Beta-blocker use and breast cancer outcomes: a meta-analysis.

PURPOSE: Beta blockers (BBs) are commonly used cardiovascular medications, and their association with breast cancer outcomes has been examined in several previous observational studies and meta-analyses. In this study, an updated meta-analysis was undertaken to ascertain the association between BBs and both breast cancer death (BCD) and breast cancer recurrence (BCR). METHODS: Articles were sourced from various databases up until the 14th of August 2023. Effect estimates were pooled using the random effects model, and the Higgins I2 statistic was computed to ascertain heterogeneity. Subgroup analyses were conducted by the potential for immortal time bias (ITB), the exposure period (prediagnosis vs postdiagnosis), and type of BB (selective vs non-selective). Publication bias was assessed using funnel plots and Egger's regression tests. RESULTS: Twenty-four studies were included. Pooled results showed that there was no statistically significant association between BB use and both BCD (19 studies, hazard ratio = 0.90, 95% CI 0.78-1.04) and BCR (16 studies, HR = 0.87, 95% CI 0.71-1.08). After removing studies with ITB, the associations were attenuated towards the null. There was no effect modification for either outcome when stratifying by the exposure period or type of BB. There was clear evidence of publication bias for both outcomes. CONCLUSION: In this meta-analysis, we found no evidence of an association between BB use and both BCD and BCR. Removing studies with ITB attenuated the associations towards the null, but there was no effect modification by the exposure period or type of BB.

An implementation analysis of a quality improvement project to reduce cesarean section in Brazilian private hospitals.

BACKGROUND: Brazil has one of the highest prevalence of cesarean sections in the world. The private health system is responsible for carrying out most of these surgical procedures. A quality improvement project called Adequate Childbirth Project ("Projeto Parto Adequado"- PPA) was developed to identify models of care for labor and childbirth, which place value on vaginal birth and reduce the frequency of cesarean sections without a clinical indication. This research aims to evaluate the implementation of PPA in private hospitals in Brazil. METHOD: Evaluative hospital-based survey, carried out in 2017, in 12 private hospitals, including 4,322 women. We used a Bayesian network strategy to develop a theoretical model for implementation analysis. We estimated and compared the degree of implementation of two major driving components of PPA-"Participation of women" and "Reorganization of care" - among the 12 hospitals and according to type of hospital (belonging to a health insurance company or not). To assess whether the degree of implementation was correlated with the rate of vaginal birth data we used the Bayesian Network and compared the difference between the group "Exposed to the PPA model of care" and the group "Standard of care model". RESULTS: PPA had a low degree of implementation in both components "Reorganization of Care" (0.17 - 0.32) and "Participation of Women" (0.21 - 0.34). The combined implementation score was 0.39-0.64 and was higher in hospitals that belonged to a health insurance company. The vaginal birth rate was higher in hospitals with a higher degree of implementation of PPA. CONCLUSION: The degree of implementation of PPA was low, which reflects the difficulties in changing childbirth care practices. Nevertheless, PPA increased vaginal birth rates in private hospitals with higher implementation scores. PPA is an ongoing quality improvement project and these results demonstrate the need for changes in the involvement of women and the care offered by the provider.

Post-diagnostic statin use and breast cancer-specific mortality: a population-based cohort study.

