Search

Neurofibromatosis (NF) is an inherited neuroectodermal abnormality that primarily affects the growth of neural tissues, and Riccardi classified it into eight types. Segmental neurofibromatosis, which is a rare form of neurofibromatosis, is classified as type 5. We report a case for very unusual presentation of segmental NF with unilateral lisch nodules and uncommon sites involving the scalp. Moreover, we could find only one case report of segmental NF with lisch nodules in the literature and could not find any case report involving the scalp.

Management of an uncorrected broncho-oesophageal fistula in the perioperative period is a challenge for the anaesthesiologist. Positive pressure ventilation which is inevitable during surgery will lead to gastric insufflation and there is a high risk of aspiration of gastric contents. In this case report, we discuss how we used a double lumen tube to occlude a pericarinal broncho-oesophageal fistula. This method was quite effective as it obviated the need for isolating the lung as well as ensured smooth delivery of positive pressure ventilation during the surgery.

BACKGROUND Chronic hepatitis B (CHB) infection remains a significant public health issue for Indigenous Australians, in particular for remote communities. AIM This study aimed to evaluate the spectrum of hepatitis B virus (HBV) care provided to a remote Aboriginal community. Measures studied included screening, seroprevalence, vaccination rates and efficacy, and HCC risk and surveillance adherence. METHODS A retrospective audit of HBV care received by all permanent residents currently attending a remote Aboriginal Health service. This study was endorsed by both the local Aboriginal Health service and the Aboriginal Health Council of South Australia. RESULTS A total of 208 patients attended the clinic, of whom 52% (109) were screened for HBV. Of these, 12% (13) had CHB and 20% (22) had evidence of past infection. Similarly, of the 208 attending patients, complete vaccination was documented in 48% (99). Of the 33 patients with post-vaccination serology, 24% (8) had sub-therapeutic (

BACKGROUND AND AIMS: Recently, there has been a considerable increase in patients with nonalcoholic fatty liver disease. Availability of high-efficacy drugs for hepatitis B and hepatitis C virus (HCV) infection may have changed the disease prevalence. We aimed to study the impact of this changing epidemiology in patients undergoing liver transplantation (LT) over a 10-year period. METHODS: The study population was stratified into Period 1 (2009–2014) and Period 2 (2015–2019). Demographics, indications for LT and changes in the epidemiology between two periods were analysed. Aetiology-based posttransplant survival analysis was carried out. RESULTS: Indication for LT among 1017 adult patients (277 in Period 1 and 740 in Period 2) showed a significant increase in nonalcoholic steatohepatitis (NASH; 85 [30.7%] and 311 [42%]; P = 0.001), decrease in hepatitis C (49 [17.7%] and 75 [10.1%]; P = 0.002), and increase in hepatocellular carcinoma from Period 1 to Period 2 (13 [26.5%] to 38 [50.7%]; P = 0.009) among HCV patients. Patients transplanted for NASH had a lower 5-year survival compared with viral hepatitis (75.9% vs 87.4%; P = 0.03). There was a strong association between coronary artery disease and NASH (hazard ratio = 1.963, 95% confidence interval, 1.19–3.22). CONCLUSION: NASH is the leading indication for liver transplantation in India, surpassing viral hepatitis in recent years.

Background and Purpose: Stroke is the leading cause of death and long-term disability worldwide. Previous genome-wide association studies identified 51 loci associated with stroke (mostly ischemic) and its subtypes among predominantly European populations. Using whole-genome sequencing in ancestrally diverse populations from the Trans-Omics for Precision Medicine (TOPMed) Program, we aimed to identify novel variants, especially low-frequency or ancestry-specific variants, associated with all stroke, ischemic stroke and its subtypes (large artery, cardioembolic, and small vessel), and hemorrhagic stroke and its subtypes (intracerebral and subarachnoid). Methods: Whole-genome sequencing data were available for 6833 stroke cases and 27 116 controls, including 22 315 European, 7877 Black, 2616 Hispanic/Latino, 850 Asian, 54 Native American, and 237 other ancestry participants. In TOPMed, we performed single variant association analysis examining 40 million common variants and aggregated association analysis focusing on rare variants. We also combined TOPMed European populations with over 28 000 additional European participants from the UK BioBank genome-wide array data through meta-analysis. Results: In the single variant association analysis in TOPMed, we identified one novel locus 13q33 for large artery at whole-genome-wide significance ( P −9 ) and 4 novel loci at genome-wide significance ( P −8 ), all of which need confirmation in independent studies. Lead variants in all 5 loci are low-frequency but are more common in non-European populations. An aggregation of synonymous rare variants within the gene C6orf26 demonstrated suggestive evidence of association for hemorrhagic stroke ( P −6 ). By meta-analyzing European ancestry samples in TOPMed and UK BioBank, we replicated several previously reported stroke loci including PITX2 , HDAC9 , ZFHX3 , and LRCH1 . Conclusions: We represent the first association analysis for stroke and its subtypes using whole-genome sequencing data from ancestrally diverse populations. While our findings suggest the potential benefits of combining whole-genome sequencing data with populations of diverse genetic backgrounds to identify possible low-frequency or ancestry-specific variants, they also highlight the need to increase genome coverage and sample sizes.

INTRODUCTION Safely increasing organ donation to meet need is a priority. Potential donors may be declined due to perceived blood borne virus (BBV) transmission risk. With hepatitis C (HCV) curative therapy, more potential donors may now be suitable. We sought to describe potential deceased donors with increased BBV transmission risk. METHODS We conducted a cohort study of all potential organ donors referred in New South Wales, Australia, 2010-2018. We compared baseline risk potential donors to potential donors with increased BBV transmission risk, due to history of HIV, HCV or hepatitis B and/or behavioural risk factors. RESULTS There were 624/5749 potential donors (10.9%) perceived to have increased BBV transmission risk. This included 298/5749 (5.2%) with HCV (including HBV co-infections) and 239/5749 (4.2%) with increased risk behaviours (no known BBV). Potential donors with HCV and those with increased risk behaviours were younger and had fewer comorbidities than baseline risk potential donors (p

Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association of CHIP with COPD remains unclear. We analyzed whole-genome sequencing and whole-exome sequencing data to detect CHIP in 48 835 patients, of whom 8444 had moderate to very severe COPD, from four separate cohorts with COPD phenotyping and smoking history. We measured emphysema in murine models in which Tet2 was deleted in hematopoietic cells. In the COPDGene cohort, individuals with CHIP had risks of moderate-to-severe, severe, or very severe COPD that were 1.6 (adjusted 95% confidence interval [CI], 1.1-2.2) and 2.2 (adjusted 95% CI, 1.5-3.2) times greater than those for noncarriers. These findings were consistently observed in three additional cohorts and meta-analyses of all patients. CHIP was also associated with decreased FEV1% predicted in the COPDGene cohort (mean between-group differences, −5.7%; adjusted 95% CI, −8.8% to −2.6%), a finding replicated in additional cohorts. Smoke exposure was associated with a small but significant increased risk of having CHIP (odds ratio, 1.03 per 10 pack-years; 95% CI, 1.01-1.05 per 10 pack-years) in the meta-analysis of all patients. Inactivation of Tet2 in mouse hematopoietic cells exacerbated the development of emphysema and inflammation in models of cigarette smoke exposure. Somatic mutations in blood cells are associated with the development and severity of COPD, independent of age and cumulative smoke exposure.

Machine learning algorithms such as support vector machine (SVM) have been widely used to detect brain tumors in big data environments. However, the SVM classifier is unsuitable for a large dataset as the complexity involved is found to be high. Therefore, in this article, a MapReduce model is introduced with SVM to handle large-scale data and deal with this issue. In this article, a framework called mutual informative MapReduce and minimum quadrangle classification (MIMR-MQC) is introduced for brain tumor detection to handle challenges associated with big data classification. Here, preprocessing is performed using MIMR, which removes unwanted and redundant attributes in the brain tumor dataset. This technique reduces the computation complexity and time using a big dataset for detecting the brain tumors. Then, the minimum quadrangle support vector machine model is created using Lagrange multipliers and radial basis kernel function for improving the efficiency of the classification process. The MIMR-MQC framework is validated on a standard dataset called Central Brain tumor Registry of the United States (CBTRUS). Results show that the proposed model observed 21% of higher detection accuracy by minimizing the computational complexity and detection time by 37% and 27%, respectively in comparison with existing models. A comparison with state-of-the-art machine learning techniques, the MIMR-MQC framework performs better in terms of brain tumor detection time and accuracy due to the better distribution of data.

