The clinical and economic costs associated with regional disparities in varicella vaccine coverage in Italy over 50 years (2020-2070).

Italy implemented two-dose universal varicella vaccination (UVV) regionally from 2003 to 2013 and nationally from 2017 onwards. Our objective was to analyze regional disparities in varicella outcomes resulting from disparities in vaccine coverage rates (VCRs) projected over a 50-year time-horizon (2020-2070). A previously published dynamic transmission model was updated to quantify the potential public health impact of the UVV program in Italy at the national and regional levels. Four 2-dose vaccine strategies utilizing monovalent (V) and quadrivalent (MMRV) vaccines were evaluated for each region: (A) MMRV-MSD/MMRV-MSD, (B) MMRV-GSK/MMRV-GSK, (C) V-MSD/MMRV-MSD, and (D) V-GSK/MMRV-GSK. Costs were reported in 2022 Euros. Costs and quality-adjusted life-years (QALYs) were discounted 3% annually. Under strategy A, the three regions with the lowest first-dose VCR reported increased varicella cases (+ 34.3%), hospitalizations (+ 20.0%), QALYs lost (+ 5.9%), payer costs (+ 22.2%), and societal costs (+ 14.6%) over the 50-year time-horizon compared to the three regions with highest first-dose VCR. Regions with low first-dose VCR were more sensitive to changes in VCR than high first-dose VCR regions. Results with respect to second-dose VCR were qualitatively similar, although smaller in magnitude. Results were similar across all vaccine strategies.

Effectiveness of an Innovative Card Game as a Supplement for Teaching Factual Content to Medical Students: A Mixed Method Study.

Introduction Lectures and small group teaching are useful to transfer conceptual knowledge. Anatomy is the foundation of medical sciences, but it is perceived to be difficult to comprehend and recall. For such clinically relevant aspects of medical education that require memorization, educational card games can be very effective. As the complex concepts and terminology of Embryology are difficult to follow and retain, we designed a card game "MedFc" for a topic on pharyngeal arches. This study was planned to determine the effectiveness of the card game on curriculum comprehension, recall of factual topics among medical undergraduates, and its utility as a supplement to interactive lecture sessions. Methods The mixed method study was conducted in the Department of Anatomy of an undergraduate medical college. Ethical approval was obtained prior to beginning the study. Convenience sampling was done. From a batch of 50 first-year medical students, a total of 40 students consented to participate in the study, 24 (60%) were males and 16 (40%) were female participants. A lecture on the pharyngeal arches was conducted for the entire batch of 50 first-year medical students. After three weeks, the students who consented to participate in the study were randomly grouped into two groups of 20 each. The groups were the game group (which played the card game in teams of five) and the control group (which discussed the same topic in small groups of five). For both the group's pretests and posttests, 10 higher order multiple choice questions, were conducted and students' feedback regarding the effectiveness of the teaching technique was obtained. Results Students opined that playing the card game was a superb experience, a positive use of time, and a very effective method of comprehension and memorizing complex topics. The scores increased from the pretest to the posttest indicating that both methods effectively reinforced the embryological concepts, but a t test showed that card game is more effective than small group discussions, with p-value = 0.008. The improvement in scores of students who had achieved <50% in pretest for the game group was statistically significant with t-value = 0.0023, when compared with the improvement in scores of similar students from the control group. Conclusions The study has demonstrated the effectiveness of "MedFc" card game in the recall of factual topics and can be used as supplementary material for enhancing learning amongst medical graduates. This educational card game applies gamification to Anatomy education to create a fun filled learning experience and is a valuable addition to the learning resources.