PURPOSE: Statins are the most widely prescribed cholesterol lowering medications and have been associated with both improved and unchanged breast cancer outcomes in previous studies. This study examines the association between the post-diagnostic use of statins and breast cancer outcomes (death and recurrence) in a large, representative sample of New Zealand (NZ) women with breast cancer. METHODS: Women diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to national pharmaceutical data, hospital discharges, and death records. Cox proportional hazard models were used to estimate the hazard of breast cancer-specific death (BCD) associated with any post-diagnostic statin use. RESULTS: Of the 14,976 women included in analyses, 27% used a statin after diagnosis and the median follow up time was 4.51 years. Statin use (vs non-use) was associated with a statistically significant decreased risk of BCD (adjusted hazard ratio: 0.74; 0.63-0.86). The association was attenuated when considering a subgroup of 'new' statin users (HR: 0.91; 0.69-1.19), however other analyses revealed that the protective effect of statins was more pronounced in estrogen receptor positive patients (HR: 0.77; 0.63-0.94), postmenopausal women (HR: 0.74; 0.63-0.88), and in women with advanced stage disease (HR: 0.65; 0.49-0.84). CONCLUSION: In this study, statin use was associated with a statistically significant decreased risk of breast cancer death, with subgroup analyses revealing a more protective effect in ER+ patients, postmenopausal women, and in women with advanced stage disease. Further research is warranted to determine if these associations are replicated in other clinical settings.

Classification of Protein-Binding Sites Using a Spherical Convolutional Neural Network.

The analysis and comparison of protein-binding sites aid various applications in the drug discovery process, e.g., hit finding, drug repurposing, and polypharmacology. Classification of binding sites has been a hot topic for the past 30 years, and many different methods have been published. The rapid development of machine learning computational algorithms, coupled with the large volume of publicly available protein-ligand 3D structures, makes it possible to apply deep learning techniques in binding site comparison. Our method uses a cutting-edge spherical convolutional neural network based on the DeepSphere architecture to learn global representations of protein-binding sites. The model was trained on TOUGH-C1 and TOUGH-M1 data and validated with the ProSPECCTs datasets. Our results show that our model can (1) perform well in protein-binding site similarity and classification tasks and (2) learn and separate the physicochemical properties of binding sites. Lastly, we tested the model on a set of kinases, where the results show that it is able to cluster the different kinase subfamilies effectively. This example demonstrates the method's promise for lead hopping within or outside a protein target, directly based on binding site information.

Post-diagnostic beta blocker use and breast cancer-specific mortality: a population-based cohort study.

PURPOSE: Beta blockers (BB) have been associated with improved, worsened, or unchanged breast cancer outcomes in previous studies. This study examines the association between the post-diagnostic use of BBs and death from breast cancer in a large, representative sample of New Zealand (NZ) women with breast cancer. METHODS: Women diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to national pharmaceutical data, hospital discharges, and death records. The median follow-up time was 4.51 years. Cox proportional hazard models were used to estimate the hazard of breast cancer-specific death (BCD) associated with any post-diagnostic BB use. RESULTS: Of the 14,976 women included in analyses, 21% used a BB after diagnosis. BB use (vs non-use) was associated with a small and nonstatistically significant increased risk of BCD (adjusted hazard ratio: 1.11; 95% CI 0.95-1.29). A statistically significant increased risk confined to short-term use (0-3 months) was seen (HR = 1.40; 1.14-1.73), and this risk steadily decreased with increasing duration of use and became a statistically significant protective effect at 3 + years of use (HR = 0.55; 0.34-0.88). CONCLUSION: Our findings suggest that any increased risk associated with BB use may be driven by risk in the initial few months of use. Long-term BB use may be associated with a reduction in BCD.

Therapeutic granulocyte infusion for patients with severe neutropaenia and neutrophilic dysfunction: New Zealand experience.

BACKGROUND AND OBJECTIVES: Studies have shown granulocyte transfusions (GTXs) may be beneficial in neutropaenic patients with severe systemic infections. New Zealand Blood Service has a policy for provision of granulocytes to New Zealand's District Health Boards. We set out to explore utilization of therapeutic granulocyte infusions in New Zealand. MATERIALS AND METHODS: Patients who received GTXs in the 16-year period between 2000 and 2016 were identified by the New Zealand electronic blood management system, eProgesa. Information pertaining to recipient demographics, disease-related factors, methods of granulocyte collection and clinical outcomes was obtained by the review of electronic transfusion and clinical records. RESULTS: Forty-five septic patients received granulocyte support for a total of 263 days. The median age of the recipients was 16 (range 0-74) years. Seventy-nine percent of the recipients had an underlying haematological malignancy with 50% having acute leukaemia. The median neutrophil count on the last day of GTX was 0.02 × 109 /L (range 0-16.32). Sixty-three percent (27/43 patients with available data) had persisting severe neutropaenia when the GTXs were stopped. The median duration of support was 3 (range 1-32) days. Forty-six percent of granulocyte collections were performed via apheresis. Of the 44 patients, for whom survival outcome was available, 18 (41%) survived the acute illness. CONCLUSION: GTXs were infrequently used, most commonly in the setting of an underlying haematological malignancy. This may be explained by the current weak evidence base supporting this therapeutic modality. Procuring a sufficiently large dose of granulocytes for infusion remains an issue for adult recipients.

