Stroke survivor attitudes toward, and motivations for, considering experimental stem cell treatments.

Purpose: Interest in stem cell treatments is increasing among some patient groups, but it is unclear whether this holds true for stroke survivors. This study examined stroke survivor attitudes toward stem cell treatments and identified a number of variables that may increase the likelihood that patients will consider these treatments.Methods: Adult stroke survivors (N = 183) were recruited (stroke advocacy/support groups, outpatient register) for a cross-sectional study. Attitudes to stem cell treatments were surveyed, guided by the Theory of Planned Behavior. Demographic information was collected, and a number of self-report medical, cognitive and psychological measures completed.Results: Twenty-five percent (n = 46) of respondents indicated they were considering undergoing stem cell treatments, although most were unsure about the safety/effectiveness and accessibility/affordability. Stroke survivors with positive attitudes toward stem cell treatments, longer post-stroke intervals, poorer physical functioning, younger age, and greater perceived caregiver burden were more likely to be considered experimental treatments (odds ratios = 1.22, 1.08, 0.95, 0.96, 1.07; respectively).Conclusions: Stroke survivors may consider undergoing experimental stem cell treatments despite uncertainty regarding the risks/benefits. Clinicians should be mindful of the factors that may increase the likelihood of patients considering these treatments and intervene, where appropriate, to clarify any misconceptions regarding the medical/financial risks.IMPLICATION FOR REHABILITATIONStem cell treatments offer a new focus for reducing stroke-related disability, although their safety and effectiveness have yet to be established.Despite uncertainty regarding the medical risks and benefits associated with stem cell injections, stroke survivors may still consider undergoing treatment in private, unregulated clinics.A number of factors, including younger age, longer post-stroke interval, poorer physical functioning, and perceived caregiver burden may place stroke survivors at an increased risk of considering these treatments.Clinicians should endeavor to educate stroke survivors regarding the risks and benefits of these experimental treatments and clarify any misconceptions, in order to reduce the likelihood that they will consider these as-yet unproven treatments.

Preliminary Screening Recommendations for Patients at Risk of Depression and/or Anxiety more than 1 year Poststroke.

GOAL: Depression and anxiety are important complications of stroke but are underdiagnosed in community settings. The current study identified which patients were at increased risk of developing either disorder more than1 year poststroke to assist in targeted screening. METHODS: Crosssectional survey of 147 adults who had a stroke more than 1 year ago were recruited from stroke advocacy/support groups and an outpatient register. Participants completed the Hospital Anxiety and Depression Scale (HADS) and reported whether they had emotional problems as a stroke inpatient (single item: yes/no). Standardized self-report measures evaluated medical (physical independence, health-related quality of life), cognitive (memory, executive functioning), and psychological (social support) variables. Demographic and stroke-related (stroke type, year) information were also recorded. FINDINGS: Between 53% and 80% of respondents (n = 117) screened positive for depressed mood and/or anxiety (HADS subscale cut-offs: ≥8 or ≥4). Logistic regression analyses indicated that stroke survivors who reported having emotional problems as inpatients (odds ratio [OR]: 0.23), were female (OR: 3.42), and had poor health-related quality of life (OR: 0.45-0.53) and cognitive problems (OR: 0.68-0.74), were more likely to screen positive for either disorder. Models based on these variables predicted screening outcomes with 91% accuracy. CONCLUSIONS: Community-based stroke survivors who reported experiencing emotional problems as inpatients, were female, or had poor health-related quality of life (chronic pain, disturbed sleep, communication difficulties) and/or cognitive issues were at greater risk of being depressed/anxious. Targeted screening of these patients may help to identify those who are most in need of more comprehensive clinical assessments and evidence-based interventions.

Cell therapies administered in the chronic phase after stroke: a meta-analysis examining safety and efficacy.

