Search

Optimizing the treatment of disabling spasticity in persons with spinal cord damage is hampered by a lack of consensus regarding the use of acceptable definitions of spasticity and disabling spasticity, and the relative absence of decision tools such as clinical guidelines and concise algorithms to support decision-making within the broader clinical community. Many people with spinal cord damage are managed outside specialist centers, and variations in practice result in unequal access to best practice despite equal need. In order to address these issues, the Ability Network-an international panel of clinical experts-was initiated to develop management algorithms to guide and standardize the assessment, treatment, and evaluation of outcomes of persons with spinal cord damage and disabling spasticity. To achieve this, consensus was sought on common definitions through facilitated, in-person meetings. To guide patient selection, an in-depth review of the available tools was performed and expert consensus sought to develop an appropriate instrument. Literature reviews are guiding the selection and development of tools to evaluate treatment outcomes (body functions, activity, participation, quality of life) as perceived by people with spinal cord damage and disabling spasticity, and their caregivers and clinicians. Using this approach, the Ability Network aims to facilitate treatment decisions that take into account the following: the impact of disabling spasticity on health status, patient preferences, treatment goals, tolerance for adverse events, and in cases of totally dependent persons, caregiver burden.

Background Bioethicists argue that inclusion of pregnant women in clinical research should be more routine to increase the evidence-base for pregnant women and foetuses. Yet, it is unknown whether pregnant women and others directly involved are willing to be routinely included. Therefore, we first need to establish what these stakeholders think about research participation in regular pregnancy-related research. However, studies on their views are scarce. In our study, we piggy-backed on a relatively conventional RCT, the APOSTEL VI study, to identify the views of stakeholders on inclusion of pregnant women in this study. Methods We conducted a prospective qualitative study using 35 in-depth semi-structured interviews and one focus group. We interviewed pregnant women (n = 14) recruited for the APOSTEL VI study, in addition to healthcare professionals (n = 14), Research Ethics Committee members (RECs) (n = 5) and regulators (n = 7) involved in clinical research in pregnant women. Results Three themes characterise stakeholders’ views on inclusion of pregnant women in the APOSTEL VI study. Additionally, one theme characterises stakeholders’ interest in inclusion of pregnant women in clinical research in general. First, pregnant women participate in the APOSTEL VI study for potential individual benefit and secondarily for altruistic motives, contrary to hypothetical studies. Second, a gatekeeping tendency hampers recruitment of pregnant women who might be eligible and willing, and questions about pregnant women’s decisional capacities surface. Third, healthcare professionals sometimes use the counselling conversation to steer pregnant women in a direction. Fourth, all stakeholders are hesitant about inclusion of pregnant women in clinical research in general due to a protective sentiment. Conclusions Pregnant women are willing to participate in the APOSTEL VI study for potential individual benefit and altruistic motives. However, an underlying protective sentiment, resulting in gatekeeping and directive counselling, sometimes hampers recruitment in the APOSTEL VI study as well as in clinical research in general. While bioethicists claim that inclusion of pregnant women should be customary, our study indicates that healthcare professionals, regulators, RECs and pregnant women themselves are not necessarily interested in inclusion. Advancing the situation and increasing the evidence-base for pregnant women and foetuses may require additional measures such as investing in the recruitment and feasibility of RCTs and stimulating pregnant women’s decisional capacities. Electronic supplementary material The online version of this article (10.1186/s12884-019-2209-7) contains supplementary material, which is available to authorized users.

The decision to stop the STRIDER trial with sildenafil (better known as Viagra) to improve uteroplacental blood flow, fetal growth, and infant outcomes for fetuses with severe growth restriction was disappointing for all involved.1 International media extensively reported on this trial, triggering debates in academic journals and (social) media.234 But one aspect remains neglected: …