Costs of inpatient hospitalisations in the last year of life in older New Zealanders: a cohort study.

BACKGROUND: Rapidly ageing populations means that many people now die in advanced age. This paper investigated public hospital and long-term care home costs in the 12 months before death in Maori and non-Maori of advanced age in New Zealand. METHODS: Data from an existing longitudinal study (LiLACS NZ) was used, in which 937 older New Zealanders were enrolled in 2010. At the time of this study, 213 Maori and 241 non-Maori in the cohort had died. National Health Index numbers were linked to the hospitalisation National Minimum Dataset to ascertain public hospitalisation and care home costs in the last year of life. RESULTS: The average total publicly funded hospital and long-term care home costs in the 12 months prior to death were $16,211 and $17,351 for Maori and non-Maori respectively. Non-Maori tended to have long lengths of stay in their last year of life, and non-Maori men had the highest proportion with high costs and long lengths of stay in care homes. Costs in the last year of life were 8.1 times higher in comparison to costs for individuals who did not die in the same time period. CONCLUSION: Despite New Zealand's commitment to providing an equitable level of healthcare, this study illustrated that ethnic and gender disparities are still apparent at the end of life. This raises questions as to whether money at the end of life is being spent appropriately, and how it could potentially be more equitably targeted to meet the diverse needs of older people and their families.

Comparing Predictions of a PBPK Model for Cyclosporine With Drug Levels From Therapeutic Drug Monitoring.

This study compared simulations of a physiologically based pharmacokinetic (PBPK) model implemented for cyclosporine with drug levels from therapeutic drug monitoring to evaluate the predictive performance of a PBPK model in a clinical population. Based on a literature search model parameters were determined. After calibrating the model using the pharmacokinetic profiles of healthy volunteers, 356 cyclosporine trough levels of 32 renal transplant outpatients were predicted based on their biometric parameters. Model performance was assessed by calculating absolute and relative deviations of predicted and observed trough levels. The median absolute deviation was 6 ng/ml (interquartile range: 30 to 31 ng/ml, minimum = -379 ng/ml, maximum = 139 ng/ml). 86% of predicted cyclosporine trough levels deviated less than twofold from observed values. The high intra-individual variability of observed cyclosporine levels was not fully covered by the PBPK model. Perspectively, consideration of clinical and additional patient-related factors may improve the model's performance. In summary, the current study has shown that PBPK modeling may offer valuable contributions for pharmacokinetic research in clinical drug therapy.

Use of Non-Cancer Medications in New Zealand Women at the Diagnosis of Primary Invasive Breast Cancer: Prevalence, Associated Factors and Effects on Survival.