AIM: To assess the safety and efficacy of cell therapies for chronic stroke. METHODOLOGY: Five databases were searched for treatments administered >90 days post-stroke. Reporting quality, adherence to research guidelines, treatment safety (risk ratios/pooled incidence rates) and neurological/functional efficacy (Hedge's g) were all evaluated. RESULTS: Twenty-three studies examined 17 treatments. Reporting quality scores were medium to high, but adherence to recommended guidelines was lower. Three treatments resulted in serious adverse events; four improved outcomes more than standard care. However, many studies were under-powered and individual patients varied in their response to some treatments. CONCLUSION: Preliminary findings suggest that some cell therapies may be relatively safe and effective, but larger double-blinded placebo-controlled studies are needed to establish the long-term risks and benefits.

Traumatic brain injury and alcohol/substance abuse: A Bayesian meta-analysis comparing the outcomes of people with and without a history of abuse.

Alcohol and substance (drugs and/or alcohol) abuse are major risk factors for traumatic brain injury (TBI); however, it remains unclear whether outcomes differ for those with and without a history of preinjury abuse. A meta-analysis was performed to examine this issue. The PubMed, Embase, and PsycINFO databases were searched for research that compared the neuroradiological, cognitive, or psychological outcomes of adults with and without a documented history of alcohol and/or substance abuse who sustained nonpenetrating TBIs. Data from 22 studies were analyzed using a random-effects model: Hedges's g effect sizes measured the mean difference in outcomes of individuals with/without a history of preinjury abuse, and Bayes factors assessed the probability that the outcomes differed. Patients with a history of alcohol and/or substance abuse had poorer neuroradiological outcomes, including reduced hippocampal (g = -0.82) and gray matter volumes (g = -0.46 to -0.82), and enlarged cerebral ventricles (g = -0.73 to -0.80). There were limited differences in cognitive outcomes: Executive functioning (g = -0.51) and memory (g = -0.39 to -0.43) were moderately affected, but attention and reasoning were not. The findings for fine motor ability, construction, perception, general cognition, and language were inconclusive. Postinjury substance and alcohol use (g = -0.97 to -1.07) and emotional functioning (g = -0.29 to -0.44) were worse in those with a history of alcohol and/or substance abuse (psychological outcomes). This study highlighted the type and extent of post-TBI differences between persons with and without a history of alcohol or substance abuse, many of which may hamper recovery. However, variation in the criteria for premorbid abuse, limited information regarding the history of abuse, and an absence of preinjury baseline data prevented an assessment of whether the differences predated the TBI, occurred as a result of ongoing alcohol/substance abuse, or reflected the cumulative impact of alcohol/substance abuse and TBI.

Safety and efficacy of cell therapies administered in the acute and subacute stages after stroke: a meta-analysis.

AIMS: To evaluate the safety and efficacy of cell therapies administered acutely/sub-acutely after stroke. METHODS: Five databases were searched for studies examining the safety/efficacy of cell therapies administered ≤90 days post-stroke. Reporting quality and adherence to research guidelines were evaluated. Safety and efficacy were assessed using risk ratios/pooled incidence rates and Hedge's g, respectively. RESULTS: 11 therapies (Nstudies= 28) were trialed: reporting quality was high, but adherence to guidelines low. Serious adverse events were observed following five treatments; six improved outcomes. There was a trend toward larger treatment effects in non-blinded studies, younger participants, and higher dosages. CONCLUSION: Although a number of therapies appear effective, many studies did not control for normal recovery (standard-care). Long-term safety also needs to be established.

Improving detection and management of drug allergy.

Suspected adverse drug reactions may be subdivided on the basis of mechanism e.g. immunological (requiring sensitisation by previous exposure) versus nonimmunological; timing (e.g. immediate or delayed), or whether the phenomenon is dose dependent or not. In the NICE guideline the main approach is to classify the event according to whether it: is immediate (within an hour of drug administration) or delayed (hours or days); affects a single or multiple systems; is clinically severe/life threatening or not. An immediate, immunologically mediated, multisystem, life-threatening reaction would for example include anaphylaxis (type 1 or typically IgE- mediated hypersensitivity) especially if the clinical features (e.g. bronchospasm, hypotension) are suggestive. Serum mast cell tryptase should be tested ideally within two hours and certainly before four hours post reaction. Detailed investigation of suspected cases in a specialist clinic is ideally delayed for 4-6 weeks after the event. Adverse drug reactions need to be meticulously recorded and the patient fully informed. Documentation should include: date of reaction; drug name (chemical and generic); route of administration; time interval between first dose and event; and nature and severity of symptoms. Written guidance should be provided on which other chemically related drugs also need to be avoided. Specialist referral is indicated for: suspected anaphylaxis; severe/life- threatening episodes e.g. Stevens-Johnson syndrome; severe NSAID reactions with ongoing need for NSAID therapy; suspected penicillin allergy (if alternative antibiotics are not available); and problems related to general and local anaesthesia.

