Successful management of elderly breast cancer patients treated without radiotherapy

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Breast cancer in the elderly may follow a less aggressive course. There are data suggesting that radiotherapy (RT) following breast conserving surgery (BCS) for invasive carcinoma may not be necessary in some elderly patients. The addition of RT to surgery might constitute an imposition to such patients due to age-related factors. The aim of this study was to assess the efficacy of BCS without adjuvant RT in this group of patients. Patients and methods A retrospective review of 92 elderly (median age 75 years; range: 70 – 87 years) patients (analysed as 93 'patients' due to one patient having bilateral cancers) managed in a dedicated breast clinic and who underwent BCS for invasive carcinoma was carried out. Eighty-three patients did not receive postoperative RT to the breast (no-RT group) whereas the remaining 10 had RT (RT-group). Results The median age in this group was 75 (range 70 – 87) years. The mean tumour size was 18 mm with a median follow-up of 37 (range 6 – 142) months. In the no RT group, adjuvant endocrine therapy with tamoxifen was given to 40/53 patients. No patients in the oestrogen receptor (ER) negative group received tamoxifen. The local recurrence (LR) rate in this group was 8.4% (2.4% per year, n = 7/83), with median time to LR of 17 months. In this no-RT group LR was correlated to ER status (2/53 ER+, 5/26ER-, p = 0.024) and margins of excision (n = 1/54 >5 mm, 2/17 1–5 mm, 4/12 <1 mm, p = 0.001). Within the ER positive group the LR rate was 0.92% per annum (0.62% per annum in patients treated with adjuvant tamoxifen, regardless of margin status). Breast cancer specific survival was correlated to histological grade (p < 0.05) and ER status (p < 0.05). Conclusion It would appear that omission of RT following successful BCS in elderly patients with ER positive tumours receiving adjuvant tamoxifen may be acceptable. The LR rate as shown in this retrospective study is highly comparable to that of younger patients treated by conventional therapy. This concept is now being evaluated prospectively following a change in treatment practice.Published versio

Comets, historical records and vedic literature

A verse in book I of Rigveda mentions a cosmic tree with rope-like aerial roots held up in the sky. Such an imagery might have ensued from the appearance of a comet having `tree stem' like tail, with branched out portions resembling aerial roots. Interestingly enough, a comet referred to as `heavenly tree' was seen in 162 BC, as reported by old Chinese records. Because of weak surface gravity, cometary appendages may possibly assume strange shapes depending on factors like rotation, structure and composition of the comet as well as solar wind pattern. Varahamihira and Ballala Sena listed several comets having strange forms as reported originally by ancient seers such as Parashara, Vriddha Garga, Narada and Garga. Mahabharata speaks of a mortal king Nahusha who ruled the heavens when Indra, king of gods, went into hiding. Nahusha became luminous and egoistic after absorbing radiance from gods and seers. When he kicked Agastya (southern star Canopus), the latter cursed him to become a serpent and fall from the sky. We posit arguments to surmise that this Mahabharata lore is a mythical recounting of a cometary event wherein a comet crossed Ursa Major, moved southwards with an elongated tail in the direction of Canopus and eventually went out of sight. In order to check whether such a conjecture is feasible, a preliminary list of comets (that could have or did come close to Canopus) drawn from various historical records is presented and discussed.Comment: This work was presented in the International Conference on Oriental Astronomy held at IISER, Pune (India) during November, 201

Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

&lt;p&gt;Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.&lt;/p&gt; &lt;p&gt;Methods: This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.&lt;/p&gt; &lt;p&gt;Results: There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.&lt;/p&gt; &lt;p&gt;Conclusions: Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.&lt;/p&gt

Dynamical differential expression (DyDE) reveals the period control mechanisms of the Arabidopsis circadian oscillator.