Role of HLA alleles polymorphism in systemic lupus erythematosus: A prospective study from North India.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder and has complex etiopathogenesis. The most appropriate hypothesis states that genetic susceptibility in the presence of environmental risk factors predisposes to SLE. HLA class II alleles are critical to immune response and are highly polymorphic. Various alleles in HLA-DR and -DQ regions were analyzed in SLE patients and healthy controls to see their role in susceptibility or protection to SLE. Materials and Methods: This was a prospective observational study, in which a total of 100 SLE patients and 100 controls were analyzed. HLA typing was done by polymerase chain reaction (PCR)-sequence-specific oligonucleotide (SSO) method (SSO probe). Results: DRß1*0301 was significantly increased in SLE patients when compared to controls and had the highest odds ratio. Other risk factor alleles found to be increased were DRß1*0701, DQß1*0202, and DQß1*0301, which had a significant positive association with SLE, suggesting their role in susceptibility to SLE. In contrast, DRß1*0401, DRß1*1401, DRß1*1404, DRß1*1501, DQß1*0501, and DQα1*0201 showed statistically significant reduction in SLE patients, while these were much more common in controls, suggesting their protective role. Conclusion: This study is only the second study in patients from North India and it determines the role of DRß1*0301, DRß1*0701, DQß1*0202, and DQß1*0301 alleles as risk factors in SLE patients.

Genome sequencing and characterization of microsatellite markers of Pterocarpus santalinus L.f.: an economically important endangered tree of Eastern Ghats, India.

Pterocarpus santalinus L.f. (red sanders) is an endemic, endangered and economically important tree species distributed in the Eastern Ghats of Andhra Pradesh, India. This tree is well known for its blood-red coloured timber which has a high value in the international market. Due to its high timber demand, illegally logging of red sanders has resulted in fragmentation and depletion of its natural populations. Assessing the genetic diversity is a prerequisite for the identification of distinct populations of red sanders in the natural habitat for prioritizing conservation efforts. The present study has focussed on genome sequencing, identification and validation of microsatellite markers of P. santalinus. A total of 282,918 simple sequence repeat (SSR) loci were identified using whole genome sequence from P. santalinus leaf tissue. A total of 28 SSRs were selected for polymorphism analysis across the 52 individuals belonging to three populations of P. santalinus and identified a sum of 502 alleles with polymorphic information content of 0.83; observed heteozygosity (Ho) 0.42 and expected heterozygosity (He) 0.69. Genetic differentiation coefficient (FST) of 0.19 (FST˂0.25) which is indicating moderate genetic differentiation among the populations. Six SSRs from P. indicus Willd. and P. erinaceus Poir. were successfully amplified in P. santalinus and produced 131 alleles. These newly identified SSRs are useful in detecting genetic diversity and further developing conservation strategies for P. santalinus.

A systematic review: impact of in-office biopsy on safety and waiting times in head and neck cancer.

OBJECTIVE: This study aimed to assess the current literature on the safety and impact of in-office biopsy on cancer waiting times as well as review evidence regarding cost-efficacy and patient satisfaction. METHOD: A search of Cinahl, Cochrane Library, Embase, Medline, Prospero, PubMed and Web of Science was conducted for papers relevant to this study. Included articles were quality assessed and critically appraised. RESULTS: Of 19 741 identified studies, 22 articles were included. Lower costs were consistently reported for in-office biopsy compared with operating room biopsy. Four complications requiring intervention were documented. In-office biopsy is highly tolerated, with a procedure abandonment rate of less than 1 per cent. When compared with operating room biopsy, it is associated with significantly reduced time-to-diagnosis and time-to-treatment initiation. It is linked to improved overall three-year survival. CONCLUSION: In-office biopsy is a safe procedure that may help certain patients avoid general anaesthetic. It was shown to significantly reduce time-to-diagnosis and time-to-treatment initiation when compared with operating room biopsy. This may have important implications for oncological outcomes. In-office biopsy requires fewer resources and is likely to be cost-saving five-years following introduction. With high rates of sensitivity and specificity, in-office biopsy should be considered as the first-line procedure to achieve tissue diagnosis.

