Publications by authors named "Reddy Neha"

20 Publications

  • Page 1 of 1

Existence of Notoriety Bias in FDA Adverse Event Reporting System Database and Its Impact on Signal Strength.

Hosp Pharm 2021 Jun 18;56(3):152-158. Epub 2019 Oct 18.

Department of Pharmacy Practice, M. S. Ramaiah University of Applied Sciences, Bengaluru, India.

Notoriety bias is defined as "a selection bias in which a case has a greater chance of being reported if the subject is exposed to the studied factor known to cause, thought to cause, or likely to cause the event of interest." This study aimed to determine the existence of notoriety bias in the FDA Adverse Event Reporting System (FAERS) database and estimate the impact of potential notoriety bias induced by safety alerts on signal estimation using disproportionality analysis. Publicly available FAERS data were downloaded and used for analysis. Thirty-one drugs which had label change/safety alert issued by FDA from 2009 to 2013 were considered. These drugs were reviewed 4 quarters before and after the safety alert notification for the existence of notoriety bias. The impact of notoriety bias induced by safety alerts was analyzed by comparing the signal strength using reporting odds ratio (ROR) and proportional reporting ratio (PRR), 2 years before and after the safety alert. Wilcoxon signed rank test was used to determine whether there were a statistically significant difference before and after the safety alert. There was increased reporting for 11 drugs after the safety alert/label change by the FDA. The reporting of 20 drugs decreased or remained unchanged after the safety alert/label change by the FDA. Wilcoxon signed rank test showed that there is no statistically significant difference with respect to the number of reports before and after the safety alert ( = .330, Z = -0.974). Fourteen (45.16%) drugs had an increase in ROR, while 17 (54.83%) drugs had a decrease in ROR after safety alert issued by FDA ( = .953, Z = -0.059). Fourteen (45.16%) drugs had an increase in PRR, while 17 (54.83%) drugs had a decrease in PRR after safety alert issued by the FDA ( = .914, Z = -0.108). Although few FDA safety alert/warnings had a strong and immediate impact, many had no impact on reporting of AE and signal strength. This study found that overreporting due to notoriety bias does not exist in the FAERS database and the overall disproportionality in signal estimates is not altered by the safety alert.
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http://dx.doi.org/10.1177/0018578719882323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114300PMC
June 2021

Integrating reproductive health care into substance use disorder services.

Int Rev Psychiatry 2021 May 11:1-7. Epub 2021 May 11.

Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA.

People who use drugs face layered stigma and barriers to accessing reproductive health care services. At the same time, they have unique needs for compassionate, trauma-informed, low-barrier reproductive health care. We review the literature on collocated reproductive health care and substance use treatment services in this population and advocate for expansion of reproductive health care services at sites providing care for substance use disorder. Through this review article, we outline the evidence for and best practices in collocating reproductive health care within substance use disorder services.
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http://dx.doi.org/10.1080/09540261.2021.1904845DOI Listing
May 2021

Adverse Psychiatric and Health Impacts of Restrictive Housing for Adolescents in Juvenile Correctional Settings.

J Am Acad Child Adolesc Psychiatry 2021 May 5. Epub 2021 May 5.

Warren Alpert Medical School of Brown University, Providence, Rhode Island; Rhode Island Hospital and Hasbro Children's Hospital, Providence, Rhode Island.

The use of solitary confinement for incarcerated adolescents has been criticized widely, including by the National Commission on Correctional Health Care, the American Academy of Pediatrics, and the American Academy of Child and Adolescent Psychiatry. Currently, 29 states prohibit the use of punitive solitary confinement in juvenile correctional facilities, and 15 others place time limits on solitary confinement of juveniles. However, the use of "restrictive housing," which is broadly defined as an intervention involving removal from the general inmate population, placement in a locked room, or inability to leave the room for the majority of the day, is still commonly practiced. Limited research and guidance exists around this practice and its health impacts on incarcerated adolescents, especially mental health and suicide risk.
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http://dx.doi.org/10.1016/j.jaac.2021.04.015DOI Listing
May 2021

Using telehealth to improve buprenorphine access during and after COVID-19: A rapid response initiative in Rhode Island.

J Subst Abuse Treat 2021 05 20;124:108283. Epub 2021 Jan 20.