Emerging data suggest that pediatric traumatic brain injury (TBI) is associated with impaired developmental plasticity and poorer neuropsychological outcomes than adults with similar head injuries. Unlike adult mild TBI (mTBI), the effects of mTBI on white matter (WM) microstructure and vascular supply are not well understood in the pediatric population. The cerebral vasculature plays an important role providing necessary nutrients and removing waste. To address this critical element, we examined the microstructure of the corpus callosum (CC) following pediatric mTBI using diffusion tensor magnetic resonance imaging (DTI), and investigated myelin, oligodendrocytes, and vasculature of WM with immunohistochemistry (IHC). We hypothesized that pediatric mTBI leads to abnormal WM microstructure and impacts the vasculature within the CC, and that these alterations to WM vasculature contribute to the long-term altered microstructure. We induced in mice a closed-head injury (CHI) mTBI at post-natal day (P) 14; then at 4, 14, and 60 days post-injury (DPI) mice were sacrificed for analysis. We observed persistent changes in apparent diffusion coefficient (ADC) within the ipsilateral CC following mTBI, indicating microstructural changes, but surprisingly changes in myelin and oligodendrocyte densities were minimal. However, vascular features of the ipsilateral CC such as vessel density, length, and number of junctions were persistently altered following mTBI. Correlative analysis showed a strong inverse relationship between ADC and vessel density at 60 DPI, suggesting increased vessel density following mTBI may restrict WM diffusion characteristics. Our findings suggest that WM vasculature contributes to the long-term microstructural changes within the ipsilateral CC following mTBI.

Evidence-based treatment for pregnant women will ultimately require research conducted in the population of pregnant women. Currently, few scholars have addressed the issue of responsible inclusion of pregnant women in drug research. Because of additional risks associated with including pregnant women in drug research and the altered ways in which drugs are processed by the pregnant body, pregnant women cannot be treated as an ordinary subgroup in the various phases of drug development. Instead, responsible inclusion of pregnant women requires careful design and planning of research for pregnant women specifically. Knowledge about these aspects is virtually nonexistent. In this article, we present a practical framework for the responsible inclusion of pregnant women in drug development. We suggest that the framework consists of using a question-based approach with five key questions in combination with three prerequisites which should be addressed when considering inclusion of pregnant women in drug research. The five questions are:A. Can we consider the drug safe (enough) for first exposure in pregnant women and fetuses? B. In which dose range (potentially depending on gestational age) can the drug be considered to remain safe in pregnant women? C. At what dose (regimen, within the range considered safe) can we expect efficacy in pregnant women? D. Can efficacy be confirmed at the target dose, either similar to the initial population or different? E. Can clinical safety be confirmed at a sufficiently acceptable level at the target dose for pregnant women and fetuses, so as to conclude a positive benefit–risk ratio? Combining questions and prerequisites leads to a scheme for appropriate timing of responsible inclusion of pregnant women in drug research. Accordingly, we explore several research design options for including pregnant women in drug trials that are feasible within the framework. Ultimately, the framework may lead to (i) earlier inclusion of pregnant women in drug development, (ii) ensuring that key prerequisites, such as proper dosing, are addressed before more substantial numbers of pregnant women are included in trials, and (iii) optimal use of safety and efficacy data from the initial (nonpregnant) population throughout the drug development process.

Background Since pregnant women are severely underrepresented in clinical research, many take the position that the exclusion of pregnant women from research must be justified unless there are compelling “scientific reasons” for their exclusion. However, it is questionable whether this approach renders research with pregnant women fair. This paper analyzes and evaluates when research with pregnant women can be considered as fair and what constitutes scientific reasons for exclusion. Methods Conceptual ethical and methodological analysis and evaluation of fair inclusion. Results Fair inclusion of pregnant women means (1) that pregnant women who are eligible are not excluded solely for being pregnant and (2) that the research interests of pregnant women are prioritized, meaning that they ought to receive substantially more attention. Fairness does not imply that pregnant women should be included in virtually every research project, as including only a few pregnant women in a population consisting only of women will not help to determine the effectiveness and safety of a treatment in pregnant women. Separate trials in pregnant women may be preferable once we assume, or know, that effects of interventions in pregnant women differ from the effects in other subpopulations, or when we assume, or know, that there are no differences. In the latter case, it may be preferable to conduct post-marketing studies or establish registries. If there is no conclusive evidence indicating either differences or equivalence of effects between pregnant and non-pregnant women, yet it seems unlikely that major differences or exact equivalence exist, the inclusion of pregnant women should be sufficient. Depending on the research question, this boils down to representativeness in terms of the proportion of pregnant and non-pregnant women, or to oversampling pregnant women. Conclusions Fair inclusion of pregnant women in research implies that separate trials in pregnant women should be promoted. Inclusion of pregnant women has to be realized at the earliest phases of the research process. In addition to researchers and research ethics committees, scientific advisory councils, funders, drug regulatory agencies, pharmaceutical companies, journal editors and others have a joint responsibility to further develop the evidence base for drug use in pregnant women.

