41 results on '"Anna Chiu"'
Search Results
2. Detecting Hate Speech on Social Media with Respect to Adolescent Vulnerability.
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Anna Chiu, Kanika Sood, Ariadne Rincon, and Davina Doran
- Published
- 2023
- Full Text
- View/download PDF
3. Synthesis of Rovafovir Etalafenamide (Part I): Active Pharmaceutical Ingredient Process Development, Scale-Up, and Impurity Control Strategy
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Mihaela M. Esanu, Edmund Leung, Nande Wright, Selcuk Calimsiz, Xiang Wang, Olivier St-Jean, Eric A. Standley, Guojun Yu, Li Wang, Dustin Bringley, Roberts Benjamin James, Jaspal Phull, Anna Chiu, Jason A. Davy, Doxsee Ian James, Jeffrey D. Ng, Wen-Tau T. Chang, Lennie Lin, Jenny Phoenix, David Allen Siler, Olga Lapina, Andrea Ambrosi, Youri Kim, Jeffrey A. O. Garber, Jinyu Shen, Bernard Kwong, Keshab Sarma, Bing Shi, and Andrew Anthony Martins
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Active ingredient ,Reverse-transcriptase inhibitor ,010405 organic chemistry ,Chemistry ,Process development ,Organic Chemistry ,Human immunodeficiency virus (HIV) ,Prodrug ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,medicine ,Physical and Theoretical Chemistry ,medicine.drug - Abstract
This manuscript describes the chemical process development and multi-kilogram synthesis of rovafovir etalafenamide (GS-9131), a phosphonamidate prodrug nucleotide reverse transcriptase inhibitor un...
- Published
- 2021
4. Clinical targeting of HIV capsid protein with a long-acting small molecule
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Qi Liu, Chien-Hung Chou, Eda Canales, Roman Sakowicz, Steven Bondy, Tomas Cihlar, Albert Liclican, Diana M. Brainard, Anita Niedziela-Majka, William Rowe, Nikolai Novikov, Shekeba Ahmadyar, John R. Somoza, Randall L. Halcomb, Cheryl K. McDonald, Carina E. Cannizzaro, Nicolas Margot, Debi Jin, George Stepan, Qiaoyin Wu, Eric Hu, Judy Mwangi, Stephanie A. Leavitt, Todd C. Appleby, Robert L. Anderson, Scott E. Lazerwith, Schroeder Scott D, Tse Winston C, Gediminas Brizgys, Rebecca Begley, Yili Xu, Scott Sellers, Scott A. Wolckenhauer, Wesley I. Sundquist, Derek Hansen, Philip Morganelli, Andrew Mulato, Sheila Clancy, Xiaohong Liu, Anna Chiu, Eric S. Daar, Renee R. Ram, S. Swaminathan, Anne E. Chester, Melanie H. Wong, Ya-Pei Liu, John O. Link, Michael Graupe, Luong K. Tsai, Christian Callebaut, Latesh Lad, William E. Lee, Rujuta A. Bam, Terrence Z. Cai, Bing Lu, John K. Ling, Roland D. Saito, Magdeleine Hung, Armando G. Villaseñor, Peter Ruane, Nikos Pagratis, Martin S. Rhee, David Koditek, Gordon Crofoot, Giuseppe A. Papalia, Stephen R. Yant, Rob Hyland, Helen Yu, Jim Zheng, Jennifer R. Zhang, Gary I. Sinclair, Jiayao Li, and Eric Singer
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Adult ,Male ,Models, Molecular ,0301 basic medicine ,Adolescent ,Anti-HIV Agents ,030106 microbiology ,Drug resistance ,Virus Replication ,Article ,Cell Line ,Young Adult ,03 medical and health sciences ,Subcutaneous injection ,In vivo ,Drug Resistance, Viral ,Humans ,Medicine ,Cells, Cultured ,Multidisciplinary ,business.industry ,Drug discovery ,Middle Aged ,Small molecule ,Virology ,030104 developmental biology ,Capsid ,Viral replication ,Drug development ,HIV-1 ,Capsid Proteins ,Female ,business - Abstract
Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis1–5. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance6. In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome of treatment—which contributes to virologic failure, resistance generation and viral transmission—as well as of pre-exposure prophylaxis, leading to new infections1,2,4,7–9. Long-acting agents from new antiretroviral classes can provide much-needed treatment options for people living with HIV who are heavily treatment-experienced, and additionally can improve adherence10. Here we describe GS-6207, a small molecule that disrupts the functions of HIV capsid protein and is amenable to long-acting therapy owing to its high potency, low in vivo systemic clearance and slow release kinetics from the subcutaneous injection site. Drawing on X-ray crystallographic information, we designed GS-6207 to bind tightly at a conserved interface between capsid protein monomers, where it interferes with capsid-protein-mediated interactions between proteins that are essential for multiple phases of the viral replication cycle. GS-6207 exhibits antiviral activity at picomolar concentrations against all subtypes of HIV-1 that we tested, and shows high synergy and no cross-resistance with approved antiretroviral drugs. In phase-1 clinical studies, monotherapy with a single subcutaneous dose of GS-6207 (450 mg) resulted in a mean log10-transformed reduction of plasma viral load of 2.2 after 9 days, and showed sustained plasma exposure at antivirally active concentrations for more than 6 months. These results provide clinical validation for therapies that target the functions of HIV capsid protein, and demonstrate the potential of GS-6207 as a long-acting agent to treat or prevent infection with HIV. The small molecule GS-6207, which disrupts the function of the HIV capsid protein, shows potential as a long-acting therapeutic agent for the treatment and prevention of HIV infection.
