Building Back Better: Applying Lessons from the COVID-19 Pandemic to Expand Critical Information Access.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic generated an unprecedented volume of evolving clinical guidelines that strained existing clinical information systems and necessitated rapid innovation in emergency departments (EDs). OBJECTIVES: Our team aimed to harness new COVID-19-related reliance on digital clinical support tools to re-envision how all clinical guidelines are stored and accessed in our ED. METHODS: We used a design-thinking approach including empathizing, defining the problem, ideating, prototyping, and testing to develop a low-cost, homegrown clinical information hub: E*Drive. To measure impact, we compared web traffic on E*Drive to our legacy cloud-based folder system and conducted a survey of end-users using a validated health technology utilization instrument. RESULTS: Our final product, E*Drive, is a centralized clinical information hub storing everything from clinical guidelines to discharge resources. Clinical guidelines are standardized and housed within the high-traffic E*Drive platform to increase accessibility. Since launch, E*Drive has averaged 84 unique weekly users, compared with less than one weekly user on the legacy system. We surveyed 52 clinicians for a total response rate of 47%. Prior to the E*Drive rollout, 12.5% of ED clinicians felt confident accessing clinical information on the legacy system, whereas 76.6% of ED clinicians felt they could more easily access clinical information using E*Drive. CONCLUSION: The COVID pandemic revealed vulnerabilities within our information dissemination system and presented an opportunity to improve clinical information delivery. Centralized web-based clinical information hubs designed around the clinician end-user experience can increase clinical guideline access in the ED.

Rapid Salivary IgG Antibody Screening for Hepatitis A.

Hepatitis A virus (HAV) is a common infection that is transmitted through the fecal-oral route, shed in the stool of infected individuals, and spread either by direct contact or by ingesting contaminated food or water. Each year, approximately 1.4 million acute cases are reported globally with a major risk factor for exposure being low household socioeconomic status. Recent trends show a decrease in anti-HAV antibodies in the general population, with concomitant increases in the numbers of HAV outbreaks. In line with a recreational water study, this effort aims to assess the prevalence of salivary IgG antibodies against HAV and subsequent incident infections (or immunoconversions) in visitors to a tropical beach impacted by a publicly owned treatment works (POTW). We applied a multiplex immunoassay to serially collected saliva samples gathered from study participants who recreated at Boquerón Beach, Puerto Rico. Analysis of assay results revealed an immunoprevalence rate of 16.17% for HAV with 1.43% of the cohort immunoconverting to HAV. Among those who immunoconverted, 10% reported chronic gastrointestinal symptoms and none experienced diarrhea. Tests on water samples indicated good water quality with low levels of fecal indicator bacteria; however, the collection and analysis of saliva samples afforded the ability to detect HAV infections in beachgoers. This rapid assay serves as a cost-effective tool for examining exposure to environmental pathogens and can provide critical information to policy makers, water quality experts, and risk assessment professionals seeking to improve and protect recreational water and public health.

A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family.

Anencephaly (APH) is characterized by the absence of brain tissues and cranium. During primary neurulation stage of the embryo, the rostral part of the neural pore fails to close, leading to APH. APH shows a heterogeneous etiology, ranging from environmental to genetic causes. The autosomal recessive inheritance of APH has been reported in several populations. In this study, we employed whole-exome sequencing and identified a homozygous missense mutation c.1522C > A (p.Pro508Thr) in the TRIM36 gene as the cause of autosomal recessive APH in an Indian family. The TRIM36 gene is expressed in the developing brain, suggesting a role in neurogenesis. In silico analysis showed that proline at codon position 508 is highly conserved in 26 vertebrate species, and the mutation is predicted to affect the conformation of the B30.2/SPRY domain of TRIM36. Both in vitro and in vivo results showed that the mutation renders the TRIM36 protein less stable. TRIM36 is known to associate with microtubules. Transient expression of the mutant TRIM36 in HeLa and LN229 cells resulted in microtubule disruption, disorganized spindles, loosely arranged chromosomes, multiple spindles, abnormal cytokinesis, reduced cell proliferation and increased apoptosis as compared with cells transfected with its wild-type counterpart. The siRNA knock down of TRIM36 in HeLa and LN229 cells also led to reduced cell proliferation and increased apoptosis. We suggest that microtubule disruption and disorganized spindles mediated by mutant TRIM36 affect neural cell proliferation during neural tube formation, leading to APH.

Diastolic dysfunction grading, echocardiographic and electrocardiogram findings in 50 patients with apical hypertrophic cardiomyopathy.