Department of Emergency Medicine, The Warren Alpert Medical School of Brown University, Providence, RI, United States of America.

Despite its proven efficacy, buprenorphine remains dramatically underutilized for management of opioid use disorder largely due to onerous barriers to treatment initiation. During the COVID-19 pandemic, many substance use disorder treatment facilities have reduced their hours and services, exacerbating existing barriers. To this end, the U.S. Drug Enforcement Administration and Substance Abuse Mental Health Services Administration adjusted their guidelines to allow for new buprenorphine prescriptions following audio-only telehealth encounters, no longer requiring an in-person evaluation prior to treatment initiation. Under this new guidance, we established a 24/7 telephone hotline to function as a "tele-bridge" clinic where people with opioid use disorder can be linked with a buprenorphine prescriber in real-time for OUD assessment and unobserved buprenorphine initiation with connection to follow-up if appropriate. Additionally, we developed an ED callback protocol to reach patients recently seen for opioid overdose and facilitate their entry into care if interested. In this commentary we describe our hotline and ED callback protocols, discuss theoretical and anecdotal benefits to this approach, and advocate for continuation of current regulatory changes post-COVID-19 to maintain expanded access to novel treatment approaches.
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http://dx.doi.org/10.1016/j.jsat.2021.108283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817486PMC
May 2021

Finding Early Improvement Threshold to Predict Response After 8 Weeks of Treatment Using Risperidone in First-Episode Psychosis.

J Clin Psychopharmacol 2021 Jan/Feb 01;41(1):58-61

A Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università Di Milano, Milan, Italy.

Purpose/background: The study aims to assess whether the early response can predict the outcome at the endpoint for the treatment of first-episode psychosis with risperidone and identify the relationship between initial symptom reduction and late response.

Methods/procedures: A prospective observational study with 4 points follow-up (weeks 2, 3, 4, and 8) was conducted in 48 adult first-episode psychosis patients. Symptoms were quantified by the Positive and Negative Syndrome Scale (PANSS) score. The initial recommended dose was 2 mg of risperidone once daily before sleep. The PANSS score on day 1 (before initiation of drug therapy) was considered as the baseline score. Treatment responses were considered as a reduction of more than 20%, 25%, 30% and 50% from the baseline score on first, second, third, and final follow-up, respectively. Receiver operating characteristic curves were generated for predicting response at the endpoint.

Findings/results: Thirty-one (65%) patients achieved more than 50% reduction (responders) in PANSS score. The mean total PANSS score of the study population after 8 weeks of therapy was found to be 49.77 (95% confidence interval, 46.10-53.43). The mean percentage reduction in PANSS score after 8 weeks of therapy was found to be 52.92% (95% confidence interval, 48.83-57.01). Week 2 response can be taken as the early response (area under the curve = 81.9, P < 0.001). However, the more accurate prediction was possible with week 4 response (area under the curve = 88.7%, P < 0.001).

Implications/conclusions: Our study suggests that patients with an early response at week 2 are likely to achieve positive response after 8 weeks.
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http://dx.doi.org/10.1097/JCP.0000000000001331DOI Listing
December 2020

Autonomous sensory meridian response: Your patients already know, do you?

Cleve Clin J Med 2020 Nov 23;87(12):751-754. Epub 2020 Nov 23.

Division of General Internal Medicine, Mayo Clinic, Rochester, MN

Public interest in autonomous sensory meridian response (ASMR) is growing on digital media platforms. Some people can elicit the response by watching videos containing triggering sounds and images. People susceptible to ASMR's effects report tingling sensations on the head and neck, as well as feelings of euphoria, relaxation, and mood elevation. Underlying mechanisms of the phenomenon are not well understood, but physiologic evidence corroborates some of the self-reported positive effects. Healthcare professionals should be aware of this emerging topic, and the potential for therapeutic applications should be investigated.
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http://dx.doi.org/10.3949/ccjm.87a.20005DOI Listing
November 2020

Vemurafenib Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Disproportionality Analysis in FAERS Database.

Curr Clin Pharmacol 2020 Jun 28. Epub 2020 Jun 28.

Department of Pharmacy Practice, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Bengaluru. India.

