It is not clear which research misconduct policies are adopted by biomedical journals. This study assessed the prevalence and content policies of the most influential biomedical journals on misconduct and procedures for handling and responding to allegations of misconduct.
We conducted a cross-sectional study of misconduct policies of 399 high-impact biomedical journals in 27 biomedical categories of the Journal Citation Reports in December 2011. Journal websites were reviewed for information relevant to misconduct policies.
Of 399 journals, 140 (35.1%) provided explicit definitions of misconduct. Falsification was explicitly mentioned by 113 (28.3%) journals, fabrication by 104 (26.1%), plagiarism by 224 (56.1%), duplication by 242 (60.7%) and image manipulation by 154 (38.6%). Procedures for responding to misconduct were described in 179 (44.9%) websites, including retraction, (30.8%) and expression of concern (16.3%). Plagiarism-checking services were used by 112 (28.1%) journals. The prevalences of all types of misconduct policies were higher in journals that endorsed any policy from editors’ associations, Office of Research Integrity or professional societies compared to those that did not state adherence to these policy-producing bodies. Elsevier and Wiley-Blackwell had the most journals included (22.6% and 14.8%, respectively), with Wiley journals having greater a prevalence of misconduct definition and policies on falsification, fabrication and expression of concern and Elsevier of plagiarism-checking services.
Only a third of top-ranking peer-reviewed journals had publicly-available definitions of misconduct and less than a half described procedures for handling allegations of misconduct. As endorsement of international policies from policy-producing bodies was positively associated with implementation of policies and procedures, journals and their publishers should standardize their policies globally in order to increase public trust in the integrity of the published record in biomedicine.
CONSORT, Consolidated Standards of Reporting Trials; ICMJE, International Committee of Medical Journal Editors; MPIP, Medical Publishing Insights and Practices
Employers may be loath to fund vaccination programs without understanding the economic consequences. We developed a decision analytic computational simulation model including dynamic transmission elements that determined the cost-benefit of employer-sponsored workplace vaccination from the employer's perspective. Implementing such programs was relatively inexpensive (<$35/vaccinated employee) and, in many cases, cost saving across diverse occupational groups in all seasonal influenza scenarios. Such programs were cost-saving for a 20% serologic attack rate pandemic scenario (−$15 to −$995) per vaccinated employee) and a 30% serologic attack rate pandemic scenario (range −$39 to −$1,494 per vaccinated employee) across all age and major occupational groups.
Influenza; Workplace; Vaccination
Smokers earn less than non-smokers, but much is still unknown about the source(s) of the smoker’s wage gap. We build on the work of Bhattacharya and Bundorf (2009), who provide evidence that obese workers receive lower wages on account of their higher expected healthcare costs. Similarly, we find that smokers who hold employer-sponsored health insurance (ESI) receive significantly lower wages than their non-smoking peers, while smokers who are not insured through their employer endure no such wage penalty. Our results have two implications: first, the incidence of smokers’ elevated medical costs appears to be borne by smokers themselves in the form of lower wages. Second, differences in healthcare costs between smokers and non-smokers are a significant source of the smoker’s wage gap.
Smoking; Wages; Employer-sponsored health insurance; Compensating differential
We evaluated the safety of coronary reactivity testing (CRT) in symptomatic women with evidence of myocardial ischemia and no obstructive coronary artery disease (CAD).
Microvascular coronary dysfunction (MCD) in women with no obstructive CAD portends an adverse prognosis of 2.5% annual major adverse cardiovascular event (MACE) rate. The diagnosis of MCD is established by invasive CRT, yet the risk of CRT is unknown.
We evaluated 293 symptomatic women with ischemia and no obstructive CAD, who underwent CRT at three experienced centers. Microvascular function was assessed using a Doppler wire and injections of adenosine, acetylcholine, and nitroglycerin in the left coronary artery. CRT-related serious adverse events (SAE), adverse events (AE), and follow-up MACE (death, nonfatal myocardial infarction (MI), nonfatal stroke, or hospitalization for heart failure) were recorded.