- Published
- 2020
5. Using symbiotic empirical ethics to explore the significance of relationships to clinical ethics: findings from the Reset Ethics research project
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Caroline A. B. Redhead, Lucy Frith, Anna Chiumento, Sara Fovargue, and Heather Draper
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Covid-19 ,Bioethics ,Empirical ethics ,Maternity ,Paediatrics ,Qualitative research ,Medical philosophy. Medical ethics ,R723-726 - Abstract
Abstract Background At the beginning of the coronavirus (Covid-19) pandemic, many non-Covid healthcare services were suspended. In April 2020, the Department of Health in England mandated that non-Covid services should resume, alongside the continuing pandemic response. This ‘resetting’ of healthcare services created a unique context in which it became critical to consider how ethical considerations did (and should) underpin decisions about integrating infection control measures into routine healthcare practices. We draw on data collected as part of the ‘NHS Reset Ethics’ project, which explored the everyday ethical challenges of resetting England’s NHS maternity and paediatrics services during the pandemic. Methods Healthcare professionals and members of the public participated in interviews and focus group discussions. The qualitative methods are reported in detail elsewhere. The focus of this article is our use of Frith’s symbiotic empirical ethics methodology to work from our empirical findings towards the normative suggestion that clinical ethics should explicitly attend to the importance of relationships in clinical practice. This methodology uses a five-step approach to refine and develop ethical theory based on a naturalist account of ethics that sees practice and theory as symbiotically related. Results The Reset project data showed that changed working practices caused ethical challenges for healthcare professionals, and that infection prevention and control measures represented harmful barriers to the experience of receiving and offering care. For healthcare professionals, offering care as part of a relational interaction was an ethically important dimension of healthcare delivery. Conclusions Our findings suggest that foregrounding the importance of relationships across a hospital community will better promote the ethically important multi-directional expression of caring between healthcare professionals, patients, and their families. We offer two suggestions for making progress towards such a relational approach. First, that there is a change of emphasis in clinical ethics practice to explicitly acknowledge the importance of the relationships (including with their healthcare team) within which the patient is held. Second, that organisational decision-making should take into account the moral significance afforded to caring relationships by healthcare professionals, and the role such relationships can play in the negotiation of ethical challenges.
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- 2024
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6. Staphylococcus aureus bacteremia in immunosuppressed patients: a multicenter, retrospective cohort study
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Marilyn Steinberg, Anthony D. Bai, Adrienne Showler, Daniel R. Ricciuto, Sumit Raybardhan, G. Sasson, Andrew Morris, Eshan Fernando, Lisa Burry, Chaim M. Bell, Anna Chiu, and Tania Fernandes
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Adult ,Male ,0301 basic medicine ,Microbiology (medical) ,Canada ,Staphylococcus aureus ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,030106 microbiology ,Bacteremia ,Immunocompromised Host ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Risk of mortality ,Humans ,030212 general & internal medicine ,Young adult ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Hazard ratio ,Immunosuppression ,Retrospective cohort study ,General Medicine ,Middle Aged ,Staphylococcal Infections ,Survival Analysis ,Confidence interval ,Surgery ,Treatment Outcome ,Infectious Diseases ,Cohort ,Female ,business - Abstract
Staphylococcus aureus bacteremia (SAB) causes significant morbidity and mortality. We assessed the disease severity and clinical outcomes of SAB in patients with pre-existing immunosuppression, compared with immunocompetent patients. A retrospective cohort investigation studied consecutive patients with SAB hospitalized across six hospitals in Toronto, Canada from 2007 to 2010. Patients were divided into immunosuppressed (IS) and immunocompetent (IC) cohorts; the IS cohort was subdivided into presence of one and two or more immunosuppressive conditions. Clinical parameters were compared between cohorts and between IS subgroups. A competing risk model compared in-hospital mortality and time to discharge. A total of 907 patients were included, 716 (79%) were IC and 191 (21%) were IS. Within the IS cohort, 111 (58%) had one immunosuppressive condition and 80 (42%) had two or more conditions. The overall in-hospital mortality was 29%, with no differences between groups (IS 32%, IC 28%, p = 0.4211). There were no differences in in-hospital mortality (sub-distribution hazard ratio [sHR] 1.17, 95% confidence interval [CI] 0.88–1.56, p = 0.2827) or time to discharge (sHR 0.94, 95% CI 0.78–1.15, p = 0.5570). Independent mortality predictors for both cohorts included hypotension at 72 h (IS: p
- Published
- 2017
7. A vision for reinvigorating global mental health.
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Anna Chiumento, Angus MacBeth, Rosie Stenhouse, Lotte Segal, Ian Harper, and Sumeet Jain
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Public aspects of medicine ,RA1-1270 - Published
- 2024
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8. Community based sociotherapy for depressive symptomatology of Congolese refugees in Rwanda and Uganda (CoSTAR): a protocol for a cluster randomised controlled trial
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Daniel M. Kagabo, Paul Bangirana, Girvan Burnside, Anna Chiumento, Rui Duarte, Darius Gishoma, Michelle Girvan, Angela Jansen, Stefan Jansen, Rosco Kasujja, Rachel Lubunga, Sarah Nevitt, Lucie Nzaramba, Emmanuel Sarabwe, Clare Jackson, Atif Rahman, Annemiek Richters, Jude Robinson, Theoneste Rutayisire, Peter Ventevogel, and Ross G. White
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refugees ,psychosocial ,mental health ,depression ,sociotherapy ,trial protocol ,Psychiatry ,RC435-571 - Abstract
Background: Conflict in the Democratic Republic of Congo has led to large numbers of refugees fleeing to Uganda and Rwanda. Refugees experience elevated levels of adverse events and daily stressors, which are associated with common mental health difficulties such as depression. The current cluster randomised controlled trial aims to investigate whether an adapted form of Community-based Sociotherapy (aCBS) is effective and cost-effective in reducing depressive symptomatology experienced by Congolese refugees in Uganda and Rwanda. Methods: A two-arm, single-blind cluster randomised controlled trial (cRCT) will be conducted in Kyangwali settlement, Uganda and Gihembe camp, Rwanda. Sixty-four clusters will be recruited and randomly assigned to either aCBS or Enhanced Care As Usual (ECAU). aCBS, a 15-session group-based intervention, will be facilitated by two people drawn from the refugee communities. The primary outcome measure will be self-reported levels of depressive symptomatology (PHQ-9) at 18-weeks post-randomisation. Secondary outcomes will include levels of mental health difficulties, subjective wellbeing, post-displacement stress, perceived social support, social capital, quality of life, and PTSD symptoms at 18-week and 32-week post-randomisation. Cost effectiveness of aCBS will be measured in terms of health care costs (cost per Disability Adjusted Life Year, DALY) compared to ECAU. A process evaluation will be undertaken to investigate the implementation of aCBS. Conclusion: This cRCT will be the first investigating aCBS for mental health difficulties experienced by refugees and will contribute to knowledge about the use of psychosocial interventions for refugees at a time when levels of forced migration are at a record high. Trial registration: ISRCTN.org identifier: ISRCTN20474555.