A 75-year-old man was initially admitted for elective inguinal hernia repair but was noted by the anaesthetist to have a ‘uvula-like’ mass in the oropharynx arising inferiorly, either from the base of the tongue or supraglottis, as seen in [figure 1][1]. He denied difficulties in swallowing

The development of colorectal cancer (CRC) is a multistage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of inflammation-associated CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC, through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.

Although there are immune checkpoint inhibitors (ICIs) available for the treatment of renal cell carcinoma (RCC), the utility of PD-L1 detection by immunohistochemistry (IHC) as a predictive biomarker in clear cell RCC (ccRCC) remains controversial. Nevertheless, alternative methods for PD-L1 detection, such as RNA sequencing (RNA-Seq), may be clinically useful in ccRCC; therefore, we sought to determine the ability of RNA-Seq to accurately and sensitively detect PD-L1 expression across different ccRCC clinical samples in comparison with IHC.Patients with ccRCC (n=127) who received treatment from Washington University in St. Louis between 2018 and 2020 were identified. Tumors from these patients were analyzed using RNA-Seq and IHC.PD-L1 detection by RNA-Seq strongly correlated with IHC (P.001), which was further validated using two independent datasets. Furthermore, RNA-Seq analysis identified an immune-enriched (higher PD-L1 positivity) and an immune-desert (lower PD-L1 positivity) microenvironment of ccRCC, which also correlated with IHC (P.00001).The results demonstrate the ability of RNA-Seq to detect PD-L1 in various ccRCC clinical samples compared to IHC. Ultimately, these findings suggest that PD-L1 detection by RNA-Seq can be further developed to determine the clinical utility of this methodology in ccRCC.

A pharmacy-based surveillance system in Kerala, India, has helped to improve TB patient notifications from the private sector, build better public-private partnerships, and improve the quality of TB diagnosis. Pharmacy-based surveillance has the potential to strengthen TB surveillance and facilitate standards of TB care., Key Findings Efforts to strengthen implementation of Schedule H1 regulation involved increasing advocacy efforts with the state government and local stakeholders, improving communication with stakeholders, educating chemists on data collection, and improving the quality of documentation of prescriptions.State program managers of the National TB Elimination Program used the information from Schedule H1 registers to identify missing TB cases and improve TB notification, identify providers who prescribe private anti-TB drugs and sensitize them to the Standards of TB Care in India, and sensitize providers on prescribing practices for TB. Key Implications Program managers may use pharmacy-based surveillance data judiciously to identify the missing TB cases, engage health care providers in prescribing practices, and improve the quality of TB diagnosis and care.Policy makers may realize the potential of pharmacy-based surveillance to improve TB patient notification, build public-private partnerships, and enhance standards for TB care., Introduction: Eleven anti-TB drugs were included in the Government of India's Schedule H1 drug regulations in 2014. The National Strategic Plan for TB Elimination in India 2017–2025 recognized the opportunity to strengthen the TB surveillance system and improve the quality of TB care by implementing the Schedule H1 regulation. However, there were no documented systematic large-scale efforts to use Schedule H1 regulation to support TB surveillance or improve the quality of care. We aimed to document the process of implementation of the Schedule H1 regulation to enhance the quality of TB care and strengthen the TB surveillance system in Kerala, India. Methods: We conducted 33 in-depth interviews of the drugs control department enforcement officers, chemist shop owners, private-sector doctors, leaders of professional medical associations, and program managers and key staff of the TB Elimination Program in Kerala. Major themes identified were the process of implementation of Schedule H1 and how the National TB Elimination Program used the information. Findings from the qualitative interviews were corroborated with the quantitative information from the annual program performance reports and anti-TB drug sales data. Results: The TB Elimination Program of Kerala used the information from the Schedule H1 drug register to identify the missing TB cases and strengthen TB notification, identify providers for engagement and extend support to them for ensuring standards of TB care, and provide feedback to providers regarding prescription practices. Stakeholders felt that implementation of Schedule H1 surveillance has helped to improve TB patient notifications from the private sector, build better public-private partnerships, and improve the quality of TB diagnosis and treatment in Kerala. Conclusion: Pharmacy-based drug sales data collected either through regulatory or non-regulatory methods have immense potential to support TB elimination programs.

OBJECTIVE Liver cirrhosis is a chronic disease complicated by recurrent hospital admissions. Self-management skills could facilitate optimal disease management. Currently there is no validated instrument for measuring self-management in these patients. Hence, we evaluated the internal reliability and construct validity of the Partners in Health (PIH) scale, a chronic condition self-management tool in cirrhotic patients. METHODS In this prospective cohort study, the PIH scale was administered to 133 consenting patients within a Chronic Liver Failure Program of a tertiary hospital from February 2017 to May 2018. A Bayesian confirmatory factor analysis (BCFA) was used to evaluate an a priori 4-factor structure. Omega coefficients and 95% credible intervals (CrI) were used to assess internal reliability. Known-group validity was assessed in patients receiving active case management (n = 60) versus those without (n = 73). RESULTS The mean (± standard deviation; SD) age of the participants was 62 (±11) years. Model fit for the hypothesised model was adequate (posterior predictive p-value = 0.073) and all hypothesised factor loadings were substantial (>0.6) and significant (p

Polydatin (POL) is an ingredient of many herbal medications and has pharmacological properties. The present study aimed to determine the antitumor potential of Polydatin loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (POL-PLGA-NPs) against the cancerous KB cell line. We evaluated the efficiency of synthesized nanoparticles on cell proliferation and apoptosis markers, in addition to the generation of reactive oxygen species (ROS) and its potential to induce damages on the mitochondrial membrane. Morphological changes in the cells (damage to DNA incurred due to cell lysis) were observed under Ethidium Bromide and Acridine orange staining techniques. The results evidenced the loss of cell viability, increased ROS, altered lipid peroxidation levels, increased DNA damage and loss of mitochondrial membrane potential in target cancerous KB cells. Further, immunoblot analysis quantified the expression of caspases-3, -9 and poly(ADP-ribose) polymerase (PARP) also supports the cell damage. Thus, the findings of the study suggested that POL-PLGA-NPs effectively induced oxidative stress by initiating cellular damage leading to apoptosis in KB cells.

BACKGROUND AND AIMS India has a significant burden of hepatitis C virus (HCV) infection and has committed to achieving national elimination by 2030. This will require a substantial scale-up in testing and treatment. The "HEAD-Start Project Delhi" aimed to enhance HCV diagnosis and treatment pathways among the general population. METHODS A prospective study was conducted at 5 district hospitals (Arm 1: one-stop shop), 15 polyclinics (Arm 2: referral for viral load (VL) testing and treatment) and 62 screening camps (Arm 3: referral for treatment). HCV prevalence, retention in the HCV care cascade, and turn-around time were measured. RESULTS Between January and September 2019, 37 425 participants were screened for HCV. The median (IQR) age of participants was 35 (26-48) years, with 50.4% male and 49.6% female. A significantly higher proportion of participants in Arm 1 (93.7%) and Arm 3 (90.3%) received a VL test compared with Arm 2 (52.5%, P

Background In adult right lobe living donor liver transplantation (LDLT), venous drainage of the anterior sector is usually reconstructed on the bench to form a neo-middle hepatic vein (MHV). Reconstruction of the MHV for drainage of the anterior sector is crucial for optimal graft function. The conduits used for reconstruction include cryopreserved allografts, synthetic grafts, or the recipient portal vein. However, the ideal choice remains a matter of debate. This study compares the efficacy of the native recipient portal vein (RPV) with PTFE grafts for reconstruction of the neo-MHV. Methods Patients in this equivalence-controlled, parallel-group trial were randomized to either RPV (62 patients) or PTFE (60 patients) for use in the reconstruction of the neo-MHV. Primary endpoint was neo-MHV patency at 14 days and 90 days. Secondary outcomes included 90-day mortality and post-transplant parameters as scored by predefined scoring systems. Results There was no statistically significant difference in the incidence of neo-MHV thrombosis at 14 days (RPV 6.5 per cent versus PTFE 10 per cent; P = 0.701) and 90 days (RPV 14.5 per cent versus PTFE 18.3 per cent; P = 0.745) between the two groups. Irrespective of the type of graft used for reconstruction, 90-day all-cause and sepsis-specific mortality was significantly higher among patients who developed neo-MHV thrombosis. Neo-MHV thrombosis and sepsis were identified as risk factors for mortality on Cox proportional hazards analysis. No harms or unintended side effects were observed in either group. Conclusion In adult LDLT using modified right lobe graft, use of either PTFE or RPV for neo-MHV reconstruction resulted in similar early patency rates. Irrespective of the type of conduit used for reconstruction, neo-MHV thrombosis is a significant risk factor for mortality. Registration number CTRI/2018/11/016315 (www.ctri.nic.in).