Background: Signal strength for any drug event combination can be determined using disproportionality analysis. Vemurafenib is a BRAF inhibitor approved by the US Food and Drug Administration (FDA) in 2011 for the treatment of metastatic melanoma. This study aims to identify the signal strength of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) associated with vemurafenib using disproportionality analysis in FDA database of Adverse Event Reporting System (FAERS).

Methods: Data were obtained from the public release of data in FAERS. Case/non-case method was adopted for the analysis of association between vemurafenib use and DRESS. The data mining algorithm used for the analysis was Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). A value of ROR-1.96SE>1, PRR≥2 were considered as positive signal strength.

Results: A total of 7,171 reports for DRESS have been reported in the FDA database. Amongst which 125 reports were associated with vemurafenib. A cumulative ROR of 17.72 (95% CI 14.83; 21.18) and PRR of 17.46 (95% CI 14.65; 20.81) were observed. Combination treatment of vemurafenib with cobimetinib had higher number of reports (100) with ROR of 103.42 (84.13- 127.14) and PRR of 94.52 (78.26- 114.15). Four deaths were reported and the non-death serious reports included hospitalization, life-threatening, disability, and other serious events with 61, 11, 2 and 39 reports respectively.

Conclusion: Positive signal strength was observed for vemurafenib associated DRESS. The signal strength was higher for vemurafenib in combination with cobimetinib than vemurafenib alone. Health care professionals should be cautious about encountering serious adverse events and should be reported to the regulatory authorities.
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http://dx.doi.org/10.2174/1574884715666200628113508DOI Listing
June 2020

Mycoplasma genitalium and Trichomonas vaginalis: addressing disparities and promoting public health control of two emerging sexually transmitted infections.

Curr Opin Pediatr 2020 08;32(4):482-488

Adolescent Medicine, John Hopkins University School of Medicine.

Purpose Of Review: Mycoplasma genitalium (M. genitalium) and Trichomonas vaginalis (T. vaginalis), sexually transmitted infections that remain non-reportable in the United States, may lead to pelvic inflammatory disease (PID) and adverse pregnancy outcomes if left untreated. Prevalence estimates have highlighted socioeconomic and racial/ethnic disparities in rates of infection. This review summarizes the recent literature on M. genitalium and T. vaginalis with a focus on the epidemiology, screening, and treatment of M. genitalium and T. vaginalis.

Recent Findings: The burden of T. vaginalis testing remains on women. Antimicrobial resistance is of great concern for M. genitalium. Comprehensive screening and treatment guidelines present an opportunity to address these public health concerns.

Summary: M. genitalium and T. vaginalis infections disproportionately affect sexual and racial/ethnic minorities and those facing socioeconomic disparities. The availability of nucleic acid amplification test testing has facilitated accurate diagnosis of both disorders. Safe and efficacious treatments are available for treatment of both disorders. Integrating macrolide resistance testing into treatment algorithms for M. genitalium and dual antibiotic therapy may prove a useful strategy for future US-based guidance. Public health reporting and increased public awareness campaigns are key next steps to addressing the observed reproductive health disparities.
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http://dx.doi.org/10.1097/MOP.0000000000000909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919501PMC
August 2020

Innovation During COVID-19: Improving Addiction Treatment Access.

J Addict Med 2020 Jul/Aug;14(4):e8-e9

Department of Emergency Medicine, The Warren Alpert Medical School of Brown University, Providence, RI (EAS, LAJK, RSW); Department of Psychiatry and Human Behavior, The Warren Alpert Medical School of Brown University, Providence, RI (SAC); Department of Medicine, The Warren Alpert Medical School of Brown University, Providence, RI (CW, RV); The Warren Alpert Medical School of Brown University, Providence, RI (NR).

: During the COVID-19 pandemic, many addiction treatment and harm reduction organizations have had to reduce their hours and services for people with substance use disorders, placing these individuals at increased risk of death. In order to address restricted treatment access during COVID-19, guidance from the Substance Abuse Mental Health Services Administration, the US Drug Enforcement Administration, and the US Department of Health and Human Services has allowed for use of audio-only telehealth encounters for buprenorphine induction without requiring an in-person evaluation or video interface. This has enabled innovations in order to try to meet the needs of the most vulnerable among us during the current pandemic. In this new regulatory environment, we established the Rhode Island Buprenorphine Hotline, a phone hotline which functions as a "tele-bridge" clinic where people with moderate to severe opioid use disorder can be linked with a DATA 2000 waivered provider who can provide an initial assessment and, if appropriate, prescribe buprenorphine for unobserved induction and linkage to outpatient treatment. In this correspondence we briefly share our experience developing this common sense approach to addressing the complex problem of access to treatment only now permissible due to regulatory changes during COVID-19.
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http://dx.doi.org/10.1097/ADM.0000000000000685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236851PMC
August 2020

Early prediction of clinical response in first episode schizophrenia (FES) patients receiving olanzapine.