BACKGROUND: Assessing the use of multiple medications in cancer patients is crucial as such use may affect cancer outcomes. This study reports the prevalence of non-cancer medication use at breast cancer diagnosis, its associated factors, and its effect on survival. METHODS: We identified all women diagnosed with primary invasive breast cancer between 1 January 2007 and 31 December 2016, from four population-based breast cancer registries, in Auckland, Waikato, Wellington, and Christchurch, New Zealand. Through linkage to the pharmaceutical records, we obtained information on non-cancer medications that were dispensed for a minimum of 90 days' supply between one year before cancer diagnosis and first cancer treatment. We performed ordered logistic regressions to identify associated factors and Cox regressions to investigate its effect on patient survival. RESULTS: Of 14,485 patients, 52% were dispensed at least one drug (mean-1.3 drugs; maximum-13 drugs), with a higher prevalence observed in patients who were older, treated at a public facility, more economically deprived, and screen-detected. The use of 2-3 drugs showed a reduced non-breast cancer mortality (HR = 0.75, 95%CI = 0.60-0.92) in previously hospitalised patients, with other groups showing non-significant associations when adjusted for confounding factors. Drug use was not associated with changes in breast cancer-specific mortality. CONCLUSIONS: Non-cancer medication use at breast cancer diagnosis was common in New Zealand, more prevalent in older and disadvantaged women, and showed no effect on breast cancer-specific mortality, but a reduction in other cause mortality with the use of 2-3 drugs.

ScaffoldGraph: an open-source library for the generation and analysis of molecular scaffold networks and scaffold trees.

SUMMARY: ScaffoldGraph (SG) is an open-source Python library and command-line tool for the generation and analysis of molecular scaffold networks and trees, with the capability of processing large sets of input molecules. With the increase in high-throughput screening data, scaffold graphs have proven useful for the navigation and analysis of chemical space, being used for visualization, clustering, scaffold-diversity analysis and active-series identification. Built on RDKit and NetworkX, SG integrates scaffold graph analysis into the growing scientific/cheminformatics Python stack, increasing the flexibility and extendibility of the tool compared to existing software. AVAILABILITY AND IMPLEMENTATION: SG is freely available and released under the MIT licence at https://github.com/UCLCheminformatics/ScaffoldGraph.

Rapid increase in endometrial cancer incidence and ethnic differences in New Zealand.

PURPOSE: Endometrial cancer accounts for 3.9% of all female cancers globally, and its incidence appears to be increasing in women under 40 years of age. This paper investigated ethnic-specific trends in endometrial cancer across different age groups in New Zealand. METHODS: Women who were diagnosed with endometrial cancer between 1996 and 2012 were identified from the New Zealand Cancer Registry. Annual age-standardized incidence and mortality rates were calculated for each ethnicity (Maori, Pacific, and non-Maori non-Pacific) in four age groups (< 40, 40-49, 50-74, and 75 +). The estimates were adjusted for hysterectomy. Joinpoint regression analysis was used to assess trends over time and annual percentage changes (APCs) were estimated. RESULTS: Between 1996 and 2012, age-standardized incidence rates increased in all women and significantly in the < 40, 40-49, and 50-74 age groups (APC 9.22, 3.56, and 1.65 respectively). Incidence rates were highest in Pacific women and increased most rapidly in those under 50 years of age (APC 9.36). Conversely, age-standardized mortality rates decreased in all women and significantly in the 50-74 and 75 + age groups (APC - 5.25 and - 5.06 respectively), with the highest rate observed in Pacific women. CONCLUSION: Pacific women had the highest incidence of endometrial cancer and the trend was increasing, particularly in young women. This could be attributed, at least in part, to a high and increasing rate of obesity in these women and should be explored in future research.

Methicillin-resistant Staphylococcus aureus in palliative care: A prospective study of Methicillin-resistant Staphylococcus aureus prevalence in a hospital-based palliative care unit.

