38 research outputs found
Factors influencing child protection professionals' decision-making and multidisciplinary collaboration in suspected abusive head trauma cases: a qualitative study
Clinicians face unique challenges when assessing suspected child abuse cases. The majority of the literature exploring diagnostic decision-making in this field is anecdotal or survey-based and there is a lack of studies exploring decision-making around suspected abusive head trauma (AHT). We aimed to determine factors influencing decision-making and multidisciplinary collaboration in suspected AHT cases, amongst 56 child protection professionals. Semi-structured interviews were conducted with clinicians (25), child protection social workers (10), legal practitioners (9, including 4 judges), police officers (8), and pathologists (4), purposively sampled across southwest United Kingdom. Interviews were recorded, transcribed and imported into NVivo for thematic analysis (38% double-coded). We identified six themes influencing decision-making: ‘professional’, ‘medical’, ‘circumstantial’, ‘family’, ‘psychological’ and ‘legal’ factors. Participants diagnose AHT based on clinical features, the history, and the social history, after excluding potential differential diagnoses. Participants find these cases emotionally challenging but are aware of potential biases in their evaluations and strive to overcome these. Barriers to decision-making include lack of experience, uncertainty, the impact on the family, the pressure of making the correct diagnosis, and disagreements between professionals. Legal barriers include alternative theories of causation proposed in court. Facilitators include support from colleagues and knowledge of the evidence-base. Participants’ experiences with multidisciplinary collaboration are generally positive, however child protection social workers and police officers are heavily reliant on clinicians to guide their decision-making, suggesting the need for training on the medical aspects of physical abuse for these professionals and multidisciplinary training that provides knowledge about the roles of each agency
Acceptability of the Predicting Abusive Head Trauma (PredAHT) clinical prediction tool: A qualitative study with child protection professionals
The validated Predicting Abusive Head Trauma (PredAHT) tool estimates the probability of abusive head trauma (AHT) based on combinations of six clinical features: head/neck bruising; apnea; seizures; rib/long-bone fractures; retinal hemorrhages. We aimed to determine the acceptability of PredAHT to child protection professionals. We conducted qualitative semi-structured interviews with 56 participants: clinicians (25), child protection social workers (10), legal practitioners (9, including 4 judges), police officers (8), and pathologists (4), purposively sampled across southwest United Kingdom. Interviews were recorded, transcribed and imported into NVivo for thematic analysis (38% double-coded). We explored participants’ evaluations of PredAHT, their opinions about the optimal way to present the calculated probabilities, and their interpretation of probabilities in the context of suspected AHT. Clinicians, child protection social workers and police thought PredAHT would be beneficial as an objective adjunct to their professional judgment, to give them greater confidence in their decisions. Lawyers and pathologists appreciated its value for prompting multidisciplinary investigations, but were uncertain of its usefulness in court. Perceived disadvantages included: possible over-reliance and false reassurance from a low score. Interpretations regarding which percentages equate to ‘low’, ‘medium’ or ‘high’ likelihood of AHT varied; participants preferred a precise % probability over these general terms. Participants would use PredAHT with provisos: if they received multi-agency training to define accepted risk thresholds for consistent interpretation; with knowledge of its development; if it was accepted by colleagues. PredAHT may therefore increase professionals’ confidence in their decision-making when investigating suspected AHT, but may be of less value in court
Interprofessional education in geriatric medicine: towards best practice. A controlled before-after study of medical and nursing students
Objectives. To investigate nursing and medical students’ readiness for interprofessional learning before and after implementing geriatric interprofessional education (IPE), based on problem-based learning (PBL) case scenarios. To define the optimal number of geriatric IPE sessions, the size and the ratio of participants from each profession in the learner groups, the outcomes related to the Kirkpatrick four-level typology of learning evaluation, students’ concerns about joint learning and impact of geriatric IPE on these concerns. The study looked at the perception of roles and expertise of the ‘other’ profession in interprofessional teams, and students’ choice of topics for future sessions. Students’ expectations, experience, learning points and the influence on the understanding of IP collaboration, as well as their readiness to participate in such education again were investigated.
Design. A controlled before–after study (2014/2015, 2015/2016) with data collected immediately before and after the intervention period. Study includes additional comparison of the results from the intervention with a control group of students. Outcomes were determined with a validated ‘Readiness for Interprofessional Learning’ questionnaire, to which we added questions with free comments, combining quantitative and qualitative research methods. The teaching sessions were facilitated by experienced practitioners/educators, so each group had both, a clinician (either geratology consultant or registrar) and a senior nurse.
