Axillary dissection versus axillary observation for low risk, clinically node-negative invasive breast cancer : a systematic review and meta-analysis

1. To systematically analyse studies comparing survival outcomes between axillary lymph-node dissection (ALND) and axilla observation (Obs), in women with low-risk, clinically node-negative breast cancer. 2. To consider results in the context of current axillary surgery de-escalation trials and studies. 9 eligible studies were identified, 6 RCTs and 3 non-randomized studies (4236 women in total). Outcomes assessed: overall survival (OS) and disease-free survival (DFS). The logged (ln) hazard ratio (HR) was calculated and used as the statistic of interest. Data was grouped by follow-up. Meta-analyses found no significant difference in OS at 5, 10 and 25-years follow-up (5-year ln HR = 0.08, 95% CI - 0.09, 0.25, 10-year ln HR =  0.33, 95% CI - 0.07, 0.72, 25-year ln HR = 0.00, 95% CI - 0.18, 0.19). ALND caused improvement in DFS at 5-years follow-up (ln HR = 0.16, 95% CI 0.03, 0.29), this was not demonstrated at 10 and 25-years follow-up (10-year ln HR = 0.07, 95% CI - 0.09, 0.23, 25-year ln HR = - 0.03, 95% CI - 0.21, 0.16). Studies supporting ALND for DFS at 5-years follow-up had greater relative chemotherapy use in the ALND cohort. ALND does not cause a significant improvement in OS in women with clinically node-negative breast cancer. ALND may improve DFS in the short term by tailoring a proportion of patients towards chemotherapy. Our evidence suggests that when the administration of systemic therapy is balanced between the two arms, axillary de-escalation studies will likely find no difference in OS or DFS. [Abstract copyright: © 2021. The Author(s).

Relationship of literacy and heart failure in adults with diabetes

<p>Abstract</p> <p>Background</p> <p>Although reading ability may impact educational strategies and management of heart failure (HF), the prevalence of limited literacy in patients with HF is unknown.</p> <p>Methods</p> <p>Subjects were drawn from the Vermont Diabetes Information System Field Survey, a cross-sectional study of adults with diabetes in primary care. Participants' self-reported characteristics were subjected to logistic regression to estimate the association of heart failure and literacy while controlling for social and economic factors. The Short Test of Functional Health Literacy was used to measure literacy.</p> <p>Results</p> <p>Of 172 subjects with HF and diabetes, 27% had limited literacy compared to 15% of 826 subjects without HF (OR 2.05; 95% CI 1.39, 3.02; <it>P </it>< 0.001). Adjusting for age, sex, race, income, marital status and health insurance, HF continued to be significantly associated with limited literacy (OR 1.55, 95% CI 1.00, 2.41, <it>P </it>= .05).</p> <p>After adjusting for education, however, HF was no longer independently associated with literacy (OR 1.31; 95% CI 0.82 – 2.08; <it>P </it>= 0.26).</p> <p>Conclusion</p> <p>Over one quarter of diabetic adults with HF have limited literacy. Although this association is no longer statistically significant when adjusted for education, clinicians should be aware that many of their patients have important limitations in dealing with written materials.</p

The Cost-Effectiveness of Early Access to HIV Services and Starting cART in the UK 1996–2008

To calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PI(boosted), comparing PLHIV with CD4≤200 cells/mm3 and CD4>200 cells/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and below CD4 200 cells/mm3.Use, costs and cost-effectiveness were calculated for PLHIV in routine pre-cART and starting first-line cART, comparing CD4≤200 cells/mm3 with CD4>200 cells/mm3 (2008 UK prices).cART naïve patients CD4≤200 cells/mm3 had an annual cost of £6,407 (95%CI £6,382 to £6,425) PPY compared with £2,758 (95%CI £2,752 to £2,761) PPY for those with CD4>200 cells/mm3; cost per life year gained of pre-cART treatment and care for those with CD4>200 cells/mm3 was £1,776 (cost-saving to £2,752). Annual cost for starting 2NRTIs+NNRTI or 2NRTIs+PI(boosted) with CD4≤200 cells/mm3 was £12,812 (95%CI £12,685-£12,937) compared with £10,478 (95%CI £10,376-£10,581) for PLHIV with CD4>200 cells/mm3. Cost per additional life-year gained on first-line therapy for those with CD4>200 cells/mm3 was £4639 (£3,967 to £2,960).PLHIV starting to use HIV services before CD4≤200 cells/mm3 is cost-effective and enables them to be monitored so they start cART with a CD4>200 cells/mm3, which results in better outcomes and is cost-effective. However, 25% of PLHIV accessing services continue to present with CD4≤200 cells/mm3. This highlights the need to investigate the cost-effectiveness of testing and early treatment programs for key populations in the UK

