Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Effectiveness of a comprehensive educational programme for Accredited Social Health Activists (ASHAs) to identify individuals in the Udupi district with bleeding disorders: A community-based survey.

INTRODUCTION: The awareness and knowledge on bleeding disorders is generally poor among the rural population. Accredited Social Health Activists (ASHAs) serve as the facilitators between the rural community and the health care system. Training of ASHAs in screening of rural population for early identification of bleeding disorders can enable prompt referral, timely detection and management of bleeding disorders. AIM: The aim of the study was to evaluate the effectiveness of an ASHA training programme for identification of suspected bleeding disorder cases. METHODS: A population-based, cross-sectional survey was implemented by 586 Accredited Social Health Activists (ASHAs) in rural Udupi district, who underwent a structured training programme on identification of bleeding disorders. A survey record book with a screening tool on assessment of bleeding symptoms was given to each ASHA. The screening tool consisted of symptoms related to bleeding disorders and family history of bleeding disorders. Using the screening tool, ASHAs carried out a door-to-door survey. After screening, those who reported with bleeding symptoms were referred by the ASHAs to the investigator, who conducted further assessment. A detailed bleeding history was documented and bleeding symptom assessment was carried out using bleeding assessment tool (BAT) at the haemophilia treatment centre. Further coagulation assessments were carried out as per the treatment centre protocol. This paper highlights the evaluation of an ASHA training programme on identification of individuals with bleeding symptoms in the rural population. RESULTS: A total of 586 trained ASHAs surveyed a population of 318 214 in rural Udupi district. Out of the 124 cases reported by ASHAs, 29 bleeding disorder cases were identified; haemophilia (A and B) was the most commonly found bleeding disorder 22 (75.8%), followed by von Willebrand disease (vWD) 3 (10.3%) and 4 (13.8%) immune-mediated thrombocytopenic purpura (ITP), with an overall prevalence of 2.2/10 000 population. CONCLUSION: Training ASHA health care workers, who are the most important link between the community and health services, resulted in increased awareness among the public for the early detection of bleeding disorders.

Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage.

INTRODUCTION: Recurrent miscarriage (RM) defined as 2 or more spontaneous miscarriage before 20 weeks of gestation, affects at least 1 % of couples trying to conceive. In over 50 % of cases, the cause of the loss of pregnancy remains unexplained. Reduced expression of Angiogenic factors such as: vascular endothelial growth factor (VEGF-A) and VEGF-C has been linked with spontaneous miscarriage, likely due to defective foetal and placental angiogenesis. AIMS AND OBJECTIVES: To investigate the relationships between serum level of VEGF-A and VEGF-C with clinical characteristic in women with URM and compare to pregnant and healthy women. MATERIALS AND METHODS: A case-control study, which was conducted between 90 non-pregnant women with history of RM, age-matched with 70 non-pregnant women without history of recurrent abortion with at least one child (controls) and 70 pregnant women without history of recurrent abortion with at least one child (controls). Those with unexplained RM were eligible. Demographic and Anthropometric data were retrieved by pre-test questionnaire and serum level of VEGF-A and VEGF-C measured by ELISA kit. RESULTS: This study showeds that maternal levels of VEGF-A and VEGF-C were distinctly lower in RSA (189.87±88.1 vs 238.8±99.6) compared to healthy (239.1±99.7 vs 275.5±133.08) and pregnant (301.5±76.4 vs 402.5±128.6) women as control groups. Univariate analysis demonstrated that clinical characteristic factors were significantly associated with concentration of VEGF-A and VEGF-C in cases and controls. CONCLUSIONS: Our findings suggest that these molecules could be used as potential predictive markers of miscarriage in these women presenting with URM (Tab. 4, Fig. 5, Ref. 40).

Simultaneous versus staged bilateral direct anterior Total Hip Arthroplasty: Are early patient-centered outcomes equivalent?

While accumulating data on the direct anterior approach to total hip arthroplasty (THA) have demonstrated clinical benefit and durable results, there is little data that exists on patient-centered outcomes and satisfaction when comparing simultaneous bilateral procedures with staged arthroplasty. The aim of this study was to determine whether simultaneous bilateral THA and staged arthroplasty result in equivalent early (1) patient-centered outcomes and patient satisfaction; while maintaining acceptable rates of (2) objective clinical outcome scores, (2) complication rates; and (3) radiographic results. In retrospective review, 41 patients who underwent bilateral one-stage THA were compared to 44 patients who underwent staged bilateral THA during the same time period. The minimum clinical follow up was two years. Generic (EQ-VAS and EuroQoL-5D index) and condition-specific (Oxford Hip Score) instruments were used to assess patient-reported outcomes. Other variables included length of hospital stay (LOS), operative and anesthetic times, blood loss, intra- and post-operative (local and systemic) complications, and radiographic analysis. No significant differences between the two groups were found for patient-reported outcomes, complications, or radiographic assessment. The simultaneous THA group had shorter LOS and operative and anesthetic times, as well as less blood loss.