CRT-SAEs occurred in 2 women (0.7%) during the procedure: one had coronary artery dissection, and one developed MI associated with coronary spasm. CRT-AEs occurred in 2 women (0.7%) and included one transient air microembolism and one deep venous thrombosis. There was no CRT-related mortality. In the mean follow-up period of 5.4 years, the MACE rate was 8.2%, including 5 deaths (1.7%), 8 non-fatal MIs (2.7%), 8 nonfatal strokes (2.7%), and 11 hospitalizations for heart failure (3.8%).
In women undergoing CRT for suspected MCD, contemporary testing carries a relatively low risk compared to the MACE rate in these women. These results support the use of CRT by experienced operators for establishing definitive diagnosis and assessing prognosis in this at-risk population.
coronary reactivity; microvascular dysfunction; endothelial dysfunction
Background and Purpose
When planning clinical trials, decisions regarding sample size are often based on educated guesses of parameters, that may in fact prove to be over- or underestimates. For example, after initiation of the SPS3 study, published data indicated that the recurrent stroke rates might be lower than initially planned for the study. Failure to account for this could result in an under-powered study. Thus, we performed a sample size re-estimation, and describe the experience herein.
We evaluated different scenarios based on a re-estimated overall event rate, including increasing the sample size and increasing the follow-up time, to determine their impact on both Type I error and the power to detect the initially planned treatment difference.
We found that by increasing the sample size from 2500 to 3000 and by following the patients for one year after the end of recruitment, we would maintain our planned Type I error rate, and increase the power to detect the prespecified clinically meaningful difference to between 67% and 87%, depending on the rate of recruitment.
We successfully implemented this unplanned design modification in the SPS3 study, in order to allow for sufficient power to detect the planned treatment differences.
Clinical Trials Registration Information
Clinical Trials Registration - http://clinicaltrials.gov/show/NCT00059306. Unique identifier: NCT00059306
sample size re-estimation; SPS3; randomized clinical trial
Urinary Kidney Injury Molecule 1 (KIM-1) is a proximal tubular injury biomarker for early detection of acute kidney injury (AKI), with variable performance characteristics depending on clinical and population settings.
Meta-analysis was performed to assess the diagnostic value of urinary KIM-1 in AKI. Relevant studies were searched from MEDLINE, EMBASE, Pubmed, Elsevier Science Direct, Scopus, Web of Science, Google Scholar and Cochrane Library. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver operating characteristic (SROC) curves.
A total of 2979 patients from 11 eligible studies were enrolled in the analysis. Five prospective cohorts, two cross-sectional and four case-control studies were identified for meta-analysis. The estimated sensitivity of urinary KIM-1 for the diagnosis of AKI was 74.0% (95% CI, 61.0%–84.0%), and specificity was 86.0% (95% CI, 74.0%–93.0%). The SROC analysis showed an area under the curve of 0.86(0.83–0.89). Subgroup analysis suggested that population settings and detection time were the key factors affecting the efficiency of KIM-1 for AKI diagnosis.
Various population settings, different definition of AKI and Serum creatinine level used as the standard might have influence on AKI diagnosis. The relatively small number of studies and heterogeneity between them also affected the evaluation.
Urinary KIM-1 may be a promising biomarker for early detection of AKI with considerable predictive value, especially for cardiac surgery patients, and its potential value needs to be validated in large studies and across a broader scope of clinical settings.
Published results suggests that high adiponectin level may decrease the risk of breast cancer. However, available evidence on breast cancer is conflicting. Therefore a meta-analysis was performed to assess the association between blood adiponectin and breast cancer risk. PubMed database, Web of Science, Elsevier Science, Springer Link and bibliographies of retrieved articles were searched for epidemiological studies published up to March 2013. Meta-analysis was performed on the combined effect values (OR) as well as standardized mean difference (SMD) including 17 studies. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. The publication bias was assessed by the Egger’s regression asymmetry test and Begg’s rank correlation test with Begg’s funnel plot. Subgroup analyses and sensitivity analysis were also performed. A total of 13 studies involving 3578 breast cancer cases and 4363 controls contributed to the OR analysis. The high adiponectin level did not significantly affect breast cancer risk (OR=0.902, 95% CI=0.773–1.053). After excluding articles that were the key contributors to between-study heterogeneity, the OR of high adiponectin level was associated with decreased breast cancer risk (OR=0.838, 95% CI=0.744–0.943). There was a significantly association between high adiponectin level and postmenopausal breast cancer women (OR=0.752, 95%CI=0.604-0.936); and it was not associated with premenopausal breast cancer women (OR=0.895, 95%CI=0.638-1.256). The result of pooled measure on SMD was that the high adiponectin level was associated with decreased breast cancer risk (SMD= -0.348, 95% CI= -0.533--0.614) after excluding articles which were the key contributors to between-study heterogeneity. Our findings indicate that high adiponectin level might decrease the risk of postmenopausal breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.