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- 2023
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9. Analysis of the Adherence to Seizure Prophylaxis Guidelines in Neurosurgery Patients
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Danette Beechinor, Karen Li, Anna Chiu, and Xueqing Rose Liao
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Phenytoin ,Pediatrics ,medicine.medical_specialty ,Neurology ,Adult patients ,business.industry ,Drug cost ,Patient characteristics ,Chart review ,medicine ,In patient ,Neurosurgery ,business ,medicine.drug - Abstract
Background: In 2000, the American Academy of Neurology guidelines recommended that long-term seizure prophylaxis should not be routine in patients with newly diagnosed brain tumours and that if anti-epileptic drugs (AEDs) are used, they should be tapered and discontinued after 7 days post-operatively. Recent data shows that most newly diagnosed brain tumour patients continue to receive prophylactic AED. Aim: This study aimed to examine the seizure prophylaxis practices at Trillium Health Partners – Mississauga Hospital, a regional neurosurgery centrelocated in Mississauga, Ontario, Canada. Materials and Methods: A retrospective chart review was performed in adult patients with a newly diagnosed brain tumour who underwent neurosurgery between January 2010 and December 2014. Results: 690 patient charts were screened and 235 patients were excluded, most commonly due to seizure on admission. Overall, 28% (N=129) of 455 included patients over 5 years received seizure prophylaxis. Phenytoin was the most common prophylactic agent used. The average post-operative length of stay was 7.98 days and the average duration of therapy was 8.73 days. In 61% of patients who received prophylaxis, it was unknown whether the AED was continued in the long-term. The drug cost savings to Trillium over 5 years if patients had not received seizure prophylaxis was $4287.52. The patient characteristics most strongly correlated with receiving seizure prophylaxis were increasing tumour size and decreasing number of tumours. Conclusion: 1 in 3 patients at Trillium received seizure prophylaxis. Increased awareness of the organization's practice patterns may help prevent unnecessary long-term AED use.
- Published
- 2016
10. Use of Transthoracic Echocardiography in the Management of Low-Risk Staphylococcus aureus Bacteremia
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Andrew Morris, Marilyn Steinberg, Daniel R. Ricciuto, Sumit Raybardhan, Adrienne Showler, Eshan Fernando, Tania Fernandes, Lisa Burry, Chaim M. Bell, Anna Chiu, and Anthony D. Bai
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medicine.medical_specialty ,business.industry ,Retrospective cohort study ,medicine.disease ,Staphylococcal infections ,Radiology Nuclear Medicine and imaging ,Infective endocarditis ,Predictive value of tests ,Bacteremia ,Internal medicine ,medicine ,Endocarditis ,Radiology, Nuclear Medicine and imaging ,Transthoracic echocardiogram ,business ,Intensive care medicine ,Cardiology and Cardiovascular Medicine ,Cohort study - Abstract
Objectives The aim of this study was to develop a prediction model to identify patients with low-risk Staphylococcus aureus bacteremia (SAB), in whom infective endocarditis (IE) can be ruled out based on transthoracic echocardiogram (TTE). Background S. aureus is a major cause of bacteremia and often leads to IE. Current guidelines recommend performing transesophageal echocardiography on all patients or treating all patients empirically with prolonged intravenous antibiotics; however, this approach is resource intensive, many physicians do not adhere to guidelines, and recent studies suggest that low-risk patients may not require transesophageal echocardiography. Methods We conducted a retrospective cohort study of 833 consecutive hospitalized patients with SAB from 7 academic and community hospitals in Toronto, Canada, over a 3-year period (2007 to 2010). Patients who received a TTE within 28 days of bacteremia (n = 536) were randomly divided into derivation and validation cohorts. Multivariable logistic regression analysis was used to determine high-risk criteria for IE in the derivation cohort, and criteria were then applied to the validation cohort to determine diagnostic properties. Results Four high-risk criteria predicted IE: indeterminate or positive TTE (p Conclusions A normal TTE ruled out IE in patients without community-acquired SAB, high-risk cardiac conditions, and intravenous drug use. This study provides evidence that clinical risk stratification combined with a normal TTE may be adequate to rule out IE in most patients with SAB.
