Post-cholecystectomy Clip Migration: A Case Report.

Surgical clip migration into the common bile duct (CBD) with subsequent stone formation is an exceedingly rare complication following both laparoscopic and open cholecystectomy, with fewer than 100 cases reported in the literature. Herein, we present the case of a 78-year-old female who presented with abdominal pain and dark urine six years after an open cholecystectomy. Her abdominal ultrasonography revealed no abnormalities, with only mild derangements noted in liver function tests. However, computed tomography of the abdomen unveiled a single metallic surgical clip lodged within the CBD, surrounded by a bile stone, alongside another clip at the gallbladder fossa. The patient underwent endoscopic retrograde cholangiopancreatography (ERCP), during which the clip was successfully removed. The procedure has utilized SpyGlass cholangioscopy. While clip migration into the CBD remains a rare phenomenon, it should be considered in the differential diagnosis of patients presenting with obstructive jaundice or biliary colic post-cholecystectomy. Minimally invasive management by ERCP is the procedure of choice for migrated clips-related complications but surgical common bile duct exploration may be necessary. This case highlights the importance of vigilance and prompt intervention in managing post-cholecystectomy clip migration (PCCM) but potentially serious postoperative complications.

4th Generation HIV screening in the emergency department: net profit or loss for hospitals?

ABSTRACTThe objective of this study was to determine hospital costs and revenue of universal opt-out HIV ED screening. An electronic medical record (EMR)-directed, automated ED screening program was instituted at an academic medical center in San Diego, California. A base model calculated net income in US dollars for the hospital by comparing annual testing costs with reimbursements using payor mixes and cost variables. To account for differences in payor mixes, testing costs, and reimbursement rates across hospitals in the US, we performed a probabilistic sensitivity analysis. The base model included a total of 12,513 annual 4th generation HIV tests with the following payor mix: 18% Medicare, 9% MediCal, 28% commercial and 8% self-payers, with the remainder being capitated contracts. The base model resulted in a net profit for the hospital. In the probabilistic sensitivity analysis, universal 4th generation HIV screening resulted in a net profit for the hospital in 81.9% of simulations. Universal 4th generation opt-out HIV screening in EDs resulted in a net profit to an academic hospital. Sensitivity analysis indicated that ED HIV screening results in a net-profit for the majority of simulations, with higher proportions of self-payers being the major predictor of a net loss.

Attitudes and perceptions of next-of-kin/loved ones toward end-of-life HIV cure-related research: A qualitative focus group study in Southern California.

As end-of-life (EOL) HIV cure-related research expands, understanding perspectives of participants' next-of-kin (NOK) is critical to maintaining ethical study conduct. We conducted two small focus groups and two one-on-one interviews using focus group guides with the NOK of Last Gift study participants at the University of California, San Diego (UCSD). Participating NOK included six individuals (n = 5 male and n = 1 female), including a grandmother, grandfather, partner, spouse, and two close friends. Researchers double-coded the transcripts manually for overarching themes and sub-themes using an inductive approach. We identified six key themes: 1) NOK had an accurate, positive understanding of the Last Gift clinical study; 2) NOK felt the study was conducted ethically; 3) Perceived benefits for NOK included support navigating the dying/grieving process and personal growth; 4) Perceived drawbacks included increased sadness, emotional stress, conflicted wishes between NOK and study participants, and concerns around potential invasiveness of study procedures at the EOL; 5) NOK expressed pride in loved ones' altruism; and 6) NOK provided suggestions to improve the Last Gift study, including better communication between staff and themselves. These findings provide a framework for ethical implementation of future EOL HIV cure-related research involving NOK.

Altruism: Scoping review of the literature and future directions for HIV cure-related research.

INTRODUCTION: The question of what motivates people to participate in research is particularly salient in the HIV field. While participation in HIV research was driven by survival in the 1980's and early 1990's, access to novel therapies became the primary motivator with the advent of combination antiretroviral therapy (cART) in the late 1990s. In the HIV cure-related research context, the concept of altruism has remained insufficiently studied. METHODS: We conducted a scoping review to better contextualize and understand how altruism is or could be operationalized in HIV cure-related research. We drew from the fields of altruism in general, clinical research, cancer, and HIV clinical research-including the HIV prevention, treatment, and cure-related research fields. DISCUSSION: Altruism as a key motivating factor for participation in clinical research has often been intertwined with the desire for personal benefit. The cancer field informs us that reasons for participation usually are multi-faceted and complex. The HIV prevention field offers ways to organize altruism-either by the types of benefits achieved (e.g., societal versus personal), or the origin of the values that motivate research participation. The HIV treatment literature reveals the critical role of clinical interactions in fostering altruism. There remains a dearth of in-depth knowledge regarding reasons surrounding research participation and the types of altruism displayed in HIV cure-related clinical research. CONCLUSION: Lessons learned from various research fields can guide questions which will inform the assessment of altruism in future HIV cure-related research.