Int J Psychiatry Clin Pract 2020 Sep 27;24(3):309-314. Epub 2020 Apr 27.

Department of Pharmacy Practice, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Bengaluru, India.

At present, schizophrenia guidelines recommend waiting for 8 weeks before considering a patient as non-responder. This study aims to detect the optimal early response threshold that best predict the final outcome of olanzapine. The study was conducted for 8-week, four points follow up (week 2,3,4, and 8) prospective observational study. A reduction of 20, 25, 30% in Positive and Negative Syndrome Scale (PANSS) score from the base line at week 2,3, and 4 respectively were considered as early response. A reduction of 50% at week 8 was considered as responders. Receiver Operating Characteristics (ROC) curves were performed to detect the optimal threshold. Mean total baseline PANSS score was 106.66(95% CI; 100.4, 112.9). Week 2 (AUC = 50.5%,  > 0.964) and week 3 (AUC = 64.9,  > 0.13) responses failed to predict the 8th week response. Week 4 response (AUC = 92%,  < 0.001) can be taken for the prediction of 8th week response (specificity = 72%, sensitivity = 100%, Positive Predictive Value = 61.1%, Negative Predictive Value = 100% and Optimum Early Response (OER) = 29.4%). 25 patients (69%) achieved more than 50% reduction (responders) in PANSS score after 8 weeks of treatment. Our study suggests that patients with early response at week 4 are likely to achieve positive response after 8 weeks. This may help in appropriate clinical decision making for early non-responders.Key PointsThe early response can forecast the outcome at the endpoint for the treatment of FESA reduction of baseline PANSS score by 30% or more after four weeks are likely to have remission after week 8 with olanzapine therapy.
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http://dx.doi.org/10.1080/13651501.2020.1757118DOI Listing
September 2020

Aromatase inhibitors associated osteonecrosis of jaw: signal refining to identify pseudo safety signals.

Int J Clin Pharm 2020 Apr 8;42(2):721-727. Epub 2020 Apr 8.

Department of Pharmacy Practice, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, New BEL Road, Bengaluru, 560054, Karnataka, India.

Background Signal generation through data mining algorithms is an innovative and emerging field in pharmacovigilance. Early detection of safety signals is important for public health safety. However, the possibility of generating pseudo signals should not be overlooked. Objective Our study aimed to identify potential signals of aromatase inhibitors associated Osteonecrosis of Jaw and assess the possibilities of the safety signal to be a pseudo signal/false positive in FDA Adverse Event Reporting System (FAERS). Setting Spontaneously reported data in FAERS database. Methods Data for this study were obtained from the public release of data in FAERS. OpenVigil, a pharmacovigilance analytical tool was used to access FAERS data. Reporting Odds Ratio (ROR) was used to assess the relation between the drug and adverse event. A value of ROR-1.96SE  > 1, (SE-standard error) was considered positive. Main outcome measure Signal strength. Results FAERS database had a total of 15,178 reports for Osteonecrosis of Jaw. Amongst which 617 reports were associated with aromatase inhibitors. Signal strength ROR (lower bound of the 95% CI) for letrozole, anastrozole and exemestane associated Osteonecrosis of Jaw without any background correction was 8.34, 6.64 and 15.14 respectively. Upon removing the reports of concomitantly administered drugs (bisphosphonates and denosumab), signal strength drastically decreased to 0.03, 0.36 and 0.47 for letrozole, anastrozole and exemestane respectively. The signal strength of bisphosphonates and denosumab associated Osteonecrosis of Jaw was not changed significantly upon removal of aromatase inhibitors. Conclusion Our study concluded that the signal generated for aromatase inhibitors associated Osteonecrosis of Jaw in FAERS database can be false positive. Careful background corrections with identification of those risk factors are imperative to exclude false positive results.
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http://dx.doi.org/10.1007/s11096-020-01018-zDOI Listing
April 2020

Postlicensure surveillance of human papillomavirus vaccine using the Vaccine Adverse Event Reporting System, 2006-2017.