Comparative evaluation of DTT treated ABO isoagglutinin titres performed by two methods with solid phase red cell adhesion (SPRCA) titres.

BACKGROUND AND AIMS: Measurement of actual concentration of IgG requires methods like treatment of serum with dithiothreitol (DTT). This study was aimed at comparing of DTT treated ABO titres performed by conventional test tube technique (CTT) and column agglutination technique (CAT) with HA/SPRCA. MATERIALS AND METHODS: This was a prospective, observational study conducted from October 2019 to March 2020. All consecutive A, B and O group donors who gave consent for participation were included. All samples were tested by CTT and CAT before and after DTT treatment (pCTT, pCAT) and with HA/SPRCA. RESULTS: A total of 300 donors were included; 100 each from A, B and O blood group donors. Group O titres were higher than group A/B titres. Group O titres were highest when performed by pCAT, followed by pCTT and lowest by HA/SPRCA. Group A/B titres were highest when performed by HA/SPRCA, followed by pCAT and pCTT for anti-A and highest when performed by pCAT, followed by HA/SPRCA and lowest by pCTT for anti-B. CONCLUSION: Results obtained by pCAT were closer to results obtained by pCTT, whereas those obtained by HA/SPRCA were variable. SPRCA offers the advantage of automation, no inter-observer variation and less time consumption because IgM interference is not observed with SPRCA, thus providing an alternative to pCTT. However, these methods cannot be used interchangeably and to discern the most suitable method, a clinical impact of these results needs to be studied.

Streptococcus pneumoniae Acquisition and Carriage in Vaccine Naïve Indian Children with HIV and their Parents: A Longitudinal Household Study.

OBJECTIVES: To investigate the difference in pneumococcal carriage, acquisition, antibiotic resistance profiles and serotype distribution, in human immunodeficiency virus (HIV) affected and unaffected families. METHODS: A prospective cohort study was conducted in children with and without HIV in West Bengal from March 2012 through August 2014, prior to 13-valent pneumococcal conjugate vaccine (PCV-13) immunization. One thousand four hundred forty one nasopharyngeal swabs were collected and cultured at five-time points from children and their parents for pneumococcal culture, and serotyping by Quellung method. RESULTS: One hundred twenty five HIV infected children and their parents, and 47 HIV uninfected children and their parents participated. Two hundred forty pneumococcal isolates were found. In children under 6 y, the point prevalence of colonization was 31% in children living with HIV (CLH) and 32% in HIV uninfected children (HUC), p = 0.6. The most common vaccine type (VT) serotypes were 6A, 6B and 19A. All isolates from parents and 71% from children in the HIV uninfected cohort were PCV-13 representative, compared to 33% of isolates from CLH and their parents. Acquisition rate in children was 1.77 times that of parents (OR = 1.77, 95%CI: 1.18-2.65). The HIV status of child or parent did not affect acquisition. Isolates from CLH were more frequently resistant to multiple antibiotics (p = 0.02). CONCLUSIONS: While the rate of pneumococcal carriage and acquisition did not differ between CLH and HUC, HIV affected families had exposure to a wider range of serotypes including non-vaccine type serotypes and antibiotic resistant serotypes, than HIV unaffected families.

Increased household exposure to respiratory pathogens in HIV exposed uninfected children due to maternal HIV.

Little is known about household exposures to respiratory pathogens in HIV-exposed uninfected children (HEU) in Indian families. This case series investigates the nasopharyngeal carriage of Streptococcus pneumoniae, Staphylococcus aureus, and respiratory viruses at multiple points in three mother child pairs: (1) an HIV-infected child and mother, (2) an HEU child and HIV-infected mother, and (3) an HIV-unexposed uninfected (HUU) child and mother. Nasopharyngeal carriage densities of Streptococcus pneumoniae and Staphylococcus aureus were higher in mothers and children living in HIV-affected households, regardless of the child's HIV status. Maternal HIV and ART status impact these household exposures.

