Correction: Expert Opinions on the Management of Hemophilia A in India: The Role of Emicizumab.

[This corrects the article DOI: 10.7759/cureus.58941.].

Expert Opinions on the Management of Hemophilia A in India: The Role of Emicizumab.

Hemophilia A (HA) is a genetic disorder of hemostasis associated with a deficiency or reduced activity of clotting factor VIII (FVIII). This disorder remains unacceptably underdiagnosed in India. Early diagnosis and appropriate management of HA can substantially prevent morbidity and mortality. Currently, HA is managed with regular replacement therapy using standard or extended half-life FVIII concentrates or non-factor drug products. The challenges associated with FVIII concentrates include plateauing of drug effect, issues with its administration and adherence to treatment, breakthrough bleeds, and the development of inhibiting antibodies against administered clotting factors. Emicizumab is a bispecific antibody, launched in India in April 2019, for managing patients with HA. To investigate the role of emicizumab in Indian patients with HA, opinions were sought from 13 eminent hematologists and experts from India on the effectiveness of emicizumab in preventing all bleeds, spontaneous bleeds, perioperative bleeds, and intracranial hemorrhage; resolving target joints; and reducing the rate of hospitalizations and fatality associated with HA in children and adults, with or without inhibitors. The benefits of emicizumab over traditional FVIII concentrates include the subcutaneous route of delivery, less frequent dosing, and a lack of inhibitor development, in addition to providing sustained hemostasis without in-depth monitoring. It is a safe and effective management option for all HA patients, especially for patients with certain archetypes, such as those with inhibitors, those with high annualized bleed rates, those living far away from hemophilia care centers, pediatric patients and infants with intravenous access challenges, and those with a history of life-threatening bleeding events.

Acceleration and transport of relativistic electrons in the jets of the microquasar SS 433.

SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.S.S.) and found an energy-dependent shift in the apparent position of the gamma-ray emission from the parsec-scale jets. These observations trace the energetic electron population and indicate that inverse Compton scattering is the emission mechanism of the gamma rays. Our modeling of the energy-dependent gamma-ray morphology constrains the location of particle acceleration and requires an abrupt deceleration of the jet flow. We infer the presence of shocks on either side of the binary system, at distances of 25 to 30 parsecs, and that self-collimation of the precessing jets forms the shocks, which then efficiently accelerate electrons.

Evaluation of self-measured blood pressure monitoring in a southern rural West Virginia health system.