Perspect Clin Res 2020 Jan-Mar;11(1):24-30. Epub 2019 Apr 26.

Department of Pharmacy Practice, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, India.

Background: The United States Food and Drug Administration (FDA) has licensed three HPV (Human papilloma virus) vaccines. The centers for disease control and prevention (CDC) and advisory committee on immunization practices (ACIP) recommends routine HPV vaccination at age 11 or 12 years. This study aimed to summarize and characterize adverse events following HPV vaccination reported to VAERS database from July 2006 to May 2017.

Methods: A systematic data mining was performed in the VAERS database for reports associated with HPV vaccine. Clinically relevant Vaccine Event Combinations (VEC) were identified in the VAERS database following HPV vaccination. A VEC was considered for analysis only if a minimum of hundred reports were present in database for the given Adverse Event (AE). The data mining algorithm used in this study was reporting odds ratio. A value of ROR-1.96SE >1 was considered as positive signal.

Results: VAERS received 49444 reports after receipt of HPV vaccine during the study period. Out of 49444, 2307 unique reactions were identified. A total of 177 death reports and 3526 non death serious reactions were reported to VAERS. ROR showed positive signals for abdominal pain, syncope, dizziness, convulsion, abortion spontaneous, alopecia, amenorrhea, anogenital warts, cervical dysplasia, anaemia, dyskinesia, migrane, blood pressure decreased, fall, head injury, loss of consciousness, pallor, presyncope, seizures.

Conclusion: The present analysis did not identify any new/unexpected safety concern and was consistent with the safety data from prelicensure trials. Further epidemiological studies are required to systematically validate the data provided by VAERS.
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http://dx.doi.org/10.4103/picr.PICR_140_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034135PMC
April 2019

Dyadic Model of Adaptation to Life-Limiting Illness.

J Palliat Med 2020 09 28;23(9):1177-1183. Epub 2020 Feb 28.

Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.

We previously developed the reintegration model to describe the adjustment process for individuals at the end of life. However, caregivers and loved ones also require significant support and must work to reimagine their relationship with one another. We sought to develop a dyadic version of the reintegration model that delineates key parts of the adjustment process that occur between the patient and another significant person rather than as two separate individuals. We refined an initial conceptual model of this dyadic process with findings from a narrative literature review on spousal dyadic mutuality. We assessed emergent themes regarding dyadic adjustment from the literature for their fit with our original reintegration model and through consensus discussion, applied the findings to a final proposed conceptual model of dyadic reintegration at the end of life. Examples of dyadic adjustment in the literature relate to the comprehension, creative adaptation, and reintegration processes described in the original reintegration model. Evidence also supported three substantive additions in the new dyadic model: (1) shared understanding that the harmony of the dyad is interrupted; (2) consideration of the "we" (the dyad) and the "I" (the individual) in mutual reflection to create a shared narrative; and (3) emphasis on relationship as a factor impacting adjustment processes. Available evidence supports interdependent relationships between members of dyads for the three adaptation processes of comprehension, creative adaptation, and reintegration in the model. This dyadic reintegration model can be useful in clinical practice to support dyads facing life-limiting illness.
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http://dx.doi.org/10.1089/jpm.2019.0444DOI Listing
September 2020

Sonic Hedgehog is expressed by hilar mossy cells and regulates cellular survival and neurogenesis in the adult hippocampus.

Sci Rep 2019 11 22;9(1):17402. Epub 2019 Nov 22.

Neural Engineering Center, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, 44106, USA.