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- 2015
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11. Comparative effectiveness of cefazolin versus cloxacillin as definitive antibiotic therapy for MSSA bacteraemia: results from a large multicentre cohort study
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Anthony D. Bai, Adrienne Showler, Lisa Burry, Marilyn Steinberg, Daniel R. Ricciuto, Tania Fernandes, Anna Chiu, Sumit Raybardhan, Michelle Science, Eshan Fernando, George Tomlinson, Chaim M. Bell, and Andrew M. Morris
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Male ,Microbiology (medical) ,Staphylococcus aureus ,medicine.medical_specialty ,Cefazolin ,Bacteremia ,medicine.disease_cause ,Cohort Studies ,Cloxacillin ,Recurrence ,Internal medicine ,polycyclic compounds ,medicine ,Humans ,Pharmacology (medical) ,Aged ,Retrospective Studies ,Aged, 80 and over ,Pharmacology ,Antistaphylococcal penicillins ,business.industry ,Retrospective cohort study ,Middle Aged ,Staphylococcal Infections ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,medicine.disease ,Survival Analysis ,Anti-Bacterial Agents ,Surgery ,Treatment Outcome ,Infectious Diseases ,Propensity score matching ,Female ,business ,medicine.drug ,Cohort study - Abstract
Objectives We compared the effectiveness of cefazolin versus cloxacillin in the treatment of MSSA bacteraemia in terms of mortality and relapse. Methods A retrospective cohort study examined consecutive patients with Staphylococcus aureus bacteraemia from six academic and community hospitals between 2007 and 2010. Patients with MSSA bacteraemia who received cefazolin or cloxacillin as the predominant definitive antibiotic therapy were included in the study. Ninety-day mortality was compared between the two groups matched by propensity scores. Results Of 354 patients included in the study, 105 (30%) received cefazolin and 249 (70%) received cloxacillin as the definitive antibiotic therapy. In 90 days, 96 (27%) patients died: 21/105 (20%) in the cefazolin group and 75/249 (30%) in the cloxacillin group. Within 90 days, 10 patients (3%) had a relapse of S. aureus infection: 6/105 (6%) in the cefazolin group and 4/249 (2%) in the cloxacillin group. All relapses in the cefazolin group were related to a deep-seated infection. Based on the estimated propensity score, 90 patients in the cefazolin group were matched with 90 patients in the cloxacillin group. In the propensity score-matched groups, cefazolin had an HR of 0.58 (95% CI 0.31–1.08, P = 0.0846) for 90 day mortality. Conclusions There was no significant clinical difference between cefazolin and cloxacillin in the treatment of MSSA bacteraemia with respect to mortality. Cefazolin was associated with non-significantly more relapses compared with cloxacillin, especially in deep-seated S. aureus infections.
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- 2015
12. 539. GS-CA2: A Novel, Potent, and Selective First-In-class Inhibitor of HIV-1 Capsid Function Displays Nonclinical Pharmacokinetics Supporting Long-Acting Potential in Humans
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Schroeder Scott D, Tse Winston C, Raju Subramanian, Anna Chiu, Tomas Cihlar, George Stepan, William Rowe, Shekeba Ahmadyar, Kelly Wang, Tiffany Chan, John O. Link, Jim Zheng, Judy Mwangi, Bing Lu, and Stephen R. Yant
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0301 basic medicine ,business.industry ,Human immunodeficiency virus (HIV) ,PK Parameters ,Metabolic stability ,Pharmacology ,medicine.disease_cause ,Peripheral blood ,03 medical and health sciences ,Abstracts ,030104 developmental biology ,Infectious Diseases ,Long acting ,Oncology ,Pharmacokinetics ,B. Poster Abstracts ,Aqueous solubility ,Medicine ,Salary ,business - Abstract
Background GS-CA2, an analog of GS-CA1, is a novel and selective inhibitor of HIV-1 capsid function. Safety and pharmacokinetics (PK) of GS-CA2 is currently being evaluated in healthy human subjects. Herein, we present the anti-HIV activity and nonclinical PK of GS-CA2, demonstrating its potential as a first-in-class long-acting antiretroviral agent. Methods GS-CA2 antiviral activity was evaluated in MT-4 cells and in human peripheral blood mononuclear cells (PBMCs) acutely infected with HIV-1 (IIIb) and clinical HIV-1 isolates, respectively. Standard in vitro methods were used to characterize compound lipophilicity (LogD), solubility and relative binding to cell culture and plasma proteins. Metabolic stability was assessed in cryopreserved hepatocytes. GS-CA2 PK parameters following intravenous and subcutaneous (SC) administration were assessed in rat and dog. GS-CA2 plasma concentrations were determined by HPLC-MS/MS. Results GS-CA2 showed potent and selective anti-HIV activity in MT-4 cells (EC50 = 0.1 nM; CC50 = 26.6 µM). In PBMCs, GS-CA2 displayed a mean EC50 of 0.05 nM (0.02–0.16 nM) against 23 HIV-1 clinical isolates representing all major subtypes. GS-CA2 is highly lipophilic (LogD of 3.7) with low aqueous solubility (3 months. These nonclinical data support clinical development of GS-CA2 as a novel long-acting antiretroviral agent suitable for the treatment of HIV-1 infection. Disclosures J. Zheng, Gilead Sciences, Inc.: Employee, Salary. S. R. Yant, Gilead Sciences, Inc.: Employee, Salary. S. Ahmadyar, Gilead Sciences, Inc.: Employee, Salary. T. Y. Chan, Gilead Sciences, Inc.: Employee, Salary. A. Chiu, Gilead Sciences, Inc.: Employee, Salary. T. Cihlar, Gilead Sciences, Inc.: Employee, Salary. J. O. Link, Gilead Sciences, Inc.: Employee, Salary. B. Lu, Gilead Sciences, Inc.: Employee, Salary. J. Mwangi, Gilead Sciences, Inc.: Employee, Salary. W. Rowe, Gilead Sciences, Inc.: Employee, Salary. S. D. Schroeder, Gilead Sciences, Inc.: Employee, Salary. G. J. Stepan, Gilead Sciences, Inc.: Employee, Salary. K. W. Wang, Gilead Sciences, Inc.: Employee, Salary. R. Subramanian, Gilead Sciences, Inc.: Employee, Salary. W. C. Tse, Gilead Sciences, Inc.: Employee, Salary.