INTRODUCTION: At the time of the 2021 Behavioral Risk Factor Surveillance System survey, an estimated 32.3% of adults in the US and nearly half (43.4%, 776 000) of adults in West Virginia (WV) had hypertension. Further, the Interactive Atlas of Heart Disease and Stroke estimates an increase in the percentage of adults with hypertension in the US from 32.3% to 47.0%, with hypertension rates in WV rising as high as 58.7%, indicating a significant public health concern in the community. Hypertension increases the risk of several negative health outcomes, including heart disease and stroke, and leads to increased economic and chronic disease burden. Although certain unmodifiable factors (sex, age, race, ethnicity, and family history) increase the risk of developing hypertension, a healthy lifestyle - including a nutritious diet, maintaining a healthy weight, avoiding nicotine products, and participating in regular moderate physical activity - can decrease the risk of developing hypertension. Self-measured blood pressure (SMBP) monitoring, or home BP monitoring, when integrated with a provider's clinical management approach, is linked to improvements in BP management and control. This study represents a mid-point assessment of a remote SMBP monitoring program implemented by Cabin Creek Health Systems (CCHS), a federally qualified health center, and its impact on BP control. METHODS: CCHS implemented SMBP programming in March 2020 as one element of a developing comprehensive program aimed at reducing uncontrolled hypertension, and therefore chronic disease burden, in its service area and patient population. The project, funded by the Health Resources and Services Administration, continued to February 2023. This report represents a mid-point analysis and was based on the retrospective analysis of de-identified data collected for 234 patients to June 2022, who were assessed for changes in BP between the date of enrollment and the most recently available BP measurement. Patients were enrolled in the SMBP program if they exhibited current or previous indicators of uncontrolled hypertension (systolic ≥140 mmHg and/or diastolic ≥90 mmHg), at the discretion of their provider, and were equipped with an iBloodPressure cellular connected home BP monitoring system, manufactured by Smart Meter. Their BP readings were documented in the integration software TimeDoc Health and electronic health record athenahealth. RESULTS: At the time of enrollment, 201 (86.0%) patients had uncontrolled hypertension, with 116 (49.6%) patients having both uncontrolled systolic (≥140 mmHg) and diastolic (≥90 mmHg) values. At follow-up, the number of patients with uncontrolled hypertension decreased from 201 to 98 (41.9%), with only 36 (15.4%) patients having both uncontrolled systolic and diastolic values. Additionally, 26 (11.1%) patients were in hypertensive crisis at the time of enrollment, and no patients remained in crisis at the time of follow-up. The number of patients with BP values in the controlled range (systolic <140 mmHg and diastolic <90 mmHg) increased from 33 (14.1%) at enrollment to 136 (58.1%) at follow-up. Overall, there was a 44.0% increase in the number of patients with BP values in the controlled range at follow-up, and a concomitant 44.1% decrease in the number of patients in the uncontrolled range. These observations were consistent across multiple demographic indicators, including clinic location, three-digit zip code, and patient sex. CONCLUSION: Systematic implementation of remote BP monitoring, when integrated into clinician workflows, was associated with a substantial reduction in the number of patients with uncontrolled hypertension in this rural federally qualified health center. Further, CCHS was successful in implementing a remote SMBP monitoring program in a community challenged with transportation insecurity, and poor cellular and broadband access, of which lessons learned are applicable to other health systems interested in pursuing comparable efforts.

The value of using emotions in solution focused brief therapy.

A commonly stated critique of Solution Focused Brief Therapy (SFBT) is a lack of attention to the client's emotional experience and the use of emotion as a mechanism for producing meaningful change. We review and define the current research regarding emotion, feeling, and affect and its value and relevance to the clinical application of SFBT. We also provide a brief history of the SFBT model and its documented emphasis on cognitive and behavioral change versus emotional change. In embodying the spirit of this approach for examining what works and doing more of it, we propose a next step of SFBT to more overtly attend to the emotional language of clients and to purposefully create emotional experiences with our clients. We demonstrate this by providing clinical examples for how SFBT practitioners can incorporate and build upon clients' emotional language to create emotionally-changing experiences to more broadly and effectively co-create long-lasting change.

Autoimmune Hemolytic Anaemias in Pregnancy: Experience in a Tertiary Care Hospital in South India.

BACKGROUND: Autoimmune hemolytic anaemia is very rare and there is limited data regarding their pregnancy outcomes. Hence we aimed to study the maternal and perinatal outcomes in pregnancies with autoimmune hemolytic anaemias (AIHA). METHODS: A retrospective descriptive study of pregnant women with AIHA, who delivered at SJMCH between January 2011 and January 2016 was carried out. Their antenatal and labour records were reviewed and demographic details noted.The primary outcome measures studied were-the prevalence of AIHA, gestational age at delivery, antepartum, intrapartum and postpartum complications, mode of delivery and requirement of transfusion of blood and blood products. The secondary outcome measures studied included neonatal outcomes such as low birth weight, intrauterine growth restriction and need for intensive care. The data is presented as descriptive statistics, including means and percentage. RESULTS: The prevalence of AIHA was (18/12,420) 0.14%. The mean gestational age at delivery was 34 weeks; 100%, 77% and 50% had antenatal, intra partum or postpartum complications, respectively. 44% had preeclampsia, 38% intrauterine growth restriction and 16% preterm labour. 83% required additional drugs for treatment of AIHA.72% had vaginal delivery; 28% had caesarean delivery; 33% were transfused antenatally and 22% postnatally; 50% of the babies were preterm and required intensive care, 66% had low birth weight. There was no maternal mortality. CONCLUSION: Multidisciplinary approach, early diagnosis and detection of autoimmune hemolytic anaemia and complications, good antenatal care, judicious transfusions and delivery at tertiary care centre are the keys to successful outcomes.