INTRODUCTION: Apical Hypertrophic Cardiomyopathy (Apical HCM) is an uncommon variant of hypertrophic cardiomyopathy, but it is relatively more common in Asian countries. This is a retrospective, non-randomised, single centre study of patients with Apical HCM focusing on their diastolic dysfunction grading, echocardiographic parameters and electrocardiograms (ECG). METHODS: All Apical HCM patients coming for clinic visits at the Institut Jantung Negara from September 2017 to September 2018 were included. We assessed their echocardiography images, grade their diastolic function and reviewed their ECG on presentation. RESULTS: Fifty patient were included, 82% (n=41) were males and 18% (n=9) females. The diastolic function grading of 37 (74%) patients were able to be determined using the updated 2016 American Society of Echocardiography (ASE) diastolic guidelines. Fifty percent (n=25) had the typical ace-ofspades shape left ventricle (LV) appearance in diastole and 12% (n=6) had apical pouch. All patients had T inversion in the anterior leads of their ECG, and only 52% (n=26) fulfilled the ECG left ventricular hypertrophy (LVH) criteria. Majority of our patients presented with symptoms of chest pain (52%, n=26) and dyspnoea (42%, n=21). CONCLUSION: The updated 2016 ASE guideline makes it easier to evaluate LV diastolic function in most patients with Apical HCM. It also helps in elucidating the aetiology of dyspnoea, based on left atrial pressure. Clinicians should have a high index of suspicion for Apical HCM when faced with deep T inversion on ECG, in addition to a thick LV apex with an aceof- spades appearance during diastole.

The Utility of Dot Phrases and SmartPhrases in Improving Physician Documentation of Interpreter Use.

Background: Patients with limited English proficiency (LEP) experience significant healthcare disparities. Clinicians are responsible for using and documenting their use of certified interpreters for patient encounters when appropriate. However, the data on interpreter use documentation in the emergency department (ED) is limited and variable. We sought to assess the effects of dot phrase and SmartPhrase implementation in an adult ED on the rates of documentation of interpreter use. Methods: We conducted an anonymous survey asking emergency clinicians to self-report documentation of interpreter use. We also retrospectively reviewed documentation of interpreter- services use in ED charts at three time points: 1) pre-intervention baseline; 2) post-implementation of a clinician-driven dot phrase shortcut; and 3) post-implementation of a SmartPhrase. Results: Most emergency clinicians reported using an interpreter "almost always" or "often." Our manual audit revealed that at baseline, interpreter use was documented in 35% of the initial clinician note, 4% of reassessments, and 0% of procedure notes; 52% of discharge instructions were written in the patients' preferred languages. After implementation of the dot phrase and SmartPhrase, respectively, rates of interpreter-use documentation improved to 43% and 97% of initial clinician notes, 9% and 6% of reassessments, and 5% and 35% of procedure notes, with 62% and 64% of discharge instructions written in the patients' preferred languages. Conclusion: There was a discrepancy between reported rates of interpreter use and interpreter-use documentation rates. The latter increased with the implementation of a clinician-driven dot phrase and then a SmartPhrase built into the notes. Ensuring accurate documentation of interpreter use is an impactful step in language equity for LEP patients.

Histopathological Study of Mucormycosis in Post COVID-19 Patients and Factors Affecting it in a Tertiary Care Hospital.

Introduction. COVID-19 is an infection caused by severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) which may be associated with a wide range of bacterial and fungal co-infections. Mucormycosis is an opportunistic fungal infection occurring in post COVID-19 patients. Objectives. To study the role of histopathology in mucormycosis and the predisposing factors associated in development of mucormycosis in post COVID-19 patients. Materials and methods. A prospective observational study was conducted in our hospital in the pathology department over a period of 3 months on 200 patients with mucormycosis who were infected with SARS-CoV-2 virus. Results. Out of the 200 patients with mucormycosis studied in post COVID-19 patients, age ranged from 21-80 years, of which 132 were men and 68 were women. Sites involved by mucormycosis were sinuses, orbit, cranium, and cutaneous. Ethmoid sinus was most involved, followed by maxillary sinus. Diabetes was present in 162 patients and hypertension in 92 patients. On histopathological examination, fungal load was severe in 49 patients, angioinvasion was present in 48 patients, perineural invasion was present in 32 patients, and necrosis was present in 121 patients. The number of patients discharged after surgery was 169, whereas 31 died. Conclusion. Histopathological features of mucormycosis like angioinvasion, perineural invasion, severe fungal load, and large areas of necrosis were directly proportional to the mortality rate. Thus, histopathologists can help in assessing prognosis at the time of tissue diagnosis, so that clinicians can optimize treatment accordingly. Diabetes and history of corticosteroid intake for treatment of COVID-19 were the two commonest predisposing factors for development of mucormycosis.

