"You should brush your teeth better": a randomized controlled trial comparing best-possible versus as-usual toothbrushing.

BACKGROUND: Most people's tooth brushing performance is deficient, even when they are encouraged to brush to the best of their abilities. The aim of the present study was to explore the nature of this deficit by comparing best-possible vs. as-usual brushing. METHODS: University students (N = 111) were randomly assigned to receive one of two instructions: "brush your teeth as usual" (AU-instruction) or "brush your teeth to the best of your abilities" (BP-instruction). Video analyses assessed brushing performance. The marginal plaque index (MPI) assessed after brushing was used as an indicator of brushing effectiveness. A questionnaire assessed subjectively perceived oral cleanliness (SPOC). RESULTS: Participants in the BP group brushed their teeth longer (p = 0.008, d = 0.57) and used interdental devices more often (p < 0.001). No group differences emerged in the distribution of brushing time among surfaces, the percentage of brushing techniques used beyond horizontal scrubbing, or the appropriate use of interdental devices (all p > 0.16, all d < 0.30). Plaque persisted at the majority of the sections of the gingival margins, and the groups did not differ in this respect (p = 0.15; d = 0.22). SPOC values in the BP group were higher than those in the AU group (p = 0.006; d = 0.54). Both groups overestimated their actual oral cleanliness by approximately twofold. CONCLUSIONS: Compared to their usual brushing effort, study participants increased their effort when asked to brush their teeth in the best possible manner. However, that increase in effort was ineffective in terms of oral cleanliness. The results indicate that people's concept of optimized brushing refers to quantitative aspects (e.g., longer duration, more interdental hygiene) rather than qualitative aspects (e.g., considering inner surfaces and gingival margins, appropriate use of dental floss). TRIAL REGISTRATION: The study was registered in the appropriate national register ( www.drks.de ; ID: DRKS00017812; date of registration: 27/08/2019 - retrospectively registered).

Good role models? Tooth brushing capabilities of parents: a video observation study.

BACKGROUND: Research in adolescents reveals that they are not capable to remove dental plaque effectively. Inconsistent application of brushing techniques and neglect of certain areas while brushing are very common. As parents play a major role in the oral health education, the present study aimed to examine and describe the tooth brushing performance of the parents of adolescents. METHODS: Parents of adolescents (N = 66) were asked to perform oral hygiene to the best of their capabilities in front of a video camera and dental plaque was recorded before and afterwards. Papillary bleeding was also assessed. RESULTS: The tooth contact time (i.e. net brushing duration) averaged 155 s ± 58 s. Gingival margins showed persistent plaque at 68% ± 14% of the sections assessed. Papillary bleeding was found at 52% ± 18% of the papillae. Parents brushed inner surfaces lesser than the outer surfaces (41 s ± 24 s vs. 73 s ± 33 s) and 29% of the parents completely missed the inner surfaces of at least one sextant. On the outer surfaces parents predominantly applied circular movements (66% ± 25% of brushing time). Vertical brushing prevailed on the inner surfaces (52% ± 30%). However, horizontal scrubbing was also very common (46% ± 31%). CONCLUSIONS: Parents' tooth brushing performance was neither effective in terms of plaque removal nor did they fully comply with tooth brushing recommendations such as considering all inner surfaces when brushing or application of other than horizontal movements to lateral surfaces. Regarding oral hygiene, parents should not only be a good role model in terms of timing, frequency and duration of tooth brushing but should also be able to demonstrate how to brush teeth completely and effectively. The current research indicates that they might lack the latter skill.

COVISHIELD (AZD1222) VaccINe effectiveness among healthcare and frontline Workers of INdian Armed Forces: Interim results of VIN-WIN cohort study.