Background International Federation of Gynaecology and Obstetrics (FIGO) staging of carcinoma cervix, although essentially clinical, acknowledges the benefits of MRI. The impact of incorporating MRI in staging of cervical cancer and the discordance between clinical-and MRI-based FIGO staging is not well studied, especially in low- and middle-income countries. Aim We aim to study the role and accuracy of MRI in staging carcinoma cervix, its correlation with clinical FIGO and histopathological staging with emphasis on how it can change treatment plan. Methods Retrospective observational cohort study (n = 193) where MRI details of different staging parameters of the study subjects were compared with clinical FIGO staging and histopathology to assess correlation and agreement between them. Change of clinical FIGO stage and hence treatment plan brought about by incorporating MRI was assessed. Results MRI had a tumor detection rate of 94.3%, overall staging accuracy of 78.3% and very strong correlation with histopathology (Spearman's coefficient of rank correlation, r = 0.886). Clinical FIGO and MRI had agreement only in 52.8% cases (r = 0.61). Incorporating MRI changed the clinical stage in 47.2% patients and subsequently modified primary treatment plan in 23.3%. Conclusion MRI is highly accurate in evaluating carcinoma cervix and has good correlation with histopathology. Our data shows low agreement between MRI and clinical FIGO staging. Thus, incorporating MRI in FIGO staging has considerable impact in altering treatment decisions and should be offered to all patients for staging carcinoma cervix.

PURPOSE To systematically review and synthesize the findings on various professionals' perspectives of elder self-neglect (ESN) and/or their experiences with ESN. DESIGN A systematic qualitative review was used. METHODS Primary qualitative studies published either in English or Chinese until August 2020 were systematically searched in the following databases: PubMed, Web of Science, Embase, CINAHL Plus, PsycINFO, Wanfang Data, and China National Knowledge Infrastructure (CNKI). FINDINGS Eleven studies were included. Five subthemes including retaining a sense of normalcy/identity, service refusal, isolation, contributing factors in ESN, and manifestations and consequences of ESN were included in the overarching theme of ESN features. Another two subthemes, emotional and ethical dilemmas in caring for self-neglecters and management strategies, were included under the second overarching theme of complicated experiences managing cases of ESN. CONCLUSIONS This qualitative synthesis provides a deep and comprehensive insight into professionals' perspectives and experiences of self-neglect in older adults. Understanding professionals' perspectives of ESN can help with the knowledge and theory development pertinent to this particular phenomenon. CLINICAL RELEVANCE Findings are valuable in informing the provision of funds and structural, informational, and emotional support systems development for professionals managing ESN cases. Establishing a strong link between ESN case management and improved outcomes in older self-neglecters is essential to establish a definite need for the provision of support, resource, and stardardized guidelines for these professionals.

BACKGROUND To describe the pattern of gestational weight gain (GWG), derive reference centiles for GWG specific to North Indian population, and to compare the weight gain across different periods of gestation with the INTERGROWTH-21st reference. METHODS A prospective pregnancy (GARBH-Ini) cohort was initiated and followed between May 2015 and June 2019 in a district hospital, Gurguram, North India. GWG centile curves were modelled by Generalized Additive Models for Location, Scale and Shape method (n = 2844) and compared with INTERGROWTH-21st reference. The independent association of GWG with biological and social predictors was assessed using multivariable regression analysis. RESULTS Percentiles (3rd, 10th, 50th, 90th and 97th) for each completed week from 18-40 weeks of gestation were derived from smoothed centile curves. The median GWG across pregnancy during specific antenatal visits was 1.29 at 18, 4.44 at 26, 5.8 at 30 and 9.06 kg at 40 weeks of gestation. Nearly 26% of participants had GWG

Objective: The objective of present study was to develop hydrogel formulations loaded with Calotropis gigantea leaves extract. Methods: The prepared hydrogel formulations were compliance with their color, odor, homogeneity, pH, and spreadability. Results: As all the formulations were complies with the all parameters and it can be suggest as a Good antibacterial gel. It is evident that, ethanolic extract of Calotropis gigantea showed a maximum inhibitory zone against bacteria associated with foot ulcer. Conclusions: The In vitro studies showed a quantity dependent increase in antibacterial activity against foot ulcer causing bacteria, a contraction which is higher than that produced by the control groups. These contractions were statistically significant (p

Introduction: Renal dysfunction at presentation is uncommon in primary membranous nephropathy (PMN). The data on the outcome of PMN patients with renal dysfunction at outset are scarce. The objective of the current study was to report the clinical outcomes of PMN patients with renal dysfunction. Material and Methods: This prospective longitudinal observational study included PMN patients (both incident and treatment resistant) with an estimated glomerular filtration rate of 2. Immunosuppressive treatment was as per the unit’s protocol. Patients were evaluated for proteinuria, creatinine, and serum albumin at monthly intervals for 6 months, then quarterly for a year, and then biannually. Both serum and tissue anti-PLA2R were performed at baseline. Outcome: Percentage of patients achieving clinical remission. Results: Sixty-four adults met study criteria and were analysed. The median (IQR) age of the patients was 48 (40, 56) years. PMN was PLA2R related in 52 (81.3%) patients. Twenty-eight (43.8%) and 30 (46.9%) patients were in remission at 12 months and at the end of the study [median (IQR) follow up: 24 months (12, 35)], respectively. Eight (12.5%) had progressed to end-stage renal disease at the last follow-up. Median (IQR) baseline anti-PLA2R titre was 150.1 RU/mL (38.5, 308). Nineteen (61.3%) and 18 (58.1%) patients with >90% reduction in anti-PLA2R titres at 12 months were in clinical remission at 12 months and at the end of the follow-up, respectively. Both cyclical cyclophosphamide/steroids (cCYC/GC) and rituximab were equally effective in inducing remission, but rituximab had a favourable adverse event profile compared to cCYC/GC. Conclusion: To conclude, both cCYC/GC and rituximab are equally effective in inducing remission of nephrotic state with compromised renal function due to PMN. Immunosuppression induces remission in up to 50% PMN patients with CKD-stage 3–4.