Food allergy testing.

Food allergy (IgE-mediated hypersensitivity) is a common clinical problem affecting approximately 15% of children in the Western world. These hypersensitivity reactions tend to be "immediate" (typically within minutes of food exposure), and clinical features may range from mild to life threatening (anaphylaxis). Detailed clinical history is critical to correct diagnosis. Available laboratory tests have limitations not least poor positive predictive value and limited repertoire. Laboratory tests should support clinical diagno sis not vice versa.

A simple immunofixation test for induced C3 degradation in disease states (including C3 nephritic factor) and its correlation with kidney biopsy.

Complement dysregulation from an uncontrolled activation of the alternate pathway can be mediated by C3 Nephritic Factor and results in C3 glomerulopathy. Identification of C3 degradation products C3c and C3d in patient serum provides evidence of uncontrolled complement activation. It is possible to detect C3c and C3d in patient serum by an immunofixation assay which induces in vitro C3 degradation. The clinical performance of the immunofixation assay has been assessed by comparing the assay results with findings from immunostaining of kidney biopsies. The immunofixation assay is a simple and reliable technique for detection of C3 degradation on a widely available platform and can be used to provide corroborative evidence of acquired complement dysregulation in patients with C3 glomerulopathy.

Following up patients after treatment for anaphylaxis.

Anaphylaxis is defined as a severe, life-threatening, generalised or systemic hypersensitivity reaction. Diagnosis is based on the presenting symptoms and signs which classically develop rapidly, typically evolving over minutes but in some cases hours. Various combinations of airway and/or breathing and/or circulatory problems are possible, as well as urticaria, and hypotension. Skin and/or mucosal changes (typically urticaria and/or angioedema) are seen in around 75% of cases, but importantly these features alone are insufficient for a diagnosis of anaphylaxis. As soon as possible after successful emergency treatment, timed blood samples should be taken for the mast cell tryptase (MCT) test. Serum samples need to be taken within 1-2 hours but no later than 4 hours from the onset of symptoms. It is important to document the acute clinical features (record BP, respiratory rate etc) and the time course of the onset of symptoms/signs and their resolution. Because of the risk of relapse patients should be observed for 6-12 hours after the onset of symptoms. Children under 16 years should be admitted and supervised by a paediatrician. An adrenaline injector device for intramuscular use only, should be prescribed as an interim measure before referral to a specialist allergy clinic. Referral to a specialist allergy service (or specialist paediatric service), is strongly recommended. Diagnosis can be confirmed, and further investigations organised.

Immunoglobulin E deficiency: a forgotten clue pointing to possible immunodeficiency?

BACKGROUND: Patients with primary antibody deficiency often have delayed diagnosis. Very low IgE, found during investigations for allergy, may be a marker for other immunodeficiency. METHODS: We introduced a new laboratory policy of testing cases with very low IgE levels for possible linked antibody deficiency. The data represent an audit of routine results collected over two years. RESULTS: Very low IgE (≤2 IU/mL) was identified in 85/2622 (3.2%) routine patient samples. Two children and four adult patients were found to have one or more classes of immunoglobulin below the reference range for age. In 2/6, the initiative of the laboratory led to a new unsuspected diagnosis of antibody immunodeficiency. CONCLUSIONS: Common variable immunodeficiency continues to be overlooked as a primary cause of lung disease in adults. Very low serum IgE should trigger appropriate investigation (immunoglobulin quantification and serum electrophoresis).