On the dielectric dispersion and absorption in nanosized manganese zinc mixed ferrites.

The temperature and frequency dependence of dielectric permittivity and dielectric loss of nanosized Mn(1-x)Zn(x)Fe(2)O(4) (for x = 0, 0.2, 0.4, 0.6, 0.8, 1) were investigated. The impact of zinc substitution on the dielectric properties of the mixed ferrite is elucidated. Strong dielectric dispersion and broad relaxation were exhibited by Mn(1-x)Zn(x)Fe(2)O(4). The variation of dielectric relaxation time with temperature suggests the involvement of multiple relaxation processes. Cole-Cole plots were employed as an effective tool for studying the observed phenomenon. The activation energies were calculated from relaxation peaks and Cole-Cole plots and found to be consistent with each other and indicative of a polaron conduction.

Visitors to a Tropical Marine Beach Show Evidence of Immunoconversions to Multiple Waterborne Pathogens.

Determining infections from environmental exposures, particularly from waterborne pathogens is a challenging proposition. The study design must be rigorous and account for numerous factors including study population selection, sample collection, storage, and processing, as well as data processing and analysis. These challenges are magnified when it is suspected that individuals may potentially be infected by multiple pathogens at the same time. Previous work demonstrated the effectiveness of a salivary antibody multiplex immunoassay in detecting the prevalence of immunoglobulin G (IgG) antibodies to multiple waterborne pathogens and helped identify asymptomatic norovirus infections in visitors to Boquerón Beach, Puerto Rico. In this study, we applied the immunoassay to three serially collected samples from study participants within the same population to assess immunoconversions (incident infections) to six waterborne pathogens: Helicobacter pylori, Campylobacter jejuni, Toxoplasma gondii, hepatitis A virus, and noroviruses GI. I and GII.4. Further, we examined the impact of sampling on the detection of immunoconversions by comparing the traditional immunoconversion definition based on two samples to criteria developed to capture trends in three sequential samples collected from study participants. The expansion to three samples makes it possible to capture the IgG antibody responses within the survey population to more accurately assess the frequency of immunoconversions to target pathogens. Based on the criteria developed, results showed that when only two samples from each participant were used in the analysis, 25.9% of the beachgoers immunoconverted to at least one pathogen; however, the addition of the third sample reduced immunoconversions to 6.5%. Of these incident infections, the highest levels were to noroviruses followed by T. gondii. Moreover, many individuals displayed evidence of immunoconversions to multiple pathogens. This study suggests that detection of simultaneous infections is possible, with far reaching consequences for the population. The results may lead to further studies to understand the complex interactions that occur within the body as the immune system attempts to ward off these infections. Such an approach is critical to our understanding of medically important synergistic or antagonistic interactions and may provide valuable and critical information to public health officials, water treatment personnel, and environmental managers.

Study of Obstetric Admissions to the Intensive Care Unit of a Tertiary Care Hospital.

PURPOSE: To analyze obstetric admissions to intensive care unit and to identify the risk factors responsible for intensive care admission. METHODS: This is a retrospective study of all obstetric cases admitted to the intensive care unit over a period of 3 years. Data were collected from case records. The risk factors responsible for ICU admission were analyzed. RESULTS: There were 765 obstetric admissions to ICU accounting for 1.24 % of all deliveries. 56.20 % were in the age group of 20-25 years. 38.43 % were in their first pregnancy. 36.48 % of cases were at 37-40 weeks of gestation. Postpartum admissions were 80.91 %. Major conditions responsible were obstetric hemorrhage in 44.05 %, hypertensive disorders of pregnancy in 28.88 %, severe anemia in 14.37 %, heart disease in 12.15 %, and sepsis in 7.97 % of ICU cases. 40.39 % cases required high dependency care. Maternal mortality was seen in 15.55 % of ICU cases. Commonest cause of mortality was hemorrhagic shock (26.89 %) and multiorgan dysfunction syndrome (26.05 %). CONCLUSION: Commonest risk factors for ICU admissions are obstetric hemorrhage and hypertensive disorders of pregnancy. Other major risk factors are severe anemia, heart disease, sepsis, more than one diagnosis on admission, and the need for cesarean delivery.