Researchers turn to citation tracking to find the most influential articles for a particular topic and to see how often their own published papers are cited. For years researchers looking for this type of information had only one resource to consult: the Web of Science from Thomson Scientific. In 2004 two competitors emerged – Scopus from Elsevier and Google Scholar from Google. The research reported here uses citation analysis in an observational study examining these three databases; comparing citation counts for articles from two disciplines (oncology and condensed matter physics) and two years (1993 and 2003) to test the hypothesis that the different scholarly publication coverage provided by the three search tools will lead to different citation counts from each.
Eleven journal titles with varying impact factors were selected from each discipline (oncology and condensed matter physics) using the Journal Citation Reports (JCR). All articles published in the selected titles were retrieved for the years 1993 and 2003, and a stratified random sample of articles was chosen, resulting in four sets of articles. During the week of November 7–12, 2005, the citation counts for each research article were extracted from the three sources. The actual citing references for a subset of the articles published in 2003 were also gathered from each of the three sources.
For oncology 1993 Web of Science returned the highest average number of citations, 45.3. Scopus returned the highest average number of citations (8.9) for oncology 2003. Web of Science returned the highest number of citations for condensed matter physics 1993 and 2003 (22.5 and 3.9 respectively). The data showed a significant difference in the mean citation rates between all pairs of resources except between Google Scholar and Scopus for condensed matter physics 2003. For articles published in 2003 Google Scholar returned the largest amount of unique citing material for oncology and Web of Science returned the most for condensed matter physics.
This study did not identify any one of these three resources as the answer to all citation tracking needs. Scopus showed strength in providing citing literature for current (2003) oncology articles, while Web of Science produced more citing material for 2003 and 1993 condensed matter physics, and 1993 oncology articles. All three tools returned some unique material. Our data indicate that the question of which tool provides the most complete set of citing literature may depend on the subject and publication year of a given article.
Approximately 170 million inhabitants of the American continent live at risk of malaria transmission. Although the continent’s contribution to the global malaria burden is small, at least 1 to 1.2 million malaria cases are reported annually. Sixty per cent of the malaria cases occur in Brazil and the other 40% are distributed in 20 other countries of Central and South America. Plasmodium vivax is the predominant species (74.2 %) followed by P. falciparum (25.7 %) and P. malariae (0.1%), and no less than 10 Anopheles species have been identified as primary or secondary malaria vectors. Rapid deforestation and agricultural practices are directly related to increases in Anopheles species diversity and abundance, as well as in the number of malaria cases. Additionally, climate changes profoundly affect malaria transmission and are responsible for malaria epidemics in some regions of South America. Parasite drug resistance is increasing, but due to bio-geographic barriers there is extraordinary genetic differentiation of parasites with limited dispersion. Although the clinical spectrum ranges from uncomplicated to severe malaria cases, due to the generally low to middle transmission intensity, features such as severe anemia, cerebral malaria and other complications appear to be less frequent than in other endemic regions and asymptomatic infections are a common feature. Although the National Malaria Control Programs (NMCP) of different countries differ in their control activities these are all directed to reduce morbidity and mortality by using strategies like health promotion, vector control and impregnate bed nets among others. Recently, international initiatives such as the Malaria Control Program in Andean-country Border Regions (PAMAFRO) (implemented by the Andean Organism for Health (ORAS) and sponsored by The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM)) and The Amazon Network for the Surveillance of Antimalarial Drug Resistance (RAVREDA) (sponsored by the Pan American Health Organization/World Health Organization (PAHO/WHO) and several other partners), have made great investments for malaria control in the region. We describe here the current status of malaria in a non-Amazonian region comprising several countries of South and Central America participating in the Centro Latino Americano de Investigación en Malaria (CLAIM), an International Center of Excellence for Malaria Research (ICEMR) sponsored by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID).
malaria; Plasmodium falciparum; Plasmodium vivax; malaria elimination; epidemiology; Latin America
Factors that have led to the increasing popularity of medical travel include the high cost of healthcare, long wait times for certain procedures, the ease and affordability of international travel, and improvements in both technology and standards of care in many countries.
