Glioblastoma (GBM) is the most frequent type of primary brain cancer, having a median survival of only 15 months. The current standard of care includes a combination of surgery, radiotherapy (RT) and chemotherapy with temozolomide, but with limited results. Moreover, multiple studies have shown that tumour relapse and resistance to classic therapeutic approaches are common events that occur in the majority of patients, and eventually leading to death. New approaches to better understand the intricated tumour biology involved in GBM are needed in order to develop personalised treatment approaches. Advances in cancer biology have widen our understanding over the GBM genome and allowing a better classification of these tumours based on their molecular profile.

A new targeted therapeutic approach that is currently investigated in multiple clinical trials in GBM is represented by molecules that target various defects in the DNA damage repair (DDR) pathway, a mechanism activated by endogenous and exogenous factors that induce alteration of DNA, and is involved for the development of chemotherapy and RT resistance. This intricate pathway is regulated by p53, two important kinases ATR and ATM and non-coding RNAs including microRNAs, long-non-coding RNAs and circular RNAs that regulate the expression of all the proteins involved in the pathway.

Currently, the most studied DDR inhibitors are represented by PARP inhibitors (PARPi) with important results in ovarian and breast cancer. PARPi are a class of tumour agnostic drugs that showed their efficacy also in other localisations such as colon and prostate tumours that have a molecular signature associated with genomic instability. These inhibitors induce the accumulation of intracellular DNA damage, cell cycle arrest, mitotic catastrophe and apoptosis.

This study aims to provide an integrated image of the DDR pathway in glioblastoma under physiological and treatment pressure with a focus of the regulatory roles of ncRNAs. The DDR inhibitors are emerging as an important new therapeutic approach for tumours with genomic instability and alterations in DDR pathways. The first clinical trials with PARPi in GBM are currently ongoing and will be presented in the article. Moreover, we consider that by incorporating the regulatory network in the DDR pathway in GBM we can fill the missing gaps that limited previous attempts to effectively target it in brain tumours. An overview of the importance of ncRNAs in GBM and DDR physiology and how they are interconnected is presented.

To identify central-line (CL)–associated bloodstream infection (CLABSI) incidence and risk factors in low- and middle-income countries (LMICs).

From July 1, 1998, to February 12, 2022, we conducted a multinational multicenter prospective cohort study using online standardized surveillance system and unified forms.

The study included 728 ICUs of 286 hospitals in 147 cities in 41 African, Asian, Eastern European, Latin American, and Middle Eastern countries.

In total, 278,241 patients followed during 1,815,043 patient days acquired 3,537 CLABSIs.

For the CLABSI rate, we used CL days as the denominator and the number of CLABSIs as the numerator. Using multiple logistic regression, outcomes are shown as adjusted odds ratios (aORs).

The pooled CLABSI rate was 4.82 CLABSIs per 1,000 CL days, which is significantly higher than that reported by the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC NHSN). We analyzed 11 variables, and the following variables were independently and significantly associated with CLABSI: length of stay (LOS), risk increasing 3% daily (aOR, 1.03; 95% CI, 1.03–1.04; P < .0001), number of CL days, risk increasing 4% per CL day (aOR, 1.04; 95% CI, 1.03–1.04; P < .0001), surgical hospitalization (aOR, 1.12; 95% CI, 1.03–1.21; P < .0001), tracheostomy use (aOR, 1.52; 95% CI, 1.23–1.88; P < .0001), hospitalization at a publicly owned facility (aOR, 3.04; 95% CI, 2.31–4.01; P <.0001) or at a teaching hospital (aOR, 2.91; 95% CI, 2.22–3.83; P < .0001), hospitalization in a middle-income country (aOR, 2.41; 95% CI, 2.09–2.77; P < .0001). The ICU type with highest risk was adult oncology (aOR, 4.35; 95% CI, 3.11–6.09; P < .0001), followed by pediatric oncology (aOR, 2.51;95% CI, 1.57–3.99; P < .0001), and pediatric (aOR, 2.34; 95% CI, 1.81–3.01; P < .0001). The CL type with the highest risk was internal-jugular (aOR, 3.01; 95% CI, 2.71–3.33; P < .0001), followed by femoral (aOR, 2.29; 95% CI, 1.96–2.68; P < .0001). Peripherally inserted central catheter (PICC) was the CL with the lowest CLABSI risk (aOR, 1.48; 95% CI, 1.02–2.18; P = .04).

The following CLABSI risk factors are unlikely to change: country income level, facility ownership, hospitalization type, and ICU type. These findings suggest a focus on reducing LOS, CL days, and tracheostomy; using PICC instead of internal-jugular or femoral CL; and implementing evidence-based CLABSI prevention recommendations.

Rates of ventilator-associated pneumonia (VAP) in low- and middle-income countries (LMIC) are several times above those of high-income countries. The objective of this study was to identify risk factors (RFs) for VAP cases in ICUs of LMICs.

Prospective cohort study.

This study was conducted across 743 ICUs of 282 hospitals in 144 cities in 42 Asian, African, European, Latin American, and Middle Eastern countries.

The study included patients admitted to ICUs across 24 years.