The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The mechanistic basis underlying the adjustment of circadian rhythms to changing external conditions, however, has yet to be clearly elucidated. We explored the mechanism of action of nicotinamide in Arabidopsis thaliana, a metabolite that lengthens the period of circadian rhythms, to understand the regulation of circadian period. To identify the key mechanisms involved in the circadian response to nicotinamide, we developed a systematic and practical modeling framework based on the identification and comparison of gene regulatory dynamics. Our mathematical predictions, confirmed by experimentation, identified key transcriptional regulatory mechanisms of circadian period and uncovered the role of blue light in the response of the circadian oscillator to nicotinamide. We suggest that our methodology could be adapted to predict mechanisms of drug action in complex biological systems

Assessment of risk of introduction of Echinococcus multilocularis to mainland Norway

Source at https://vkm.no/In the light of the recent findings of the tapeworm Echinococcus multilocularis (EM) in four red foxes from three different locations in Sweden, the Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen; VKM), Panel of Biological Hazards (Faggruppe hygiene og smittestoffer) took the initiative to undertake a risk assessment regarding the probability of this parasite being introduced to mainland Norway and thus becoming a threat to public health in the country.Med bakgrunn i funnet av bendelorm Echinococcus multilocularis (EM) i fire rødrev fra tre forskjellige steder i Sverige, har VKM ved Faggruppe hygiene og smittestoffer tatt initiativ til å foreta en vurdering av sannsynligheten for at EM kan bli introdusert til fastlands Norge og sannsynligheten for at mennesker i så fall også kan bli smittet

Screening for atrial fibrillation – a cross-sectional survey of healthcare professionals in primary care

Introduction: Screening for atrial fibrillation (AF) in primary care has been recommended; however, the views of healthcare professionals (HCPs) are not known. This study aimed to determine the opinions of HCP about the feasibility of implementing screening within a primary care setting. Methods: A cross-sectional mixed methods census survey of 418 HCPs from 59 inner-city practices (Nottingham, UK) was conducted between October-December 2014. Postal and web-surveys ascertained data on existing methods, knowledge, skills, attitudes, barriers and facilitators to AF screening using Likert scale and open-ended questions. Responses, categorized according to HCP group, were summarized using proportions, adjusting for clustering by practice, with 95% C.Is and free-text responses using thematic analysis. Results: At least one General Practitioner (GP) responded from 48 (81%) practices. There were 212/418 (51%) respondents; 118/229 GPs, 67/129 nurses [50 practice nurses; 17 Nurse Practitioners (NPs)], 27/60 healthcare assistants (HCAs). 39/48 (81%) practices had an ECG machine and diagnosed AF in-house. Non-GP HCPs reported having less knowledge about ECG interpretation, diagnosing and treating AF than GPs. A greater proportion of non-GP HCPs reported they would benefit from ECG training specifically for AF diagnosis than GPs [proportion (95% CI) GPs: 11.9% (6.8–20.0); HCAs: 37.0% (21.7–55.5); nurses: 44.0% (30.0–59.0); NPs 41.2% (21.9–63.7)]. Barriers included time, workload and capacity to undertake screening activities, although training to diagnose and manage AF was a required facilitator. Conclusion: Inner-city general practices were found to have adequate access to resources for AF screening. There is enthusiasm by non-GP HCPs to up-skill in the diagnosis and management of AF and they may have a role in future AF screening. However, organisational barriers, such as lack of time, staff and capacity, should be overcome for AF screening to be feasibly implemented within primary care

CWD in Norway. Opinion of the Panel on Biological Hazards of the Norwegian Scientific Committee for Food Safety