Short-term outcomes of a program developed to inculcate research essentials in undergraduate medical students.

BACKGROUND: Participation in research during undergraduate studies may increase students' interest in research and inculcate research essentials in them. AIMS: The purpose of this study was to evaluate the effectiveness of the mentored student project (MSP) program. SETTINGS AND DESIGN: In the MSP program, students in groups (n = 3 to 5) undertook a research project, wrote a scholarly report, and presented the work as a poster presentation with the help of a faculty mentor. To begin with, the logic model of the program was developed to identify short-term outcomes of the program on students, mentors, and the institution. A quasi-experimental design was used to measure the outcomes. MATERIALS AND METHODS: A mixed method evaluation was done using a newly-developed questionnaire to assess the impact of the MSP on students' attitude, a multiple-choice question (MCQs) test to find out the impact on students' knowledge and grading of students' project reports and posters along with a survey to check the impact on skills. Students' satisfaction regarding the program and mentors' perceptions were collected using questionnaires. Evidence for validity was collected for all the instruments used for the evaluation. STATISTICAL ANALYSIS: Non-parametric tests were used to analyze data. Based on the scores, project reports and posters were graded into A (>70% marks), B (60-69% marks), and C (<59% marks) categories. The number of MSPs that resulted in publications, conference presentation and departmental collaborations were taken as impact on the institution. RESULTS: Students' response rate was 91.5%. The students' attitudes regarding research changed positively (P = 0.036) and score in the MCQ test improved (P < 0.001) after undertaking MSP. Majority of project reports and posters were of grade A category. The majority of the items related to skills gained and satisfaction had a median score of 4. The MSPs resulted in inter-departmental and inter-institutional collaborations, 14 publications and 15 conference presentations. An area for improvement noted was to have the MSP implemented in the curriculum without increasing students' overall workload and stress. CONCLUSION: The study identified strengths and weaknesses of the MSP program. Our model of undergraduate research project may be incorporated in undergraduate medical programs to foster positive attitude and knowledge base about scientific research and to instil research skills among students.

Femoroacetabular impingement inducing non-union of a femoral neck fracture: a case report.

INTRODUCTION: We describe a case in which femoroacetabular impingement (FAI) was identified as the cause of non-union of a femoral neck fracture and the subsequent treatment strategy. MATERIALS AND METHODS: Retrospective review of a 35-year-old patient, without any risk factors for non-union, who sustained a femoral neck fracture. Pre-existing FAI was identified as the cause for the non-union of the femoral neck fracture, with successful treatment of the non-union according to established arthroscopic treatment of the hip. RESULTS: After treatment of the FAI, the non-union healed uneventfully within 3 months. CONCLUSIONS: FAI may be a less common but potential cause of delayed union or non-union in the setting of femoral neck fracture in the young.

Establishing a clinic-based pancreatic cancer and periampullary tumour research registry in Quebec.

BACKGROUND: Enrolling patients in studies of pancreatic ductal adenocarcinoma (pdac) is challenging because of the high fatality of the disease. We hypothesized that a prospective clinic-based study with rapid ascertainment would result in high participation rates. Using that strategy, we established the Quebec Pancreas Cancer Study (qpcs) to investigate the genetics and causes of pdac and other periampullary tumours (pats) that are also rare and underrepresented in research studies. METHODS: Patients diagnosed with pdac or pat were introduced to the study at their initial clinical encounter, with a strategy to enrol participants within 2 weeks of diagnosis. Patient self-referrals and referrals of unaffected individuals with an increased risk of pdac were also accepted. Family histories, epidemiologic and clinical data, and biospecimens were collected. Additional relatives were enrolled in families at increased genetic risk. RESULTS: The first 346 completed referrals led to 306 probands being enrolled, including 190 probands affected with pdac, who represent the population focus of the qpcs. Participation rates were 88.4% for all referrals and 89.2% for pdac referrals. Family history, epidemiologic and clinical data, and biospecimens were ascertained from 91.9%, 54.6%, and 97.5% respectively of patients with pdac. Although demographics and trends in risk factors in our patients were consistent with published statistics for patients with pdac, the qpcs is enriched for families with French-Canadian ancestry (37.4%), a population with recurrent germ-line mutations in hereditary diseases. CONCLUSIONS: Using rapid ascertainment, a pdac and pat research registry with high participation rates can be established. The qpcs is a valuable research resource and its enrichment with patients of French-Canadian ancestry provides a unique opportunity for studies of heredity in these diseases.