Food allergy: which tests are worth doing and which are not?

Adverse reactions to foods may arise by a variety of mechanisms, both immune (IgE and non-IgE) and non-immune mediated. This article considers those assays useful in the diagnosis of Type 1 hypersensitivity to foods (IgE-based) and, importantly, discusses those assays where evidence is lacking for their use. In all cases of suspected food allergy, a full clinical history is indispensable in facilitating diagnosis. Total serum IgE is not a suitable screen for food allergy. Suspect allergens may be confirmed by either skin prick testing or serological assays for specific IgE. Several studies suggest concentrations of food-specific IgE at which there is a high probability of reaction on food challenge. These cut-off levels are now being used by physicians to direct clinical advice. However, it is important to note that not all studies agree on these limits and the chosen cut-off is dependent on the population studied and the assay used.

Cerebellar ataxia, peripheral neuropathy, "gluten sensitivity" and anti-neuronal autoantibodies.

"Gluten sensitive" neurological syndromes (ataxia, peripheral neuropathy, and other conditions) have been hypothesised in patients with various idiopathic neuropathologies, detectable anti-gliadin antibodies and HLA-DQ2 or DQ7. Further investigation of these cases has suggested a high incidence of anti-neuronal antibodies (anti-Purkinje, anti- neuronal nuclear, anti-GAD). This study investigates this contentious area. Over a two-year period, from a local UK population base of two million, seeing over 5000 general neurology referrals per year, we collected 20 cases with idiopathic ataxia, and 32 with idiopathic peripheral neuropathy, and referred them all for blinded antibody testing. 30 adult healthy blood donors, and 7 cases of hereditary ataxia were used as control subjects. Anti-gliadin antibodies (IgG and or IgA) were found in 40% of cases with idiopathic ataxia, 34% with idiopathic peripheral neuropathy, 17% healthy blood donors and 43% with hereditary ataxia. None was positive for antiPurkinje cell or anti-neuronal nuclear antibodies. Only two patients with idiopathic ataxia were positive for antiGAD antibodies (one also being anti-gliadin positive). We were unable to confirm the findings of other groups. First, cases of so-called "gluten sensitive" neurological syndromes were extremely rare in our centre. Second, our idiopathic cases, whether they be gliadin antibody seropositive or not (i.e. "gluten sensitive" or not) were rarely neuronal autoantibody positive.

Celiac disease with mild to moderate histologic changes is a common cause of chronic diarrhea in Indian children.

OBJECTIVES: In developed countries, small bowel histology in coeliac disease is a spectrum, ranging from normal with increased intraepithelial lymphocytes to the classic flat mucosa. In developing countries, mild to moderate enteropathies in children with chronic diarrhea and growth failure are assumed to be caused by tropical sprue, persistent infections, or malnutrition with bacterial overgrowth. We report the prevalence and histology of coeliac disease in children with chronic diarrhea at a tertiary referral hospital in North India. METHODS: Two hundred fifty-nine children with symptoms indicating coeliac disease attended the All India Institute of Medical Sciences. Histology was graded after a modified Marsh classification. Serum immunoglobulin A anti-endomysial antibodies (AEA) were assayed using indirect immunofluorescence. Subjects with abnormal histology and positive AEA were put on a gluten free diet (GFD). Coeliac disease was diagnosed on small intestinal biopsy changes and a clinical response to a GFD. RESULTS: Severe enteropathies were present in 63 (24%) subjects, and 58 (92%) responded to a GFD. Sixty-six (25%) had moderate histologic changes, 61 responding to a GFD. AEA was positive in 56 of 63 patients with severe and 65 of 66 with moderate enteropathies. Fifty-seven children had mild enteropathies, and 19 of 20 with positive AEA responded clinically to a GFD. CONCLUSIONS: Coeliac disease is more common than previously believed. It presents a variable histology, and diagnoses may be missed or delayed if based only on severe enteropathies. Serology is a useful adjunct to diagnosis, and diagnostic criteria need to be developed appropriately for coeliac disease in developing countries despite limited facilities.