Developing a Salivary Antibody Multiplex Immunoassay to Measure Human Exposure to Environmental Pathogens.

The etiology and impacts of human exposure to environmental pathogens are of major concern worldwide and, thus, the ability to assess exposure and infections using cost effective, high-throughput approaches would be indispensable. This manuscript describes the development and analysis of a bead-based multiplex immunoassay capable of measuring the presence of antibodies in human saliva to multiple pathogens simultaneously. Saliva is particularly attractive in this application because it is noninvasive, cheaper and easier to collect than serum. Antigens from environmental pathogens were coupled to carboxylated microspheres (beads) and used to measure antibodies in very small volumes of human saliva samples using a bead-based, solution-phase assay. Beads were coupled with antigens from Campylobacter jejuni, Helicobacter pylori, Toxoplasma gondii, noroviruses (G I.1 and G II.4) and hepatitis A virus. To ensure that the antigens were sufficiently coupled to the beads, coupling was confirmed using species-specific, animal-derived primary capture antibodies, followed by incubation with biotinylated anti-species secondary detection antibodies and streptavidin-R-phycoerythrin reporter (SAPE). As a control to measure non-specific binding, one bead set was treated identically to the others except it was not coupled to any antigen. The antigen-coupled and control beads were then incubated with prospectively-collected human saliva samples, measured on a high throughput analyzer based on the principles of flow cytometry, and the presence of antibodies to each antigen was measured in Median Fluorescence Intensity units (MFI). This multiplex immunoassay has a number of advantages, including more data with less sample; reduced costs and labor; and the ability to customize the assay to many targets of interest. Results indicate that the salivary multiplex immunoassay may be capable of identifying previous exposures and infections, which can be especially useful in surveillance studies involving large human populations.

Direct typing of Canine parvovirus (CPV) from infected dog faeces by rapid mini sequencing technique.

Canine parvovirus (CPV) is a non-enveloped single stranded DNA virus with an icosahedral capsid. Mini-sequencing based CPV typing was developed earlier to detect and differentiate all the CPV types and FPV in a single reaction. This technique was further evaluated in the present study by performing the mini-sequencing directly from fecal samples which avoided tedious virus isolation steps by cell culture system. Fecal swab samples were collected from 84 dogs with enteritis symptoms, suggestive of parvoviral infection from different locations across India. Seventy six of these samples were positive by PCR; the subsequent mini-sequencing reaction typed 74 of them as type 2a virus, and 2 samples as type 2b. Additionally, 25 of the positive samples were typed by cycle sequencing of PCR products. Direct CPV typing from fecal samples using mini-sequencing showed 100% correlation with CPV typing by cycle sequencing. Moreover, CPV typing was achieved by mini-sequencing even with faintly positive PCR amplicons which was not possible by cycle sequencing. Therefore, the mini-sequencing technique is recommended for regular epidemiological follow up of CPV types, since the technique is rapid, highly sensitive and high capacity method for CPV typing.

Efficacy and tolerability of controlled-release paroxetine in the treatment of panic disorder.

OBJECTIVE: To assess the efficacy and tolerability of controlled-release paroxetine (paroxetine CR) in the treatment of adults with panic disorder. METHOD: Paroxetine CR (25-75 mg/day; N = 444) was compared with placebo (N = 445) in patients with DSM-IV panic disorder with or without agoraphobia in 3 identical, double-blind, placebo-controlled, 10-week clinical trials that were pooled for analysis. RESULTS: Paroxetine CR was statistically superior to placebo in the primary outcome measure, percentage of patients who were free of panic attacks in the 2 weeks prior to endpoint. Of the total population that completed or prematurely terminated treatment, 63% and 53% of paroxetine CR-and placebo-treated patients, respectively, were panic-free during the final 2 weeks (p < .005; odds ratio [OR] = 1.63; 95% CI = 1.21 to 2.19). For week 10 completers (72% of total), 73% and 60% of paroxetine CR- and placebo-treated patients, respectively, were panic-free at week 10 (p < .005; OR = 2.11; 95% CI = 1.45 to 3.07). Paroxetine CR was also statistically superior to placebo on the global improvement and severity items of the Clinical Global Impressions scale and in reducing anxiety symptoms as measured by the Hamilton Rating Scale for Anxiety total score and total fear and avoidance on the Marks-Sheehan Phobia Scale. Adverse events leading to study withdrawal were minimal and occurred in 11% of the paroxetine CR group and 6% of the placebo group. Most of the treatment-emergent adverse events were rated as mild to moderate in severity and occurred early in the study. There were no unexpected adverse events, and serious adverse events were uncommon (10 [2.3%] of the 444 patients treated with paroxetine CR vs. 8 [1.8%] of the 445 patients treated with placebo). CONCLUSION: Paroxetine CR is an effective and well-tolerated treatment for panic disorder. Paroxetine CR is associated with low rates of treatment-emergent anxiety as well as low dropout rates from adverse events.