- Published
- 2018
13. What Is Hidden in Patients with Unknown Nephropathy? Genetic Screening Could Be the Missing Link in Kidney Transplantation Diagnosis and Management
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Adele Mitrotti, Ighli Di Bari, Marica Giliberti, Rossana Franzin, Francesca Conserva, Anna Chiusolo, Maddalena Gigante, Matteo Accetturo, Cesira Cafiero, Luisa Ricciato, Emma Diletta Stea, Cinzia Forleo, Anna Gallone, Michele Rossini, Marco Fiorentino, Giuseppe Castellano, Paola Pontrelli, and Loreto Gesualdo
- Subjects
CKD ,unknown ESRD ,FSGS ,genetic testing ,next-generation sequencing ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Between 15–20% of patients with end stage renal disease (ESRD) do not know the cause of the primary kidney disease and can develop complications after kidney transplantation. We performed a genetic screening in 300 patients with kidney transplantation, or undiagnosed primary renal disease, in order to identify the primary disease cause and discriminate between overlapping phenotypes. We used a custom-made panel for next-generation sequencing (Agilent technology, Santa Clara, CA, USA), including genes associated with Fabry disease, podocytopaties, complement-mediated nephropathies and Alport syndrome-related diseases. We detected candidate diagnostic variants in genes associated with nephrotic syndrome and Focal Segmental Glomerulosclerosis (FSGS) in 29 out of 300 patients, solving about 10% of the probands. We also identified the same genetic cause of the disease (PAX2: c.1266dupC) in three family members with different clinical diagnoses. Interestingly we also found one female patient carrying a novel missense variant, c.1259C>A (p.Thr420Lys), in the GLA gene not previously associated with Fabry disease, which is in silico defined as a likely pathogenic and destabilizing, and associated with a mild alteration in GLA enzymatic activity. The identification of the specific genetic background may provide an opportunity to evaluate the risk of recurrence of the primary disease, especially among patient candidates living with a donor kidney transplant.
- Published
- 2024
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14. A Case of Remote Asymmetric Induction in the Peptide-Catalyzed Desymmetrization of a Bis(phenol)
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Scott J. Miller, Jaume Balsells, Robert A. Reamer, Jeffrey L. Gustafson, Jerry A. Murry, Anna Chiu, David Pollard, Chad A. Lewis, and Karl Hansen
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Models, Molecular ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Stereoisomerism ,Acetates ,Biochemistry ,Desymmetrization ,Article ,Catalysis ,Acylation ,Colloid and Surface Chemistry ,Databases, Protein ,Molecular Structure ,Phenol ,Chemistry ,Temperature ,Enantioselective synthesis ,Substrate (chemistry) ,General Chemistry ,Asymmetric induction ,Kinetics ,Mucor ,Enantiomer ,Peptides - Abstract
We report a catalytic approach to the synthesis of a key intermediate on the synthetic route to a pharmaceutical drug candidate in single enantiomer form. In particular, we illustrate the discovery process employed to arrive at a powerful, peptide-based asymmetric acylation catalyst. The substrate this catalyst modifies represents a remarkable case of desymmetrization, wherein the enantiotopic groups are separated by nearly a full nanometer, and the distance between the reactive site and the pro-stereogenic element is nearly six Angstroms. Differentiation of enantiotopic sites within molecules that are removed from the prochiral centers by long distances presents special challenges to the field of asymmetric catalysis. As the distance between enantiotopic sites increases within a substrate, so too may the requirements for size and complexity of the catalyst. The approach presented herein contrasts enzymatic catalysts and small-molecule catalysts for this challenge. Ultimately, we report here a synthetic, miniaturized enzyme mimic that catalyzes a desymmetrization reaction over a substantial distance. In addition, studies relevant to mechanism are presented, including (a) the delineation of structure-selectivity relationships through the use of substrate analogs, (b) NMR experiments documenting catalyst-substrate interactions, and (c) the use of isotopically labeled substrates to illustrate unequivocally an asymmetric catalyst-substrate binding event.
- Published
- 2008
15. A Novel and Facile One-Pot Method for the Synthesis of N-Substituted Sulfamates
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Anna Chiu, Guy R. Humphrey, Tao Pei, and Hallena Rogers
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chemistry.chemical_classification ,chemistry.chemical_compound ,Reaction mechanism ,Aromatic acid ,Chemistry ,Carboxylic acid ,Organic Chemistry ,Pyridine ,Organic chemistry ,Dicarbonate ,Catalysis - Abstract
A one-pot approach to the formation of N-substituted sulfamates from carboxylic acids using di-tert-butyl dicarbonate, tetrabutylammonium sulfamate, and pyridine under mild conditions is described. A reaction mechanism with two competing pathways is proposed; in reactions with aliphatic and electron-deficient aromatic acid substrates, the desired sulfamate products are formed, in contrast, symmetrical anhydride intermediates are observed with electron-neutral or electron-rich aromatic substrates.
- Published
- 2008
16. Use of Transthoracic Echocardiography in the Management of Low-Risk Staphylococcus aureus Bacteremia: Results From a Retrospective Multicenter Cohort Study
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Adrienne, Showler, Lisa, Burry, Anthony D, Bai, Marilyn, Steinberg, Daniel R, Ricciuto, Tania, Fernandes, Anna, Chiu, Sumit, Raybardhan, Michelle, Science, Eshan, Fernando, Chaim M, Bell, and Andrew M, Morris
- Subjects
Male ,Endocarditis ,Bacteremia ,Middle Aged ,Staphylococcal Infections ,Cohort Studies ,Community-Acquired Infections ,Echocardiography ,Predictive Value of Tests ,Humans ,Female ,Aged ,Forecasting ,Retrospective Studies - Abstract
The aim of this study was to develop a prediction model to identify patients with low-risk Staphylococcus aureus bacteremia (SAB), in whom infective endocarditis (IE) can be ruled out based on transthoracic echocardiogram (TTE).S. aureus is a major cause of bacteremia and often leads to IE. Current guidelines recommend performing transesophageal echocardiography on all patients or treating all patients empirically with prolonged intravenous antibiotics; however, this approach is resource intensive, many physicians do not adhere to guidelines, and recent studies suggest that low-risk patients may not require transesophageal echocardiography.We conducted a retrospective cohort study of 833 consecutive hospitalized patients with SAB from 7 academic and community hospitals in Toronto, Canada, over a 3-year period (2007 to 2010). Patients who received a TTE within 28 days of bacteremia (n = 536) were randomly divided into derivation and validation cohorts. Multivariable logistic regression analysis was used to determine high-risk criteria for IE in the derivation cohort, and criteria were then applied to the validation cohort to determine diagnostic properties.Four high-risk criteria predicted IE: indeterminate or positive TTE (p 0.001), community-acquired bacteremia (p = 0.034), intravenous drug use (p 0.001), and high-risk cardiac condition (p 0.004). In the validation cohort, the presence of any 1 of the high-risk criteria had 97% sensitivity (95% confidence interval [CI]: 87% to 100%) and 99% negative predictive value (95% CI: 96% to 100%) for IE. The negative likelihood ratio was 0.05 (95% CI: 0.007 to 0.35).A normal TTE ruled out IE in patients without community-acquired SAB, high-risk cardiac conditions, and intravenous drug use. This study provides evidence that clinical risk stratification combined with a normal TTE may be adequate to rule out IE in most patients with SAB.