Baleen whales (Mysticeti) are known to use low frequencies (LF; 200 Hz and below) and infrasound ( 20 kHz), reach low frequencies. Researchers have tried to understand the evolution of LF and infrasonic hearing in mysticetes by linking the shape of the inner ear cochlea or individual cochlear measurements to known hearing frequencies and making inferences to extinct species. Using landmark-based shape analysis of complete cochlear coiling, we show that cochlear coiling shape correlates with LF and high-frequency (HF; > 10 kHz) hearing limits in cetaceans. Very LF (≤ 50 Hz) and infrasonic hearing are associated with, for example, a protruding second turn, a descending apex, and a high number of turns. Correlations between cochlear and cranial variables and cochlear and cranial shape indicate that low LF hearing limits are furthermore connected to longer cochleae and relatively larger cranial widths. Very LF hearing in Mysticeti appeared in the middle Miocene, and mysticete infrasonic hearing had evolved by the late Miocene. Complete cochlear coiling is suitable for estimating hearing limits in cetaceans, closely approximated by cochlear length times number of cochlear turns.

As early as 2002, CIOMS stated that pregnant women should be presumed eligible for participation in research. Despite this position and calls of other well‐recognized organizations, the health needs of pregnant women in research remain grossly under‐researched. Although the presumption of eligibility remains unchanged, the revision of the 2002 CIOMS International ethical guidelines for biomedical research involving human subjects involved a substantive rewrite of the guidance on research with pregnant women and related guidelines, such as those on fair inclusion and vulnerability. However, close reading of the guidelines reveals morally relevant different approaches to fair inclusion of pregnant women and other under‐represented groups, such as children and incompetents. Where CIOMS sets out that children and adolescents must be included unless a good scientific reason justifies their exclusion, no such claim of having to justify exclusion appears in the guideline on pregnant women. Instead, CIOMS claims that research relevant to pregnant women’s health needs must be promoted. This paper analyses how and to what extent the guideline on pregnant women differs from other guidance on fair inclusion in the document. Accordingly, the paper evaluates to what extent the current phrasing may contribute to fair inclusion of pregnant women in research. We will conclude that a system change towards a learning health system is essential to break down the status quo of knowledge generation in the field of medication use during pregnancy and argue that the CIOMS guidelines allow for this system change.

The recognition, evaluation, and management of disabling spasticity in persons with spinal cord damage (SCD) is a challenge for health care professionals, institutions, health systems, and patients. To guide the assessment and management of disabling spasticity in individuals with SCD, the Ability Network, an international panel of clinical experts, developed a clinical care pathway. The aim of this pathway is to facilitate treatment decisions that take into account the effect of disabling spasticity on health status, individual preferences and treatment goals, tolerance for adverse events, and burden on caregivers. The pathway emphasizes a patient-centered, individualized approach and the need for interdisciplinary coordination of care, patient involvement in goal setting, and the use of assessment and outcome measures that lend themselves to practical application in the clinic. The clinical care pathway is intended for use by health care professionals who provide care for persons with SCD and disabling spasticity in various settings. Barriers to optimal spasticity management in these people are also discussed. There is an urgent need for the clinical community to clarify and overcome barriers (knowledge-based, organizational, health system) to optimizing the management of spasticity in people with SCD. (C) 2017 by the American Congress of Rehabilitation Medicine