The present study aims to elaborate the factors that attract international cardiac patients to India, to document the proportion of the admissions into the paediatric cardiac ward who are international patients, and to identify the sources of funding of the international patients.
This was a prospective, cross-sectional, and analytical study carried out between May 2009 and October 2009 in the paediatric cardiac care unit of a large tertiary care cardiac centre in India paediatric wards. Structured questionnaires were administered.
A total of 1372 patients were admitted during the study period, of which 155 (11.3%) were patients from countries outside India. Majority of the patients were from Malaysia (45%), Nigeria (23%), and Tanzania (15%). The age ranged from 1 month to 39 years with an average of 61 months. The male to female ratio was 1:1.4 and the majority of subjects (72.5%) were in social classes 3 and 4. cheaper cost and better expertise was the prominent reason for choosing India. More than half of the respondents were either sponsored by the government or self-funded. For patients from Nigeria 53% (9) were sponsored by self (parent), 29% (5) by non-governmental organisations (NGO), 12% (2) by the parent employer, and 6% (1) by the government.
There is a need for local development of facilities and training of personnel in specialised areas of healthcare to provide succour for a significant number of nationals who might otherwise have suffered and possibly have even died of their ailment. There is also the added advantage that such facilities would save foreign currency and help boost our economy.
International patients; Medical tourism
Mucormycosis is an emergent and threatening invasive fungal invasion underdiagnosed by clinicians due to lack of awareness and aspecific clinical picture. The authors describe a clinical case of a diabetic and cirrhotic patient who developed rhino-orbital-cerebral and pulmonary mucormycosis, non-responsive to treatment. Typical gaps in the management of this deadly disease are addressed. There is a strong need for novel therapies and an expectation that sponsors will recognize the critical need for randomized clinical trials.
Mucormycosis; Diabetes; High mortality; Delays; Hyperbaric medicine; Randomized clinical trials
The ethics of research continue to attract considerable debate, particularly when that research is sponsored by partners from the North and carried out in the South. Ethical research should contribute to social value in the country where research is being carried out, but there is significant debate around how this might be achieved and who is responsible. The literature suggests that researchers might employ two inter-related strategies to maximise social value: collaborative partnerships with policy makers and communities from the outset of research, and dissemination of research results to participants, policy makers and implementers once the research is over. These areas have received relatively little empirical attention. In this study, we carried out 40 in-depth interviews to explore the role of collaborative partnerships in health research priority setting, and the way in which research findings are disseminated to aid policy making and implementation in Kenya. Interviewees included policy makers, researchers, policy implementers and representatives of organisations funding health reforms in Kenya. Two policy issues were drawn upon as tracers wherever possible: (1) the introduction of Artemesinin- based Combination Therapies (ACTs), an anti-malarial treatment policy; and (2) Haemophilus influenzae (Hib) vaccine for the prevention of pneumococcal diseases among children.
The findings point to significant gaps in the ‘research to policy to practice’ pathway, particularly for national research institutions with a focus on clinical/biomedical research. These gaps reflect poorly effective partnerships among stakeholders and limit the potential social value of much research. While more investment is needed to establish strong structures for promoting and directing collaboration and partnership, how to target this investment is not entirely clear, especially in the context of the considerable power of the global health agenda and the research financing tied to it.
Kenya; Ethics; Social value; Research benefits; Collaborative research
Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise.