Eotaxin-1 is involved in parasite clearance during chronic filarial infection.

Eosinophil migration as key feature of helminth infection is increased during infection with filarial nematodes. In a mouse model of filariasis, we investigated the role of the eosinophil-attracting chemokine Eotaxin-1 on disease outcome. BALB/c and Eotaxin-1(-/-) mice were infected with the rodent filaria Litomosoides sigmodontis, and parasitic parameters, cellular migration to the site of infection, and cellular responsiveness were investigated. We found increased parasite survival but unaffected eosinophil migration to the site of infection in Eotaxin-1(-/-) mice. Expression of CD80 and CD86 was reduced on eosinophils from Eotaxin-1(-/-) mice after in vitro TLR2 stimulation and exposure to filarial antigen, respectively, suggesting a potential reduced activation state of eosinophils in Eotaxin-1 deficient mice. We further demonstrated that macrophages from Eotaxin-1(-/-) mice produce decreased amounts of IL-6 in vitro, a cytokine found to be associated with parasite containment, suggesting possible mechanisms by which Eotaxin-1 regulates activation of inflammatory cells and thus parasite survival.

Do geriatrics require dose titration for antidiabetic agents?

OBJECTIVE: To evaluate the antidiabetic drug dosage differences between geriatric and nongeriatric diabetics with reference to duration of disease and creatinine clearance (Crcl). MATERIALS AND METHODS: Prospective study conducted for 6 months in a tertiary care hospital. Patients with type 2 diabetes mellitus were grouped into geriatric (age ≥60 years) and nongeriatric (age <60 years). Patients' demographic data, duration of diabetes, medication, and serum creatinine were recorded. Crcl was calculated using Cockcroft-Gault formula. Doses of sulfonylureas (SU) were converted into equivalent doses, taking glibenclamide as standard. Univariate analysis was done for comparison of drug doses between groups. RESULT: A total of 320 geriatric and 157 nongeriatric diabetics completed the study. The duration of diabetes and Crcl adjusted dose reduction of glibenclamide (mean dose: Geriatrics 7.2±0.4 mg, nongeriatrics 9.6±0.7 mg; P=0.01) and gliclazide (mean dose: Geriatrics 85.5±11.5 mg, nongeriatrics 115.3±32.7 mg; P=0.42) was 25%, glimepiride (mean dose: Geriatrics 1.62±0.13 mg, nongeriatrics 2.1±0.18 mg; P=0.06) was 22%. Glipizide did not require dose reduction. Mean converted equivalent dose of sulfonylurea monotherapy was significantly lower in geriatrics than nongeriatrics (3.2±0.5 vs 6.4±1.02 mg; P=0.01) and showed 50% dose reduction. Mean dose of metformin was lower in geriatrics (901±32.2 mg vs 946.7±45.8 mg; P=0.45) and showed 5% reduction in dosage. There was no difference in the mean drug doses of thiazolidinediones and insulin between the groups. CONCLUSION: A substantial dose reduction of glibenclamide (25%), gliclazide (25%), glimepiride (22%), and metformin (5%) in geriatrics compared to nongeriatrics was observed. Smaller dosage formulations like 0.75 mg glibenclamide, 0.5 mg glimepiride, 20 mg gliclazide, and 250 mg metformin may be of value in geriatric diabetic practice.

Avenues for professional development: faculty perspectives from an Indian medical school.