The DNA vaccine, AV-1959D, targeting N-terminal epitope of Aβ peptide, has been proven immunogenic in mice, rabbits, and non-human primates, while its therapeutic efficacy has been shown in mouse models of Alzheimer's disease (AD). Here we report for the first time on IND-enabling biodistribution and safety/toxicology studies of cGMP-grade AV-1959D vaccine in the Tg2576 mouse model of AD. We also tested acute neuropathology safety profiles of AV-1959D in another AD disease model, Tg-SwDI mice with established vascular and parenchymal Aβ pathology in a pre-clinical translational study. Biodistribution studies two days after the injection demonstrated high copy numbers of AV-1959D plasmid after single immunization of Tg2576 mice at the injection sites but not in the tissues of distant organs. Plasmids persisted at the injection sites of some mice 60 days after vaccination. In Tg2576 mice with established amyloid pathology, we did not observe short- or long-term toxicities after multiple immunizations with three doses of AV-1959D. Assessment of the repeated dose acute safety of AV-1959D in cerebral amyloid angiopathy (CAA) prone Tg-SwDI mice did not reveal any immunotherapy-induced vasogenic edema detected by magnetic resonance imaging (MRI) or increased microhemorrhages. Multiple immunizations of Tg-SwDI mice with AV-1959D did not induce T and B cell infiltration, glial activation, vascular deposition of Aβ, or neuronal degeneration (necrosis and apoptosis) greater than that in the control group determined by immunohistochemistry of brain tissues. Taken together, the safety data from two different mouse models of AD substantiate a favorable safety profile of the cGMP grade AV-1959D vaccine supporting its progression to first-in-human clinical trials.

Aim: This study aimed to evaluate the effectiveness of soya bean supplementation on nutritional status of schoolchildren available in selected schools of Nellore, Andhra Pradesh. Methodology: A True –Experimental study was conducted in Z.P.H.School, located in T.P.Gudur, at Nellore District. Sample sizes of 60 school age children were selected by using stratified random sampling technique. Anthropometric measurements, food frequency questionnaire and 24 hours dietary recall were used to assess the nutritional status of a child. Results &Conclusion: The results reveal that with regard to nutritional status, in experimental group, during pre test, 22 (73.3%) had normal weight, 8 (26.7%) had Grade-I malnutrition whereas in post test, 29 (96.7%) had normal weight and 1(3.3%) had Grade-I malnutrition. In control group, during pre test 23 (76.6%) had normal weight, 7 (23.4%) had Grade-I malnutrition whereas in post test, 24 (80%) had normal weight and 6 (20%) had Grade-I malnutrition. The study concludes that the soya bean supplementation is effective in improving nutrition status in aspects of weight, skin fold thickness among school children.

Background/aim: Chemotherapy for intraocular retinoblastoma is used to shrink individual retinal tumours to a size amenable to focal treatments. Quantitative data regarding retinal tumour response following treatment with primary systemic carboplatin are reported. Methods: Changes in area and largest basal diameter of tumours that were exposed to carboplatin, had no concomitant focal treatment, and had digital funduscopic photography performed before and after treatment, were measured. Response was evaluated. Results: 36 tumours were measured following one treatment: 34/36 (94.4%) responded, with a 37.1% mean decrease in area (median = 37.0%; range 4.0%–76.7%). Mean reduction in basal diameter was 21.3% (med = 21.0%; −7.9%–52.5%). 20 tumours were treated with a second cycle: 15/20 (75.0%) responded. Mean decrease in area was 17.8% (med = 15.3%; −7.0%–49.7%). The mean cumulative decrease in area after two treatments was 55.1% (med = 56.2%; 33.0%–74.5%). Mean cumulative reduction in basal diameter was 33.6% (med = 33.6%; 10.9%–53.2%). 12 tumours were treated with a third cycle: 3/12 (25.0%) responded, 8/12 were stable, and one progressed. Mean decrease in area was 5.4% (med = 7.2%; −17.7%–20.6%). Cumulative decrease in area after three treatments was 58.1% (med = 57.3%; 34.8%–77.2%). Mean cumulative reduction in basal diameter was 38.8% (med = 38.2%; 19.1%–54.1%). Conclusions: Carboplatin caused measurable shrinkage of retinoblastoma tumours. Response was greatest following the initial treatment and decreased with subsequent treatments.