We undertook a phase-2 randomised placebo controlled trial in adults awaiting kidney or liver transplantation at the Royal Free Hospital, London, UK. Exclusion criteria were pregnancy, receipt of blood products (except albumin) in the previous 3 months, and simultaneous multiorgan transplantation. 70 patients seronegative and 70 seropositive for cytomegalovirus were randomly assigned from a scratch-off randomisation code in a 1:1 ratio to receive either cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant or placebo, each given at baseline, 1 month and 6 months later. If a patient was transplanted, no further vaccinations were given and serial blood samples were tested for cytomegalovirus DNA by real-time quantitative PCR (rtqPCR). Any patient with one blood sample containing more than 3000 cytomegalovirus genomes per mL received ganciclovir until two consecutive undetectable cytomegalovirus DNA measurements. Safety and immunogenicity were coprimary endpoints and were assessed by intention to treat in patients who received at least one dose of vaccine or placebo. This trial is registered with ClinicalTrials.gov, NCT00299260.
67 patients received vaccine and 73 placebo, all of whom were evaluable. Glycoprotein-B antibody titres were significantly increased in both seronegative (geometric mean titre 12 537 (95% CI 6593–23 840) versus 86 (63–118) in recipients of placebo recipients; p<0·0001) and seropositive (118 395; 64 503–217 272) versus 24 682 (17 909–34 017); p<0·0001) recipients of vaccine. In those who developed viraemia after transplantation, glycoprotein-B antibody titres correlated inversely with duration of viraemia (p=0·0022). In the seronegative patients with seropositive donors, the duration of viraemia (p=0·0480) and number of days of ganciclovir treatment (p=0·0287) were reduced in vaccine recipients.
Although cytomegalovirus disease occurs in the context of suppressed cell-mediated immunity post-transplantation, humoral immunity has a role in reduction of cytomegalovirus viraemia. Vaccines containing cytomegalovirus glycoprotein B merit further assessment in transplant recipients.
National Institute of Allergy and Infectious Diseases, Grant R01AI051355 and Wellcome Trust, Grant 078332. Sponsor: University College London (UCL).
To estimate lifetime risk for HF by sex and race.
Prior estimates of lifetime risk for developing heart failure (HF) range from 20% to 33% in predominantly white cohorts. Short-term risks for HF appear higher for blacks than whites, but only limited comparisons of lifetime risk for HF have been made.
Using public-release and internal datasets from NHLBI-sponsored cohorts, we estimated lifetime risks for developing HF to age 95, with death free of HF as the competing event, among participants in Chicago Heart Association Detection Project in Industry (CHA), Atherosclerosis Risk in Communities (ARIC), and Cardiovascular Health Study (CHS) cohorts.
There were 39,578 participants (33,652 [85%] white; 5,926 [15%] black) followed for 716,976 person-years; 5,983 participants developed HF. At age 45 years, lifetime risks for HF through age 95 years in CHA and CHS were 30-42% in white men, 20-29% in black men, 32-39% in white women, and 24-46% in black women. Results for ARIC demonstrated similar lifetime risks for HF in blacks and whites through age 75 years (limit of follow-up). Lifetime risk for HF was higher with higher BP and BMI at all ages in both blacks and whites and did not diminish substantially with advancing index age.
These are among the first data to compare lifetime risks for HF between blacks and whites. Lifetime risks for HF are high and appear similar for black and white women, yet are somewhat lower for black compared with white men due to competing risks.
lifetime risk; heart failure; epidemiology
In 2005, the National Institutes of Health sponsored a Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-vs-Host (GVHD) to achieve consensus about key elements of chronic GVHD research, including definitions for diagnosis, severity scoring, and response measures. To test these proposed definitions, a multi-center prospective cohort study of people with chronic GVHD is ongoing. This study will evaluate the performance of proposed prognostic factors, measures of disease activity and surrogate endpoints for therapeutic response. Data are collected at 6 month intervals in a heterogeneous population of patients reflecting modern transplant techniques and post-transplant clinical management (target enrollment 672 with chronic GVHD from ten transplant centers). This report describes the rationale, design, and methods of the chronic GVHD cohort study, and invites other investigators to collaborate with the Consortium to analyze data or specimens.