BACKGROUND: On 16 Jan 2021, India launched its immunization program against COVID-19. Among the first recipients were 1.59 million Health Care Workers (HCWs) and Frontline Workers (FLWs) of the Indian Armed Forces, who were administered COVISHIELD (Astra Zeneca). We present an interim analysis of vaccine effectiveness (VE) estimates till 30 May 2021. METHODS: The VIN-WIN cohort study was carried out on anonymized data of HCWs and FLWs of Indian Armed Forces. The existing surveillance system, enhanced for COVID-19 monitoring, was sourced for data. The cohort transitioned from Unvaccinated (UV) to Partially Vaccinated (PV) to Fully Vaccinated (FV), serving as its own internal comparison. Outcomes studied in the three groups were breakthrough infections and COVID related deaths. Incidence Rate Ratio (IRR) was used to compare outcomes among the three groups to estimate VE. RESULTS: Data of 1,595,630 individuals (mean age 27.6 years; 99% male) over 135 days was analysed. Till 30 May 21, 95.4% and 82.2% were partially and fully vaccinated. The UV, PV and FV compartments comprised 106.6, 46.7 and 58.7 million person-days respectively. The number of breakthrough cases in the UV, PV and FV groups were 10061, 1159 and 2512; while the deaths were 37, 16 and 7 respectively. Corrected VE was 91.8-94.9% against infections. CONCLUSION: Interim results of the VIN-WIN cohort study of 1.59 million HCWs and FLWs of Indian Armed Forces showed a ∼93% reduction in COVID-19 breakthrough infections with COVISHIELD vaccination.

Vaccination status and COVID-19 related mortality: A hospital based cross sectional study.

BACKGROUND: Efficacy of vaccines studied in clinical trial settings are likely to be different from their effectiveness in a real-world scenario. Indian Armed Forces launched its vaccine drive against COVID-19 on 16 Jan 2021. This study evaluated the effect of vaccination on mortality amongst hospitalized COVID patients. METHODS: A cross sectional study was done on all admitted moderate to severe COVID-19 patients at a designated COVID hospital in New Delhi. The primary outcome assessed the association of being fully vaccinated with mortality. Unadjusted odds ratios (OR) (with 95% CI) was performed for each predictor. Logistic regression was used for multivariable analysis and adjusted odds ratios obtained. RESULTS: The 1168 patients included in the study had a male preponderance with a mean age of 54.6 (± 17.51) years. A total of 266 (23%) patients were partially vaccinated with COVISHIELD® and 184 (16%) were fully vaccinated. Overall, 518 (44.3%) patients had comorbidities and 332 (28.4%) died. Among those fully vaccinated, there was 12.5% (23/184) mortality while it was 31.45 % (309/984) among the unvaccinated (OR 0.3, 95% CI 0.2 to 0.5, p<0.0001). In a logistic regression model, complete vaccination status and younger age were found to be associated with survival. CONCLUSIONS: Vaccination with two doses of COVISHIELD® was associated with lower odds of mortality among hospitalized patients with moderate to severe COVID.

Systematic review of predictive mathematical models of COVID-19 epidemic.

BACKGROUND: Various mathematical models were published to predict the epidemiological consequences of the COVID-19 pandemic. This systematic review has studied the initial epidemiological models. METHODS: Articles published from January to June 2020 were extracted from databases using search strings and those peer-reviewed with full text in English were included in the study. They were analysed as to whether they made definite predictions in terms of time and numbers, or contained only mathematical assumptions and open-ended predictions. Factors such as early vs. late prediction models, long-term vs. curve-fitting models and comparisons based on modelling techniques were analysed in detail. RESULTS: Among 56,922 hits in 05 databases, screening yielded 434 abstracts, of which 72 articles were included. Predictive models comprised over 70% (51/72) of the articles, with susceptible, exposed, infectious and recovered (SEIR) being the commonest type (mean duration of prediction being 3 months). Common predictions were regarding cumulative cases (44/72, 61.1%), time to reach total numbers (41/72, 56.9%), peak numbers (22/72, 30.5%), time to peak (24/72, 33.3%), hospital utilisation (7/72, 9.7%) and effect of lockdown and NPIs (50/72, 69.4%). The commonest countries for which models were predicted were China followed by USA, South Korea, Japan and India. Models were published by various professionals including Engineers (12.5%), Mathematicians (9.7%), Epidemiologists (11.1%) and Physicians (9.7%) with a third (32.9%) being the result of collaborative efforts between two or more professions. CONCLUSION: There was a wide diversity in the type of models, duration of prediction and the variable that they predicted, with SEIR model being the commonest type.