- Published
- 2014
17. Translating, contextually adapting, and pilot testing of psychosocial and mental health assessment instruments for Congolese refugees in Rwanda and Uganda
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Rosco Kasujja, Paul Bangirana, Anna Chiumento, Tasdik Hasan, Stefan Jansen, Daniel M. Kagabo, Maria Popa, Peter Ventevogel, and Ross G. White
- Subjects
Mental health and psychosocial support ,Refugees ,Humanitarian settings ,Post-conflict ,Assessment ,Depression ,Special situations and conditions ,RC952-1245 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Background Forcibly displaced people are at elevated risk of experiencing circumstances that can adversely impact on mental health. Culturally and contextually relevant tools to assess their mental health and psychosocial needs are essential to inform the development of appropriate interventions and investigate the effectiveness of such interventions. Methods We conducted two related studies: (1) to translate and contextually adapt the Patient Health Questionnaire (PHQ-9), a measure of depressive symptomatology, along with assessment instruments measuring levels of daily stress (Checklist for Daily & Environmental Stressors; CDES), social capital (Shortened and Adapted Social Capital Assessment Tool; SASCAT) and perceived social support (Multidimensional Scale of Perceived Social Support; MSPSS) for use with Congolese refugees; (2) to conduct pilot testing of the assessment instruments (including cognitive interviewing about participants’ views of completing them) and a validation of the adapted PHQ-9 using a ‘known group’ approach by recruiting Congolese refugees from refugee settings in Rwanda (n = 100) and Uganda (n = 100). Results Study 1 resulted in the translation and adaptation of the assessment instruments. No substantive adaptations were made to the SASCAT or MSPSS, while notable linguistic and contextual adaptations were made in both sites to the CDES and the PHQ-9. The cognitive interviewing conducted in Study 2 indicated that the adapted assessment instruments were generally well received by members of the refugee communities. Participants recruited on the basis that local informants adjudged them to have high levels of depressive symptoms had significantly higher PHQ-9 scores (M = 11.02; SD = 5.84) compared to those in the group adjudged to have low levels of depressive symptoms (M = 5.66; SD = 5.04). In both sites, the adapted versions of the PHQ-9 demonstrated concurrent validity via significant positive correlations with levels of daily stressors. Each of the four adapted assessment instruments demonstrated at least adequate levels of internal consistency in both sites. Conclusions The adapted versions of the PHQ-9, CDES, SASCAT and MSPSS are appropriate for use amongst Congolese refugees in Rwanda and Uganda. We recommend further application of the approaches used in the current studies for contextually adapting other assessment instruments in humanitarian settings.
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- 2022
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18. Asymmetric Syntheses of Pectenotoxins-4 and -8, Part II: Synthesis of the C20–C30 and C31–C40 Subunits and Fragment Assembly
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Dirk Stenkamp, Hemaka A. Rajapakse, David A. Evans, and Anna Chiu
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chemistry.chemical_classification ,Ketone ,Stereochemistry ,Phosphonium salt ,General Chemistry ,Primary alcohol ,Medicinal chemistry ,Aldehyde ,Catalysis ,Claisen rearrangement ,chemistry.chemical_compound ,chemistry ,Aldol reaction ,Wittig reaction ,Tetrahydrofuran - Abstract
In the preceding communication,[1] the proposed synthesis plan identified the two principal pectenotoxin-4 subunits II and III (Figure 1). It was our intention to couple these fragments through the alkylation of the metalloenamine derived from hydrazone III, readily available from the coupling of advanced intermediates IV and V (transform T2), by epoxide II. However, this investigation revealed that the above bond construction was not feasible due to the decomposition of metalloeneamine III under the reaction conditions.[2] Accordingly, the objective in the present communication is the synthesis of the subunits IV and V, and the completion of the syntheses of pectenotoxin-4 (1) and pectenotoxin-8 by a revised fragment coupling strategy, where epoxide alkylation (transform T1) precedes diene formation (transform T2). The plan for the construction of the F-ring tetrahydrofuran IV was to involve a C37 hydroxy-directed epoxidation of olefin VI with a subsequent ring closure by the C32 hydroxy moiety (transform T3). Finally, the stereoselective formation of the E-ring tetrahydrofuran V from its acyclic precursor VII was based on an iodoetherification precedent provided by Bartlett and Rychnovsky (transform T4). The synthesis of the ring-E synthon V began with the known aldol adduct adduct 2 (Scheme 1).[4] Reduction of 2 (LiBH4, THF, 0 8C), and selective protection of the primary alcohol (TBSCl, Im, CH2Cl2, 100% over two steps) afforded allylic alcohol 3.[5] Acylation of 3 with the PMB-protected lactic acid 4[6] (DCC, DMAP, CH2Cl2, 52%), followed by carbonyl olefination of 5a with Tebbe reagent[7] afforded the 1,5-diene 5b. Claisen rearrangement of 5b in refluxing toluene gave the desired rearrangement product 6 in 82% yield for the two steps. Chelate-controlled reduction of the resulting ketone (Zn(BH4)2, Et2O, 78 8C, 86%, d.r. 86:14) provided the precursor for the key iodoetherification reaction. In spite of the modest selectivity that was observed for the formation of the desired tetrahydrofuran 7 (NIS, CH3CN, 40 8C, 89%, d.r. 72:28), this outcome proved sufficient to pursue the planned route. Successive radical dehalogenation of 7 (Bu3SnH, AIBN, toluene, 100%) and deprotection of the primary TBS ether (TBAF, THF, 95%) afforded alcohol 8. Oxidation with Dess± Martin reagent[8] (py, CH2Cl2, 99%), Wittig homologation (EtOC(O)CC(CH3)PPh3, THF, 65 8C; 100% E :Z> 95:5), and ester reduction (LiAlH4, Et2O, 0 8C, 92%) completed the carbon assembly of the E-ring fragment. Benzyl protection (NaH, BnBr, TBAI, THF/DMF, 94%) followed by PMB deprotection (DDQ, CH2Cl2/pH 7 buffer, 95%) gave alcohol 10. Oxidation to the methyl ketone[8] (Dess±Martin periodinane, py, CH2Cl2, 93%), and hydrazone formation (TMSCl, CH2Cl2/Me2NNH2, 100%) completed the synthesis of hydrazone 11. As summarized in Figure 1, the first stage of the synthesis of the ring-F fragment IV will be simplified to the construction of the C31±C35 phosphonium salt, the C36±C40 aldehyde, and their union through a Wittig coupling to afford the Zolefin VI. The synthesis of the C31±C35 phosphonium salt began with the known triol derivative 12 (Scheme 2).