BACKGROUND: Methicillin-resistant Staphylococcus aureus is a common organism in hospitals worldwide and is associated with morbidity and mortality. However, little is known about the prevalence in palliative care patients. Furthermore, there is no standardized screening protocol or treatment for patients for whom therapy concentrates on symptom control. AIM: Examining the prevalence of methicillin-resistant Staphylococcus aureus in palliative care patients as well as the level of morbidity and mortality. DESIGN: We performed a prospective study where methicillin-resistant Staphylococcus aureus screening was undertaken in 296 consecutive patients within 48 h after admission to our palliative care unit. Medical history was taken, clinical examination was performed, and the Karnofsky Performance Scale and Palliative Prognostic Score were determined. Prevalence of Methicillin-resistant Staphylococcus aureus was compared to data of general hospital patients. RESULTS: In total, 281 patients were included in the study having a mean age of 69.7 years (standard deviation = 12.9 years) and an average Karnofsky Performance Scale between 30% and 40%. The mean length of stay was 9.7 days (standard deviation = 7.6 days). A total of 24 patients were methicillin-resistant Staphylococcus aureus positive on the first swab. Median number of swabs was 2. All patients with a negative methicillin-resistant Staphylococcus aureus swab upon admission remained Methicillin-resistant Staphylococcus aureus negative in all subsequent swabs. CONCLUSION: Our study suggests that the prevalence of Methicillin-resistant Staphylococcus aureus among patients in an in-hospital palliative care unit is much higher than in other patient populations.

Adsorbate-induced curvature and stiffening of graphene.

The adsorption of the alkane tetratetracontane (TTC, C44H90) on graphene induces the formation of a curved surface stabilized by a gain in adsorption energy. This effect arises from a curvature-dependent variation of a moiré pattern due to the mismatch of the carbon-carbon separation in the adsorbed molecule and the period of graphene. The effect is observed when graphene is transferred onto a deformable substrate, which in our case is the interface between water layers adsorbed on mica and an organic solvent, but is not observed on more rigid substrates such as boron nitride. Our results show that molecular adsorption can be influenced by substrate curvature, provide an example of two-dimensional molecular self-assembly on a soft, responsive interface, and demonstrate that the mechanical properties of graphene may be modified by molecular adsorption, which is of relevance to nanomechanical systems, electronics, and membrane technology.

Radiological assessment of vascular access in haemodialysis patients.

Clinical examination is still the most important diagnostic tool and duplex ultrasonography is the imaging method of first choice. Radiological assessment of vascular access for haemodialysis includes preoperative analysis of vessel anatomy and postoperative surveillance for access maturation as well as diagnosis in vascular access insufficiency. Compared to ultrasonography digital subtraction angiography is superior for the evaluation of the central veins and allows diagnosis and treatment in one session. Computed tomography should only be used in patients with inconclusive ultrasonography results, for example, for the assessment of the central veins and visualization of the vascular tree. Gadolinium-enhanced magnetic resonance imaging is no longer recommended in dialysis patients, because it may trigger nephrogenic systemic fibrosis. In patients with a history of previous central venous catheters additional preoperative imaging of the central veins should be performed. In this article we review the different radiological imaging methods for preoperative assessment and suspected vascular access dysfunction.

Antioxidant treatment and outcome of Cortinarius orellanus poisoning: a case series.

OBJECTIVES: To study the frequency, severity, and long-term outcome of renal injury in Cortinarius orellanus poisoning, to evaluate the association between the ingested amount of C. orellanus and outcome, and to evaluate the effect of N-acetylcysteine and corticosteroid treatment on outcome. METHODS: Case series of eight patients. Diagnosis and severity of acute kidney injury (AKI) and chronic kidney disease (CKD) were classified according to current AKI and CKD definitions. N-acetylcysteine and corticosteroids were administered to six patients, former according to the standard for paracetamol poisoning. MAIN FINDINGS: All patients developed AKI, six in the most severe stage and four required renal replacement therapy (RRT). After 12 months, seven patients presented with CKD, of whom three required chronic RRT and further two were in advanced CKD. AKI and CKD severity highly correlated with the consumed amounts of Cortinarius orellanus (r = 0.98, p < 0.001 and r = 0.78, p = 0.02, respectively) but not with N-acetylcysteine and corticosteroid treatment. CONCLUSIONS: AKI and CKD by current definitions and classifications are frequent and severe after Cortinarius orellanus poisoning. The ingested amount of Cortinarius orellanus correlates with the severity of both AKI and CKD. N-acetylcysteine and corticosteroid treatment do not seem to have a beneficial effect on either AKI or CKD.