chronic graft-versus-host disease; allogeneic hematopoietic cell transplantation; outcomes research; observational clinical study
Frontotemporal Degeneration (FTD) is a common cause of dementia for which there are currently no approved therapies. Over the past decade there has been an explosion of knowledge about the biology and clinical features of FTD that has identified a number of promising therapeutic targets as well as animal models in which to develop drugs. The close association of some forms of FTD with neuropathological accumulation of tau protein or increased neuroinflammation due to progranulin protein deficiency suggests that a drug’s success in treating FTD may predict efficacy in more common diseases such as Alzheimer’s disease (AD). A variety of regulatory incentives, clinical features of FTD, such as rapid disease progression, and relatively pure molecular pathology, suggest that there are advantages to developing drugs for FTD as compared to other more common neurodegenerative diseases such as AD. In March 2011, the Frontotemporal Dementia Treatment Study Group (FTSG) sponsored a conference entitled,“ FTD, the Next Therapeutic Frontier,” focused on pre-clinical aspects of FTD drug development. The goal of the meeting was to promote collaborations between academic researchers and biotechnology and pharmaceutical researchers to accelerate the development of new treatments for FTD. Here we report the key findings from the conference, including the rationale for FTD drug development, epidemiological, genetic and neuropathological features of FTD, FTD animal models and how best to use them and examples of successful drug-development collaborations in other neurodegenerative diseases.
Frontotemporal Degeneration (FTD) encompasses a spectrum of related neurodegenerative disorders with behavioral, language and motor phenotypes for which there are currently no effective therapies. This manuscript is the second of two articles that summarize the presentations and discussions that occurred at two symposia in 2011 sponsored by the Frontotemporal Dementia Treatment Study Group (FTSG), a collaborative group of academic and industry researchers that is devoted to developing treatments for FTD. This manuscript discusses the current status of FTD clinical research that is relevant to the conduct of clinical trials and why FTD research may be an attractive pathway for developing therapies for neurodegenerative disorders. The clinical and molecular features of FTD, including rapid disease progression and relatively pure molecular pathology, suggest that there are advantages to developing drugs for FTD as compared to other dementias. FTD qualifies as orphan indication, providing additional advantages for drug development. Two recent sets of consensus diagnostic criteria will facilitate the identification of patients with FTD, and a variety of neuropsychological, functional and behavioral scales have been shown to be sensitive to disease progression. Moreover, quantitative neuroimaging measurements demonstrate progressive brain atrophy in FTD at rates that may surpass Alzheimer's disease (AD). Finally, the similarities between FTD and other neurodegenerative diseases with drug development efforts already underway suggest that FTD researchers will be able to draw upon this experience to create a roadmap for FTD drug development. We conclude that FTD research has reached sufficient maturity to pursue clinical development of specific FTD therapies.
Perception has been identified by the NIMH-sponsored Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) group as a useful domain for assessing cognitive deficits in patients with schizophrenia. Specific measures of contrast gain derived from recordings of steady-state visual evoked potentials (ssVEP) have demonstrated neural deficits within the visual pathways of patients with schizophrenia. Psychophysical measures of contrast sensitivity have also shown functional loss in these patients. In the current study, functional magnetic resonance imaging (fMRI) was used in conjunction with ssVEP and contrast sensitivity testing to elucidate the neural underpinnings of these deficits. During fMRI scanning, participants viewed 1) the same low and higher spatial frequency stimuli used in the psychophysical contrast sensitivity task, at both individual detection threshold contrast and at a high contrast; and 2) the same stimuli used in the ssVEP paradigm, which were designed to be biased toward either the magnocellular or parvocellular visual pathway. Patients showed significant impairment in contrast sensitivity at both spatial frequencies in the psychophysical task, but showed reduced occipital activation volume for low, but not higher, spatial frequency at the low and high contrasts tested in the magnet. As expected, patients exhibited selective deficits under the magnocellular-biased ssVEP condition. However, occipital lobe fMRI responses demonstrated the same general pattern for magnocellular- and parvocellular-biased stimuli across groups. These results indicate dissociation between the fMRI measures and the psychophysical/ssVEP measures. These latter measures appear to have greater value for the functional assessment of the contrast deficits explored here.