Innate Immune Cytokine Profiling and Biomarker Identification for Outcome in Dengue Patients.

Background: Early biomarkers of progression to severe dengue are urgently required to enable effective patient management and control treatment costs. Innate immune cells, which comprise the earliest responders to infection and along with the cytokines and chemokines they secrete, play a vital role in orchestrating the subsequent adaptive immune response and have been implicated in the enhancement of infection and "cytokine storm" associated with dengue severity. We investigated the early innate immune cytokine profile of dengue patients during acute phase of disease in a prospective blinded study that included subjects with acute dengue and febrile controls from four major hospitals in Bengaluru, India along with healthy controls. We used intracellular cytokine staining and flow cytometry to identify innate immune biomarkers that can predict progression to severe dengue. Results: Dengue infection resulted in enhanced secretion of multiple cytokines by all queried innate immune cell subsets, dominated by TNF-α from CD56+CD3+ NKT cells, monocyte subsets, and granulocytes along with IFN-γ from CD56+CD3+ NKT cells. Of note, significantly higher proportions of TNF-α secreting granulocytes and monocyte subsets at admission were associated with mild dengue and minimal symptoms. Dengue NS1 antigenemia used as a surrogate of viral load directly correlated with proportion of cytokine-secreting innate immune cells and was significantly higher in those who went on to recover with minimal symptoms. In patients with secondary dengue or those with bleeding or elevated liver enzymes who revealed predisposition to severe outcomes, early activation as well as efficient downregulation of innate responses were compromised. Conclusion: Our findings suggested that faulty/delayed kinetics of innate immune activation and downregulation was a driver of disease severity. We identified IFN-γ+CD56+CD3+ NKT cells and IL-6+ granulocytes at admission as novel early biomarkers that can predict the risk of progression to severity (composite AUC = 0.85-0.9). Strong correlations among multiple cytokine-secreting innate cell subsets revealed that coordinated early activation of the entire innate immune system in response to dengue virus infection contributed to resolution of infection and speedy recovery.

Preparing Teachers to Teach in K-12 Blended Environments: A Systematic Mapping Review of Research Trends, Impact, and Themes.

Despite evidence concerning the widespread growth of K-12 blended teaching and the impact that emergency remote teaching during the COVID-19 pandemic has had on the spread of K-12 online and blended teaching, we could find no systematic reviews focused on preparing K-12 teachers for blended teaching. Previous literature reviews, such as those from Halverson et al. (2012) and Drysdale et al. (2013), have noted the lack of research focused on K-12 blended teaching contexts. This systematic mapping review (Grant & Booth, 2009) of 88 K-12 blended teacher preparation articles focused on identifying trends in author impact according to citation count and number of publications, journal impact according to number of publications, prevalence of research methods, and prevalence of research themes according to research questions and findings. The analysis provides a valuable snapshot of current literature, sets a foundation for a deeper thematic analysis of K-12 blended teacher preparation literature, and identifies some potential areas for future K-12 blended teaching research.

MYSTAT: A compact potentiostat/galvanostat for general electrochemistry measurements.

An open-source potentiostat/galvanostat instrument design is introduced that provides the ability to take accurate measurements over a current range of ±200 mA and a potential range of ±12 V. The improved capability of the instrument compared to the previously published design upon which it is based makes it suitable for performing a wider range of electrochemical measurements including the ability to use larger working electrodes, study of high current density processes, study of electrochemistry in nonaqueous solutions and use in high voltage processes such as electrophoretic deposition. The instrument can be controlled from any computer capable of running the Python programming language, including a low-cost Raspberry Pi. Unlike many commercial potentiostat designs, the instrument is completely open-source, giving researchers the ability to modify the hardware and software as needed for custom measurement techniques. The low cost makes the instrument attractive for research and teaching laboratories in which multiple electrochemical measurements need to be carried out in parallel.