Efficacy and tolerability of paroxetine for the long-term treatment of generalized anxiety disorder.

BACKGROUND: Paroxetine has demonstrated efficacy in depression and anxiety disorders, including generalized anxiety disorder (GAD). This 32-week study evaluated the maintained efficacy and safety of paroxetine in GAD by assessing the potential for relapse after discontinuation of medication. METHOD: Adults (N = 652) with DSM-IV GAD and a Clinical Global Impressions-Severity of Illness (CGI-S) score > or = 4 received paroxetine (20-50 mg/day) for 8 weeks. Patients whose CGI-S score had decreased by at least 2 points to < or = 3 at week 8 were randomly assigned to double-blind treatment with paroxetine (N = 278) or placebo (N = 288) for a further 24 weeks. The primary efficacy parameter was the proportion of patients relapsing (an increase in CGI-S score of at least 2 points to a score < or = 4 or withdrawal resulting from lack of efficacy) during double-blind treatment. RESULTS: Significantly fewer paroxetine than placebo patients relapsed during the 24-week double-blind phase (10.9% vs. 39.9%; p <.001). Placebo patients were almost 5 times more likely to relapse than paroxetine patients (estimated hazard ratio = 0.213 [95% CI = 0.1 to 0.3]; p <.001). Statistical significance in favor of paroxetine was demonstrated for all secondary efficacy parameters, including functional status. Twice as many paroxetine patients as placebo patients (73%) achieved remission. Paroxetine was well tolerated, with no unexpected adverse events reported. CONCLUSION: Paroxetine was found to be effective and well tolerated for both the short- and long-term treatment of DSM-IV GAD. Continued treatment with paroxetine significantly reduced the potential for relapse of GAD symptoms.

Synthesis of some new 2,4-disubstituted thiazoles as possible antibacterial and anti-inflammatory agents.

A series of arylthioureas (1), aromatic aldehyde thiosemicarbazones (2) and 5-aryl-2-furfuraldehyde thiosemicarbazones (3) were condensed with 2,4-dichloro-5-fluorophenacyl bromide to yield respective arylaminothiazoles, arylidene/5-aryl-2-furfurylidene hydrazinothiazoles (4). The newly synthesized compounds were characterized by IR, 1H-NMR and mass spectral studies. These compounds were also screened for their antibacterial and anti-inflammatory activities. Two of the newly synthesized compounds showed anti-inflammatory activity comparable with that of Ibuprofen.

Partographic analysis of spontaneous labour at term in primigravida.

PURPOSE OF THE STUDY: To study the use of partogram in the analysis of spontaneous labour at term in primigravida with cephalic presentation. METHODOLOGY: Partographic analysis of labour was done in 200 primigravidae. Partographic variables are plotted, and the study population was divided into three groups. Group I: Cervix dilatation and descent curve falling to the left of alert line; Group II: Cervix dilatation and descent curve falling to the right of alert line; and Group III: Cervix dilatation and descent curve falling to the right of action line. Maternal and neonatal outcomes were studied in each of three groups. RESULTS: Amongst the 200 primigravid labours analysed, 133 (66.5 %) belonged to group I, 40 (20.0 %) belonged to group II and 27 (13.5 %) belonged to group III. Mean durations of active phases of labour were 4.1 h, 6.9 h and 9.6 h, in groups I, II and III, respectively. In group I, 130 women (97.7 %) delivered vaginally, 3 (2.3 %) underwent LSCS. In group II, 29 (72.5 %) delivered vaginally, 4 (10 %) delivered instrumentally and 7 (17.5 %) underwent LSCS, and in group III, 5 (18.5 %) delivered vaginally, 7 (25.9 %) delivered instrumentally and 15 (55.5 %) delivered by LSCS. CONCLUSION: Mean duration of active phase of labour increased as the partographic curve fell to the right of alert and action line. Increased rates of instrumental deliveries, LSCS, babies with lower APGAR score at 5 min, and NICU admissions were observed in group III compared with groups I and II.