Aging is associated with an increased prevalence of subclinical atherosclerosis and stiffening of the arterial walls (arteriosclerosis). These 2 coexisting conditions are mitigated by the presence of ideal cardiovascular health (optimal levels of fasting blood glucose, cholesterol, resting blood pressure, body mass index, no smoking, good dietary quality, and regular physical activity). We hypothesized that the concomitant presence of subclinical atherosclerosis (coronary artery calcification), arteriosclerosis (higher carotid-femoral pulse wave velocity), and suboptimal cardiovascular health is associated with increased risk of cardiovascular disease relative to the absence of these 3 conditions. We tested our hypothesis in the community-based Framingham Heart Study cohort (N=2580, mean age 52 years, 49% women). We classified participants based on (1) the presence versus absence of coronary artery calcium; (2) higher (>sex-specific median) carotid-femoral pulse wave velocity; (3) poor cardiovascular health (score 0–7). Thus, participants could have no abnormalities (referent group), 1, 2, or 3 suboptimal measures. We used Cox regression to relate the number of suboptimal measures (0–3) to the incidence of cardiovascular disease during follow-up (median 14 years). Cardiovascular disease incidence rates/1000 person-years in groups with 0 to 3 suboptimal measures were 1.93 (95% CI, 1.28–2.90), 4.68 (95% CI, 3.48–6.29), 8.93 (95% CI, 6.99–11.41), and 18.26 (95% CI, 14.65–22.77), respectively. Compared with the group with no abnormalities, corresponding multivariable-adjusted hazards ratios for cardiovascular disease were 1.81, 2.18, and 3.71, respectively ( P

Dose to the contralateral breast (CLB) from radiotherapy treatment has the potential to induce secondary breast cancer. Electronic tissue compensation (eComp) for breast cancer patients is one of the alternative methods to conventional 3D-conformal radiotherapy that eliminates the use of wedges. Several studies have investigated dose to the CLB using tangential fields involving wedges, intensity-modulated radiation therapy and volumetric modulated arc radiation therapy and various other techniques via treatment planning system calculations, Monte Carlo methods and phantoms. However, there are limited data published in assessing the actual dose received by the CLB from treatment with eComp-based tangential fields. In this study, the CLB dose for patients undergoing tangential field radiotherapy with eComp and enhanced dynamic wedged (standard) tangential fields was measured and compared to assess the CLB dose between the two methods. Measurements were conducted on a randomised trial of 40 patients, 20 of them had undergone standard planning, and the remaining 20 were treated with eComp. The mean surface dose measured with TLDs at 3cm from the medial tangential border for eComp and standard techniques was 10.04±1.37% and 10.14±2.05%, respectively for a prescription dose of 2.65Gy/fraction. The estimated dose at 1cm depth in tissue, measured with the use of perspex domes placed over the TLD at the same location, was 5.12±0.87% and 6.29±2.01% for eComp and standard, respectively. The CLB dose is dependent on the proximity of the medial tangential field edge to the contralateral breast and is patient-specific. The results of this study show that at 1cm depth, eComp technique delivers significantly less dose (p

PURPOSE For patients with surgically resected disease, multiple studies suggest a benefit of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in delaying cancer recurrence. The necessary duration of therapy for benefit is unknown. MATERIALS AND METHODS This randomized phase II study enrolled patients with completely resected stage IA-IIIB EGFR-mutant non–small-cell lung cancer (American Joint Committee on Cancer 7th edition) after stage-appropriate standard-of-care adjuvant therapy. Patients were randomly assigned 1:1 to 3 months or 2 years of adjuvant afatinib starting at 30 mg by mouth daily. Computed tomography imaging was performed every 6 months for 3 years and then annually. The primary study end point for this planned 92-patient trial was recurrence rate at 2 years from randomization. A 20% improvement (from 70% with 3 months to 90% with 2 years) was targeted. RESULTS Forty-six patients enrolled and 45 were treated. The assigned course of afatinib treatment was completed by 96% (22/23) of patients in the 3-month group and only 41% (9/22) in the 2-year group. The 2-year recurrence-free survival (RFS) rates were 70% in the 3-month group and 81% in the 2-year group ( P = .55). The median RFS was 42.8 months in the 3-month group and 58.6 months in the 2-year group. Side effects were consistent with those previously described for afatinib. CONCLUSION Recurrences at 2 years were 11% less common with 2 years versus 3 months of adjuvant afatinib. This difference did not meet the 20% primary study target, likely because of underaccrual and early drug discontinuation on the 2-year group. With the availability of osimertinib with better efficacy and tolerability than earlier-generation agents, the optimal duration of adjuvant EGFR TKI therapy remains an important question.

Objectives: This study sought to investigate the mortality associated with atrial fibrillation (AF) in men and women with heart failure (HF) according to the sequence of presentation and rhythm versus rate control. Background: The sex-specific epidemiology of AF in HF is sparse. Methods: Using the Danish nationwide registries, all first-time cases of HF were identified and followed for all-cause mortality from 1998 to 2018. Results: Among 252,988 patients with HF (mean age: 74 ± 13 years, 45% women), AF presented before HF in 54,064 (21%) and on the same day in 27,651 (11%) individuals, similar in women and men. Among patients without AF, the cumulative 10-year incidence of AF was 18.7% (95% confidence interval [CI]: 18.2% to 19.1%) in women and 21.3% (95% CI: 21.0% to 21.6%) in men. On follow-up (mean: 6.2 ± 5.8 years), adjusted mortality rate ratios were 3.33 (95% CI: 3.25 to 3.41) in women and 2.84 (95% CI: 2.78 to 2.90) in men if AF antedated HF, 3.45 (95% CI: 3.37 to 3.56) in women versus 2.76 (95% CI: 2.69 to 2.83) in men when AF and HF were diagnosed concomitantly, and 4.85 (95% CI: 4.73 to 4.97) in women versus 3.89 (95% CI: 3.80 to 3.98) in men when AF developed after HF. Compared with rate control for AF, a rhythm-controlling strategy was associated with lowered mortality in inverse probability–weighted models across all strata and in both sexes (hazard ratio: 0.75 to 0.83), except for women who developed AF after HF onset (hazard ratio: 1.03). Conclusions: More than half of all men and women with HF will develop AF during their clinical course, with prognosis associated with AF being worse in women than men. Further studies are needed to understand the underlying mechanisms.

Background & aims A unique model of care was adopted in Australia following introduction of universal subsidised direct-acting antiviral (DAA) access in 2016 in order to encourage rapid scale-up of treatment. Community-based medical practitioners and integrated hepatitis nurses initiated DAA treatment with remote hepatitis specialist approval of the planned treatment without physical review. We aimed to evaluate outcomes of community-based treatment of hepatitis C (HCV) through this remote consultation process in the first 12 months of this model of care. Methods A retrospective chart review of patients undergoing community-based HCV treatment from general practitioners and integrated hepatitis nurse consultants through the remote consultation model in three state jurisdictions in Australia from 1 March 2016 to 28 February 2017. Results SVR12 was confirmed in 383/588 (65.1%) subjects intended for treatment with a median follow-up time of 12 months (IQR 9-14 months). The SVR12 test was not performed in 159/588 (27.0%) and 307/588 (52.2%) did not have liver biochemistry rechecked following treatment. Subjects who completed follow-up exhibited high SVR12 rates (383/392,97.7%). Nurse-led treatment was associated with higher confirmation of SVR12 (73.7% v 62.4%, p = 0.01) and liver biochemistry testing post treatment (57.5% v 45.0%, p = 0.01). Conclusions Community-based management of HCV through remote specialist consultation may be an effective model of care. Failure to check SVR12, recheck liver biochemistry and appropriate surveillance in patients with cirrhosis may emerge as significant issues requiring further support, education and refinement of the model to maximise effectiveness of future elimination efforts. This article is protected by copyright. All rights reserved.

Background In individuals with chronic kidney disease (CKD), healthy dietary patterns are inversely associated with CKD progression. Metabolomics, an approach that measures many small molecules in biofluids, can identify biomarkers of healthy dietary patterns. Objectives We aimed to identify known metabolites associated with greater adherence to 4 healthy dietary patterns in CKD patients. Methods We examined associations between 486 known plasma metabolites and Healthy Eating Index (HEI)-2015, Alternative Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension (DASH) diet, and alternate Mediterranean diet (aMED) in 1056 participants (aged 21-74 y at baseline) in the Chronic Renal Insufficiency Cohort (CRIC) Study. Usual dietary intake was assessed using a semiquantitative FFQ. We conducted multivariable linear regression models to study associations between healthy dietary patterns and individual plasma metabolites, adjusting for sociodemographic characteristics, health behaviors, and clinical factors. We used principal component analysis to identify groups of metabolites associated with individual food components within healthy dietary patterns. Results After Bonferroni correction, we identified 266 statistically significant diet-metabolite associations (HEI: n = 60; AHEI: n = 78; DASH: n = 77; aMED: n = 51); 78 metabolites were associated with >1 dietary pattern. Lipids with a longer acyl chain length and double bonds (unsaturated) were positively associated with all 4 dietary patterns. A metabolite pattern low in saturated diacylglycerols and triacylglycerols, and a pattern high in unsaturated triacylglycerols was positively associated with intake of healthy food components. Plasmalogens were negatively associated with the consumption of nuts and legumes and healthy fat, and positively associated with the intake of red and processed meat. Conclusions We identified many metabolites associated with healthy dietary patterns, indicative of food consumption. If replicated, these metabolites may be considered biomarkers of healthy dietary patterns in patients with CKD.