Progress will come in the balancing of needs: Professional desires, consumer demand, and why we have to specialize.

Conoley, Powers, and Gutkin (2020) have provided an assessment of the progress and lack thereof of school psychology as a profession toward school reformation, especially as related to their various earlier calls for changes in training and practice. Conoley and Gutkin especially (and I have been colleagues of both) have called for decades for an emphasis on working with teachers, other adults in the school system, and the school system itself to alter the delivery of education. In some earlier work, they have characterized this as adult school psychology. In many ways this is a reconceptualization of earlier mental health consultation models of school psychology practice that were not widely adopted for reasons Conoley et al. (2020) explain. School psychology has a long history of wanting to be seen and to practice differently from in a primary role of test and place, and indeed I would characterize the primary organizations that represent the profession (the National Association of Psychologists and the American Psychological Association's Division of School Psychology) as being in many ways antagonistic toward psychological testing. Yet, it is what most school psychologists are in fact hired to do as their primary role, and training in psychological testing and assessment is one of the key skills that sets us apart and distinguishes us from others in the schools. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Pathologic findings and causes of death in southern right whales Eubalaena australis, Brazil.

Southern right whales Eubalaena australis (SRWs) migrate to southern Brazil for breeding and calving from June through November. Overall, there is scarce knowledge on health status and pathologic conditions in SRWs. We report the pathologic and molecular investigation results of 8 SRWs that were necropsied between 2010 and 2017 within a breeding and calving ground in Santa Catarina state, Brazil. The animals were of various ages (7 newborns/calves, 1 adult) and sex (3 females, 5 males). Five whales stranded dead; 3 stranded alive and died shortly after (n = 2) or were euthanized (n = 1). The causes of stranding and/or death were neonatal respiratory distress syndrome with meconium aspiration (n = 3) with concomitant congenital hepatopathy in one of them; trauma of unknown origin (n = 3), infectious renal and lung disease with presumed sepsis (n = 1), and euthanasia (n = 1). Three animals were PCR-positive for cetacean morbillivirus; one of them also had morbilliviral antigen in kidney via immunohistochemical analysis. These results, integrating novel findings and a published report, contribute to the pathology knowledge of this species.

RhoC regulates radioresistance via crosstalk of ROCK2 with the DNA repair machinery in cervical cancer.

BACKGROUND: Radioresistance remains a challenge to the successful treatment of various tumors. Intrinsic factors like alterations in signaling pathways regulate response to radiation. RhoC, which has been shown to modulate several tumor phenotypes has been investigated in this report for its role in radioresistance. In vitro and clinical sample-based studies have been performed to understand its contribution to radiation response in cervical cancer and this is the first report to establish the role of RhoC and its effector ROCK2 in cervical cancer radiation response. METHODS: Biochemical, transcriptomic and immunological approaches including flow cytometry and immunofluorescence were used to understand the role of RhoC and ROCK2. RhoC variants, siRNA and chemical inhibitors were used to alter the function of RhoC and ROCK2. Transcriptomic profiling was performed to understand the gene expression pattern of the cells. Live sorting using an intracellular antigen has been developed to isolate the cells for transcriptomic studies. RESULTS: Enhanced expression of RhoC conferred radioprotection on the tumor cells while inhibition of RhoC resulted in sensitization of cells to radiation. The RhoC overexpressing cells had a better DNA repair machinery as observed using transcriptomic analysis. Similarly, overexpression of ROCK2, protected tumor cells against radiation while its inhibition increased radiosensitivity in vitro. Further investigations revealed that ROCK2 inhibition abolished the radioresistance phenotype, conferred by RhoC on SiHa cells, confirming that it is a downstream effector of RhoC in this context. Additionally, transcriptional analysis of the live sorted ROCK2 high and ROCK2 low expressing SiHa cells revealed an upregulation of the DNA repair pathway proteins. Consequently, inhibition of ROCK2 resulted in reduced expression of pH2Ax and MRN complex proteins, critical to repair of double strand breaks. Clinical sample-based studies also demonstrated that ROCK2 inhibition sensitizes tumor cells to irradiation. CONCLUSIONS: Our data primarily indicates that RhoC and ROCK2 signaling is important for the radioresistance phenotype in cervical cancer tumor cells and is regulated via association of ROCK2 with the proteins of DNA repair pathway involving pH2Ax, MRE11 and RAD50 proteins, partly offering insights into the mechanism of radioresistance in tumor cells. These findings highlight RhoC-ROCK2 signaling involvement in DNA repair and urge the need for development of these molecules as targets to alleviate the non-responsiveness of cervical cancer tumor cells to irradiation treatment.

