Atherosclerosis in the vertebral artery: an intrinsic risk factor in the use of spinal manipulation?

The presence of atherosclerotic plaques and their influence on the vertebral artery is of clinical importance within the scope of spinal manipulation. Manipulation may stimulate the development of atherosclerotic plaques, could detach an embolus with ensuing infarction, injure the endothelium or may directly cause a dissection in the presence of atherosclerotic plaques. In order to identify the sites and frequency of atherosclerotic plaques and to determine its relation to the tortuous course of the vertebral artery, a cadaveric study was performed. The vertebral arteries of 57 human cadavers were studied. The vertebral artery was virtually divided into four segments: the pre-vertebral (V1), the vertebral (V2), the atlanto-axial (V3), and the intracranial segment (V4). Abnormalities in the origin and course of the vertebral artery were noted, along with any associated osseous, or cartilaginous anomalies in the neck. After dissection, the artery was opened and macroscopically screened for the presence of atherosclerotic plaques. In 22.8% of the cases, no atherosclerotic plaques were present. In 35.1% of the cases, the atherosclerotic plaques were unilateral, of which 60.0% was on the left side, 40.0% on the right side, and in 42.1%, the occurrence was bilateral. Atherosclerotic plaques were significantly more present in the V3 segment than in the V1 (0.007) and V2 segment (0.049). In the V1 (P=0.008) and V2 segment (P=0.002), there was a correlation between a tortuous course of the vessel and the occurrence of atherosclerotic plaques. In individuals with marked atherosclerotic disease, stretching and compression effects of rotational manipulative techniques on atherosclerotic vessels impose a further risk factor for vertebrobasilar insufficiency. As direct evidence of atherosclerotic plaques are rarely available, therapists should avoid manipulative techniques at all levels of the cervical spine in the presence of any indirect sign of atherosclerotic disease or in the presence of calcified arterial walls or tortuosities of the vessels visible on routinely available X-ray images of the cervical or thoracic spine. It is strongly recommended, that if any doubt exists about the nature of a clinical presentation, vigorous manual procedures should be avoided until either the diagnosis is definitive or gentle manual therapy has proven effective.     

Can pre-procedural MRI signal intensity ratio predict the success of uterine artery embolization in treatment of myomas?

Background/aim Magnetic resonance (MR) images, signal intensity ratios calculated using region of interests (ROI) in T2W images by proportioning the dominant myoma to iliac muscle can aid patient selection and, thus, in achieving better outcomes with the uterine artery embolization (UAE) procedure. The present study investigates the association between the success of UAE treatment with signal intensity (SI) ratio of the dominant myoma to the iliac muscle in MR imaging performed prior to the procedure.Materials and methods This is a retrospective study and included 30 patients who admitted to our clinic between February 2017 and July 2019 due to symptoms associated with myoma and who underwent MR imaging before and after UAE treatment. All patients, MR images obtained before UAE treatment and at the 12th month after the procedure were evaluated. In MRI, SI values were calculated by proportioning the dominant myoma to the iliac muscle using circular ROI in T1 weighted (W), T2W, and post-contrast T1W images. In the present study, 50% or more volumetric regression of the myoma with infarction of fibroids (loss of enhancement) at the 12-month follow-up MRI after the procedure was considered a successful procedure. Results Myoma volumes calculated in MR images showed significant differences between the MRI performed before UAE procedure and the MRI performed at the 12th month after the procedure (p < 0.0001). SI ratio calculated from pre-procedure T2W MR images was found to be a significant determinant of 50% or more volumetric regression in the myoma after UAE procedure (p = 0.017), T1W, post-contrast T1W images were not statistically significant (p = 0.211).Conclusion Our results indicate that SI ratio of the dominant myoma to the iliac muscle calculated using ROI in T2W images of MR studies performed before UAE procedure can predict the success of the procedure.     

