Predicting outcomes in older patients undergoing vascular surgery using the Hospital Frailty Risk Score.

BACKGROUND: Frailty may explain why some older patients having vascular surgery are at high risk of adverse outcomes. The Hospital Frailty Risk Score (HFRS) has been designed specifically for use with administrative data and has three categories of frailty risk (low, intermediate and high). The aim of this study was to evaluate the HFRS in predicting mortality, and hospital use in older patients undergoing vascular surgery. METHODS: Routinely collected hospital data linked to death records were analysed for all patients aged 75 years or older who had undergone either endovascular or open vascular surgery between 2010 and 2012 in New South Wales, Australia. Multilevel logistic regression models were used to compare outcomes adjusted for patient and procedural factors, with and without frailty. RESULTS: Some 9752 patients were identified, of whom 1719 (17·6 per cent) had a high-risk HFRS. Patients in the high-risk frailty category had an adjusted odds ratio for death by 30 days after surgery of 4·15 (95 per cent c.i. 2·99 to 5·76) compared with those in the low-risk frailty category, and a similarly increased odds of death by 2 years (odds ratio 4·27, 3·69 to 4·95). Adding the HFRS to a model adjusted for age, sex, co-morbidity score, socioeconomic status, previous hospitalization and vascular procedure type improved the prediction of 2-year mortality and prolonged hospital stay, but there was minimal improvement for 30-day mortality and readmission. CONCLUSION: Adjusting for the HFRS in addition to other patient and procedural risk factors provided greater discrimination of outcomes in this cohort of older patients undergoing vascular surgery.

Peripheral artery disease in the lower limbs: The importance of secondary risk prevention for improved long-term prognosis.

BACKGROUND: Patients with lower limb peripheral artery disease (PAD) are at high risk of cardiovascular mortality and morbidity along with limb loss. PAD is underdiagnosed in the community and presents a missed opportunity to prescribe evidence-based secondary prevention therapy. OBJECTIVE: The aim of this article is to summarise key updates in the management of patients with PAD, with particular reference to newly published guidelines. DISCUSSION: PAD continues to be a major contributor to the mortality and morbidity of patients with atherosclerosis in Australia. For patients with chronic limb-threatening ischaemia, revascularisation remains the mainstay of limb salvage, and expedited access to vascular surgery assessment is necessary. Both prescription of, and adherence to, evidence-based secondary prevention therapy is low. A greater emphasis on cardiovascular risk factor modification for all patients with PAD is required to improve long-term outcomes. General practitioners and vascular surgeons can work collaboratively to provide patient-centred, effective care to patients with PAD.

Aortic aneurysm trials in octogenarians: Are we really measuring the outcomes that matter?

PURPOSE: This study is a systematic review to determine the types of outcomes reported in abdominal aortic aneurysm (AAA) studies of patients aged 80 and over. Specifically, it determines the types of patient-centered outcomes reported. METHOD: MEDLINE and EMBASE were searched from 2000 to 2014 for studies on AAA surgery with outcome data on patients aged 80 and over. Outcomes were categorized according to Donabedian's framework for health quality indicators, with further classification as procedural, complication, resource or patient-centered outcome indicators. FINDINGS: Forty studies were reviewed. Patient-centered outcomes were infrequently reported (13%, n=5), with limited outcomes specifically relevant to older patients. No studies reported physical function, activities of daily living or cognition using validated assessment methods. Short-term mortality (95%, n=38) and complications (85%, n=34) were reported most frequently. CONCLUSION: Reporting of aortic surgery outcomes in patients aged 80 and over requires a focus upon outcomes of primary importance to people of this age.

Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases.

BACKGROUND: Assessment of receptors [estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)] is routinely carried out on primary tumour in order to select appropriate adjuvant therapy; the same analysis is not carried out on nodal metastases. Since de novo resistance to therapy is common, we quantified differences in receptor expression between primary and nodal disease in order to assess whether this might contribute to therapeutic resistance. PATIENTS AND METHODS: A total of 385 patients with invasive primary breast carcinomas and paired lymph nodes (n = 211) were assessed for ER, PR and HER2 expression using quantitative immunofluorescence. Cut-points were defined by comparison with tumours scored by immunohistochemistry (IHC) and FISH. Differences in expression for each of the markers and molecular phenotype were analysed. RESULTS: Quantitative receptor expression shows a wide dynamic range compared with IHC. Overall, 46.9% cases had disparate breast/node receptor status of at least one receptor. Many of the differences in expression between primary tumour and node are large magnitude (greater than fivefold) changes. Triple-negative phenotype changes in 23.1% of cases. CONCLUSIONS: A significant number of patients show discordant quantitative expression of molecular markers between primary and nodal disease. Appropriately measured, lymph node receptor status could be a more accurate measurement for guiding adjuvant therapy, which requires testing in a clinical trial.

Immunological evidence for the localization of a 110 kDa poly(A) binding protein from rat liver in nuclear envelopes and its phosphorylation by protein kinase C.

We have purified a 110 kDa poly(A) binding protein (P110) from rat liver which is thought to be involved in mRNA translocation through the nuclear pores and have demonstrated its localisation in the nuclear envelope using polyclonal antibodies and confocal laser scanning microscopy. Although P110 was prepared from highly purified nuclear envelopes, the polyclonal antibodies raised against them bind to nucleo- and cytoplasmic structures to a minor extent, but not to nucleolar structures. P110 decays spontaneously into several fragments which are also recognized by the polyclonal antibodies. The 110 kDa polypeptide and its fragments were phosphorylated by a nuclear envelope kinase and this phosphorylation was inhibited by a monoclonal antibody against protein kinase C and by a specific protein kinase C inhibitor obtained from bovine brain. Scatchard analysis was used to determine the influence of protein kinase C activators and inhibitors on nuclear envelope protein phosphorylation and RNA binding. The data indicate a close association between the RNA translocation machinery (the 110 kDa protein) and protein kinase C within the nuclear envelope. We suggest that the fragmentation of P110 is triggered before or during mRNA export and is not due to nonspecific proteolysis.

Immunogenicity of combined diphtheria, tetanus, and pertussis vaccine given at 2, 3, and 4 months versus 3, 5, and 9 months of age.

In the UK an accelerated schedule for immunisation against diphtheria, tetanus, and pertussis (injections at 2, 3, and 4 months of age) was introduced in 1990 to replace the more widely spaced schedule of 3, 5, and 9 months. There is concern, however, that the new schedule may be less immunogenic and therefore less protective than the old schedule. We have measured serum concentrations of antibodies against diphtheria, pertussis, and tetanus in infants immunised according to the two regimens. Both schedules resulted in protective concentrations of antibody against tetanus and diphtheria and in satisfactory antibody responses to three pertussis antigens (filamentous haemagglutinin, pertussis toxin, fimbriae). However, immunisation by the old schedule led to significantly higher antibody concentrations against both diphtheria and tetanus than did immunisation by the new schedule (p less than 0.01). In infants immunised with the new schedule, postimmunisation antibody concentrations against tetanus toxoid and against two pertussis antigens (pertussis toxin and fimbriae) were significantly lower in infants in whom preimmunisation (maternally derived) antibody concentrations were high (p less than 0.02). The findings suggest that with an accelerated immunisation schedule maternal antibodies can have an inhibitory effect on the responses to immunisation against tetanus and pertussis.