Cetacean morbillivirus in Southern Right Whales, Brazil.

Cetacean morbillivirus (CeMV) has caused repeated epizootics and interepizootic fatalities in a variety of cetacean species worldwide. Recently, a novel CeMV strain (GD-CeMV) was linked to a mass die-off of Guiana dolphins (Sotalia guianensis) in Brazil. Southern right whales (SRWs; Eubalaena australis) migrate to the southern Brazilian coast during austral winter and spring (June through November) for breeding and calving. Because unexplained high calf mortality rates have recurrently been documented in SRWs, we hypothesized they could be infected with CeMV. We developed a novel real-time RT-PCR method based on SYBR® GREEN for detection of CeMV and identified the virus in three out of five stranded SRWs from Santa Catarina state, Brazil. The partial sequences of the morbillivirus phosphoprotein gene suggest that the virus is similar to the GD-CeMV strain. Our results indicate CeMV can infect SRWs and should be considered in the differential aetiologic diagnosis of infectious diseases in this species. It also raises concern for potential conservation implications for this species in its main coastal breeding area off Southern Brazil.

Enhanced Child Psychiatry Access and Engagement via Integrated Care: A Collaborative Practice Model With Pediatrics.

OBJECTIVE: This study examined mental health service use outcomes for children receiving integrated care via a collaborative-practice model (CPM). The study hypothesis was that the delivery of intensively integrated clinical care within pediatrics, combined with community-based parent support from family support specialists (FSSs), would facilitate mental health or substance use disorder treatment access and engagement for youths at risk of experiencing disparities. METHODS: The study sample consisted of 228 children referred by pediatricians for outpatient child psychiatry evaluation within an urban safety-net hospital system in 2013. In the pilot clinic, 32 youths were referred to the CPM intervention. Among the remaining seven clinics, 196 youths were referred to usual care (control group). Differences in treatment access and engagement between the intervention and control groups were assessed using propensity-score weighted logistic regression models. RESULTS: Holding all else constant, children receiving the CPM intervention had four times higher odds of accessing psychiatric evaluations than children in the usual care control group (adjusted odds ratio [AOR]=4.16, p<.01). The odds of engagement (i.e., participation in follow-up appointments) were seven times greater for youths in the CPM than youths in the control group (AOR=7.54, p<.01). CONCLUSIONS: Access and engagement were significantly higher for children receiving CPM than for usual care participants. This suggests that integrated CPM warrants further investigation as an approach for improving the odds that children and families will receive needed mental health or substance use disorder treatment.

Evidence-based assessment of ADHD diagnosis in children and adolescents.

This study illustrates the accuracy and efficiency of using an evidence-based assessment (EBA) strategy for diagnosis of attention-deficit/hyperactivity disorder (ADHD) by integrating the scale scores obtained on BASC-3 teacher and parent rating scales. The examined process used empirical diagnostic likelihood ratios (DLRs) derived from a sample of children with ADHD (N = 339) matched on demographic characteristics from the normative sample. The results show that behavioral scales of executive functioning and functional communication provided incremental utility in ADHD diagnosis. With a revised probability of .80 or higher as the diagnostic criterion, teachers, and parents positively diagnosed 70% and 94% of the ADHD cases respectively. The EBA approach was efficient, with four scales on average used to reach the proposed posterior probability for final diagnosis. Finally, teachers and parents demonstrated a high agreement with respect to the diagnosis results and scales used for the diagnosis.