Practical consensus recommendations on management of HR + ve early breast cancer with specific reference to genomic profiling.

Breast cancer is a heterogeneous disease and patients are managed clinically based on ER, PR, HER2 expression, and key risk factors. The use of gene expression assays for early stage disease is already common practice. These tests have found a place in risk stratifying the heterogeneous group of stage I-II breast cancers for recurrence, for predicting chemotherapy response, and for predicting breast cancer-related mortality. Most guidelines for hormone receptor (HR)-positive early breast cancer recommend addition of adjuvant chemotherapy for most women, leading to overtreatment, which causes considerable morbidity and cost. Expert oncologist discussed about strategies of gene expression assays and aid in chemotherapy recommendations for treatment of HR + ve EBC and the expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Practical consensus recommendation on when to do BRCA testing.

BRCA-mutation associated breast cancer and to future cancer risks and sensitivity to systemic therapies. Now that rapid genetic testing for BRCA1 and BRCA2 mutations is available, BRCA mutation status can be considered when making treatment and prevention decisions for BRCA testing, BRCA mutation carriers with breast cancer. Expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.

Role of circumferential subannular tympanoplasty in anterior and subtotal perforations.

OBJECTIVE: This study aimed to evaluate the surgical success of a modified inlay tympanoplasty technique, known as circumferential subannular tympanoplasty, for anterior and subtotal perforations. METHODS: This prospective study was performed in a tertiary care teaching hospital between October 2013 and April 2016. A total of 58 adult patients of both sexes with anterior or subtotal perforations underwent circumferential subannular tympanoplasty under local anaesthesia. In this technique, after tympanomeatal flap elevation, the temporalis fascia graft is placed directly onto the annulus instead of being tucked underneath the tympanic membrane remnant. Outcome data were graft uptake and hearing improvement. RESULTS: This technique had a surgical success rate of 97 per cent and led to significant hearing improvement. CONCLUSION: Circumferential subannular tympanoplasty has a definitive role in managing anterior and subtotal perforations.

Thrombomodulin-dependent protein C activation is required for mitochondrial function and myelination in the central nervous system.

Essentials The role of protein C (PC) activation in experimental autoimmune encephalitis (EAE) is unknown. PC activation is required for mitochondrial function in the central nervous system. Impaired PC activation aggravates EAE, which can be compensated for by soluble thrombomodulin. Protection of myelin by activated PC or solulin is partially independent of immune-modulation. SUMMARY: Background Studies with human samples and in rodents established a function of coagulation proteases in neuro-inflammatory demyelinating diseases (e.g. in multiple sclerosis [MS] and experimental autoimmune encephalitis [EAE]). Surprisingly, approaches to increase activated protein C (aPC) plasma levels as well as antibody-mediated inhibition of PC/aPC ameliorated EAE in mice. Hence, the role of aPC generation in demyelinating diseases and potential mechanisms involved remain controversial. Furthermore, it is not known whether loss of aPC has pathological consequences at baseline (e.g. in the absence of disease). Objective To explore the role of thrombomodulin (TM)-dependent aPC generation at baseline and in immunological and non-immunological demyelinating disease models. Methods Myelination and reactive oxygen species (ROS) generation were evaluated in mice with genetically reduced TM-mediated protein C activation (TMPro/Pro ) and in wild-type (WT) mice under control conditions or following induction of EAE. Non-immunological demyelination was analyzed in the cuprizone-diet model. Results Impaired TM-dependent aPC generation already disturbs myelination and mitochondrial function at baseline. This basal phenotype is linked with increased mitochondrial ROS and aggravates EAE. Reducing mitochondrial ROS (p66Shc deficiency), restoring aPC plasma levels or injecting soluble TM (solulin) ameliorates EAE in TMPro/Pro mice. Soluble TM additionally conveyed protection in WT-EAE mice. Furthermore, soluble TM dampened demyelination in the cuprizone-diet model, demonstrating that its myelin-protective effect is partially independent of an immune-driven process. Conclusion These results uncover a novel physiological function of TM-dependent aPC generation within the CNS. Loss of TM-dependent aPC generation causes a neurological defect in healthy mice and aggravates EAE, which can be therapeutically corrected.