Tooth brushing performance in adolescents as compared to the best-practice demonstrated in group prophylaxis programs: an observational study.

BACKGROUND: Research indicates that adolescents may have difficulties to adopt the tooth brushing recommendations delivered in prophylaxis programs. However, it is not clear whether these difficulties are seen amongst the entire age range of adolescence (10-19 years) or only occur at certain developmental stages of the adolescence. The present study analyzes the tooth brushing performance of adolescents and compares it to the best-practice of tooth brushing demonstrated during prophylaxis programs. METHODS: A random sample of N = 66 adolescents, comprising 10-year-olds (n = 42) and 15-year-olds (n = 24), were asked to perform oral hygiene to the best of their abilities in front of a tablet camera. Videos were analyzed for tooth brushing duration, location, and brushing movements, and the difference between the actual and expected behaviour was tested for consistency using repeated measures ANOVAs and Student's t-tests. For the direct comparison across different age groups, already available data from 12- and 18-year-olds were reanalysed. RESULTS: The average brushing time (mean ± SD) of the 10-year-olds and 15-year-olds was 195.8 s (74.6 s) and 196.1 s (75.8 s), respectively. Regardless of age, the adolescents distributed their brushing time unevenly across the inner, outer and occlusal surfaces. The inner surfaces in particular were neglected to a considerable extent, as no age group spent more than 15.8% of the total brushing time on them. Furthermore, all age groups showed a high proportion of horizontal movements on the inner and outer surfaces, regardless of the movements instructed for the respective surfaces. CONCLUSION: Even if adolescents brush to the best of their abilities, they neglect or skip one or many of the tooth surfaces. The reasons for the lack of compliance to tooth brushing instructions are discussed in light of the methods used in prophylaxis programs and the influence of parents.

Coronavirus disease 2019 in India: Post-lockdown scenarios and provisioning for health care.

BACKGROUND: With the rise of Coronavirus disease 2019 (COVID-19) cases in India, lockdown was imposed from March 25, 2020. We studied post-lockdown scenarios and evaluated health-care constraints. Our aim was to identify the scenarios in which health-care availability would not be overwhelmed. METHODS: A modified compartmental SEIR stochastic model was used to calculate peak cases at various levels of effectiveness of prevention of transmission. Health-care constraints were evaluated using a Delphi study. We developed "q-metric" to evaluate the epidemic. Key constraints were matched against scenarios generated, and a monitoring mechanism was devised. RESULTS: Continuing lockdown ("q-metric" of >50) until mid-August was theoretically the most effective solution to end the epidemic. Lockdown might however be lifted earlier owing to various compulsions. The key constraints were identified as trained manpower and ventilators. It was estimated that shortfall of specialists to operate ventilators for COVID-19 intensive care units was approximately 40,000. This requires re-purposing of other specialists and short-term training to meet the surge. The shortage of ventilators is around 40,000-50,000. Procuring beyond those numbers would be infructuous owing to limits of training manpower. After lifting lockdown, the aim should be to contain the epidemic within the availability of key constraints. Our model suggests that this can be achieved by community containment and other non-pharmacological interventions at a "q-metric" of 19. An algorithm using "q-metric" was developed to monitor the epidemic. CONCLUSION: Various post-lockdown scenarios were simulated. Trained manpower and ventilators were identified as key health-care constraints. Partial community containment measures will require to be continued after the current lockdown is lifted.

Healthcare impact of COVID-19 epidemic in India: A stochastic mathematical model.