Introduction Kidney Disease: Improving Global Outcomes (KDIGO) 2012 recommends cyclical cyclophosphamide plus glucocorticoids (GC) (modified Ponticelli regimen) or calcineurin inhibitors (CNIs) such as tacrolimus (TAC) or cyclosporine as the first-line agents for the management of primary membranous nephropathy (PMN) that is resistant to antiproteinuric therapy with renin-angiotensin system blockers. However, the long-term outcome of patients treated with CNIs is not known. Methods We report the outcomes of 70 patients randomized 1:1 to receive modified Ponticelli regimen or TAC/GC for renin-angiotensin system–resistant PMN who were prospectively followed for 6 years. Patients were followed monthly for 12 months, then quarterly for 12 months, and then every 6 months through the end of 6 years. Results At the end of 6 years, 21 (61.76%) and 9 (28.12%) patients maintained relapse-free remission in modified Ponticelli regimen and TAC/GC groups, respectively (relative risk [RR]: 2.19, 95% confidence interval [CI]: 1.23 to 4.15), and 30 (88.23%) and 17 (53.12%) patients were in remission (including relapses) in modified Ponticelli regimen and TAC/GC groups (RR: 1.66; 95% CI: 1.21 to 2.45), respectively. There was no significant difference in the proportion of patients who had a 40% decline in the estimated glomerular filtration rate (eGFR), death, or end-stage kidney disease between the groups. None of the patients treated with modified Ponticelli regimen reported a solid organ or hematological malignancy. Conclusions To conclude, in the long-term, modified Ponticelli regimen is superior to TAC/GC as first-line therapy for the management of antiproteinuric-resistant PMN., Graphical abstract

Inhaled corticosteroids (ICS) have a central role in the management of obstructive airway diseases. Use of ICS in asthma and chronic obstructive pulmonary disease (COPD) is associated with a small but clear increase in incidence of pneumonia and tuberculosis. Since ICS use in obstructive airway diseases has beneficial effects with regard to symptoms, lung function, quality of life and exacerbations, denying the benefit of ICS solely based on this small elevated risk of pneumonias and tuberculosis is not justified. The present article attempts to elucidate mechanisms contributing to the increased risk, assesses the magnitude and risk factors of tuberculosis in patients using ICS and provides practical suggestions for practising clinicians.

Study the changing clinical and therapeutic profiles of type 2 diabetes (T2D) patients during a 10-year period in a diabetes care centre in Southern India.Retrospective, cross-sectional data of newly registered and review patients at four periods between 2009 and 2018 were analysed (n = 50,322). Clinical findings, anthropometry, blood pressure (BP), glycaemia, lipids, treatment, and co-morbid conditions were analysed. We studied the trends in age and gender distributions, body mass index (BMI), glycaemia, (Glycosylated haemoglobin A1c (HbA1c) levels), BP, cholesterol, triglycerides and therapeutic regimen during this period. Trend analyses were done.Approximately 60% of patients were men. Percentages in 30-40 years increased, ∼60% were aged 50-69 years and proportion of older patients decreased (p 0.0001). In 10 years, 85.9% was overweight, obesity increased from 22.1% to 25.0% (p 0.0001) and13% maintained normal BMI. HbA1c7.0% remained approximately at 22%, percentage with moderate glycaemic control (HbA1c 7.0-7.9%) increased significantly, HbA1c of ≥9.0% decreased from 35.1% to 29.1% (p 0.0001). Use of monotherapy decreased. Prevalence of hypertension increased from 16.2% to 21.6% (p 0.0001); use of Angiotensin Receptor Blockers (ARB) and calcium channel blockers increased, Angiotensin Converting Enzyme Inhibitors and thiazides decreased (p 0.0001). Increased use of statins paralleled with reduction in total cholesterol and LDLc.Increasing percentages of younger patients and obesity, use of multiple drugs and reduction in HbA1c were the important observations. Rising prevalence of hypertension, increased use of ARB and statins with better control of dyslipidaemia was observed. Achievement of ideal HbA1c and BP were suboptimal.

Background Cognitive decline is a non-hemorrhagic, major complication of intracranial dural arteriovenous fistula (DAVF), thought to be primarily related to venous hypertension. However, imaging features to predict cognitive decline are scanty in the literature. Purpose To evaluate functional connectivity (FC) changes of resting-state networks (RSNs) in DAVF before and after treatment and its relation to cognitive impairment. Study type Prospective. Subjects DAVF subjects were screened for inclusion. Pre-embolization (N = 33, mean age 45.9 years, 29 males), 1 month post-embolization (N = 20, mean age 42.7 years, 19 males), and healthy controls (HC, N = 33, mean age 45.09 years, 27 males). Field strength/sequence 3.0 T, resting-state functional magnetic resonance imaging (MRI), three-dimensional (3D) T1, T2 fast spin echo (FSE), diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), fluid-attenuated inversion recovery, and time of flight. Assessment Data quality assessment was performed. FC analysis was done using group independent component analysis (ICA) and seed to voxel analysis. Neuropsychology (NP) scores of patients were compared with HC and correlated with FC changes. Statistical tests Voxel-wise parametric T-statistics for F-test was executed in FC analysis (p-FDR corrected Results Both RSNs analysis methods showed reduced FC at the precuneus-posterior cingulate cortex (PC-PCC) of default mode network (DMN), anterior cingulate cortex (ACC) of the salience network (SN), and possible compensatory increased connectivity at the frontoparietal (FPN) and dorsal attention (DAN) networks. DAVF with low NP scores showed reduced FC at DMN and SN and minimal to absent connectivity at FPN and DAN. At post-embolization 1-month follow-up, improvement in FC at PC-PCC of DMN and ACC of SN were noted. Data conclusion RS-fMRI in DAVF displayed FC changes that may be related to cognitive decline and its subsequent reversibility after treatment. FC changes at DMN, SN, FPN, and DAN were linked to cognitive decline and the corresponding NP scores. Level of evidence 2 TECHNICAL EFFICACY: Stage 2.

Background Junctional kyphosis (JK) is usually observed in long-level instrumented fusion surgeries. Various contributing factors are proposed, the pre-existing and postoperative spinal imbalance is considered as the single most important factor for the development of JK in adult spinal deformity surgeries. Distal JK (DJK) is seldom reported compared to proximal JK (PJK), and scarce literature exists. Methods We report 2 unique cases of distal junctional failure (DJF) with worsening of neurology, secondary to nontraumatic fracture of a lower instrumented vertebra operated for thoracic canal stenosis without deformity. The first case had acute worsening of the Neurology during follow up and on evaluation, the supine CT and MRI scan revealed well decompressed spinal canal, no implant migration to the canal, no screw loosening, or rod failure. Supine sitting radiographs demonstrated DJK with Fracture and the patient underwent extension of fusion till the pelvis with 3-rod construct and interbody fusion, because of the instability at the L1 level. The second case remained neurologically stable for a month and then had an acute onset of back pain, sensory deficit, and urine incontinence. The supine-sitting dynamic radiograph done demonstrated L1 fracture with DJK at D12–L1 levels. The patient was counseled for extension of fusion, which was deferred by the patient. Results Patients in our series, had an acute worsening of neurological deficit within a month of posterior spinal fixation. Their supine imaging was almost normal, and the diagnosis of DJK with L1 fracture instability was possible only on a supine-sitting dynamic radiograph. Various factors like obesity, TL kyphosis, osteoporosis, etc. can be the attributing factors for the development of DJK Conclusion A high index of suspicion is required for diagnosing nontraumatic fracture in long-level fusion patients with acute neurological worsening. The supine-sitting dynamic radiograph is an important diagnostic tool for DJF in patients having difficulty standing erect. Level of Evidence 4. Clinical Relevance Application of sitting and supine dynamic radiographs to diagnose instability in patients unable to stand for flexion and extension radiographs.