Can I be sued for that? Liability risk and the disclosure of clinically significant genetic research findings

Genomic researchers increasingly are faced with difficult decisions about whether, under what circumstances, and how to return research results and significant incidental findings to study participants. Many have argued that there is an ethical—maybe even a legal—obligation to disclose significant findings under some circumstances. At the international level, over the last decade there has begun to emerge a clear legal obligation to return significant findings discovered during the course of research. However, there is no explicit legal duty to disclose in the United States. This creates legal uncertainty that may lead to unmanaged variation in practice and poor quality care. This article discusses liability risks associated with the disclosure of significant research findings for investigators in the United States.The return of individual research results and incidental findings to participants in genome research has stimulated extensive policy discussion and intense scholarly debate over the past several years. In the context of genome-wide research, it has been identified as one of the most pressing ethical challenges warranting immediate policy attention (Caulfield et al. 2008). Several professional bodies, in the United States and abroad, have published ethics recommendations suggesting an obligation to offer at least some individual research results to participants (National Bioethics Advisory Council 1999; Council for International Organizations of Medical Sciences 2002; United Nations Educational, Scientific and Cultural Organization 2003; Knoppers et al. 2006; Fabsitz et al. 2010; Office of Biorepositories and Biospecimen Research 2010; Cassa et al. 2012; World Medical Association 2013). Despite this, research suggests that genome scientists are not routinely returning research results or incidental findings to study participants (Heaney et al. 2010; Fullerton et al. 2012; McGuire et al. 2013; Ramoni et al. 2013). A survey of genome-wide association study (GWAS) investigators suggests that the fear of legal liability serves as both a motivation and a barrier to the return of results (Ramoni et al. 2013). On the one hand, investigators are concerned about their potential liability for failure to return results. In fact, Hank Greely suggests that not offering to return results may be illegal, at least in extreme circumstances where the results “pose a very high risk of a serious disease” (Greely 2007). On the other hand, investigators worry that they could be sued for adverse outcomes resulting from premature disclosure, the disclosure of inaccurate findings, or medical mismanagement resulting from disclosure. Yet, no United States regulations directly address this issue, and there is no clear case law to rely on. This creates legal uncertainty that may lead to unmanaged variation in practice and poor quality care (Wennberg 2004).This article focuses on the disclosure of research results and clinically significant incidental findings (hereinafter “significant findings”) in the context of genetic research. We do not address the equally important and controversial issue of potential liability related to disclosure of incidental findings in the clinical context. We also focus specifically on genomic research but recognize that the liability issues are similar for other areas of research, such as neuroimaging research, where investigators are likely to discover clinically significant findings in the research context. We therefore look to case law in these other areas to help inform our analysis. We limit our discussion to findings that the researcher has knowledge of. Some have argued that there is a moral duty to hunt for significant findings, at least in the clinical context (Evans 2013). For example, the American College of Medical Genetics and Genomics (ACMG) recently published “Recommendations on Incidental Findings for Clinical Exome and Genome Sequencing” (Green et al. 2013) that suggests that clinical laboratories have a duty to seek out certain genetic variants that meet a high threshold of clinical utility. The recommendations are limited explicitly to clinical sequencing, and we do not think they should apply to research because of important differences between the nature of research and clinical care, which we describe elsewhere (Clayton and McGuire 2012) and summarize below. However, the authors of the “Recommendations” recognize that they may inform the development of research standards (Green et al. 2013). To the extent that they become widely adopted by the genome research community, they could create a new standard of care.Finally, we limit our analysis to United States law. At the international level, over the last decade there has begun to emerge a clear legal obligation to return significant findings discovered during the course of research (Open in a separate window     

Can a good short form of the MMPI ever be developed?

At least seven short forms of the MMPI have been proposed in the last 15 years. In each case, the initial enthusiasm has been replaced by questions about the clinical utility of the abbreviated version. It is argued that the statistical properties of the test (high intercorrelations among scales) and reduced reliability due to shortening the scales always will produce these poor results. Our efforts would be better spent in developing new tests rather than attempting to validate new versions of a dated instrument.     