Participants. 300 medical, 150 nursing students.
Setting. Tertiary care university teaching hospital.
Results. Analysis of the returned forms in the intervention group had shown that nursing students scored higher on teamwork and collaboration post-IPE (M=40.78, SD=4.05) than pre-IPE (M=34.59, SD=10.36)—statistically significant. On negative professional identity, they scored lower post-IPE (M=7.21, SD=4.2) than pre-IPE (M=8.46, SD=4.1)—statistically significant. The higher score on positive professional identity post-IPE (M=16.43, SD=2.76) than pre-IPE (M=14.32, SD=4.59) was also statistically significant. Likewise, the lower score on roles and responsibilities post-IPE (M=5.41, SD=1.63) than pre-IPE (M=6.84, SD=2.75).
Medical students scored higher on teamwork and collaboration post-IPE (M=36.66, SD=5.1) than pre-IPE (M=32.68, SD=7.4)—statistically significant. Higher positive professional identity post-IPE (M=14.3, SD=3.2) than pre-IPE (M=13.1, SD=4.31)—statistically significant. The lower negative professional identity post-IPE (M=7.6, SD=3.17) than pre-IPE (M=8.36, SD=2.91) was not statistically significant. Nor was the post-IPE difference over roles and responsibilities (M=7.4, SD=1.85), pre-IPE (M=7.85, SD=2.1).
In the control group, medical students scored higher for teamwork and collaboration post-IPE (M=36.07, SD=3.8) than pre-IPE (M=33.95, SD=3.37)—statistically significant, same for positive professional identity post-IPE (M=13.74, SD=2.64), pre-IPE (M=12.8, SD=2.29), while negative professional identity post-IPE (M=8.48, SD=2.52), pre-IPE (M=9, SD=2.07), and roles and responsibilities post-IPE (M=7.89, SD=1.69), pre-IPE (M=7.91, SD=1.51) shown no statistically significant differences. Student concerns, enhanced understanding of collaboration and readiness for future joint work were addressed, but not understanding of roles.
Conclusions. Educators with nursing and medical backgrounds delivered geriatric IPE through case-based PBL. The optimal learner group size was determined. The equal numbers of participants from each profession for successful IPE are not necessary. The IPE delivered by clinicians and senior nurses had an overall positive impact on all participants, but more markedly on nursing students. Surprisingly, it had the same impact on medical students regardless if it was delivered to the mixed groups with nursing students, or to medical students alone. Teaching successfully addressed students’ concerns about joint learning and communication and ethics were most commonly suggested topics for the future
Adiposity and cardiovascular outcomes in three-year-old children of participants in UPBEAT, an RCT of a complex intervention in pregnant women with obesity
Background: Maternal obesity is associated with offspring cardiometabolic risk. UPBEAT was a randomised controlled trial of an antenatal diet and physical activity intervention in 1555 women with obesity. The intervention was associated with lower gestational weight gain, healthier diet and metabolic profile in pregnancy, and reduced infant adiposity at six months. Objective: We have investigated whether the UPBEAT intervention influenced childhood cardiometabolic outcomes or was associated with sustained improvements in maternal lifestyle 3-years after delivery. Methods: In UPBEAT mother-child dyads at the 3-year follow-up, we assessed childhood blood pressure, resting pulse rate, and adiposity (body mass index, skinfold thicknesses, body fat, waist and arm circumferences) and maternal diet, physical activity, and anthropometry. Results: 514 three-year-old children attended the appointment (49% intervention, 51% standard care). There was no difference in the main outcome of interest, subscapular skinfold thickness, between the trial arms (−0.30 mm, 95% confidence interval: −0.92, 0.31). However, the intervention was associated with a lower resting pulse rate (−5 bpm [−8.41, −1.07]). There was also a non-significant lower odds of overweight/obesity (OR 0.73; 0.50, 1.08). Maternal dietary improvements observed in the UPBEAT trial, including glycaemic load and saturated fat were maintained 3-years postpartum. Conclusion: This study has demonstrated that an antenatal dietary and physical activity intervention in women with obesity is associated with lower offspring pulse rate and sustained improvement in maternal diet. Whilst larger than previous cohorts, there remains potential for bias from attrition and these findings require validation in future cohorts
Whole Blood Interferon-Gamma Responses to Mycobacterium tuberculosis Antigens in Young Household Contacts of Persons with Tuberculosis in Uganda