BACKGROUND: In India, the SARS-CoV-2 COVID-19 epidemic has grown to 1251 cases and 32 deaths as on 30 Mar 2020. The healthcare impact of the epidemic in India was studied using a stochastic mathematical model. METHODS: A compartmental SEIR model was developed, in which the flow of individuals through compartments is modeled using a set of differential equations. Different scenarios were modeled with 1000 runs of Monte Carlo simulation each using MATLAB. Hospitalization, intensive care unit (ICU) requirements, and deaths were modeled on SimVoi software. The impact of nonpharmacological interventions (NPIs) including social distancing and lockdown on checking the epidemic was estimated. RESULTS: Uninterrupted epidemic in India would have resulted in more than 364 million cases and 1.56 million deaths with peak by mid-July. As per the model, at current growth rate of 1.15, India is likely to reach approximately 3 million cases by 25 May, implying 125,455 (±18,034) hospitalizations, 26,130 (±3298) ICU admissions, and 13,447 (±1819) deaths. This would overwhelm India's healthcare system. The model shows that with immediate institution of NPIs, the epidemic might still be checked by mid-April 2020. It would then result in 241,974 (±33,735) total infections, 10,214 (±1649) hospitalizations, 2121 (±334) ICU admissions, and 1081 (±169) deaths. CONCLUSION: At the current growth rate of epidemic, India's healthcare resources will be overwhelmed by the end of May. With the immediate institution of NPIs, total cases, hospitalizations, ICU requirements, and deaths can be reduced by almost 90%.

Stem cell transplant in systemic sclerosis: An Indian experience.

AIM: To prospectively evaluate long term outcomes in a cohort of patients with Systemic sclerosis treated with Hematopoietic stem cell transplant (HSCT). METHOD: This is a prospective observational study of four SSc patients who underwent HSCT at a tertiary care center in India between 2008-2012. The selection criteria included young individuals with rapidly progressive disease and at least one major organ involvement. We used granulocyte colony-stimulating factor for peripheral blood stem cell mobilization, pre-transplant conditioning with fludarabine, cyclophosphamide and rabbit anti-thymocyte globulin followed by re-infusion of autologous stem cells as per standard institute protocol. RESULTS: A total of four patients (one male and three females) underwent autologous HSCT for SSc. Patients had heterogeneous disease manifestations including severe Raynaud's phenomenon with vasculopathic ulcers, gastrointestinal problems and mild interstitial lung disease (ILD). Patients were followed up for a mean duration of 7 years. There was significant sustained improvement in skin score, vasculopathy and gastrointestinal manifestations. Interstitial lung disease did not show any deterioration. The quality of life indices showed remarkable improvement in all subjects. No complications related to transplant were noted. CONCLUSION: In absence of an effective pharmacotherapy for SSc, autologous HSCT has a huge potential in management of cutaneous and internal organ manifestations.

HIV drug resistance following a decade of the free antiretroviral therapy programme in India: A review.

OBJECTIVE: The objective of this review was to assess the burden of HIV drug resistance mutations (DRM) in Indian adults exposed to first-line antiretroviral therapy (ART) as per national guidelines. METHODS: An advanced search of the published literature on HIV drug resistance in India was performed in the PubMed and Scopus databases. Data pertaining to age, sex, CD4 count, viral load, and prevalence of nucleoside reverse transcriptase inhibitor (NRTI)/non-nucleoside reverse transcriptase inhibitor (NNRTI) DRM were extracted from each publication. Year-wise Indian HIV-1 reverse transcriptase (RT) sequences were retrieved from the Los Alamos HIV database and mutation analyses were performed. A time trend analysis of the proportion of sequences showing NRTI resistance mutations among individuals exposed to first-line ART was conducted. RESULTS: Overall, 23 studies (1046 unique RT sequences) were identified indicating a prevalence of drug resistance to NRTI and NNRTI. The proportion of RT sequences with any DRM, any NRTI DRM, and any NNRTI DRM was 78.39%, 68.83%, and 73.13%, respectively. The temporal trend analysis of individual DRM from sequences retrieved during 2004-2014 indicated a rising trend in K65R mutations (p=0.013). CONCLUSIONS: Although the overall burden of resistance against first-line ART agents remained steady over the study decade, periodic monitoring is essential. There is the need to develop an HIV-1 subtype C-specific resistance database in India.