Background Notwithstanding the need to produce evidence-based knowledge on medications for pregnant women, they remain underrepresented in clinical research. Sometimes they are excluded because of their supposed vulnerability, but there are no universally accepted criteria for considering pregnant women as vulnerable. Our aim was to explore whether and if so to what extent pregnant women are vulnerable as research subjects. Method We performed a conceptual and empirical analysis of vulnerability applied to pregnant women. Analysis A conceptual analysis supports Hurst9s definition of vulnerability. Consequently, we argue that pregnant women are vulnerable if they encounter an identifiably increased likelihood of incurring additional or greater wrong. According to the literature, this increased likelihood could exist of four alleged features for pregnant women9s vulnerability: (i) informed consent, (ii) susceptibility to coercion, (iii) higher exposure to risk due to lack of knowledge, (iv) vulnerability of the fetus. Discussion Testing the features against Hurst9s definition demonstrates that they all concern the same issue: pregnant women are only vulnerable because a higher exposure to risk due to lack of scientific knowledge comprises an increased wrong. Research Ethics Committees have a responsibility to protect the vulnerable, but a higher exposure to risk due to lack of scientific knowledge is a much broader issue and also needs to be addressed by other stakeholders. Conclusions The only reason why pregnant women are potentially vulnerable is to the extent that they are increasingly exposed to higher risks due to a lack of scientific knowledge. Accordingly, the discussion can advance to the development of practical strategies to promote fair inclusion of pregnant women in clinical research.

Respiratory complications are a leading cause of morbidity and mortality during the acute and chronic phases after spinal cord injury (SCI). This article reviews the respiratory impairments resulting from SCI and discusses a range of management strategies to be considered from the acute care phase through long-term follow up. The treatment of specific complications and preventive measures are reviewed.

Background Congenital hemangiomas are benign abnormal proliferation of blood vessels. Noninvoluting congenital hemangiomas are a rare variant which persist, and may become bigger. Hemangiomas are known to be associated with thrombocytopenia, microangiopathic hemolytic anemia and Kasabach-Merritt phenomenon. Kasabach-Merritt phenomenon is characterized by consumptive coagulopathy with microangiopathic haemolyic anemia and thrombocytopenia. Platelet sequestration in the hemangioma or increased destruction which may either be immune or non immune are also further contributors to thrombocytopenia. Case presentation A 45 year old female with a non involuting hemangioma and baseline thrombocytopenia was observed to develop repeated episodes of transient severe thrombocytopenia associated with a variety of infectious conditions. Laboratory investigations suggested a peripheral mechanism. Platelet counts always returned to baseline levels on resolution of the precipitating infection. Conclusion The authors report this phenomenon as the first reported case of baseline thrombocytopenia complicated by recurrent episodes of transient severe thrombocytopenia following infections associated with a non involuting congenital hemangioma. The observations made in this patient were unique and hitherto unreported in medical literature. Both peripheral sequestration and destructive consumption were considered likely. Consumptive mechanisms were likely to encompass either or both immune and non immune causes. Further studies are needed to establish the precise pathogenesis.

