Patient attendance at a primary health care centre in Malta : a cross-sectional observational study

Introduction The aim of the study was to describe the reason for consultation of patients attending the General Practitioner (GP) service at a major local health centre and also to get a clinical profile of the patients making use of such health service. This study is based in the publiclyfunded primary health system in Malta and focuses on Mosta Health Centre. Methodology This was a cross-sectional observational study carried out in January 2017. Only the patients seen in the GP clinics were included. All six authors are practicing GPs. All the patients that the authors encountered in the GP clinics were included in the study. The fact that all authors work in different shifts and days allowed for a broad and random inclusion of patients. Patients attending out-ofhours and in weekends were also included. A pilot oneweek period of data collection was carried out. Thereafter, all six authors had an Excel spreadsheet uploaded on the work computer system in the GP consulting rooms, so that patient data was inputted in real-time at the end of each consultation. Data was inputted in Excel 2010 and analysed using the Statistical Package for the Social Sciences (SPSS) 22. Results A total of 820 patients were included in the study. 51.8% of patients were females, whilst 74.8% of patients were born in Malta. 50.2% of patients raised more than one issue during a single consultation, whilst the most common co-morbidity noted was hypertension. The most common reasons for consultation were related to the respiratory and musculoskeletal systems. Various significant associations were observed, most importantly being between the time of attendance and number of issues brought up during a consultation; between being born in Malta and number of issues brought up during a consultation; and between age and number of issues brought up during a single consultation. Conclusion This study involved 820 patients attending Mosta Health Centre over a one-month period during winter 2017. During a single episode of care (visit), Maltese nationals consult for a greater number of issues. In addition, they have a greater number of co-morbidities than non-Maltese nationals. People attending between 08.00 and 17.00 hours tend to present with a greater number of issues for management. Suggestions for service development have been put forward in the discussion. Ideally, such studies should be conducted independently in different health centres given the notable differences in the catchment areas, and during different months of the year.peer-reviewe

Cancer-associated abdominal vein thrombosis

Cancer is associated with an increased risk of developing venous thromboembolism, due to its direct influence on the three pillars of Virchow’s triad (e.g., compression on the blood vessels by the tumour, blood vessels invasion, and cytokine release), together with the effect of exogenous factors (such as chemotherapy, radiotherapy, surgery). In cancer patients, the risk of thrombosis at unusual sites, such as splanchnic, ovarian and renal vein thrombosis, is also increased. Abdominal vein thromboses are frequently incidental findings on abdominal imaging performed as part of the diagnostic/staging workup or the follow-up care of malignancies. There is little evidence on the management of unusual site venous thromboembolism in cancer patients since there are only a few specific recommendations; thus, the management follows the general principles of the treatment of cancer-associated deep vein thrombosis and pulmonary embolism. This narrative review summarises the latest evidence on cancer-associated abdominal vein thrombosis, i.e., thrombosis of the splanchnic, ovarian and renal veins.peer-reviewe

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

BASELINE CIRCULATING TUMOR CELL COUNTS SIGNIFICANTLY ENHANCE A PROGNOSTIC SCORE FOR PATIENTS PARTICIPATING IN PHASE I ONCOLOGY TRIALS

BACKGROUND: High circulating tumor cell (CTC) counts are associated with poor prognosis in several cancers. Enrollment of patients on phase I oncology trials requires a careful assessment of the potential risks and benefits. Many patients enrolled on such trials using established eligibility criteria have a short life expectancy and are less likely to benefit from trial participation. We hypothesized that the incorporation of CTC counts might improve patient selection for phase I trials. METHODS: This retrospective analysis evaluated patients who had baseline CTCs enumerated prior to their starting on a phase I trial. CTCs were enumerated using the CellSearch System. RESULTS: Between January 2006 and December 2009 a total of 128 patients enrolled in phase I trials had CTC counts evaluated. Higher CTC counts as a continuous variable independently correlated with risk of death in this patient population (P = 0.006). A multivariate point-based risk model was generated using CTCs as a dichotomous variable (≥3 or 2 metastatic sites. Comparison of receiver operating characteristic curves demonstrated that the addition of baseline CTC counts improved the performance of the prospectively validated Royal Marsden Hospital phase I prognostic score, which now identifies three risk groups (P < 0.0001): good prognosis [score 0-1, median overall survival (OS) 63.7 weeks], intermediate prognosis (score 2-3, median OS 37.3 weeks), and poor prognosis (score 4, median OS 13.4 weeks). CONCLUSION: CTC enumeration improved the performance of a validated prognostic score to help select patients for phase I oncology trials

The Association of PI3 Kinase Signaling and Chemoresistance in Advanced Ovarian Cancer

Evidence that the phosphoinositide 3-kinase (PI3K) pathway is deregulated in ovarian cancer is largely based on the analysis of surgical specimens sampled at diagnosis and may not reflect the biology of advanced ovarian cancer. We aimed to investigate PI3K signaling in cancer cells isolated from patients with advanced ovarian cancer. Ascites samples were analyzed from 88 patients, of whom 61 received further treatment. Cancer cells were immunomagnetically separated from ascites, and the signaling output of the PI3K pathway was studied by quantifying p-AKT, p-p70S6K, and p-GSK3? by ELISA. Relevant oncogenes, such as PIK3CA and AKT, were sequenced by PCR-amplified mass spectroscopy detection methods. In addition, PIK3CA and AKT2 amplifications and PTEN deletions were analyzed by FISH. p-p70S6K levels were significantly higher in cells from 37 of 61 patients who did not respond to subsequent chemotherapy (0.7184 vs. 0.3496; P = 0.0100), and this difference was greater in patients who had not received previous chemotherapy. PIK3CA and AKT mutations were present in 5% and 0% of samples, respectively. Amplification of PIK3CA and AKT2 and deletion of PTEN was seen in 10%, 10%, and 27% of samples, respectively. Mutations of PIK3CA and amplification of PIK3CA/AKT2 or deletion of PTEN did not correlate with levels of p-AKT, p-p70S6K, and p-GSK3?. In patients with advanced ovarian cancer, there is an association between levels of p-p70S6K and response to subsequent chemotherapy. There is no clear evidence that this is driven specifically by PIK3CA or AKT mutations or by amplifications or deletion of PTEN

DNA concentrations (ng/mL) classified by tumor types.

<p>Box and whisker plots showing 25^th, 50^th and 75^th percentiles, upper and lower adjacent values (whiskers) and Tukey outliers (•). P value is for a two-sided unpaired t-test on log10 DNA concentrations using Welch's correction for unequal variances.</p

Univariate and multivariate analysis.

<p>Univariate and multivariate analysis.</p

Relationship between cpDNA concentration and survival.

<p>(<b>3A</b>) Kaplan-Meier graph showing survival curves by cpDNA concentration in 101 patients with advanced solid tumors. Patients in the unfavorable category had concentrations greater than a healthy volunteer cohort maximum of 13.3 ng/ml (logrank p = 0.0383). (<b>3B</b>) Survivor function estimated from univariate Cox regression showing predicted survival curves for a range of cpDNA concentrations. A hazard ratio of 2.4 (p = 0.002) is depicted between adjacent curves.</p

Concordance in detected mutations between paired FFPE tumors and cpDNA.

<p>Concordance in detected mutations between paired FFPE tumors and cpDNA.</p