Predictors of first line antiretroviral therapy failure and burden of second line antiretroviral therapy.

BACKGROUND: As HIV steps into the third decade, there are more number of patients living on lifelong (antiretroviral therapy) ART and facing the threat of drug resistance with subsequent treatment failure. The aim of this study was to determine predictors of first-line ART failure with the objectives to estimate the burden of 2nd line ART. METHODS: A retrospective 5-year cohort of HIV patients who were initiated on first line ART in 2008-09 was studied. Patients were followed from the time of ART initiation. Kaplan-Meier methods and Cox proportional hazards regression models were used to estimate probabilities and predictors of first line ART failure. RESULTS: Of the total of 195 patients initiated on first line ART, 15 patients were switched to second line ART yielding 7.69% failure rate. During the 7178 person-years of follow-up, the incidence of first line ART failure was 2.09 per 1000 person-years. The Kaplan-Meier survival analysis gave a mean survival time of 55.6 months. BMI, CD4 count at ART initiation and presence of opportunistic infections were significant predictors of first line ART failure. The burden of second line ART patients by the end of 5 years of first line ART is expected to be 151 patients. CONCLUSION: Though the first line ART failure is quite low in this study, we still need to be vigilant for lower BMI, low baseline CD4 count and occurrence of opportunistic infections to efficiently manage failures on first line ART.

Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India.

The free antiretroviral therapy (ART) program in India has scaled up to register second largest number of people living with HIV/AIDS across the globe. To assess the effectiveness of current first-line regimen we estimated virological suppression on completion of 1 year of ART. The study describes the correlates of virological failure (VF) and multinucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations (DRMs).In this cross-sectional study conducted between June and August 2014, consecutive adults from 4 State sponsored ART clinics of western India were recruited for plasma viral load screening at 12 ±â€Š2 months of ART initiation. Individuals with plasma viral load >1000 copies/mL were selected for HIV drug resistance (HIVDR) genotyping. Logistic regression analyses were performed to assess factors associated with VF and multi-NRTI resistance mutations. Criteria adopted for multi-NRTI resistance mutation were either presence of K65R or 3 or more thymidine analog mutations (TAMs) or presence of M184V along with 2 TAMs.Of the 844 study participants, virological suppression at 1 year was achieved in 87.7% of individuals. Factors significantly associated with VF (P < 0.005) were 12 months CD4 count of ≤100 cells/µL (adjusted OR -7.11), low reported adherence (adjusted OR -4.44), and those living without any partner (adjusted OR -1.98). In patients with VF, the prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) DRM (78.75%) were higher as compared to NRTI (58.75%). Multi-NRTI DRMs were present in 32.5% of sequences and were significantly associated with CD4 count of ≤100 cells/µL at baseline (adjusted OR -13.00) and TDF-based failing regimen (adjusted OR -20.43). Additionally, low reported adherence was negatively associated with multi-NRTI resistance (adjusted OR -0.11, P = 0.015). K65R mutation was significantly associated with tenofovir (TDF)-based failing regimen (P < 0.001).The study supports early linkage of HIV-infected individuals to the program for ART initiation, adherence improvement, and introduction of viral load monitoring. With recent introduction of TDF-based regimen, the emergence of K65R needs to be monitored closely among HIV-1 subtype C-infected Indian population.