Background: The background of the work stems from the observation due to the prevalence of antipsychotic drugs in causing metabolic disorder. The metabolic disorder is one of the major concern of antipsychotic drugs for schizophrenic patients. The present study is mainly aimed to establish the role of haloperidol and risperidone or olanzapine in causing metabolic syndrome of schizophrenic patients. Methods: Sixty-four schizophrenic patients were divided into two groups. First and second group received haloperidol and risperidone or olanzapine respectively for three months. Body mass index, random blood sugar and lipid profile were investigated before and after the treatment. Results: Both groups of schizophrenic patients have shown a significant increase in the BMI, random blood sugar and lipid profile indicating a propensity to cause metabolic disorder. Conclusion: From the present study it is concluded that there is a high prevalence of metabolic disorder those who received antipsychotic drugs like haloperidol and risperidone or olanzapine.

Background and Purpose: Novel noninvasive measures of vascular function are emerging as subclinical markers for cardiovascular disease (CVD) and may be useful to predict CVD events. The purpose of our prospective study was to assess associations between digital peripheral arterial tonometry (PAT) measures and first-onset major CVD events in a sample of FHS (Framingham Heart Study) participants. Methods: Using a fingertip PAT device, we assessed pulse amplitude in Framingham Offspring and Third Generation participants (n=3865; mean age, 55±14 years; 52% women) at baseline and in 30-second intervals for 4 minutes during reactive hyperemia. The PAT ratio (relative hyperemia index) was calculated as the post-to-pre occlusion pulse signal ratio in the occluded arm, relative to the same ratio in the control (nonoccluded) arm, and corrected for baseline vascular tone. Baseline pulse amplitude and PAT ratio during hyperemia are measures of pressure pulsatility and microvascular function in the finger, respectively. We used Cox proportional hazards regression to relate PAT measures in the fingertip to incident CVD events. Results: During follow-up (median, 9.2 years; range, 0.04–10.0 years), 270 participants (7%) experienced new-onset CVD events (n=270). In multivariable models adjusted for cardiovascular risk factors, baseline pulse amplitude (hazard ratio [HR] per 1 SD, 1.04 [95% CI, 0.90–1.21]; P =0.57) and PAT ratio (HR, 0.95 [95% CI, 0.84–1.08]; P =0.43) were not significantly related to incident composite CVD events, including myocardial infarction or heart failure. However, higher PAT ratio (HR, 0.76 [95% CI, 0.61–0.94]; P =0.013), but not baseline pulse amplitude (HR, 1.15 [95% CI, 0.89–1.49]; P =0.29), was related to lower risk for incident stroke. In a sensitivity analysis by stroke subtype, higher PAT ratio was related to lower risk of incident ischemic stroke events (HR, 0.68 [95% CI, 0.53–0.86]; P =0.001). Conclusions: Novel digital PAT measures may represent a marker of stroke risk in the community.

BACKGROUND: Glaucoma and ocular hypertension (OHT) are prevalent diseases with baseline intraocular pressure (IOP) elevations that future astronauts and spaceflight participants may suffer from. Preflight, in-flight, and postflight IOP measurements were collected aboard two U.S. Space Shuttle Program missions in normotensive control, OHT, and glaucomatous crewmembers. METHODS: Five subjects (three controls, one glaucomatous, one OHT) were studied aboard 2-wk Space Shuttle missions. Baseline IOP (triplicate; handheld tonometry) was recorded during training 12 mo preflight, in flight (114 d), and postflight (329 d). Subjective symptoms were recorded via questionnaires. Data were analyzed using a spreadsheet with two-sample t-tests. P-value < 0.05 determined significance. RESULTS: IOP increased for all in-flight vs. preflight measurements for controls (N 3, 48.9, 16.9, 5.85), OHT (N 1, 20.3), and glaucomatous (N 1, 32.2) groups. IOP eventually returned to baseline postflight [Return (R)35 d], except for the astronaut with OHT (R917). Subjective symptoms, likely multifactorial, included blurredvision, decreased visual acuity, and headaches. DISCUSSION: IOP increased during spaceflight and normalized upon return. Astronauts and commercial spaceflight participants may need screening for elevated IOP to potentially prevent sequelae related to glaucoma and OHT, the former which requires treatment in flight and the latter which may need prophylaxis. Previous studies have shown elevated IOP upon entry into microgravity with various normalization timeframes in flight and postflight. It is unclear how increased IOP relates to spaceflight-associated neuro-ocular syndrome (SANS); however, several hypotheses exist. Treatment strategies should be available for acute and chronic ocular pathology during spaceflight despite the unique challenges of eye-drop application in microgravity. Dalal SR, Ramachandran V, Khalid R, Manuel FK, Knowles JR, Jones JA. Increased intraocular pressure in glaucomatous, ocular hypertensive, and normotensive space shuttle crew. Aerosp Med Hum Perform. 2021; 92(9):728733.

Purpose To examine the benefits and feasibility of a mobile, real-time, community-based, teleophthalmology program for detecting eye diseases in the New York metro area. Design Single site, nonrandomized, cross-sectional, teleophthalmologic study. Methods Participants underwent a comprehensive evaluation in a Wi-Fi-equipped teleophthalmology mobile unit. The evaluation consisted of a basic anamnesis with a questionnaire form, brief systemic evaluations and an ophthalmologic evaluation that included visual field, intraocular pressure, pachymetry, anterior segment optical coherence tomography, posterior segment optical coherence tomography, and nonmydriatic fundus photography. The results were evaluated in real-time and follow-up calls were scheduled to complete a secondary questionnaire form. Risk factors were calculated for different types of ophthalmological referrals. Results A total of 957 participants were screened. Out of 458 (48%) participants that have been referred, 305 (32%) had glaucoma, 136 (14%) had narrow-angle, 124 (13%) had cataract, 29 had (3%) diabetic retinopathy, 9 (1%) had macular degeneration, and 97 (10%) had other eye disease findings. Significant risk factors for ophthalmological referral consisted of older age, history of high blood pressure, diabetes mellitus, Hemoglobin A1c measurement of ≥6.5, and stage 2 hypertension. As for the ocular parameters, all but central corneal thickness were found to be significant, including having an intraocular pressure >21 mm Hg, vertical cup-to-disc ratio ≥0.5, visual field abnormalities, and retinal nerve fiber layer thinning. Conclusions Mobile, real-time teleophthalmology is both workable and effective in increasing access to care and identifying the most common causes of blindness and their risk factors.

Objective To examine the relationship of visual function as assessed by visual acuity, contrast sensitivity, and multifocal electroretinography (mfERG) to macular structural and microvascular measures on optical coherence tomography (OCT) and angiography (OCTA) in individuals with diabetes. Methods This is a prospective observational study conducted at a tertiary eye care centre in India. Right eyes of 121 adults with type 2 diabetes with no diabetic retinopathy (DR), mild or moderate nonproliferative DR (NPDR) were examined. Severe NPDR, proliferative DR and diabetic macular oedema were excluded. Participants underwent assessment of glycated haemoglobin (HbA1C), blood pressure, best corrected visual acuity (LogMAR), contrast sensitivity (CS), mfERG, ultrawide field fundus photography, OCT and OCTA. Correlations were assessed by Spearman's rank correlation (rho). Results Of the total of 121 eyes, 89 had No DR, 32 had mild to moderate NPDR. In the No DR group, the LogMAR acuity was significantly and negatively correlated to central subfoveal thickness (CST) (rho = -0.420), macular vessel density (rho = -0.270) and perfusion (rho = -0.270). (ii) Contrast sensitivity correlated to foveal avascular zone circularity (rho = 0.297); (iii) mfERG P1 response densities were better with higher macular perfusion index (rho = 0.240). In the NPDR group, the LogMAR acuity also showed a significant negative correlation to CST (rho = -0.379). Other correlations were not significant. Conclusion Retinal and visual functional changes are evident in diabetic patients with No DR and are correlated to subclinical retinal structural changes detectable using multimodal imaging.