Clostridium difficile infections in HIV-positive patients with diarrhoea.

BACKGROUND: Patients with HIV/AIDS are at a high risk of being infected with toxin-producing strains of Clostridium difficile (C. difficile) because of frequent hospitalization, exposure to antibiotics and antibiotic prophylaxis for opportunistic infections. There are little data from India on the prevalence of C. difficile infection in such patients. METHODS: We assessed the occurrence of C. difficile infections in HIV-positive patients with diarrhoea by looking for the presence of its toxin as well as by culturing. Enzyme immunoassay (EIA, Premier toxins A and B; Meridian Diagnostic Inc.) was used to detect toxin from 237 fresh stool samples collected from HIV-positive patients with diarrhoea. Culture was done on cycloserine-cefoxitin-fructose agar and brain- heart infusion agar. RESULTS: C. difficile was found in 12 of 237 (5.1%, 95% CI 2.64%-8.68%) HIV-positive patients with diarrhoea (9 patients were positive by EIA and 3 by culture). The presence of C. difficile in patients who had received antiretroviral therapy (7/66 [10.6%]) was significantly higher (p < 0.016) compared with those who had not (5/171 [3%]). Of the 12 patients positive for C. difficile, 7 were on antiretroviral therapy for a mean (SD) of 34.4 months with mean CD4+ count of 186 (98.81) cells/cmm and 5 patients were anti-retroviral-naïve with mean CD4+ count of 181 (68.7) cells/cmm. All the 12 patients were on antibiotics for previous 2 months and 4 of 12 had been hospitalized in the previous 30 days. CONCLUSION: C. difficile infections occurred more frequently in patients who had received antiretroviral therapy. Our study population had a lower frequency of C. difficile infections compared to previous studies.

Small-incision cataract surgery in patients with Fuch's heterochromic iridocyclitis.

INTRODUCTION: Fuch's heterochromic iridocyclitis (FHI) is often complicated by cataract formation. OBJECTIVE: To assess the results of small-incision cataract surgery (SICS) in FHI and to study the effect of preoperative factors on postoperative vision. MATERIALS AND METHODS: Sixty-three eyes of 59 patients with Fuchs heterochromic iridocyclitis who had SICS with in-the-bag implantation of intraocular lens (IOL) were evaluated retrospectively; and the primary and secondary outcome measures evaluated were the postoperative vision and complication rate. RESULTS: The mean age was 39.22±4.95 years. The mean pre-operative vision was 0.75±0.24 Log MAR units. The mean final vision was 0.27±0.10 Log MAR units (P=less than 0.001). At the final follow-up, 84.1% of the patients had a final Snellen's vision of 6/12 or better. The mean follow-up period was 12.06±2.06 months. The causes of corrected distance visual acuity (CDVA) worse than 6/60 were vitreous opacities, posterior keratic precipitates (KPs), glaucoma, persistent uveitis and cystoid macular edema (CME). Preoperative factors like iris atrophy (P=0.973), heterochromia (P=0.10) and vessels in angle (P=0.074) did not have a significant effect on the final vision. On the contrary, vitreous opacities (P=0.002) and posterior KPs (P=0.009) had a significant effect on the final visual outcome. CONCLUSION: SICS with in-the-bag implantation of IOL in patients with Fuch's heterochromic iridocyclitis resulted in good visual outcomes. SICS in complicated cataracts can be performed in rural settings and eye camps with minimal instrumentation, obviating the need for referral to tertiary care centers. Pre-operative factors like vitreous opacities and posterior KPs have a significant effect on the final vision.