"[It] is now my responsibility to fulfill that wish:" Clinical and rapid autopsy staff members' experiences and perceptions of HIV reservoir research at the end of life.

INTRODUCTION: Little is known about the effects of HIV reservoir research at the end of life on staff members involved. Staff members' perceptions and experiences were assessed related to their involvement in the Last Gift, a rapid autopsy study at the University of California San Diego enrolling people living with HIV who are terminally ill and have a desire to contribute to HIV cure-related research. METHODS: Two focus group discussions consisting of clinical (n = 7) and rapid research autopsy (n = 8) staff members were conducted to understand the perspectives of staff members and the impact the Last Gift rapid autopsy study had on them. The total sample consisted of 66.7% females and 33.3% males and was ethnically diverse (66.7% Caucasian, 6.7% African American, 20.0% Asian descent, 6.7% Hispanic descent and American Indian) with a range of experience in the HIV field from 1 year to 30 years. RESULTS: Qualitative focus group data revealed five major themes underlying study staff members' multilayered mental and practical involvement: 1) positive perceptions of the Last Gift study, with sub-themes including Last Gift study participants' altruism, fulfillment, and control at the end of life, 2) perceptions of staff members' close involvement in the Last Gift study, with sub-themes related to staff members' cognitive processing, self-actualization and fulfillment, stress management and resilience, coping mechanisms, and gratitude toward Last Gift participants and toward the study itself, 3) considerations for successful and sustainable study implementation, such as ethical awareness and sustained community and patient engagement, 4) collaborative learning and organizational processes and the value of interdependence between staff members, and 5) considerations for potential study scale-up at other clinical research sites. DISCUSSION: Understanding staff members' nuanced emotional and procedural experiences is crucial to the Last Gift study's sustainability and will inform similar cure research studies conducted with people living with HIV at the end of life. The study's potential reproducibility depends on a robust research infrastructure with established, interdependent clinical and rapid autopsy teams, continuous community engagement, and an ethical and well-informed engagement process with people living with HIV.

Perceptions of Next-of-Kin/Loved Ones About Last Gift Rapid Research Autopsy Study Enrolling People with HIV/AIDS at the End of Life: A Qualitative Interview Study.

A growing number of people living with HIV/AIDS are participating in HIV cure-related research at the end of life (EOL). Due to the novelty of EOL HIV cure-related research, there is a need to understand how their next-of-kin (NOK) perceive such research. We conducted in-depth interviews with NOK of the Last Gift study participants at the University of California, San Diego. The Last Gift study occurs in the context of the EOL and involves a full body donation. NOK completed two interviews: (1) shortly after the participants' enrollment in the study and (2) following death. We applied thematic analysis to analyze qualitative data. NOK included seven individuals (five males and two females), including two spouses, one ex-partner, one sister, a grandmother/grandfather, and a close friend. Thematic analysis revealed five key themes: (1) NOK viewed the Last Gift program in a positive light and had an accurate overall understanding of the study; (2) NOK identified factors that motivated participants to donate their body to science; (3) NOK identified benefits of the Last Gift program for both the donors and themselves; (4) NOK did not perceive any physical risks or decisional regrets of study but wanted to minimize psychosocial impacts and ensure the dignity of participants at all times; and (5) NOK noted elements that remained essential to the successful implementation of EOL HIV cure-related research, such as early involvement and clear communication. Our study uniquely contributes to increased understanding and knowledge of what is important from the point of view of supportive NOK to ensure successful implementation of EOL HIV cure-related research. More research will be needed to understand perspectives of less supportive NOK.

"My Death Will Not [Be] in Vain": Testimonials from Last Gift Rapid Research Autopsy Study Participants Living with HIV at the End of Life.

End-of-life (EOL) HIV cure-related research provides a novel approach to studying HIV reservoirs. The Last Gift is a rapid autopsy research study at the University of California San Diego that enrolls terminally ill people living with HIV (PLWHIV) with a desire to contribute to HIV cure-related research. We conducted in-depth baseline and follow-up interviews with Last Gift study participants. We analyzed interview data applying conventional content analysis. Since summer 2017, 13 participants have been enrolled (n = 11 males and 2 females; aged 45-89 years) and 8 participants interviewed. Terminal illnesses included cancers, heart diseases, and neurodegenerative illnesses. Our analysis revealed five key themes: (1) The Last Gift study has tremendous meaning for participants at the end of their life. (2) HIV-specific altruism was a primary motivator to join the Last Gift study, nested within the context of community, scientific advancement, and moral obligation. (3) Participants did not expect physical benefits yet they perceived emotional/psychological, financial, and societal/scientific benefits. (4) There were minimal participant-perceived risks and concerns. (5) Last Gift participants expressed immense gratitude toward study staff. The Last Gift study provides a framework for ethical HIV cure-related research at EOL and highlighted participants' perspectives, motivations, and experiences. Knowing how PLWHIV understand and experience such studies will remain critical to designing ethical, fully informed HIV cure research protocols that are acceptable to PLWHIV.