A genetic risk score for hypertension associates with the risk of ischemic stroke in a Swedish case–control study

Genetic risk scores (GRS), summing up the total effect of several single-nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS based on 29 SNPs discovered by genome-wide association studies and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other ‘traditional risk factors'', also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case–control study. Twenty-nine SNPs were genotyped in 3677 stroke cases and 2415 controls included in the Lund Stroke Register (LSR), the Malmö Diet and Cancer (MDC) study and the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The analysis was conducted in the combined sample, and separately for the three studies. After adjustment for hypertension, diabetes mellitus and smoking habits, the GRS was associated with ischemic stroke in the combined sample (OR (95% CI) 1.086 (1.029–1.147) per SD increase in the GRS P=0.003) with similar trends in all three samples: LSR (1.050 (0.967–1.140); P=0.25), MDC (1.168 (1.060–1.288); P=0.002) and SAHLSIS (1.124 (0.997–1.267); P=0.055). Measures of risk discrimination and reclassification improved marginally using the GRS. A blood pressure GRS is independently associated with ischemic stroke risk in three Swedish case–control studies, however, the effect size is low and adds marginally to prediction of stroke on top of traditional risk factors including hypertension.     

Aging of the immune system: a risk factor for autoimmunity?

Aging of the immune system, or immunosenescence, is characterized by changes in T cell subsets, cellular and molecular level alterations and thymic atrophy, resulting in a decline of T and B cell function. These alterations have been shown to be accompanied by a loss of ability to recognize "self" and "foreign" antigens. Therefore the development of autoimmune responses like production of autoantibodies has been hypothesized to be secondary to thymus involution with a decline of na?ve T cells and accumulation of clonal T cells with activation due to "neoantigens" during the aging process. Altered apoptosis and altered T cell homeostasis have been emphasized to promote a chronic inflammatory state and lead to the concept of a immune-risk phenotype. However, it has to be proven which kinds of mechanisms turn the immune system to manifest autoimmune disease and how speculated defects in T cell differentiation and interaction leading to premature aging of the immune system may contribute to the development of autoimmune diseases.     

Can Cantonese rhymes be used in the assessment of hemispheric dominance for language?

English vowels had been proposed in previous studies to be used as a simple tool for the brain mapping of language. A proper fMRI study of Cantonese rhymes, each of which being a required and fundamental unit of a Cantonese syllable, remains to be carried out. Using an auditory task with Cantonese rhymes which carry no semantic meaning, we observed a minimal amount of positive BOLD signal at the caudate nucleus when Cantonese rhymes were contrasted with their corresponding filtered sounds. Typical language activating regions of the prefrontal cortex, the medial prefrontal cortex and the lateral temporal cortex on both left and right sides were not activated by Cantonese rhymes. Based on the absence of brain activation at the typical language areas in the contrast of Cantonese rhymes relative to filtered sounds, the auditory task with Cantonese rhymes may not be a robust tool for the individual clinical assessment of hemispheric dominance for language.     

How can a cost/benefit ratio be optimized for an output measurement program of external photon radiotherapy beams?

We estimated cost/benefit ratios for different quality control programs of radiation output measurements of medical linear accelerators. The cost/benefit ratios of quality control (QC) programs (a combination of output measurement time interval and measurement action levels) were defined as workload divided by achievable dose accuracy. Dose accuracy was assumed to be inversely proportional to the 99% confidence limit of shifts of total treatment doses and workload as inversely proportional to the output measurement time interval. Our previously reported method was used to estimate the distribution of shifts of total treatment doses due to changes in accelerator radiation output (Gy/MU). The confidence limits of dose shifts were estimated for different QC programs and for different levels of output measurement reproducibility. Output shifts used in the estimations had previously been observed for four linear accelerators over 5 years. We observed that the cost/benefit ratio increases remarkably when the output measurement time interval is less than 1 month. The ratio depends strongly on the action levels and reproducibility of the QC measurements. Improvement of these factors optimizes the cost/benefit ratio by a factor of several times. The most cost-effective output measurement time interval to achieve 99% confidence limits of ±2, ±2.5 or ±3% for dose shifts ranged from 0.25 month to as much as 6 months depending on the factors given above and the intended accuracy level. It is several times more cost effective to increase dose accuracy by lowering the action levels of the QC measurements and by attempting to improve their reproducibility than by simply shortening the time interval of the output measurements. Methods improving utilization and interpretation of the results of the QC measurements play a key role in further optimization of cost/benefit ratios in dosimetric QC.     