Flap cover in a patient with severe haemophilia type A.

Haemophilia A is a rare haematological disorder due to deficiency of Factor VIII, causing an abnormal coagulation response to injury. In severe haemophilia A, Factor VIII level is < 1%, often manifesting with spontaneous bleeding into joints. Judicious use of recombinant Factor VIII therapy to maintain adequate levels in the intraoperative, immediate and late post-operative periods, together with adjuvant pro-coagulants, can ensure a safe outcome following surgery. We describe the successful management of one such patient suffering from Marjolin's ulcer of the right gluteal region, who needed wide local excision followed by flap cover. A protocol for management of such patients is also suggested. This is the first such case report from the Indian subcontinent, with only a few such published reports from the West.

Lesbian, Gay, Bisexual, and Transgender Families.

Families headed by sexual minorities encounter unique barriers to care and health equity despite greater cultural acceptance and visibility. Empirical research suggests that children in lesbian, gay, bisexual, and transgender (LGBT) families develop and function comparably to those from traditional families. In helping families, awareness of family structure is important. The health care provider should be familiar with family composition, and their community, social supports, race/ethnic concerns, financial issues, and other vulnerabilities. Cultivating an office culture and practice that supports all patients to comfortably discuss their family history, interpersonal experiences, needs, and vulnerabilities is essential for excellence in clinical care.

SDH with Bleeding Diathesis-a Management Protocol.

Chronic subdural hematoma (SDH) is one of the leading causes of morbidity and mortality in elderly. Patients taking antiplatelets and/or anticoagulants have increased risk of bleeding during the perioperative period. Precise dose blood products and specific surgical technique have been effective in preventing hemorrhagic complications perioperatively. From Jan 2010 to Dec 2012, 25 patients who were on antiplatelets and/or oral anticoagulants underwent emergency surgery for chronic or acute on chronic SDH. Patients were divided into three groups: group I-patients on antiplatelets, group II-patients on oral anticoagulants, and group III-patients taking both. Of these, 21 patients underwent minicraniotomy with microsurgical membranectomy and 4 patients underwent burr hole craniostomy. Random donor platelet concentrate (RDPC) and fresh frozen plasma (FFP) were used depending on whether patient was on antiplatelets or oral anticoagulants. Results were evaluated on the basis of ease of intraoperative hemostasis, incidence of rebleeding in postoperative period, postoperative imaging, and reversal of neurological deficits. Group I, group II, and group III had 16, 4, and 5 patients, respectively. Group I received a mean of 7 units of RDPC. Group II received a mean of 4 units of FFP. Group III received a mean of 7 units of RDPC and 4 units FFPs. There was no problem with intraoperative hemostasis and no incidence of rebleeding. We suggest specific dose protocol for reversal of antiplatelet and anticoagulant effect and specific surgical procedure in preventing intraoperative bleeding and postoperative rebleeding in the above group of patients.

Using i2b2 to Bootstrap Rural Health Analytics and Learning Networks.

We demonstrate that the open-source i2b2 (Informatics for Integrating Biology and the Bedside) data model can be used to bootstrap rural health analytics and learning networks. These networks promote communication and research initiatives by providing the infrastructure necessary for sharing data and insights across a group of healthcare and research partners. Data integration remains a crucial challenge in connecting rural healthcare sites with a common data sharing and learning network due to the lack of interoperability and standards within electronic health records. The i2b2 data model acts as a point of convergence for disparate data from multiple healthcare sites. A consistent and natural data model for healthcare data is essential for overcoming integration issues, but challenges such as those caused by weak data standardization must still be addressed. We describe our experience in the context of building the West Virginia/Kentucky Health Analytics and Learning Network, a collaborative, multi-state effort connecting rural healthcare sites.