Effect of artificial sweeteners on insulin resistance among type-2 diabetes mellitus patients.

INTRODUCTION: Incidence of diabetes mellitus has increased over the past few years, mainly due to our eating habits and physical inactivity. This also includes the use of artificial sweetening agents which have broadly replaced other forms of sugars and have shown a paradoxical, negative effect on blood glucose. Ingestion of these artificial sweeteners (AS) results in the release of insulin from pancreas which is mistaken for glucose (due to their sweet taste). This increases the levels of insulin in blood eventually leading to decreased receptor activity due to insulin resistance. METHODOLOGY: It is a crosssectional study that was conducted on patients diagnosed with type-2 diabetes mellitus of a tertiary care hospital in Central India. All the diabetics that presented in the OPD were divided into 2 groups based on whether they use AS (group A) or not (group B). Insulin resistance was calculated for each group using HOMA-IR and graphs were plotted. RESULTS: The HOMAIR values for Group A and B ranged from 0.9-24.33 and 0.12-10.83 with mean values 7.39 and 2.6, respectively, showing that the ones who used AS had a higher insulin resistance. The study also showed that the duration of use of artificial sweeteners had a direct impact on insulin resistance.

Assessment of knowledge and attitude about child abuse amongst parents visiting rural tertiary care hospital in central India.

INTRODUCTION: Child abuse is one of the pressing human rights issues which still needs to be highlighted for general public, especially in traditional societies. This study depicts perspectives of parents and caregivers. METHODS: The study was, conducted amongst parents visiting paediatric department (OPD and ward) at Rural Tertiary care Hospital in central India. A questionnaire was prepared and filled by parents and then was statistically analysed. RESULTS: It was seen that: 1. Majority of parents lack knowledge regarding children's education and protection (POSCO and RTE) 2. Most parents were in favour of having better career prospects for Male child. 3. Parents were also asked regarding physical, emotional and mental health of a child. Majority of the parents were of the opinion that children should be distinguished based on academic performances. The study also recommended various measures to combat child abuse.

Universal HIV and Birth Cohort HCV Screening in San Diego Emergency Departments.

Universal HIV and HCV screening in emergency departments (ED) can reach populations who are less likely to get tested otherwise. The objective of this analysis was to evaluate universal opt-out HIV and HCV screening in two EDs in San Diego. HIV screening for persons aged 13-64 years (excluding persons known to be HIV+ or reporting HIV testing within last 12 months) was implemented using a 4th generation HIV antigen/antibody assay; HCV screening was offered to persons born between 1945 and 1965. Over a period of 16 months, 12,575 individuals were tested for HIV, resulting in 33 (0.26%) new HIV diagnoses, of whom 30 (90%) were successfully linked to care. Universal screening also identified 74 out-of-care for >12-months HIV+ individuals of whom 50 (68%) were successfully relinked to care. Over a one-month period, HCV antibody tests were conducted in 905 individuals with a seropositivity rate of 9.9% (90/905); 61 seropositives who were newly identified or never treated for HCV had HCV RNA testing, of which 31 (51%) resulted positive (3.4% of all participants, including 18 newly identified RNA positives representing 2% of all participants), and 13/31 individuals (42%) were linked to care. The rate of newly diagnosed HCV infections exceeded the rate of newly diagnosed HIV infections by >7-fold, underlining the importance of HCV screening in EDs.

Differential sensitivity of structural, diffusion, and resting-state functional MRI for detecting brain alterations and verbal memory impairment in temporal lobe epilepsy.