Cardiovascular diseases are the emerging causes of the mortality which is looming large in India also. Particularly, the Indian populations are genetically more susceptible to them [1]. Dyslipidaemia (especially high LDL-C levels) is the promoter of atherosclerosis, whereas the HDL-C fraction is protective [2]. The oxidatively modified LDL associated conversion of macrophages to foam cells is reportedly atherogenic [3]. The pro-inflammatory oxidative milieu favours this process [4]. The dyslipidaemia associated acute phase response was shown to develop a pro-inflammatory state which promoted atherosclerosis [5, 6]. The usual practice of assaying the entire lipid profile may not be cost effective for predicting the cardiovascular risk burden. Oxidized-LDL and/or malondialdehyde modified-LDL, appear as informative markers [7]. However, technically, they do not appear to be suitable for a routine clinical laboratory setting. Hence, there is an ardent need of reasonably effective and affordable tests. In this study, the plasma lipid profile parameters, namely HDL-C (high density lipoprotein), LDL-C (low density lipoprotein), TG (triglyceride) and TC (total cholesterol) were assessed in both myocardial infarction (MI) cases and in healthy controls; each parameter was correlated with the lipid peroxidative parameter, MDA to find out any possible single parameter which was most closely associated with its oxidative pathology, so as to draw any meaningful association for prognostic purposes. A case cohort was formed by selecting 42 clinically as well as electrocardiographically confirmed and previously untreated cases of MI (median age 58 years). Diabetes Mellitus, or any other major diseases and a past history of smoking were ruled out. Similarly, an age and sex matched cohort was formed by selecting 38 healthy volunteers from among the hospital staff (median age 54 years). Plasma samples were collected from all the individuals of both the groups after taking informed consents from them. The patients’ samples were collected within 12 hours of their admissions. Their lipid profiles, along with the direct LDL measurements, were assessed by using commercial kits as per the manufacturer’s protocol. The MDA estimation was done by a spectrophotometric method [8]. Except for HDL-C which was found to be significantly low in the cases, the mean levels of the lipid profile parameters in the cases were significantly high as compared to those in the corresponding control group; the MDA levels were also found to be significantly high among the cases [Table/Fig-1]. This showed a marked dyslipidaemia in the patient populace. Pearson’s correlation analysis showed a high degree of positive correlation between MDA and TC and also with LDL cholesterol (r = 0.79 and 0.72 respectively) in the MI cases. The positive correlation between MDA and the TG level was not comparably high. Similarly, the negative correlation between HDL-C and the MDA level was also not very significant. The control group parameters did not show any significant correlations. This result conformed to the view of the oxidative pathology being associated with such metabolic abnormalities. Total cholesterol and LDL-C, being significantly associated with lipid peroxidation in the cases, suggested a direct contribution of these fractions in the pathogenesis. However, in the general practice, LDL-C is calculated from the Friedwald’s formula and it may thus incorporate considerable error [9]. Moreover, the highest correlation value was observed between total cholesterol and MDA. This finding corroborated with that of an earlier study which reported a relative risk predictive efficacy of TC, which showed its direct association with the mortality in coronary heart disease [10, 11]. Hence, with the perspective of this small scale pilot type study (considering the huge prevalence of cardiovascular diseases in the general population), total cholesterol alone, as a single parameter, demands a large-scale multi-centric trial for being considered as an effective and an economic option for the prediction of the severity of cardiovascular health hazards in the MI cases. [Table/Fig-1]: Comparative display of lipid Profile parameters and malondialdehyde (MDA) in MI patients and control groups

With the growth of wheelchair athletics at both grassroots and national levels, there has been an increased incidence of sports-related and overuse syndromes in the wheelchair-user population. This article provides an overview of the available literature on the incidence, prevalence, evaluation, prevention, and rehabilitative management of these types of clinical syndromes.

Purpose To report on the treatment of primary mucosa-associated lymphoid tumors (MALT)/low grade lymphomas of the conjunctiva/orbit treated solely with systemic antibiotics. Design Retrospective interventional case series. Methods Three adult patients with biopsy/marker proven MALT lymphomas of the conjunctiva/orbit were treated with systemic antibiotics and followed for signs of local or systemic relapse. Results All three patients showed a response to antibiotics based on clinical, ultrasonographic, and MRI/CT imaging studies. Two patients have had complete remissions (42 months follow-up) and one a partial remission (18 months). No systemic relapses have occurred. Conclusion MALT/low grade lymphomas of the conjunctiva/orbit respond to systemic antibiotic therapy and may have complete remissions.

Purpose To InternetAdvance publication at ajo.com Feb 26, 2002. investigate the effect of photodynamic therapy using verteporfin on choroidal melanoma. Design Interventional case series. Methods Four patients with choroidal melanoma who showed recurrence or no response after previous brachytherapy and transpupillary thermotherapy were treated with photodynamic therapy. Results One tumor decreased in size and remained stable for 18 months. One tumor had no growth for 11 months. Two melanomas continued to grow, necessitating enucleation. Conclusion Of the four eyes that had failed conventional therapies, two would have been salvaged (to date) with photodynamic therapy. However, additional studies are needed to determine if photodynamic therapy can play a role in the management of choroidal melanoma.