BACKGROUND: Medical school faculty in India are challenged to balance teaching and professional development. Melaka Manipal Medical College (MMMC), Manipal Campus, Manipal University, India offers the Bachelor of Medicine and Bachelor of Surgery (MBBS) program. The institution incorporates certain effective practices based on adult learning principles which are aimed at fostering the professional development of faculty members. OBJECTIVES: The present study was undertaken to explore the perceptions of faculty members regarding the scope for professional development at Melaka Manipal Medical College, Manipal Campus. METHODS: In September 2009, a questionnaire comprising items (23) focusing on five adult learning principles (active participation, relevant learning, constructive feedback, safe, non-threatening environment and previous experiences) was designed and faculty members (n=23) were asked to respond to it on a 5-point Likert scale. Additionally, a force field analysis was conducted by asking the faculty to identify three factors which facilitated them to consciously get involved in professional development activities. They were also asked to identify three unfavorable factors that hindered their professional development. RESULTS: Among the five characteristics, relevant learning was found to have a high mean score. Frequency analysis of responses revealed that at Melaka Manipal Medical College, there was ample scope for relevant self-learning that fosters professional development (91.3%). Force field response analysis revealed Melaka Manipal Medical College offered considerable flexibility and opportunities for continuing professional development along with faculty members' prevailing role as teachers. Nevertheless, the need for more research facilities and funds was highlighted. CONCLUSIONS: Adherence to adult learning principles may provide avenues for professional development in medical schools. An organized attempt to make the medical school faculty aware of the scope of these practices appears to be necessary to nurture professional development in settings where there are resource constraints.

Dental caries and salivary alterations in Type I Diabetes.

UNLABELLED: Insulin dependent diabetes mellitus is a severe disease that raises blood glucose levels because of hyperglycemia and insulinopenia. Fluctuations in water and electrolyte levels may result in xerostomia and other changes in the salivary composition. Since diabetes has an influence on oral health, it is important for the dentist to be aware of newer advances in the field of diabetes and to recognize specific oral problems related to diabetes. Thus, the dentist becomes an important part of the health care team for the patients with diabetes. AIM: The present study correlated salivary flow rate, salivary pH and total salivary antioxidant levels and dental caries in type I diabetic patients. METHOD: A total of 200 children that included 100 known diabetic children (study group) and 100 healthy children (controls) of both the sexes and from similar socioeconomic backgrounds formed the part of this study. Dental caries was assessed using DMFT index. The salivary total anti-oxidant level was estimated using phospho molybdic acid using spectrophotometric method. The salivary flow rate was recorded using the Zunt method and the salivary pH using the pH indicating paper. The results were statistically analyzed using t-test. CONCLUSIONS: The analyzed parameters showed increase in salivary anti-oxidant levels, reduced salivary flow rate, increase incidence of dental caries, salivary pH was decreased when compared to the control group.

Clinical Characteristics and Outcomes in Patients with COVID-19 and Cancer: a Systematic Review and Meta-analysis.

Much of routine cancer care has been disrupted due to the perceived susceptibility to SARS-CoV-2 infection in cancer patients. Here, we systematically review the current evidence base pertaining to the prevalence, presentation and outcome of COVID-19 in cancer patients, in order to inform policy and practice going forwards. A keyword-structured systematic search was conducted on Pubmed, Cochrane, Embase and MedRxiv databases for studies reporting primary data on COVID-19 in cancer patients. Studies were critically appraised using the NIH National Heart, Lung and Blood Institute's quality assessment tool set. The pooled prevalence of cancer as a co-morbidity in patients with COVID-19 and pooled in-hospital mortality risk of COVID-19 in cancer patients were derived by random-effects meta-analyses. In total, 110 studies from 10 countries were included. The pooled prevalence of cancer as a co-morbidity in hospitalised patients with COVID-19 was 2.6% (95% confidence interval 1.8%, 3.5%, I2: 92.0%). Specifically, 1.7% (95% confidence interval 1.3%, 2.3%, I2: 57.6.%) in China and 5.6% (95% confidence interval 4.5%, 6.7%, I2: 82.3%) in Western countries. Patients most commonly presented with non-specific symptoms of fever, dyspnoea and chest tightness in addition to decreased arterial oxygen saturation, ground glass opacities on computer tomography and non-specific changes in inflammatory markers. The pooled in-hospital mortality risk among patients with COVID-19 and cancer was 14.1% (95% confidence interval 9.1%, 19.8%, I2: 52.3%). We identified impeding questions that need to be answered to provide the foundation for an iterative review of the developing evidence base, and inform policy and practice going forwards. Analyses of the available data corroborate an unfavourable outcome of hospitalised patients with COVID-19 and cancer. Our findings encourage future studies to report detailed social, demographic and clinical characteristics of cancer patients, including performance status, primary cancer type and stage, as well as a history of anti-cancer therapeutic interventions.

Maternal risk factors and anaemia in pregnancy: a prospective retrospective cohort study.

