. CONCLUSIONS: Clinical quality indicators allow for valuable insights into patterns of care. These indicators are easily reproduced and may be of use to other cancer centres and health services.

Real-world impact of anti-HER2 therapy-related cardiotoxicity in patients with advanced HER2-positive breast cancer.

BACKGROUND: Anti-HER2 therapy-related cardiotoxicity is well described in the context of clinical trials, particularly in the setting of early stage disease, but there is more limited data in advanced breast cancer and in the real world setting. MATERIAL AND METHODS: A prospectively-maintained registry database with 312 consecutive patients diagnosed with HER2 positive advanced breast cancer in Australia was analysed. RESULTS: 287 patients (92%) received anti-HER2 therapy, 17 (6%) experienced anti-HER2 therapy-related cardiotoxicity. Patients who experienced cardiotoxicity were more likely to have ≥2 risk factors for cardiotoxicity (OR 3.9 95% CI 1.4-11.3 p = 0.01). A prior diagnosis of cardiovascular disease was significantly associated with cardiotoxicity (OR 7.1 95% CI 1.3-39.5). Cardiotoxicity resolved on imaging in 65% of patients; there was no association between severity and resolution. 11 patients (65%) received cardiologist input. Of the patients who developed cardiotoxicity, 12 patients (71%) received further anti-HER2 therapy in the first- or second-line setting without recurrent cardiotoxicity. DISCUSSION AND CONCLUSION: Therapy-related cardiotoxicity is an uncommon complication of anti-HER2 therapy in the real world setting. Cardiac toxicity resolved in the majority of affected patients, and further anti-HER2 therapy was administered without recurrence of cardiac issues. Our data suggests anti-HER2 therapy can be safely given in routine care, even in patients with risk factors for toxicity.

Regulation of the Extracellular Matrix by Ciliary Machinery.

The primary cilium is an organelle involved in cellular signalling. Mutations affecting proteins involved in cilia assembly or function result in diseases known as ciliopathies, which cause a wide variety of phenotypes across multiple tissues. These mutations disrupt various cellular processes, including regulation of the extracellular matrix. The matrix is important for maintaining tissue homeostasis through influencing cell behaviour and providing structural support; therefore, the matrix changes observed in ciliopathies have been implicated in the pathogenesis of these diseases. Whilst many studies have associated the cilium with processes that regulate the matrix, exactly how these matrix changes arise is not well characterised. This review aims to bring together the direct and indirect evidence for ciliary regulation of matrix, in order to summarise the possible mechanisms by which the ciliary machinery could regulate the composition, secretion, remodelling and organisation of the matrix.

Consumer and clinician perspectives on personalising breast cancer prevention information.

BACKGROUND: Personalised prevention of breast cancer has focused on women at very high risk, yet most breast cancers occur in women at average, or moderately increased risk (≤moderate risk). OBJECTIVES: To determine; 1) interest of women at ≤ moderate risk (consumers) in personalised information about breast cancer risk; 2) familial cancer clinicians' (FCCs) perspective on managing women at ≤ moderate risk, and; 3) both consumers' and FCCs reactions to iPrevent, a personalised breast cancer risk assessment and risk management decision support tool. METHODS: Seven focus groups on breast cancer risk were conducted with 49 participants; 27 consumers and 22 FCCs. Data were analysed thematically. RESULTS: Consumers reported some misconceptions, low trust in primary care practitioners for breast cancer prevention advice and frustration that they often lacked tailored advice about breast cancer risk. They expressed interest in receiving personalised risk information using iPrevent. FCCs reported an inadequate workforce to advise women at ≤ moderate risk and reacted positively to the potential of iPrevent to assist. CONCLUSIONS: While highlighting a potential role for iPrevent, several outstanding issues remain. For personalised prevention of breast cancer to extend beyond women at high risk, we must harness women's interest in receiving tailored information about breast cancer prevention and identify a workforce willing to advise women.

A comparative study of mechanisms of the adsorption of CO2 confined within graphene-MoS2 nanosheets: a DFT trend study.