Sonic hedgehog (Shh) is a multifunctional signaling protein governing pattern formation, proliferation and cell survival during embryogenesis. In the adult brain, Shh has neurotrophic function and is implicated in hippocampal neurogenesis but the cellular source of Shh in the hippocampus remains ill defined. Here, we utilize a gene expression tracer allele of Shh (Shh-nlacZ) which allowed the identification of a subpopulation of hilar neurons known as mossy cells (MCs) as a prominent and dynamic source of Shh within the dentate gyrus. AAV-Cre mediated ablation of Shh in the adult dentate gyrus led to a marked degeneration of MCs. Conversely, chemical stimulation of hippocampal neurons using the epileptogenic agent kainic acid (KA) increased the number of Shh MCs indicating that the expression of Shh by MCs confers a survival advantage during the response to excitotoxic insults. In addition, ablation of Shh in the adult dentate gyrus led to increased neural precursor cell proliferation and their migration into the subgranular cell layer demonstrating that MCs-generated Shh is a key modulator of hippocampal neurogenesis.
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http://dx.doi.org/10.1038/s41598-019-53192-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874678PMC
November 2019

Development of a Training Game to Coordinate Torques Produced Between Arms.

IEEE Int Conf Rehabil Robot 2019 06;2019:447-452

The ability of individuals to accurately judge the forces that they generate is integral to seamlessly controlling their movements during everyday life. Individuals with chronic hemiparetic stroke have been shown to be impaired when matching forces between arms; this impairment may make activities as simple as carrying a tray challenging. Our goal was to develop a training protocol that individuals with stroke could use to improve their accuracy in judging the torques that they generate between arms. We designed a torque coordination game for this goal and tested its feasibility in six individuals without neurological impairments. Participants interacted with an instrumented isometric device at each arm and received automated audiovisual cues in response to the torques that they generated about each elbow joint. During the game, the participant's task was to keep a launched ball on its planned course. The participant achieved this task by sequentially applying required elbow torques at the correct times to close a left flap using the left arm and a right flap using the right arm. Participants performed this task 20 times when initiating with their left arm and 20 times when initiating with their right arm. Results indicate that all participants had a success rate in the range of 60% to 80% regardless of the arm dominance of the leading arm. Additionally, all participants anecdotally reported the game to be intuitive, and they provided an average difficulty rating that indicated the task was relatively easy to learn (i.e., 3 out of 10). Based on these findings, we conclude that this game may be suitable, enjoyable, and motivational for training coordination of torques between arms in individuals with stroke.
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http://dx.doi.org/10.1109/ICORR.2019.8779455DOI Listing
June 2019

IFN-γ-inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5.

Sci Signal 2018 11 20;11(557). Epub 2018 Nov 20.

Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

It is well established that activation of the transcription factor signal transducer and activator of transcription 1 (STAT1) is required for the interferon-γ (IFN-γ)-mediated antiviral response. Here, we found that IFN-γ receptor stimulation also activated Unc-51-like kinase 1 (ULK1), an initiator of Beclin-1-mediated autophagy. Furthermore, the interaction between ULK1 and the mitogen-activated protein kinase kinase kinase MLK3 (mixed lineage kinase 3) was necessary for MLK3 phosphorylation and downstream activation of the kinase ERK5. This autophagy-independent activity of ULK1 promoted the transcription of key antiviral IFN-stimulated genes (ISGs) and was essential for IFN-γ-dependent antiviral effects. These findings define a previously unknown IFN-γ pathway that appears to be a key element of the antiviral response.
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http://dx.doi.org/10.1126/scisignal.aap9921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684240PMC
November 2018

Robot-assisted anterior mediastinal mass excision with pericardium and adjacent lung for locally advanced thymic carcinoma.

J Vis Surg 2018 31;4:115. Epub 2018 May 31.

Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine and the University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Robot-assisted surgery for anterior mediastinal mass resection has been increasingly adopted as an alternative method to open sternotomy and conventional video-assisted thoracic surgery. However, more evidence is needed to expand the indication of this technique to more complicated cases. We present a case of robot-assisted resection of a 7-cm anterior mediastinal mass with pericardium and adjacent lung for thymic squamous cell carcinoma, accompanied by reconstruction of pericardium with polytetrafluoroethylene patch. In conclusion, complex anterior mediastinal mass excision is feasible with robotic thoracic surgery.
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http://dx.doi.org/10.21037/jovs.2018.05.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994450PMC
May 2018

"And Yet It Was a Blessing": The Case for Existential Maturity.

J Palliat Med 2017 04 27;20(4):318-327. Epub 2017 Jan 27.