OBJECTIVE Despite the availability of effective medications, only a minority of asthma patients achieve guideline defined asthma control. Treatment success depends on patient concurrence to the prescribed drug and adherence to treatment. It is therefore crucial to identify the patient preferences as well as attitudes towards asthma medications. Omalizumab is recommended as a preferred option in step 5 of asthma therapy. There have been few studies to address patient perspectives on omalizumab therapy in India. METHODS This was a retrospective study. Patients with inadequate asthma control were considered for the study. Systematic evaluation was done to identify and correct modifiable factors that can worsen asthma control. Patients with persisting poor asthma control who were deemed suitable to receive this agent were evaluated with their attitudes toward acceptance or refusal and the reasons for opting out were noted. The patients who received omalizumab were followed up to determine the results of treatment and duration of adherence to therapy. RESULTS Thirty-five patients out of 51 patients chose to avoid this drug. The reasons for opting out included erroneous perception of optimal asthma control, cost of therapy, and concern about adverse effects. Patients took omalizumab for a median duration of 6 months. Improved asthma control and decreased frequency of exacerbation was noted in all patients which persisted during the 6-month follow-up. CONCLUSIONS The majority of patients needing step 5 therapy opt out of omalizumab. Cost of drug, duration of therapy and erroneous perception of good asthma control account for refusing treatment. Omalizumab affords excellent clinical benefits to patients who receive it, and the benefits extend beyond the duration of therapy.

N-acetylcysteine (NAC) is the only clinically approved antidote against acetaminophen (APAP) hepatotoxicity. Despite its efficacy in patients treated early after APAP overdose, NAC has been implicated in impairing liver recovery in mice. More recently, 4-methylpyrazole (4MP, Fomepizole) emerged as a potential antidote in the mouse APAP hepatotoxicity model. The objective of this manuscript was to verify the detrimental effect of NAC and its potential mechanism and assess whether 4MP has the same liability. C57BL/6J mice were treated with 300 mg/kg APAP; 9 h after APAP and every 12 h after that, the animals received either 100 mg/kg NAC or 184.5 mg/kg 4MP. At 24 or 48 h after APAP, parameters of liver injury, mitochondrial biogenesis and cell proliferation were evaluated. Delayed NAC treatment had no effect on APAP-induced liver injury at 24 h but reduced the decline of plasma ALT activities and prevented the shrinkage of the areas of necrosis at 48 h. This effect correlated with down-regulation of key activators of mitochondrial biogenesis (AMPK, PGC-1α, Nrf1/2, TFAM) and reduced expression of Tom 20 (mitochondrial mass) and PCNA (cell proliferation). In contrast, 4MP attenuated liver injury at 24 h and promoted recovery at 48 h, which correlated with enhanced mitochondrial biogenesis and hepatocyte proliferation. In human hepatocytes, 4MP demonstrated higher efficacy in preventing cell death compared to NAC when treated at 18 h after APAP. Thus, due to the wider treatment window and lack of detrimental effects on recovery, it appears that at least in preclinical models, 4MP is superior to NAC as an antidote against APAP overdose.

A nurse-led cirrhosis clinic model for management of stable, compensated cirrhotic patients is practised in our unit since 2013, wherein these patients are reviewed every six months by specialist nurses in community clinics under remote supervision of hepatologists. We evaluated the experiences of patients and healthcare providers involved in the model to understand the acceptability, strengths, and limitations of the model and obtain suggestions to improve. A qualitative design using in-depth interviews was employed, followed by thematic analysis of eight patients, one attending physician both nurse and hospital clinics, four hepatologists, and three experienced specialist nurses running the nurse-led cirrhosis clinic. Patients expressed satisfaction and a good understanding of the nurse-led cirrhosis clinic, preferring it to hospital clinics for better accessibility and the unique nurse-patient relationship. Upskilling and provision of professional care in a holistic manner were appreciated by specialist nurses. The hepatologists expressed confidence and satisfaction, although they acknowledged the difference between the medical training of specialist nurses and hepatologists. The greater availability of hospital clinic time for sick patients was welcomed. Increased specialist nurse staffing, regular forums to promote specialist nurse learning, and formalization of the referral process were suggested. No adverse experiences were reported by patients or staff. The nurse-led cirrhosis clinic model for compensated liver cirrhosis was well received by patients, hepatologists, and specialist nurses. Wider implementation of the model could be considered after further investigations in other settings.

Background Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing. Methods The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation Results We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10−8) on chromosome X with ARMCX3. Additional rare-variant associations include ARMCX3-AS1, MRPS33, and C16orf90. Novel common-variant loci were identified in the NRG1 and SLC45A2 regions, and previously associated loci in the IL18RAP and ATP2B4 regions were associated with novel phenotypes. Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Additional analyses identified significantly associated pathways. Conclusions We have identified the first gene-based rare-variant associations with objectively measured sleep-disordered breathing traits. Our results increase the understanding of the genetic architecture of sleep-disordered breathing and highlight associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis, and HIF1A-mediated hypoxic response.

Introduction Association between arterial vascular dysfunction and risk of venous thromboembolism (VTE) is uncertain. We determined the associations between comprehensive measures of arterial vascular function and risk of incident VTE in a community-based cohort study with robust longitudinal follow-up. Materials and methods In the Framingham Heart Study Original, Offspring, Third Generation, and Omni cohorts, we measured carotid-femoral pulse wave velocity and central pulse pressure (n = 8261, age 51.5 ± 15.5 years, 54% women), flow-mediated dilation and hyperemic velocity (n = 6540, age 47.9 ± 14.1 years, 54% women), and peripheral arterial tonometry ratio (n = 4998, age 54.3 ± 16.0 years, 52% women). Deep venous thrombosis and pulmonary embolism were diagnosed with imaging studies and adjudicated by three Framingham Heart Study physicians. Results and conclusions The rate of incident VTE was 1.6–2.1 per 1000 person-years during mean follow-up of 8.5–11.2 years. In age- and sex-adjusted Cox proportional hazards regression models, carotid-femoral pulse wave velocity was associated with increased risk of VTE (HR 1.32, 95% CI 1.05–1.66, p = 0.02), however the association was no longer statistically significant after multivariable adjustment (HR 1.24, 95% CI 0.96–1.61, p = 0.10). None of the other vascular variables were associated with the risk of VTE in any of the models. In our comprehensive examination of arterial vascular function and risk of VTE, we did not observe any association between select arterial function measures and risk of VTE after multivariable adjustment.

Objective To determine the threshold of the inotropic score (IS) and vasoactive–inotropic score (VIS) for predicting mortality in pediatric septic shock. Method This retrospective cohort study included children aged 1 mo to 13 y with septic shock, requiring vasoactive medication. The area under curve receiver operating characteristic (AUROC) was calculated using mean IS and mean VIS to predict PICU mortality, and Youden index cut points were generated. Sensitivity, specificity, and binary regression analysis were performed. Results A total of 176 patients were enrolled (survivor, n = 72, 41% and nonsurvivor, n = 104, 59%). For predicting the PICU mortality, AUROC (95% CI) of IS was 0.80 (0.74–0.86) [sensitivity of 88.5 (80.7–94) and specificity of 58.3 (46.1–69.8)] and AUROC of VIS was 0.88 (0.82–0.92) [sensitivity of 83.7 (75.1–90.2) and specificity of 80.6 (69.5–89)]. The respective cutoff scores of IS and VIS were 28 and 42.5. On regression analysis (adjusted odds ratio, 95% CI), illness severity (PRISM-III) (1.12, 1.05–1.12), worst lactate value (1.31, 1.08–1.58), IS (> 28) (3.98, 1.24–12.80), and VIS (> 42.5) (4.66, 1.57–13.87) independently predicted the PICU mortality (r2 = 0.625). Conclusion Threshold of inotropic score (> 28) and vasoactive–inotropic score (> 42.5) were independently associated with PICU mortality. In addition to IS and VIS, severity and worst lactate value independently predicted septic shock mortality in PICU.