Due to immunologic immaturity, IFN-gamma-producing T cell responses may be decreased in young children compared to adults, thus we hypothesized that IFN-gamma responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb) would be impaired in young children relative to adults. The objective of this study was to compare whole blood IFN-gamma production in response to mycobacterial antigens between children and adults in Uganda.We studied household contacts of persons with culture-positive pulmonary tuberculosis (TB) enrolled in a cohort study conducted in Kampala, Uganda. Whole blood IFN-gamma production in response to Mtb culture-filtrate antigens was measured by ELISA and compared between infants (<2 years old, n = 80), young children (2 <5 years old, n = 216), older children (5 <15 years old, n = 443) and adults (> or =15 years old, n = 528). We evaluated the relationship between IFN-gamma responses and the tuberculin skin test (TST), and between IFN-gamma responses and epidemiologic factors that reflect exposure to Mtb, and the effect of prior BCG vaccination on IFN-gamma responses. Young household contacts demonstrated robust IFN-gamma responses comparable to those of adults that were associated with TST and known risk factors for infection. There was no effect of prior BCG immunization on the IFN-gamma response.Young children in a TB endemic setting can mount robust IFN-gamma responses generally comparable to those of adults, and as in adults, these responses correlated with the TST and known epidemiologic risk factors for Mtb infection
SARS-CoV-2 aptasensors based on electrochemical impedance spectroscopy and low-cost gold electrode substrates
SARS-CoV-2 diagnostic practices broadly involve either quantitative polymerase chain reaction (qPCR)-based nucleic amplification of viral sequences or antigen-based tests such as lateral flow assays (LFAs). Reverse transcriptase-qPCR can detect viral RNA and is the gold standard for sensitivity. However, the technique is time-consuming and requires expensive laboratory infrastructure and trained staff. LFAs are lower in cost and near real time, and because they are antigen-based, they have the potential to provide a more accurate indication of a disease state. However, LFAs are reported to have low real-world sensitivity and in most cases are only qualitative. Here, an antigen-based electrochemical aptamer sensor is presented, which has the potential to address some of these shortfalls. An aptamer, raised to the SARS-CoV-2 spike protein, was immobilized on a low-cost gold-coated polyester substrate adapted from the blood glucose testing industry. Clinically relevant detection levels for SARS-CoV-2 are achieved in a simple, label-free measurement format using sample incubation times as short as 15 min on nasopharyngeal swab samples. This assay can readily be optimized for mass manufacture and is compatible with a low-cost meter
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Neurotype-Matching, but Not Being Autistic, Influences Self and Observer Ratings of Interpersonal Rapport
The Double Empathy Problem suggests that communicative difficulties between autistic and non-autistic people are due to bi-directional differences in communicative style and a reciprocal lack of understanding. If true, there should be increased similarity in interaction style, resulting in higher rapport during interactions between pairs of the same neurotype. Here, we provide two empirical tests of rapport, with data revealing whether self- and observer- rated rapport varies depending on the match or mismatch in autism status within a pair. An additional opportunity afforded by these data is to examine the effect of the autism status of the rater on the perceived rapport between matched and mismatched pairs. In Study 1 72 participants were allocated to one of three dyad conditions: autistic pairs (n = 24), non-autistic pairs (n = 24) and mixed pairs (n = 12 autistic; n = 12 non-autistic). Each participant completed three semi-structured interactions with their partner, rating rapport after each interaction. Non-autistic pairs experienced higher self-rated rapport than mixed and autistic pairs, and autistic pairs experienced higher rapport than mixed pairs. In Study 2 (n = 80) autistic and non-autistic observers rated interactional rapport while watching videoed interactions between autistic pairs, non-autistic pairs, and mixed pairs (n = 18, a subset of participants in Study 1). Mixed pairs were rated significantly lower on rapport than autistic and non-autistic pairs, and autistic pairs were rated more highly for rapport than non-autistic pairs. Both autistic and non-autistic observers show similar patterns in how they rate the rapport of autistic, non-autistic, and mixed pairs. In summary, autistic people experience high interactional rapport when interacting with other autistic people, and this is also detected by external observers. Rather than autistic people experiencing low rapport in all contexts, their rapport ratings are influenced by a mismatch of diagnosis. These findings suggest that autistic people possess a distinct mode of social interaction style, rather than demonstrating social skills deficits. These data are considered in terms of their implications for psychological theories of autism, as well as practical impact on educational and clinical practice