contrast sensitivity; fMRI; gain control; magnocellular; schizophrenia; visual
Many patients are living longer with Metastatic Breast Cancer (MBC) than ever before. However, complete responses remain uncommon, and progression of disease is often inevitable. The experience of living with MBC exposes patients to a wide variety of clinical, psychological, social and spiritual issues. Although much research effort has focused on decision-making and coping strategies among women with early breast cancer, relatively little attention has been given to the needs, experiences, and perceptions of women living with MBC. Furthermore, there are major research gaps in understanding and prioritizing the types of psycho-social interventions that would make the most difference in the lives of these patients. Fortunately, the tide is turning. This communication represents a joint effort of the Breast International Group and the National Cancer Institute (NCI)-sponsored North American Breast Cancer Group (BIG-NABCG) to highlight perceptions and needs of patients living with MBC and current obstacles facing them, and recommends strategies for better addressing some of these unmet needs.
Perceptions; Metastatic; Breast; Cancer; BIG-NABCG
This review describes the neuroendocrinological aspects of catamenial epilepsy, a menstrual cycle-related seizure disorder in women with epilepsy. Catamenial epilepsy is a multifaceted neuroendocrine condition in which seizures are clustered around specific points in the menstrual cycle, most often around perimenstrual or periovulatory period. Three types of catamenial seizures (perimenstrual, periovulatory and inadequate luteal) have been identified. The molecular pathophysiology of catamenial epilepsy remains unclear. Cyclical changes in the circulating levels of estrogens and progesterone (P) play a central role in the development of catamenial epilepsy. Endogenous neurosteroids such as allopregnanolone (AP) and allotetrahydrodeoxycorticosterone (THDOC) that modulate seizure susceptibility could play a critical role in catamenial epilepsy. In addition, plasticity in GABA-A receptor subunits could play a role in the enhanced seizure susceptibility in catamenial epilepsy. P-derived neurosteroids such as AP and THDOC potentiate synaptic GABA-A receptor function and also activate extrasynaptic GABA-A receptors in the hippocampus and thus may represent endogenous regulators of catamenial seizure susceptibility. Experimental studies have shown that neurosteroids confer greater seizure protection in animal models of catamenial epilepsy, especially without evident tolerance to their actions during chronic therapy. In the recently completed NIH-sponsored, placebo controlled Phase 3 clinical trial, P therapy proved to be beneficial only in women with perimenstrual catamenial epilepsy but not in non-catamenial subjects. Neurosteroid analogs with favorable profile may be useful in the treatment of catamenial epilepsy.
Allopregnanolone; estradiol; neurosteroids; progesterone; catamenial epilepsy; GABA-A receptor
The study of malaria parasites on the Indian subcontinent should help us understand unexpected disease outbreaks and unpredictable disease presentations from Plasmodium falciparum and from Plasmodium vivax infections. The Malaria Evolution in South Asia (MESA) research program is one of ten International Centers of Excellence for Malaria Research (ICEMR) sponsored by the US National Institute of Health. In this second of two reviews, we describe why population structures of Plasmodia in India will be characterized and how we will determine their consequences on disease presentation, outcome and patterns. Specific projects will determine if genetic diversity, possibly driven by parasites with higher genetic plasticity, plays a role in changing epidemiology, pathogenesis, vector competence of parasite populations, and whether innate human genetic traits protect Indians from malaria today. Deep local clinical knowledge of malaria in India will be supplemented by basic scientists who bring new research tools. Such tools will include whole genome sequencing and analysis methods; in vitro assays to measure genome plasticity, RBC cytoadhesion, invasion, and deformability; mosquito infectivity assays to evaluate changing parasite-vector compatibilities; and host genetics to understand protective traits in Indian populations. The MESA-ICEMR study sites span diagonally across India, including a mixture of very urban and rural hospitals, each with very different disease patterns and patient populations. Research partnerships include government-associated research institutes, private medical schools, city and state government hospitals, and hospitals with industry ties. Between 2012-2017, in addition to developing clinical research and basic science infrastructure at new clinical sites, our training workshops will engage new scientists and clinicians throughout South Asia in the malaria research field.
malaria; Plasmodium falciparum; Plasmodium vivax; India; South Asia; epidemiology; drug resistance; ICEMR