The space within the interlayer of 2-dimensional (2D) nanosheets provides new and intriguing confined environments for molecular interactions. However, atomic level understanding of the adsorption mechanism of CO2 confined within the interlayer of 2D nanosheets is still limited. Herein, we present a comparative study of the adsorption mechanisms of CO2 confined within graphene-molybdenum disulfide (MoS2) nanosheets using density functional theory (DFT). A comprehensive analysis of CO2 adsorption energies (E AE) at various interlayer spacings of different multilayer structures comprising graphene/graphene (GrapheneB) and MoS2/MoS2 (MoS2B) bilayers as well as graphene/MoS2 (GMoS2) and MoS2/graphene (MoS2G) hybrids is performed to obtain the most stable adsorption configurations. It was found that 7.5 Å and 8.5 Å interlayer spacings are the most stable conformations for CO2 adsorption on the bilayer and hybrid structures, respectively. Adsorption energies of the multilayer structures decreased in the following trend: MoS2B > GrapheneB > MoS2G > GMoS2. By incorporating van der Waals (vdW) interactions between the CO2 molecule and the surfaces, we find that CO2 binds more strongly on these multilayer structures. Furthermore, there is a slight discrepancy in the binding energies of CO2 adsorption on the heterostructures (GMoS2, MoS2G) due to the modality of the atom arrangement (C-Mo-S-O and Mo-S-O-C) in both structures, indicating that conformational anisotropy determines to a certain degree its CO2 adsorption energy. Meanwhile, Bader charge analysis shows that the interaction between CO2 and these surfaces causes charge transfer and redistributions. By contrast, the density of states (DOS) plots show that CO2 physisorption does not have a substantial effect on the electronic properties of graphene and MoS2. In summary, the results obtained in this study could serve as useful guidance in the preparation of graphene-MoS2 nanosheets for the improved adsorption efficiency of CO2.

Correlating ultrasonic impulse and addition of ZnO promoter with CO2 conversion and methanol selectivity of CuO/ZrO2 catalysts.

The thermal characteristics of Cu-based catalysts for CO2 utilization towards the synthesis of methanol were analysed and discussed in this study. The preparation process were varied by adopting ultrasonic irradiation at various impulses for the co-precipitation route and also, by introducing ZnO promoters using the solid-state reaction route. Prepared catalysts were characterised using XRD, TPR, TPD, SEM, BET and TG-DTA-DSC. In addition, the CO2 conversion and CH3OH selectivity of these samples were assessed. Calcination of the catalysts facilitated the interaction of the Cu catalyst with the respective support bolstering the thermal stability of the catalysts. The characterisation analysis clearly reveals that the thermal performance of the catalysts was directly related to the sonication impulse and heating rate. Surface morphology and chemistry was enhanced with the aid of sonication and introduction of promoters. However, the impact of the promoter outweighs that of the sonication process. CO2 conversion and methanol selectivity showed a significant improvement with a 270% increase in methanol yield.

Ultrasonic and hydrothermal mediated synthesis routes for functionalized Mg-Al LDH: Comparison study on surface morphology, basic site strength, cyclic sorption efficiency and effectiveness.

Amine functionalized layered double hydroxide (LDHs) adsorbents prepared using three different routes: co-precipitation, sono-chemical and ultrasonic-assisted high pressure hydrothermal. The prepared adsorbent samples were characterized using X-ray diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), Scanning electron microscope-Energy dispersive X-ray spectroscopy (SEM-EDX), Temperature Programmed Desorption (TPD), Brunauer-Emmett-Teller (BET), and Thermogravimetric analysis (TGA), respectively. The performance of the prepared adsorbents was tested in a controlled thermal-swing adsorption process to measure its adsorption capacity, regeneration and cyclic efficiencies subsequently. The characterisation results were compared with those obtained using the conventional preparation routes but taking into account of the impact of sonochemical and hydrothermal pre-treatment on textural properties, adsorption capacity, regeneration and cyclic efficiencies. Textural results depicts a surge in surface area of the adsorbent synthesised by hydrothermal route (311m2/g) from 25 to 171m2/g for conventional and ultrasonic routes respectively. Additionally, it has been revealed from the present study that adsorbents prepared using ultrasonic-assisted hydrothermal route exhibit a better CO2 uptake capacity than that prepared using sonochemical and conventional routes. Thus, the ultrasonic-assisted hydrothermal treatment can effectively promote the adsorption capacity of the adsorbent. This is probably due to the decrease of moderate (M-O) and weak (OH- groups) basic sites with subsequent surge in the number of strong basic sites (O2-) resulting from the hydrothermal process. Moreover, the cyclic adsorption efficiency of the ultrasonic mediated process was found to be 76% compared with 60% for conventional and 53% for hydrothermal routes, respectively. According to the kinetic model analysis, adsorption mechanism is mostly dominated by physisorption before amine modification and by chemisorption after the modification process.