[9] Protection of the hydroxy group at C33 of 12 as a PMB ether (PMBBr, NaH, THF/DMF, 95%) followed by reductive ozonolysis (O3, EtOH, then DMS, then NaBH4, 95%) afforded alcohol 13. Transformation of 13 to the corresponding iodide (I2, Im, Ph3P, CH2Cl2, 0 8C, 89%) proceeded smoothly, but careful control of the temperature was required to access phosphonium salt 14 (Ph3P, CH3CN, 55 8C, 89%).[10] The synthesis of the aldehyde partner 17 began with protection of the hydroxy group at C37 of aldol adduct 15[11] as a base-sensitive triphenylsilyl ether (TPSCl, Im, DMAP, DMF, 0 8C, 98%; Scheme 2). Half reduction of the S-phenyl thioester[12] (Pd/C, Et3SiH, acetone, 95%), and olefination under modified Lombardo conditions[13] ([Cp2ZrCl2], Zn dust, CH2I2, THF, 0 8C, 84%) afforded olefin 16. RhodiumCOMMUNICATIONS
- Published
- 2002
19. Maximising impactful, locally relevant global mental health research conducted in low and middle income country settings: ethical considerations [version 2; peer review: 2 approved, 1 not approved]
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Amit Chakrabarti, Clara Calia, Anna Chiumento, and Emmanuel Sarabwe
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Global Mental Health ,Bioethics ,Research ethics ,Low and middle income countries ,Community engagement ,Impact ,eng ,Medicine ,Science - Abstract
Background: Achieving ethical and meaningful mental health research in diverse global settings requires approaches to research design, conduct, and dissemination that prioritise a contextualised approach to impact and local relevance. Method: Through three case studies presented at the 2021 Global Forum on Bioethics in Research meeting on the ethical issues arising in research with people with mental health conditions, we consider the nuances to achieving ethical and meaningful mental health research in three diverse settings. The case studies include research with refugees Rwanda and Uganda; a neurodevelopmental cohort study in a low resource setting in India, and research with Syrian refugees displaced across the Middle East. Results: Key considerations highlighted across the case studies include how mental health is understood and experienced in diverse contexts to ensure respectful engagement with communities, and to inform the selection of contextually-appropriate and feasible research methods and tools to achieve meaningful data collection. Related to this is a need to consider how communities understand and engage with research to avoid therapeutic misconception, exacerbating stigma, or creating undue inducement for research participation, whilst also ensuring meaningful benefit for research participation. Central to achieving these is the meaningful integration of the views and perspectives of local stakeholders to inform research design, conduct, and legacy. The case studies foreground the potential tensions between meeting local community needs through the implementation of an intervention, and attaining standards of scientific rigor in research design and methods; and between adherence to procedural ethical requirements such as ethical review and documenting informed consent, and ethical practice through attention to the needs of the local research team. Conclusions: We conclude that engagement with how to achieve local relevance and social, practice, and academic impact offer productive ways for researchers to promote ethical research that prioritises values of solidarity, inclusion, and mutual respect.
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- 2023
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20. Impact of Infectious Disease Consultation on Quality of Care, Mortality, and Length of Stay in Staphylococcus aureus Bacteremia: Results From a Large Multicenter Cohort Study
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Anthony D, Bai, Adrienne, Showler, Lisa, Burry, Marilyn, Steinberg, Daniel R, Ricciuto, Tania, Fernandes, Anna, Chiu, Sumit, Raybardhan, Michelle, Science, Eshan, Fernando, George, Tomlinson, Chaim M, Bell, and Andrew M, Morris
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Adult ,Aged, 80 and over ,Male ,Bacteremia ,Length of Stay ,Middle Aged ,Staphylococcal Infections ,Survival Analysis ,Hospitals ,Cohort Studies ,Young Adult ,Treatment Outcome ,Humans ,Female ,Referral and Consultation ,Aged ,Quality of Health Care ,Retrospective Studies - Abstract
We assessed the impact of infectious disease (ID) consultation on management and outcome in patients with Staphylococcus aureus bacteremia (SAB).A retrospective cohort study examined consecutive SAB patients from 6 academic and community hospitals between 2007 and 2010. Quality measures of management including echocardiography, repeat blood culture, removal of infectious foci, and antibiotic therapy were compared between ID consultation (IDC) and no ID consultation (NIDC) groups. A competing risk model with propensity score adjustment was used to compare in-hospital mortality and time to discharge.Of 847 SAB patients, 506 (60%) patients received an ID consultation and 341 (40%) patients did not. Echocardiography was done for 371 (73%) IDC and 191 (56%) NIDC patients (P.0001) in hospital. Blood cultures were repeated within 2-4 days of bacteremia in 207 (41%) IDC and 107 (31%) NIDC patients (P = .0058). The infectious foci removal rate was not statistically different between the 2 groups. For empiric therapy, 474 (94%) IDC and 297 (87%) NIDC patients received appropriate antibiotics (P = .0013). For patients who finished the planned course of antibiotics, 285 of 422 (68%) IDC and 141 of 262 (54%) NIDC patients received the appropriate duration of antibiotic therapy (P = .0004). In hospital, 204 (24%) patients died: 104 of 506 (21%) IDC and 100 of 341 (29%) NIDC patients. Matched by propensity score, ID consultation had a subdistribution hazard ratio of 0.72 (95% confidence interval [CI], .52-.99; P = .0451) for in-hospital mortality and 1.28 (95% CI, 1.06-1.56; P = .0109) for being discharged alive.ID consultation is associated with better adherence to quality measures, reduced in-hospital mortality, and earlier discharge in patients with SAB.