The Norwegian Food Safety Authority (NFSA) and Norwegian Environmental Authority (NEA) asked the Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) for an opinion on factors associated with the introduction of Chronic Wasting Disease (CWD) to Norway. VKM appointed a working group consisting of two members of the Panel on Biological Hazards, one member of Panel on Animal Health and Welfare, and two external experts to prepare the answer to the questions. The Panel on Biological Hazards has reviewed and revised the draft prepared by the working group and approved the opinion. CWD was diagnosed in March 2016 in a wild reindeer (Rangifer tarandus) from the Nordfjella mountain area in Norway and in May and June in two mooses (Alces alces) in Selbu in South Trøndelag County, approximately 300 km north from the first case. There is currently no information to determine the origin(s) of CWD agents in Norway. However, the sporadic or genetic (somatic mutation) occurrence of prion disease in cervids cannot be excluded, nor can introduction from North America or other countries. Furthermore, there is no evidence that it has not been circulating at low levels in the Norwegian cervid populations for years, but has not previously been identified. In this scientific opinion, information on prion diseases in general, and CWD in particular, is presented in the light of experiences with this disease in North America. Prions are among the most resilient pathogens known and dissemination of prions into ecosystems is likely to result in long-term problems. Prions bind strongly to soil and remain infectious. In CWD, prions are present in most peripheral organs and also shed into the environment via saliva, faeces, and urine, as well as with the placenta. CWD transmits easily among cervids, either through direct contact, or indirectly via the environment. Migration of animals is relevant for the spread between areas. Strain diversification might occur in CWD and may influence transmission properties of the agents. Clinical signs of CWD are non-specific and do not alone enable confirmation of the diagnosis. Analysis of tissue from the brainstem at the level of the obex by approved methods is necessary for diagnosis of CWD. Prion infectivity is assessed by bioassays, often involving transgenic mice. In vitro conversion assays, like protein misfolding cyclic amplification (PMCA), provide sensitive quantification of converting activity, which is a good approximation of infectivity. Genetic variation (polymorphisms) in the gene that encodes PrP (PRNP) can modulate sensitivity towards CWD. The level of such genetic variation in Norwegian wild and semi- domesticated cervids is currently unknown. Cattle and sheep are at very low risk of developing CWD and it is highly unlikely that prion diseases in sheep or cattle are the origin of CWD. VKM Report 2016: 26 6 Although transmission of CWD to humans has never been known to occur, and animals other than cervids have not been found to be infected, indicating a species barrier, this possibility cannot be excluded. Thus, measures for reduction of human exposure are recommended. Taking into account uncertainties regarding the plasticity of the CWD agents and the lack of transmission data from the Norwegian isolates, this scientific opinion considers the zoonotic risk of CWD to be very low.publishedVersio

Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

<p>Abstract</p> <p>Background</p> <p>It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy".</p> <p>Methods</p> <p>Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1) estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years), locally advanced or metastatic breast cancer; (2) disease deemed suitable for treatment by hormonal manipulation; (3) disease assessable by UICC criteria; (4) received "withdrawal" from a prior endocrine agent as a form of therapy; (5) on "withdrawal therapy" for ≥ 6 months unless they progressed prior.</p> <p>Results</p> <p>Seventeen patients with median age of 84.3 (53.7-92.5) had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10), an aromatase inhibitor (n = 5), megestrol acetate (n = 1) or fulvestrant (n = 1). Ten patients (58.8%) had clinical benefit (CB) (complete response/partial response/stable disease ≥ 6 months) with a median duration of Clinical Benefit (DoCB) of 10+ (7-27) months. Two patients remain on "withdrawal therapy" at the time of analysis.</p> <p>Conclusion</p> <p>"Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.</p

CWD in Norway

Source at https://vkm.no/The Norwegian Food Safety Authority (NFSA) and Norwegian Environmental Authority (NEA) asked the Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) for an opinion on factors associated with the introduction of Chronic Wasting Disease (CWD) to Norway. VKM appointed a working group consisting of two members of the Panel on Biological Hazards, one member of Panel on Animal Health and Welfare, and two external experts to prepare the answer to the questions. The Panel on Biological Hazards has reviewed and revised the draft prepared by the working group and approved the opinion.Mattilsynet og Miljødirektoratet har bedt Vitenskapskomitéen for mattrygghet (VKM) om å besvare spørsmål knyttet til mattrygghet og dyrehelse etter at den uhelbredelige sykdommen Chronic Wasting Disease (CWD) nylig ble påvist hos en villrein og senere hos to elger i Norge. VKM nedsatte en arbeidsgruppe bestående av to medlemmer fra Faggruppen for hygiene og smittestoffer, ett medlem fra Faggruppen for dyrehelse- og velferd samt to eksterne eksperter, for å utarbeide en vurdering knyttet til de stilte spørsmålene. Faggruppen for hygiene og smittestoffer har lest utkast til rapporten og godkjent vurderingen