Blocking Mineralocorticoid Receptors prior to Retrieval Reduces Contextual Fear Memory in Mice

BACKGROUND: Corticosteroid hormones regulate appraisal and consolidation of information via mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) respectively. How activation of these receptors modulates retrieval of fearful information and the subsequent expression of fear is largely unknown. We tested here whether blockade of MRs or GRs during retrieval also affects subsequent expression of fear memory. METHODOLOGY/PRINCIPAL FINDINGS: Mice were trained in contextual or tone cue fear conditioning paradigms, by pairing mild foot shocks with a particular context or tone respectively. Twenty-four hours after training, context-conditioned animals were re-exposed to the context for 3 or 30 minutes (day 2); tone-conditioned animals were placed in a different context and re-exposed to one or six tones. Twenty-four hours (day 3) and one month later, freezing behavior to the aversive context/tone was scored again. MR or GR blockade was achieved by giving spironolactone or RU486 subcutaneously one hour before retrieval on day 2. Spironolactone administered prior to brief context re-exposure reduced freezing behavior during retrieval and 24 hours later, but not one month later. Administration of spironolactone without retrieval of the context or immediately after retrieval on day 2 did not reduce freezing on day 3. Re-exposure to the context for 30 minutes on day 2 significantly reduced freezing on day 3 and one month later, but freezing was not further reduced by spironolactone. Administration of spironolactone prior to tone-cue re-exposure on day 2 did not affect freezing behavior. Treatment with RU486 prior to re-exposure did not affect context or tone-cue fear memories at any time point. CONCLUSIONS/SIGNIFICANCE: We conclude that MR blockade prior to retrieval strongly reduces the expression of contextual fear, implying that MRs, rather than GRs, play an important role in retrieval of emotional information and subsequent fear expression

Influence of an outpatient multidisciplinary pain management program on the health-related quality of life and the physical fitness of chronic pain patients

BACKGROUND: Approximately 10 to 20 percent of the population is suffering from chronic pain. Since this represents a major contribution to the costs of the health care system, more efficient measures and interventions to treat these patients are sought. RESULTS: The development of general health and physical activity of patients with chronic pain was assessed in an interdisciplinary outpatient pain management program (IOPP). 36 patients with an average age of 48 years were included in the IOPP. Subjective assessment of well-being was performed at five time points (baseline, post intervention and 3, 6, and 12 months thereafter) by using standardized questionnaires. The study focused on the quality of life survey Medical Outcomes Study Short Form-36, which is a validated instrument with established reliability and sensitivity. In addition, the patients participated in physical assessment testing strength, power, endurance, and mobility. Prior to therapy a substantial impairment was found on different levels. Marked improvements in the psychological parameters were obtained by the end of the program. No success was achieved with regard to the physical assessments. CONCLUSION: Although many different studies have evaluated similar programs, only few of them have attained positive results such as improvements of general quality of life or of physical strength. Often no difference from the control group could be detected only some months after the intervention. In the present study no significant persistent improvement of well-being occurred. Possible reasons are either wrong instruments, wrong selection of patients or wrong interventions

Nuclear Factor Kappa B Activation Occurs in the Amnion Prior to Labour Onset and Modulates the Expression of Numerous Labour Associated Genes