Anaemia in pregnancy is still a concern during the reproductive period, as it is associated with increased maternal and perinatal mortality and morbidity. This study examined the maternal risk factors associated with increased prevalence of anaemia among antenatal and postnatal women. A prospective-retrospective cohort approach was carried out among 1,077 antenatal and 1,000 postnatal women. The haemoglobin was estimated using the cyanmethaemoglobin method. The maternal factors included were age, parity, education, socioeconomic status, spacing, history of bleeding, worm infestation, period of gestation, knowledge regarding anaemia in pregnancy, food selection ability and compliance to iron supplementation. Of the 1,077 antenatal women studied, 540 were anaemic. Among the 1,000 postnatal women, the prevalence was 537 (53.7%). The high prevalence was strongly associated with low socioeconomic status (OR 1.409 [1.048-1.899]; p < 0.023) which affected their knowledge and health seeking behaviour in both the groups. Hence it can be concluded that empowering women in terms of education and economic status is the key factor in combating anaemia in pregnancy to prevent the vicious cycle of associated problems.

Fostering research skills in undergraduate medical students through mentored students projects: example from an Indian medical school.

BACKGROUND: Healthcare decision-making is largely reliant on evidence-based medicine; building skills in scientific reasoning and thinking among medical students becomes an important part of medical education. Medical students in India have no formal path to becoming physicians, scientists or academicians. OBJECTIVES: This study examines students' perceptions regarding research skills improvement after participating in the Mentored Student Project programme at Melaka Manipal Medical College, Manipal Campus, India. Additionally, this paper describes the initiatives taken for the continual improvement of the Mentored Student Project programme based on faculty and student perspectives. METHODS: At Melaka Manipal Medical College, Mentored Student Project was implemented in the curriculum during second year of Bachelor of Medicine and Bachelor of Surgery programme with the intention of developing research skills essential to the career development of medical students. The study design was cross-sectional. To inculcate the spirit of team work students were grouped (n=3 to 5) and each group was asked to select a research project. The students' research projects were guided by their mentors. A questionnaire (Likert's five point scale) on students' perceptions regarding improvement in research skills after undertaking projects and guidance received from the mentor was administered to medical students after they had completed their Mentored Student Project. The responses of students were summarised using percentages. The median grade with inter-quartile range was reported for each item in the questionnaire. The median grade for all the items related to perceptions regarding improvement in research skills was 4 which reflected that the majority of the students felt that Mentored Student Project had improved their research skills. The problems encountered by the students during Mentored Student Project were related to time management for the Mentored Student Project and mentors. RESULTS: This study shows that students acknowledged that their research skills were improved after participating in the Mentored Student Project programme. CONCLUSIONS: The Mentored Student Project programme was successful in fostering positive attitudes among medical students towards scientific research. The present study also provides scope for further improvement of the Mentored Student Project programme based on students' and faculty perspectives.

Performance of CURB-65 and CURB-age in community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is common and associated with significant mortality. In this study, we validated a newly proposed severity assessment rule for CAP, CURB-age, and also compared with to the currently recommended criteria in UK, CURB-65. METHODS: We conducted a prospective study in three hospitals in Norfolk and Suffolk, UK. One hundred and ninety patients were included and followed up for 6 weeks. RESULTS: Of 190 patients, 100 were men (53%). The age range was 18-101 years (median 76 years). Sixty-five (34%) had severe pneumonia by CURB-65 and 54 (28%) had severe pneumonia by CURB-age. There were 54 deaths during follow-up. There were 32 deaths (50%) in severe and 22 deaths (18%) in non-severe group by CURB-65. There were 27 deaths each in both the groups by CURB-age (50% of severe cases and 20% of non-severe cases). For CURB-65, sensitivity, specificity, and positive and negative predictive values were 59.3% (45.0-72.4), 75.7% (67.6-82.7), 49.2% (36.6-61.9) and 82.4% (74.6-88.6), respectively. For CURB-age, the respective values were 50.0% (31.1-63.9), 80.1% (72.4-86.5), 50.0% (36.1-63.9) and 80.1% (72.4-86.5). Exclusion of patients aged < 65 years did not alter the results. CONCLUSIONS: Despite better specificity in correctly identifying 6-week mortality for CAP, CURB-age appears to be less sensitive than CURB-65. Our findings further assure the usefulness of CURB-65 for predicting mortality in CAP.

Potential pitfalls of a double PCL sign.

The double posterior cruciate ligament (PCL) sign is seen on a midline sagittal MR image of the knee as a low-signal-intensity linear band paralleling the antero-inferior part of the PCL. Although the sign has a high specificity for a displaced bucket-handle tear of the medial meniscus, it can be mimicked by several normal and abnormal structures in the intercondylar region. Familiarity with these variants and identifying the other features supportive of meniscal injury will help to make a confident diagnosis of bucket-handle tear of the medial meniscus.