Ocular myocysticercosis: an unusual case of ptosis.

BACKGROUND: Cysticercosis is common in endemic countries like India. It can have various clinical manifestations depending on the tissue involved. It refers to a parasitic infestation by Cysticercus cellulosae, the larval form of the pork tapeworm or Taenia solium. OBJECTIVE: To report an unusual case of ocular cysticercosis involving the levator palpebrae superioris and superior rectus muscle of the right eye. CASE DESCRIPTION: A young, male adult was diagnosed by Magnetic Resonance Imaging (MRI) scan of the skull and orbit to have right-sided ocular cysticercosis. The patient was treated with oral prednisolone and albendazole, to which he showed a significant improvement. CONCLUSION: Ocular myocysticercosis can be diagnosed by MRI and be treated medically with steroid and albendazole.

Progressive multifocal leucoencephalopathy in HIV/AIDS: observational study from a tertiary care centre in northern India.

BACKGROUND & OBJECTIVES: Progressive multifocal leucoencephalopathy (PML) is seen mostly in advanced human immunodeficiency virus (HIV) infection. Little is known about the epidemiology and disease course of these patients from India. This study was aimed to determine the frequency of PML in patients with HIV/AIDS, and the clinical features and survival of these patients. METHODS: The charts of HIV/AIDS patients with PML seen over a period of five years (2006-2011) at the Antiretroviral treatment (ART) centre at a tertiary care centre in New Delhi, India, were retrospectively reviewed. RESULTS: Of 1465 patients with HIV/AIDS, 18 (1.2%) were diagnosed with PML; four were laboratory confirmed and 14 had consistent clinical and radiological features. PML was the initial presentation of HIV infection in 10 (56%) patients, and 16 (89%) patients had CD4 count less than 200/µl. Insidious onset focal limb weakness (78%) and visual disturbance (28%) were common symptoms. Magnetic resonance imaging (MRI) of the brain revealed characteristic white matter lesions in all the patients. The estimated median survival was 7.6 months (95% CI, 0-20 months). INTERPRETATION & CONCLUSIONS: Our results show that the patients present late to access treatment with advanced immunosuppression at presentation. PML is associated with high morbidity and mortality despite institution of highly active antiretroviral therapy (HAART). There is a need to address the lacuna in diagnostic and management services for these patients in India.

Challenges of setting up psychiatric services in Nepal: Lessons from the first year of Janakpur Project.

In Nepal psychiatric services outside big cities are virtually non-existent. This paper reports the observations and findings of a mental health project jointly run by private and voluntary sector organisations at Janakpur in southeast Nepal. The services included monthly outpatient clinics, day care, home visits and psychiatric training for medical students. At the monthly clinic, altogether 396 patients attended the service in 2009: a high proportion had psychoses (30% schizophrenia and 25% bipolar disorder); most (54%) were young; they came mainly from rural areas. Medical students also benefited from the clinical exposure, but the intake of the day care service was poor. The overall success of the innovative project shows how low-cost basic psychiatric services can be delivered in Nepal by private and voluntary sectors in the absence of state health care system.

Evaluation of the persistent activity of moxidectin (10%) long-acting (LA) injectable formulation against Dictyocaulus viviparus, Haemonchus placei, Trichostrongylus axei and Oesophagostomum radiatum infections in cattle.

Two controlled studies were conducted to evaluate the persistent efficacy of moxidectin (10%) long-acting (LA) injectable formulation against Dictyocaulus viviparus, Haemonchus placei, Trichostrongylus axei and Oesophagostomum radiatum in cattle. The moxidectin LA injectable formulation was administered as a single subcutaneous injection into the proximal third of the ear at a dose rate of 0.01ml/kg BW to provide 1.0mg moxidectin/kg BW. The product had persistent efficacy of >90% against D. viviparus, H. placei and Oe. radiatum for at least 150 days post-treatment and against T. axei for at least 90 days post-treatment.