The drug of choice in the treatment of postmenopausal osteoporosis is alendronate. Antidepressive agents are currently used in combination with alendronate to protect against depression and may affect the condition of osteoporosis. The aim is to study the comparative effects of venlafaxine and alendronate on biochemical, bone mechanical and anti-inflammatory properties in osteoporotic induced rats. 36 female Wistar albino rats were included (6 rats/group). Treated groups were ovariectomized bilaterally to induce osteoporosis. Rats were treated orally with alendronate (3mg/kg/day) and venlafaxine (20mg/kg/day) and combined alendronate and venlafaxine for 28 days. Body weight, serum alkaline phosphates, serum calcium, three point bending test, bone mineral mass and inflammatory cytokines The induction of osteoporosis showed significant elevated serum alkaline phosphatase, decreased serum calcium, body weight, bone mineral mass and inflammatory cytokines. Venlafaxine treatment did not ameliorate the changes in tested parameters, where at end of the experiment alendronate has significant improved with serum alkaline phosphatase, serum calcium, bone mineral mass, bone mineral density. The improvement was not affected by combining venlafaxine with alendronate whereas the venlafaxine treatment alone caused a significant deterioration of tested parameters. Venlafaxine is an anti-depressive agent that inhibits brain serotonin which leads to decrease in bone formation. Hence, from the above findings the combination of alendronate and venlafaxine showed worsen the condition of osteoporosis rats.

Objective: Goodpasture's syndrome (GPS) is the association of pulmonary haemorrhage with acute kidney injury (AKI) resulting from injury by auto-antibodies. Its de novo occurrence in pregnancy is extremely rare with only few cases reported. High risk of mortality and lack of consensus in treatment warrants its reporting. Case report: A 24 year old primigravida, with no history suggestive of renal disease, presented to us in her third trimester with anuria. She was initially managed as sepsis or preeclampsia related AKI. However, even after delivery there was no improvement in kidney function with hemodialysis and she developed hemoptysis. Renal biopsy made a diagnosis of Anti-Glomerular Basement Membrane disease. With careful multi-disciplinary treatment, she delivered a live born baby and was discharged under stable condition on hemodialysis, currently awaiting a kidney transplant. Conclusion: This case highlights that the current management for GPS should be revised to improve the outcome of AKI. Also, it determines how important it is for obstetricians to consider whether a pregnancy should be terminated to improve the outcome of AKI in pregnant patients with GPS

Aim To measure the influence of rotatory pediatrics postings for dental residents on the outpatient census of the pediatric dentistry department. The secondary aims were to assess the change in trend toward the number of preschool children visiting the department before and after the initiation of pediatrics posting and also to find the percentage of children affected with caries among children visiting the pediatricians. Materials and methods Retrospectively, the census of the pediatric dentistry department was calculated from 2010 to 2016. The number of preschool children who visited the pediatric dentistry department during this period was determined. From the pediatrics posting records, the dental status of the children, the number screened, the number referred, and the number reported to dentistry following referral were tabulated. Descriptive statistics and Chi-square tests were performed. Results After the initiation of pediatrics postings for residents, the outpatient census has increased by 26%. There was a significant increase in the number of preschool children visiting the pediatric dentist. About 57.09% of children screened in the pediatrics department had dental disease. Conclusion There is an increase in the patient flow of the pediatric dentistry department with a greater number of preschool children visiting the pediatric dentist after initiation of the pediatrics postings for residents. More than half the children visiting pediatricians had dental disease requiring professional care. Clinical significance Pediatrics postings for residents can be used in teaching centers as an opportunity to spread awareness and increase the number of preschool children visiting pediatric dentists, thereby increasing prevention and early intervention of early childhood caries. How to cite this article Mohan A, Muthu MS, Ramachandran P, et al. Impact of Pediatric Dentistry Residents Posted in Pediatrics Department: A Retrospective Assessment of 6 Years. Int J Clin Pediatr Dent 2021;14(1):84–87.

BACKGROUND: Chronic non-cancer pain (CNCP) is highly prevalent in older adults and long-term opioid therapy (LTOT) has been used to manage chronic pain. However, the safety of LTOT among older adults with CNCP is not well-established and there is a need to identify therapy-related risk factors of opioid-related adverse events among older adults. OBJECTIVE: To evaluate the relationship between opioid dose and formulation and the risk of opioid-related adverse events among Medicare-eligible older adults on LTOT. DESIGN: Nested case-control study. PARTICIPANTS: Older Medicare beneficiaries (N=35,189) who received > 3 opioid prescriptions with a total days-supply of >45 days within a 90-day period for CNCP between 2012 and 2016. MAIN MEASURES: This study utilized Medicare 5% medical and prescription claims data. Outcome measures included opioid-induced respiratory depression (OIRD), opioid overdose, all-cause mortality, and a composite outcome, defined as the first occurrence of any of the previous three events. Key independent variables were opioid formulation and opioid dose (measured in morphine milligram equivalents (MME)) prescribed during LTOT. KEY RESULTS: Seventy-four OIRD, 133 overdose, 982 all-cause mortality, and 1122 composite outcome events were observed during follow-up. In unadjusted analyses, the use of combination opioids (OR: 4.52 [95%CI: 1.51–13.47]) was significantly associated with OIRD compared to short-acting (SA) opioids. In adjusted analyses, opioid-related adverse events were significantly associated with the use of LA (overdose OR: 13.00 [95%CI: 1.30–130.16] and combination opioids (overdose OR: 6.27 [95%CI: 1.91–20.55]; mortality OR: 2.75 [95%CI: 1.87–4.04]; composite OR: 2.82 [95%CI: 2.01–3.96]) when compared to SA opioids. When compared to an average dose of less than 20 MME, outcomes were significantly associated with doses of 20–50 MME (mortality OR: 1.61 [95%CI: 1.24–2.10]; composite OR: 1.59 [95%CI: 1.26–2.01]) and >50 MME (mortality OR: 1.99 [95%CI: 1.28–3.10]; composite OR: 2.09 [95%CI: 1.43–3.04]). CONCLUSIONS: Older adults receiving medically prescribed opioids at higher doses and those using LA and combination of LA and SA opioids are at increased risks for opioid-related adverse events, highlighting the need for close patient supervision. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-06792-8.

This qualitative study aimed to understand occupational therapists' experiences of providing home programs to stroke survivors in India. Using an interpretative phenomenological approach, eight practicing occupational therapists were interviewed in depth about home programs for individuals recovering from stroke. Two broad themes with subthemes emerged describing the organizational factors, sociocultural and economic influences on home program provision as well as describing how the occupational therapists addressed the challenges to facilitate home program provision and adherence. The findings can inform occupational therapy practice in lower- and middle-income countries like India and other countries where existing practice recommendations for stroke rehabilitation and core professional tenets may be challenged.

Background: Slipped capital femoral epiphysis (SCFE) results in alterations to femoral head anatomy, predisposing patients to degenerative hip disease at a young age. Total hip arthroplasty (THA) is performed to relieve symptoms and improve function. However, it can be associated with a variable outcomes and little evidence exists on the functional outcomes, complications and revision rate following such procedures. Purpose: The aim of this systematic review is to determine the safety and effectiveness of performing hip arthroplasty in patients with degenerative hips secondary to SCFE. Methodology: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature review was conducted of MEDLINE and Embase. Both single-arm and comparative studies were included. The outcomes of interest were functional scores, post-operative complications and revision rate. Results: Six studies fit the inclusion criteria. Of these, five were retrospective single-arm studies and one was a retrospective comparative study based on registry data. All studies reported significant improvement in hip function and quality of life after THA. An overall revision rate of 11.9% was reported, occurring at a mean of 6.5 years (0.75–18.7 years). THA in patients after SCFE leads to improved functional outcomes that are comparable to patients receiving THA for osteoarthritis. The revision rate appears to be higher than is reported in patients undergoing THA for osteoarthritis at mid-term follow-up. Further prospective comparative studies are needed to evaluate the efficacy of the treatment in more detail. Cite this article: EFORT Open Rev 2021;6:539-544. DOI: 10.1302/2058-5241.6.200038