Background: Prior to the onset of human labour there is an increase in the synthesis of prostaglandins, cytokines and chemokines in the fetal membranes, particular the amnion. This is associated with activation of the transcription factor nuclear factor kappa B (NFkB). In this study we characterised the level of NFkB activity in amnion epithelial cells as a measure of amnion activation in samples collected from women undergoing caesarean section at 39 weeks gestation prior to the onset of labour. Methodology/Principal Findings: We found that a proportion of women exhibit low or moderate NFkB activity while other women exhibit high levels of NFkB activity (n = 12). This activation process does not appear to involve classical pathways of NFkB activation but rather is correlated with an increase in nuclear p65-Rel-B dimers. To identify the full range of genes upregulated in association with amnion activation, microarray analysis was performed on carefully characterised nonactivated amnion (n = 3) samples and compared to activated samples (n = 3). A total of 919 genes were upregulated in response to amnion activation including numerous inflammatory genes such cyclooxygenase-2 (COX-2, 44-fold), interleukin 8 (IL-8, 6-fold), IL-1 receptor accessory protein (IL-1RAP, 4.5-fold), thrombospondin 1 (TSP-1, 3-fold) and, unexpectedly, oxytocin receptor (OTR, 24-fold). Ingenuity Pathway Analysis of the microarray data reveal the two main gene networks activated concurrently with amnion activation are i) cell death, cancer and morphology and ii) cell cycle, embryoni

Self-Reported Physical Activity: Its Correlates and Relationship with Health-Related Quality of Life in a Large Cohort of Colorectal Cancer Survivors

Background: Physical activity (PA) is suggested to be an important non-pharmacologic means to improve health-related outcomes among cancer survivors. We aimed to describe the PA level, its correlates, and association with health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors. Methods: CRC survivors identified from the Eindhoven Cancer Registry treated between 1998 and 2007 were included. Survivors completed validated questionnaires on PA, distress, fatigue, and HRQoL. Moderate-to-vigorous physical activity (MVPA) levels were calculated by summing the time spent on walking, bicycling, gardening and sports ($3 MET). Multiple linear regression analyses were conducted to study which socio-demographic and clinical factors were associated with MVPA. Furthermore, we examined associations between MVPA and physical and mental HRQoL, and whether these associations were mediated by fatigue and distress. Results: Cross-sectional data of 1371 survivors (response: 82%) were analysed. Participants were 69.5 (SD 9.7) years old, 56% were male, and survival duration was 3.9 (SD 2.5) years. Participants self-reported on average 95.5 (SD 80.3) min on MVPA per day. Younger age, male sex, being employed, non-smoking, lower BMI, colon cancer (vs. rectal cancer), chemotherapy treatment and having no co-morbidities were associated with higher MVPA (p,0.05). MVPA was positively associated with physical HRQoL (regression coefficient of total association (c) = 0.030; se = 0.004) after adjusting for socio-demographic an

Evaluating comorbidities in total hip and knee arthroplasty: available instruments

Each year millions of patients are treated for joint pain with total joint arthroplasty, and the numbers are expected to rise. Comorbid disease is known to influence the outcome of total joint arthroplasty, and its documentation is therefore of utmost importance in clinical evaluation of the individual patient as well as in research. In this paper, we examine the various methods for obtaining and assessing comorbidity information for patients undergoing joint replacement. Multiple instruments are reliable and validated for this purpose, such as the Charlson Index, Index of Coexistent Disease, and the Functional Comorbidity Index. In orthopedic studies, the Charnley classification and the American Society of Anesthesiologists physical function score (ASA) are widely used. We recommend that a well-documented comorbidity index that incorporates some aspect of mental health is used along with other appropriate instruments to objectively assess the preoperative status of the patient

Standard versus prosocial online support groups for distressed breast cancer survivors: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The Internet can increase access to psychosocial care for breast cancer survivors through online support groups. This study will test a novel prosocial online group that emphasizes both opportunities for getting and giving help. Based on the helper therapy principle, it is hypothesized that the addition of structured helping opportunities and coaching on how to help others online will increase the psychological benefits of a standard online group.</p> <p>Methods/Design</p> <p>A two-armed randomized controlled trial with pretest and posttest. Non-metastatic breast cancer survivors with elevated psychological distress will be randomized to either a standard facilitated online group or to a prosocial facilitated online group, which combines online exchanges of support with structured helping opportunities (blogging, breast cancer outreach) and coaching on how best to give support to others. Validated and reliable measures will be administered to women approximately one month before and after the interventions. Self-esteem, positive affect, and sense of belonging will be tested as potential mediators of the primary outcomes of depressive/anxious symptoms and sense of purpose in life.</p> <p>Discussion</p> <p>This study will test an innovative approach to maximizing the psychological benefits of cancer online support groups. The theory-based prosocial online support group intervention model is sustainable, because it can be implemented by private non-profit or other organizations, such as cancer centers, which mostly offer face-to-face support groups with limited patient reach.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01396174">NCT01396174</a></p