Sonochemical surface functionalization of exfoliated LDH: Effect on textural properties, CO2 adsorption, cyclic regeneration capacities and subsequent gas uptake for simultaneous methanol synthesis.

To improve CO2 adsorption, amine modified Layered double hydroxide (LDH) were prepared via a two stage process, SDS/APTS intercalation was supported by ultrasonic irradiation and then followed by MEA extraction. The prepared samples were characterised using Scanning electron microscope-Energy dispersive X-ray spectroscopy (SEM-EDX), X-ray Photoelectron Spectroscopy (XPS), X-ray diffraction (XRD), Temperature Programmed Desorption (TPD), Brunauer-Emmett-Teller (BET), and Thermogravimetric analysis (TGA), respectively. The characterisation results were compared with those obtained using the conventional preparation method with consideration to the effect of sonochemical functionalization on textural properties, adsorption capacity, regeneration and lifetime of the LDH adsorbent. It is found that LDHs prepared by sonochemical modification had improved pore structure and CO2 adsorption capacity, depending on sonic intensity. This is attributed to the enhanced deprotonation of activated amino functional groups via the sonochemical process. Subsequently, this improved the amine loading and effective amine efficiency by 60% of the conventional. In addition, the sonochemical process improved the thermal stability of the adsorbent and also, reduced the irreversible CO2 uptake, CUirrev, from 0.18mmol/g to 0.03mmol/g. Subsequently, improving the lifetime and ease of regenerating the adsorbent respectively. This is authenticated by subjecting the prepared adsorbents to series of thermal swing adsorption (TSA) cycles until its adsorption capacity goes below 60% of the original CO2 uptake. While the conventional adsorbent underwent a 10 TSA cycles before breaking down, the sonochemically functionalized LDH went further than 30 TSA cycles.

Salvage of failed odontoid fixation through anterior C1/C2 transarticular screws.

Odontoid fracture fixation allows for early mobilisation out of orthosis. Both anterior and posterior fixation techniques have been described but anterior surgery has less post-operative morbidity through the use of natural cleavage planes. We described the use of anterior transarticular stabilisation as a salvage procedure following a failed odontoid screw fixation.

Electronic clinical decision support systems attitudes and barriers to use in the oncology setting.

BACKGROUND: There is little evidence regarding attitudes to clinical decision support systems (CDSS) in oncology. AIMS: We examined the current usage, awareness, and concerns of Irish medical oncologists and oncology pharmacists in this area. METHODS: A questionnaire was sent to 27 medical oncologists and 34 oncology pharmacists, identified through professional interest groups. Respondents ranked concerns regarding their use of a CDSS on a scale from 1 to 4, with 4 being most important. RESULTS: Overall, 67% (41/61) responded, 48% (13/27) of oncologists and 82% (28/34) of pharmacists surveyed. Concerns included "difficulty defining complex clinical situations with a set of rules" (mean ± SD) (3.2 ± 0.9), "ensuring evidence base is up to date and relevant" (3.2 ± 0.9) and "lack of clinically relevant suggestions" (2.9 ± 0.9). Ninety-three percent reported using a CDSS but 54% were unaware of this. CONCLUSION: While there are benefits to using a CDSS, concerns must be addressed through user education. This may be a starting point for a user-centred design approach to the development of future local systems through a consultative process.

Strategies for fertility preservation after chemotherapy: awareness among Irish cancer specialists.

The potential effect on fertility for patients undergoing cancer treatments is an important issue. The aim of this study was to assess awareness of fertility preservation strategies among cancer specialists involved in the management of young women with malignancy. A 10 question survey was sent to 94 cancer specialists in Ireland, comprising 28 medical oncologists, 32 haematologists and 34 breast surgeons, assessing awareness of; guidelines, facilities in Ireland, and potential barriers to referral. Fifty of 94 responded (53% response rate). Awareness of current success rates associated with assisted reproductive therapy was poor. Ten respondents (20%) identified the estimated time delay to the delivery of chemotherapy due to fertility preservation. Three important potential barriers to referral were identified; time delays, poor prognosis disease and clinical features of the cancer. Awareness of the impact of reduced fertility is important in these patients but early consideration is vital.