Can parents adjust to the idea that their child is at risk for a sudden death?: Psychological impact of risk for long QT syndrome

Can a parent adjust to the idea that its child is at risk for a sudden death? This question is raised by a diagnostic procedure in which children were tested for an inherited Long QT Syndrome (LQTS). This potentially life-threatening but treatable cardiac arrhythmia syndrome may cause sudden death, especially in children and young adults. The long-term psychological effects are described for parents whose children were tested for inherited LQTS. The adverse short-term impact of such testing has been described previously. The goal of this investigation is to determine whether this distress endures. Thirty-six parents completed measures of psychological distress. With the twenty-four parents of carrier children, a semi-structured interview was held 18 months after DNA disclosure. Parents of carrier children reported more distress than parents of non-carrier children. Parents of carrier children remained vulnerable to high levels of distress; up to one-third of these parents showed clinically relevant high levels of distress. High levels of distress were reported by parents of carrier children who (1) were highly distressed at previous assessments, (2) were familiar with the disease for a longer time, (3) had experienced a sudden death in the family, (4) were lesser educated, and who (5) were unsatisfied with the given information. Parents were particularly concerned about possible hazardous behavior during puberty. We conclude that the continuous threat of developing LQTS symptoms despite prophylactic treatment affected the psychological well-being of the parents for a long time. In light of the tempetuous developments in the areas of cardiac genetics, periodical information on new insight and developments may act as a buffer for the parents' (growing) concerns about their child's inherited disorder.     

Can a transient exertion-related carotid (TERC) murmur heard during a symptom-limited exercise test be used as a means for managing sports concussion?

We hypothesize that a transient exertion-related carotid (TERC) murmur flow murmur similar in nature to a “bruit” heard best at the carotid artery during exercise in healthy individuals can be used as a means for assessing post-concussion injury exertion tolerance.Typically there are no arterial sounds heard at the carotid artery in healthy individuals. Bruit, heard at rest, is an indicator of cardiovascular disease. Listening for a flow murmur or bruit-like sounds during exercise may indicate brain blood flow autoregulation and that this audible change in brain blood flow autoregulation could be used to assess exercise tolerance.We present very preliminary evidence supporting our hypothesis in that a transient exertion-related carotid (TERC) murmur is heard at a HR (HR) of approximately 150 beats per minute (bpm) in healthy individuals and 120 bpm in concussion patients. Future prospective clinical studies to validate this hypothesis and these methods may aid clinicians who manage concussion patients by using this method to help guide exertion protocols.     

Can NSAID/ASA-induced erosions of the gastric mucosa be identified at histology?

Studies in animals have shown that NSAID/ASA-induced erosions have an ischaemic pathogenesis. We therefore studied the question of whether such erosions in human gastric biopsy material can be identified on the basis of the ischaemic necrosis. Histological sections prepared from forceps biopsy material obtained from 122 patients with erosions (at least three biopsy specimens from the erosion and two from antrum and corpus each) were classified by a pathologist blinded to the endoscopic findings and the medication used by the patients. NSAID/ASA erosions were diagnosed when a homogeneous eosinophilic ischaemic necrosis blending into the adjoining lamina propria presented. Helicobacter pylori (Hp)-induced erosions were diagnosed when, in the presence of Hp gastritis, erosive defects were covered with a non-homogeneous fibrinoid necrosis containing granulocytes and cell debris. Finally, the histological classification was compared with data on medication usage. The histological diagnosis was Hp-induced erosions in 59 patients, NSAID/ASA-induced erosions with no Hp gastritis in 23, and NSAID/ASA-induced erosions with concomitant Hp gastritis in 40. A comparison of this histological classification with the data provided by the referring physicians on patient medication revealed that 70% of the patients with histological diagnosis of NSAID/ASA-induced erosions in the absence of Hp gastritis, and 65% of those diagnosed to have NSAID/ASA-induced erosions and concomitant Hp gastritis, had been taking such drugs. Among the erosions diagnosed as H. pylori-induced, 81% of the patients were reported not to take such medication. The sensitivity of the diagnosis of NSAID/ASA-induced erosions was 72.9%, and specificity 79.6%. The results of the present study show that a high percentage of the NSAID/ASA-induced erosions of the gastric mucosa can indeed be correctly diagnosed at histology.     