4 Brookline , Massachusetts.

We are interested in the kind of well-being that can occur as a person approaches death; we call it "existential maturity." We describe a conceptual model of this state that we felt was realized in an individual case, illustrating the state by describing the case. Our goal is to articulate a generalizable, working model of existential maturity in concepts and terms taken from fundamentals of psychodynamic theory. We hope that a recognizable case and a model-based way of thinking about what was going on can both help guide care that fosters existential maturity and stimulate more theoretical modeling of the state.
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http://dx.doi.org/10.1089/jpm.2016.0540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385420PMC
April 2017

Roux-en-Y near esophagojejunostomy for failed antireflux operations: outcomes in more than 100 patients.

Ann Thorac Surg 2014 Dec 29;98(6):1905-11; discussion 1911-3. Epub 2014 Oct 29.

Division of Thoracic and Foregut Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: Intractable gastroesophageal reflux disease (GERD) after antireflux operations presents a challenge-particularly in obese patients and patients with esophageal dysmotility-and increases the complexity of the redo operation. This study evaluated the results of Roux-en-Y near esophagojejunostomy (RNYNEJ) in the management of recurrent GERD after antireflux operations.

Methods: We conducted a retrospective review of overweight patients with intractable GERD who underwent RNYNEJ for failed antireflux operations. We evaluated perioperative outcomes, dysphagia (ranging from 1 = no dysphagia to 5 = unable to swallow saliva), and quality of life (QOL) (assessed using the GERD health-related quality-of-life instrument (HRQOL).

Results: Over a 12-year period, 105 patients with body mass index (BMI) greater than 25 underwent RNYNEJ for failed antireflux operations. Most were obese (BMI > 30; 82 patients [78%]); esophageal dysmotility was demonstrated in more than one-third of patients. Forty-eight (46%) patients had multiple antireflux operations before RNYNEJ, and 27 patients had undergone a previous Collis gastroplasty. There was no perioperative mortality. Major complications, including anastomotic leak requiring surgical intervention (n = 3 [2.9%]), were noted in 25 patients (24%).The median length of stay was 6 days. During follow-up (mean, 23.39 months), median BMI decreased from 35 to 27.6 (p < 0.0001), and the mean dysphagia score decreased from 2.9 to 1.5 (p < 0.0001). The median GERD HRQOL score, assessed in a subset of patients, was 9 (classified as excellent).

Conclusions: RNYNEJ for persistent GERD after antireflux operations in appropriately selected patients can be performed safely with good results in experienced centers. RNYNEJ should be considered an important option for the treatment of intractable recurrent symptoms after antireflux operations, particularly in obese patients.
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http://dx.doi.org/10.1016/j.athoracsur.2014.07.004DOI Listing
December 2014

The results of a breast cancer screening cAMP at a district level in rural India.

Asian Pac J Cancer Prev 2012 ;13(12):6067-72

Northwestern University, Evanston, IL, USA.

Background: Breast cancer in developing countries is on the rise. There are currently no guidelines to screen women at risk in India. Since mammography in the western world is a well-accepted screening tool to prevent late presentation of breast cancer and improve mortality, it is intuitive to adopt mammography as a screening tool of choice. However, it is expensive and fraught with logistical issues in developing countries like India.

Materials And Methods: Our breast cancer screening camp was done at a local district hospital in India after approval from the director and administrators. After initial training of local health care workers, a one-day camp was held. Clinical breast examination, mammograms, as well as diagnostic evaluation with ultrasound and fine needle aspiration biopsy were utilized.

Results: Out of total 68 women screened only 2 women with previous history of breast cancer were diagnosed with breast cancer recurrence. None of the women in other groups were diagnosed with breast cancer despite suspicious lesions either on clinical exam, mammogram or ultrasound. Most suspicious lesions were fibroadenomas. The average cost of screening women who underwent mammography, ultrasound and fine needle aspiration was $30 dollars, whereas it was $16 in women who had simple clinical breast examination.

Conclusions: Local camps act as catalysts for women to seek medical attention or discuss with local health care workers concerns of discovering new lumps or developing breast symptoms. Our camp did diagnose recurrence of breast cancer in two previously treated breast cancer patients, who were promptly referred to a regional cancer hospital. Further studies are needed in countries like India to identify the best screening tool to decrease the presentation of breast cancer in advanced stages and to reduce mortality.
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http://dx.doi.org/10.7314/apjcp.2012.13.12.6067DOI Listing
April 2016