In total, 289,643 patients were followed during 1,951,405 patient days and acquired 8,236 VAPs. We analyzed 10 independent variables. Multiple logistic regression identified the following independent VAP RFs: male sex (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.16–1.28; P < .0001); longer length of stay (LOS), which increased the risk 7% per day (aOR, 1.07; 95% CI, 1.07–1.08; P < .0001); mechanical ventilation (MV) utilization ratio (aOR, 1.27; 95% CI, 1.23–1.31; P < .0001); continuous positive airway pressure (CPAP), which was associated with the highest risk (aOR, 13.38; 95% CI, 11.57–15.48; P < .0001); tracheostomy connected to a MV, which was associated with the next-highest risk (aOR, 8.31; 95% CI, 7.21–9.58; P < .0001); endotracheal tube connected to a MV (aOR, 6.76; 95% CI, 6.34–7.21; P < .0001); surgical hospitalization (aOR, 1.23; 95% CI, 1.17–1.29; P < .0001); admission to a public hospital (aOR, 1.59; 95% CI, 1.35-1.86; P < .0001); middle-income country (aOR, 1.22; 95% CI, 15–1.29; P < .0001); admission to an adult-oncology ICU, which was associated with the highest risk (aOR, 4.05; 95% CI, 3.22–5.09; P < .0001), admission to a neurologic ICU, which was associated with the next-highest risk (aOR, 2.48; 95% CI, 1.78–3.45; P < .0001); and admission to a respiratory ICU (aOR, 2.35; 95% CI, 1.79–3.07; P < .0001). Admission to a coronary ICU showed the lowest risk (aOR, 0.63; 95% CI, 0.51–0.77; P < .0001).

Some identified VAP RFs are unlikely to change: sex, hospitalization type, ICU type, facility ownership, and country income level. Based on our results, we recommend focusing on strategies to reduce LOS, to reduce the MV utilization ratio, to limit CPAP use and implementing a set of evidence-based VAP prevention recommendations.

Pain, depression, anxiety, and psychosis are common non-cognitive symptoms of dementia. They are often underdiagnosed and can cause significant distress and carer strain. Numerous standardised assessment tools (SATs) exist and are recommended for the assessment of non-cognitive symptoms of dementia. Anecdotal evidence suggests that SATs are used rarely and inconsistently. This study aims to explore which SATs to detect non-cognitive symptoms of dementia are recommended in local guidelines and used in practice across different organisations. Secondary aims were to identify barriers and facilitators to using these tools.

This service evaluation is cross-sectional in design. A questionnaire was developed and distributed to clinicians working with patients with advanced dementia in any setting, across four geographical locations (Leeds, Bradford, Hull, and Cambridge). Quantitative data were analysed descriptively, and qualitative data from free-text comments were interpreted using thematic analysis.

135 professionals from a range of backgrounds and clinical settings completed the survey. Respondents indicated that SATs for non-cognitive symptoms in dementia were rarely used or recommended. Respondents were unaware of the existence of most SATs listed. 80% respondents felt that SATs were a useful adjunct to a structured clinical assessment. The most recommended tool was the Abbey Pain Scale, with 41 respondents indicating its recommendation by their Trust. Perceived facilitators to using SATs include education and training, reliable IT systems and accessibility. Barriers include lack of time and training.

Numerous SATs are available for use in dementia, but they are rarely recommended in local policy or used in practice. There appears to be a lack of consensus on which, if any, are superior diagnostic tools, and on how or when they should be applied.

Life stress and blunted reward processing each have been associated with the onset and maintenance of major depressive disorder. However, much of this work has been cross-sectional, conducted in separate lines of inquiry, and focused on recent life stressor exposure, despite the fact that theories of depression posit that stressors can have cumulative effects over the lifespan. To address these limitations, we investigated whether acute and chronic stressors occurring over the lifespan interacted with blunted reward processing to predict increases in depression over time in healthy youth.

Participants were 245 adolescent girls aged 8–14 years old (Mage = 12.4, s.d. = 1.8) who were evaluated at baseline and two years later. The reward positivity (RewP), an event-related potential measure of reward responsiveness, was assessed at baseline using the doors task. Cumulative lifetime exposure to acute and chronic stressors was assessed two years later using the Stress and Adversity Inventory for Adolescents (Adolescent STRAIN). Finally, depressive symptoms were assessed at both baseline and follow-up using the Children's Depression Inventory.

As hypothesized, greater lifetime acute stressor exposure predicted increases in depressive symptoms over two years, but only for youth exhibiting a blunted RewP. This interaction, however, was not found for chronic stressors.

Lifetime acute stressor exposure may be particularly depressogenic for youth exhibiting a blunted RewP. Conversely, a robust RewP may be protective in the presence of greater acute lifetime stressor exposure.

Limited data exist on training of European paediatric and adult congenital cardiologists.

A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries.

Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87–9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63–10.72 million), and one training centre per 4.29 million population (range 1.63–10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1–17), and duration of training was 3 years (range 2–5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R2 = 0.41).

Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.

The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.

Face-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.

3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.

ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

Existing research on psychological distress and mental health service utilization has focused on common types of solid tumor cancers, leaving significant gaps in our understanding of patients experiencing rare forms of hematologic cancers.

To examine distress, quality of life, and mental health service utilization among patients with aggressive, refractory B-cell lymphomas.

Patients (n = 26) with B-cell lymphomas that relapsed after first- or second-line treatment completed self-report measures of distress (Hospital Anxiety and Depression Scale) and quality of life (Short-Form Health Survey, SF-12). Patients also reported whether they had utilized mental health treatment since their cancer diagnosis.

Approximately 42% (n = 11) of patients reported elevated levels of psychological distress. Of patients with elevated distress, only one quarter (27.2%; n = 3) received mental health treatment, while more than half did not receive mental health treatment (54.5%; n = 6), and 18.1% (n = 2) did not want treatment. Patients with elevated distress reported lower mental quality of life than patients without elevated distress [F (1, 25) = 15.32, p = 0.001].

A significant proportion of patients with advanced, progressive, B-cell lymphomas may experience elevated levels of distress. Yet, few of these distressed patients receive mental health treatment. Findings highlight the need to better identify and address barriers to mental health service utilization among patients with B-cell lymphoma, including among distressed patients who decline treatment.