OBJECTIVES: Temporal lobe epilepsy (TLE) is known to affect large-scale gray and white matter networks, and these network changes likely contribute to the verbal memory impairments observed in many patients. In this study, we investigate multimodal imaging patterns of brain alterations in TLE and evaluate the sensitivity of different imaging measures to verbal memory impairment. METHODS: Diffusion tensor imaging (DTI), volumetric magnetic resonance imaging (vMRI), and resting-state functional MRI (rs-fMRI) were evaluated in 46 patients with TLE and 33 healthy controls to measure patterns of microstructural, structural, and functional alterations, respectively. These measurements were obtained within the white matter directly beneath neocortex (ie, superficial white matter [SWM]) for DTI and across neocortex for vMRI and rs-fMRI. The degree to which imaging alterations within left medial temporal lobe/posterior cingulate (LMT/PC) and left lateral temporal regions were associated with verbal memory performance was evaluated. RESULTS: Patients with left TLE and right TLE both demonstrated pronounced microstructural alterations (ie, decreased fractional anisotropy [FA] and increased mean diffusivity [MD]) spanning the entire frontal and temporolimbic SWM, which were highly lateralized to the ipsilateral hemisphere. Conversely, reductions in cortical thickness in vMRI and alterations in the magnitude of the rs-fMRI response were less pronounced and less lateralized than the microstructural changes. Both stepwise regression and mediation analyses further revealed that FA and MD within SWM in LMT/PC regions were the most robust predictors of verbal memory, and that these associations were independent of left hippocampal volume. SIGNIFICANCE: These findings suggest that microstructural loss within the SWM is pronounced in patients with TLE, and injury to the SWM within the LMT/PC region plays a critical role in verbal memory impairment.

Beyond depression: The impact of executive functioning on quality of life in patients with temporal lobe epilepsy.

OBJECTIVE: Individuals with temporal lobe epilepsy (TLE) often experience diminished quality of life (QoL). Although comorbid depression is one of the most recognized predictors of poor QoL in TLE, impairments in verbal memory (VM) and executive functioning (EF), have also been identified as risk factors, independent of other biological and psychosocial factors. In this study, we examine the contribution of depression, VM, and EF to QoL in 52 well-characterized medically-refractory TLE patients. METHODS: Quality of life was assessed with the Quality of Life in Epilepsy (QOLIE-31) questionnaire and depression symptomatology was evaluated with the Beck Depression Inventory-II (BDI-II). Tests of VM included the California Verbal Learning Test-Second Edition and the Wechsler Memory Scale-Third Edition, Logical Memory and Verbal Paired Associates subtests. Tests of EF included the D-KEFS Category Switching and Color Word Interference Tests, and the Trail Making Test. Using these measures, a principal component (PC) was derived for VM and for EF. Hierarchical multiple linear regression analysis was used to evaluate the unique contributions of BDI-II Score, VM PC, and EF PC to the QOLIE-31 Total Score, while controlling for important clinical and demographic variables. Post-hoc analyses were also performed to examine the contribution of each variable to specific QOLIE subscales. RESULTS: Of the clinical variables, only number of antiepileptic drugs contributed to QOLIE scores. As expected, severity of depressive symptoms was the most significant predictor of QOLIE Total Score, explaining 43.4% of the variance in total QoL. The VM PC did not contribute to the QOLIE Total Score. Rather, our EF PC emerged as an important predictor of QoL, explaining an additional 5% of the variance, after controlling for clinical variables, depression severity, and VM performance. SIGNIFICANCE: These findings suggest that a combination of clinical, affective, and cognitive factors influence QoL in patients with TLE. Designing interventions with careful attention to depression and EF may be needed to optimize QoL in patients with refractory TLE and potentially other epilepsy syndromes.

Ethical considerations for HIV cure-related research at the end of life.

BACKGROUND: The U.S. National Institute of Allergies and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH) have a new research priority: inclusion of terminally ill persons living with HIV (PLWHIV) in HIV cure-related research. For example, the Last Gift is a clinical research study at the University of California San Diego (UCSD) for PLWHIV who have a terminal illness, with a prognosis of less than 6 months. DISCUSSION: As end-of-life (EOL) HIV cure research is relatively new, the scientific community has a timely opportunity to examine the related ethical challenges. Following an extensive review of the EOL and HIV cure research ethics literature, combined with deliberation from various stakeholders (biomedical researchers, PLWHIV, bioethicists, and socio-behavioral scientists) and our experience with the Last Gift study to date, we outline considerations to ensure that such research with terminally ill PLWHIV remains ethical, focusing on five topics: 1) protecting autonomy through informed consent, 2) avoiding exploitation and fostering altruism, 3) maintaining a favorable benefits/risks balance, 4) safeguarding against vulnerability through patient-participant centeredness, and 5) ensuring the acceptance of next-of-kin/loved ones and community stakeholders. CONCLUSION: EOL HIV cure-related research can be performed ethically and effectively by anticipating key issues that may arise. While not unique to the fields of EOL or HIV cure-related research, the considerations highlighted can help us support a new research approach. We must honor the lives of PLWHIV whose involvement in research can provide the knowledge needed to achieve the dream of making HIV infection curable.