Synovial fluid proteome in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoinflammatory disorder that affects small joints. Despite intense efforts, there are currently no definitive markers for early diagnosis of RA and for monitoring the progression of this disease, though some of the markers like anti CCP antibodies and anti vimentin antibodies are promising. We sought to catalogue the proteins present in the synovial fluid of patients with RA. It was done with the aim of identifying newer biomarkers, if any, that might prove promising in future. METHODS: To enrich the low abundance proteins, we undertook two approaches-multiple affinity removal system (MARS14) to deplete some of the most abundant proteins and lectin affinity chromatography for enrichment of glycoproteins. The peptides were analyzed by LC-MS/MS on a high resolution Fourier transform mass spectrometer. RESULTS: This effort was the first total profiling of the synovial fluid proteome in RA that led to identification of 956 proteins. From the list, we identified a number of functionally significant proteins including vascular cell adhesion molecule-1, S100 proteins, AXL receptor protein tyrosine kinase, macrophage colony stimulating factor (M-CSF), programmed cell death ligand 2 (PDCD1LG2), TNF receptor 2, (TNFRSF1B) and many novel proteins including hyaluronan-binding protein 2, semaphorin 4A (SEMA4D) and osteoclast stimulating factor 1. Overall, our findings illustrate the complex and dynamic nature of RA in which multiple pathways seems to be participating actively. CONCLUSIONS: The use of high resolution mass spectrometry thus, enabled identification of proteins which might be critical to the progression of RA.

An integrated signal transduction network of macrophage migration inhibitory factor.

Macrophage migration inhibitory factor (MIF) is a glycosylated multi-functional protein that acts as an enzyme as well as a cytokine. MIF mediates its actions through a cell surface class II major histocompatibility chaperone, CD74 and co-receptors such as CD44, CXCR2, CXCR4 or CXCR7. MIF has been implicated in the pathogenesis of several acute and chronic inflammatory diseases. Although MIF is a molecule of biomedical importance, a public resource of MIF signaling pathway is currently lacking. In view of this, we carried out detailed data mining and documentation of the signaling events pertaining to MIF from published literature and developed an integrated reaction map of MIF signaling. This resulted in the cataloguing of 68 molecules belonging to MIF signaling pathway, which includes 24 protein-protein interactions, 44 post-translational modifications, 11 protein translocation events and 8 activation/inhibition events. In addition, 65 gene regulation events at the mRNA levels induced by MIF signaling have also been catalogued. This signaling pathway has been integrated into NetPath ( http://www.netpath.org ), a freely available human signaling pathway resource developed previously by our group. The MIF pathway data is freely available online in various community standard data exchange formats. We expect that data on signaling events and a detailed signaling map of MIF will provide the scientific community with an improved platform to facilitate further molecular as well as biomedical investigations on MIF.

A network map of Interleukin-10 signaling pathway.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine with important immunoregulatory functions. It is primarily secreted by antigen-presenting cells such as activated T-cells, monocytes, B-cells and macrophages. In biologically functional form, it exists as a homodimer that binds to tetrameric heterodimer IL-10 receptor and induces downstream signaling. IL-10 is associated with survival, proliferation and anti-apoptotic activities of various cancers such as Burkitt lymphoma, non-Hodgkins lymphoma and non-small scell lung cancer. In addition, it plays a central role in survival and persistence of intracellular pathogens such as Leishmania donovani, Mycobacterium tuberculosis and Trypanosoma cruzi inside the host. The signaling mechanisms of IL-10 cytokine are not well explored and a well annotated pathway map has been lacking. To this end, we developed a pathway resource by manually annotating the IL-10 induced signaling molecules derived from literature. The reactions were categorized under molecular associations, activation/inhibition, catalysis, transport and gene regulation. In all, 37 molecules and 76 reactions were annotated. The IL-10 signaling pathway can be freely accessed through NetPath, a resource of signal transduction pathways previously developed by our group.

Bilateral chylothorax as a complication of internal jugular vein cannulation.

Central venous catheterization is one of the most prevalent procedures in the Intensive Care Unit. Complications are reported in about 15% of the patients and usually comprise of infection, arterial puncture, malpositioning, pneumothorax, local hematoma, hemothorax, and so on. Chylothorax is a rare complication of this procedure. We present a 42-year-old lady, who developed bilateral massive chylothorax after cannulation of her left internal jugular vein (IJV), due to direct injury to the thoracic duct during the procedure. The patient was successfully managed with bilateral chest tube drainage and omission of oral feeds for four days. Development of bilateral chylothorax as a complication of IJV cannulation is rare, but merits reporting, in view of a large number of central venous cannulations being undertaken. Critical care professionals should be aware of this rare complication of a common procedure to facilitate early identification and institute appropriate therapy.