Is rheumatoid arthritis a risk factor for oral bisphosphonate-induced osteonecrosis of the jaws?

Bisphosphonate-related osteonecrosis of the jaws is a relevant side-effect of these drugs that has been generating a great concern through increasing reports, worldwide, of this bone necrosis. Among several BRONJ hypothetical co-factors that could play a role in BRONJ pathogenesis, rheumatoid arthritis (RA) has been included as a relevant risk factor for BRONJ; however, until now the relationship between these diseases has not been fully explained. Thus, the purpose of this paper is to establish hypothetical factors that could link these two diseases, considering mainly inflammatory components and the organism effects of medicines used to treat RA, particularly steroids and methotrexate (MTX).     

Can the use of HIV-1 derived gene transfer vectors for clinical application be justified?

Vectors derived from human immunodeficiency virus type 1 (HIV-1) are an attractive option for many gene therapy applications as they can transduce non-cycling cell populations, and can integrate their genome into the host cell chromosome. The rationale underlying the design of most retroviral vector systems is to segregate the viral cis sequences, which are required for transfer of the viral genome, from the trans sequences that encode viral proteins. This allows the efficient production of replication incompetent virus and has been successfully applied to the generation of HIV-1 vectors. Nonetheless, the possibility that recombination events in the vector production system can generate replication-competent virus, combined with the pathogenic nature of HIV-1, raises major bio-safety issues. Numerous HIV-1 vectors have now been reported, with each generation significantly improved in ways designed to reduce the risk of replication-competent virus being produced. However, progress in vector design needs to be complemented by the development of methods for the quantitation of the probability of replication competent virus being produced. Assaying individual events in the multi-step pathway that can lead to the production of replication-competent virus, rather than relying on the detection of replication-competent virus per se, will be important for quality control purposes. This review will specifically examine the approaches to HIV-1 vector design that have been postulated as increasing bio-safety, possible methods for evaluating bio-safety and whether these approaches are likely to be sufficient to overcome resistance to the use of HIV-1 for clinical application. In addition, we discuss the possible justifications for developing vectors from lentiviruses other than HIV-1.     

Can patients’ preferences for involvement in decision-making regarding the use of medicines be predicted?

OBJECTIVE: The current study aimed to develop a model of patients' preferences for involvement in decision-making concerning the use of medicines for chronic conditions in the UK and test it in a large representative sample of patients with one of two clinical conditions. METHODS: Following a structured literature review, an instrument was developed which measured the variables that had been identified as predictors of patients' preferences for involvement in decision making in previous research. Five hundred and sixteen patients with rheumatoid arthritis or type 2 diabetes were recruited from outpatient and primary care clinics and asked to complete the instrument. RESULTS: Multivariate analysis revealed that age, social class and clinical condition were associated with preferences for involvement in decision-making concerning the use of medicines for chronic illness but gender, ethnic group, concerns about medicines, beliefs about necessity of medicines, health status, quality of life and time since diagnosis were not. In total, the fitted model explained only 14% of the variance. CONCLUSION: This study has demonstrated that current research does not provide a basis for predicting patients' preferences for involvement in decision-making. PRACTICE IMPLICATIONS: Building concordant relationships may depend on practitioners developing strategies to establish individuals' preferences for involvement in decision-making as part of the ongoing prescriber-patient relationship.