- Published
- 2014
21. A Randomized Controlled Trial of Low-Dose Recombinant Human Growth Hormone in the Treatment of Malnourished Elderly Medical Patients1
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Anna Chiu, Wayne J. H. C. Hu, Ka-Chun Chiu, Sidney Tam, Sau-Lan Hui, Leung-Wing Chu, Karen S.L. Lam, and P Ng
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medicine.medical_specialty ,Chemotherapy ,business.industry ,Endocrinology, Diabetes and Metabolism ,Human growth hormone ,medicine.medical_treatment ,Biochemistry (medical) ,Clinical Biochemistry ,Low dose ,Nutritional status ,Anthropometry ,medicine.disease ,Biochemistry ,Placebo group ,law.invention ,Malnutrition ,Endocrinology ,Randomized controlled trial ,law ,Internal medicine ,Medicine ,business - Abstract
High-dose recombinant human GH (rhGH) has been shown to improve the nutritional status of malnourished older adults. It is uncertain whether low-dose rhGH is effective and whether its effect on nutritional status will lead to any improvement in physical function. There is also no data on the outcome after a short course of rhGH treatment. The objectives of this study were to determine the efficacy of low-dose rhGH treatment for 4 weeks in malnourished elderly patients, its effect on physical functions, and the intermediate term outcome after a 4-week rhGH treatment. The study design was a randomized, placebo-controlled, double-blind trial conducted in a university teaching hospital. The patients were 19 medically stable malnourished elderly subjects. Intervention in the rhGH group was as follows: rhGH (Saizen, Serono, Switzerland) 0.09 IU/kg body weight (BW) 3 times weekly were given together with appropriate dietary intervention as prescribed by the dietitian. In the placebo group, equal volumes of norma...
- Published
- 2001
22. Application of the capability approach to Indigenous People’s health and well-being: protocol for a mixed-methods scoping review
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Anna Chiumento, Catharina van der Boor, Carlos Iván Molina-Bulla, and Ross G White
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Medicine - Abstract
Background Indigenous Peoples are subject to marginalisation, and experience systematic disadvantage in relation to health outcomes. Human development initiatives may help determine whether, and how, Indigenous Peoples are able to be agents of their own development and improve their health and well-being. This scoping review protocol outlines a process for synthesising the existing evidence that has applied the capability approach (CA) to Indigenous People’s health and/or well-being.Methods and analysis A mixed-method scoping review is proposed including academic peer-reviewed publications and grey literature. Screening inclusion criteria will include Indigenous populations, using the CA approach to conceptualise health and/or well-being, and be available in English, Spanish, French or Portuguese. Publications that meet these criteria will undergo data extraction. Qualitative and quantitative data will be thematically and descriptively analysed and interpreted.Ethics and dissemination The proposed scoping review does not involve collecting data directly from Indigenous Peoples but will be based on previous research conducted within Indigenous settings. The current protocol and the proposed scoping review incorporate aspects of community involvement to guide the research process.This scoping review constitutes the first phase of a wider participatory action research project conducted with the Indigenous Kankuamo Peoples of Colombia. The findings of this review will be reported to local partners, published in a peer-reviewed journal and an executive summary will be shared with wider stakeholders. Within the wider project, the review will be considered alongside primary data to inform the development of tools/approaches of mental health and well-being for the Kankuamo communities.
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- 2022
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23. Exploring the acceptability of a WHO school-based mental health program in Egypt: A qualitative study
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Anna Chiumento, Walaa Hosny, Eman Gaber, Maha Emadeldin, Walaa El Barabry, Hesham M. Hamoda, and Olakunle Alonge
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Child and adolescent ,Mental health ,Psychosocial ,School-based services ,Qualitative ,Implementation science ,Mental healing ,RZ400-408 ,Public aspects of medicine ,RA1-1270 - Abstract
Mental health interventions should target critical developmental stages, such as childhood and adolescence; and be embedded into cross-sectoral settings including education. The World Health Organization, Eastern Mediterranean Regional office has developed a school-based mental health program (SMHP), encouraging implementation research to inform its scale-up. We contribute to this by exploring stakeholder acceptability of the SMHP as a key assumption underpinning successful program implementation.This qualitative study, conducted January to July 2019 in Al Obour, Egypt, explores stakeholder views of SMHP acceptability, the roles of teachers and school psychologists in supporting child mental health, and barriers to SMHP implementation and scale-up. Focus group discussions (n = 4) and individual in-depth interviews (n = 7) were conducted with 30 stakeholders (parents, teachers, psychologists, and support centre managers). Data were analysed thematically against the theoretical framework of acceptability.Our results indicate that the SMHP is highly acceptable to teachers, psychologists, parents, and other education professionals. Key findings indicate the SMHP fits with teachers' and school psychologists' values, and highlight the importance of collaboration among these stakeholders for program effectiveness. Program features such as a community-based centre and respect for privacy and confidentiality are recognised to reduce parents’ opportunity costs, and influence their affective attitudes, leading to increased engagement. Factors such as teacher burden require additional exploration and strategies to address them as potential impediments to successful SMHP implementation. This qualitative study yields important insights from multiple stakeholders into the acceptability of a school-based mental health intervention, providing support for scale-up of the SMHP in Egypt and the Region.
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- 2022
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24. The chemistry-medicine continuum: Synthetic, computer, spectroscopic and biological studies on new chemotherapeutic leads
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James A. Morrison, Anna Chiu, Kazuhiro Irie, Michael F. T. Koehler, Jef K. De Brabander, Stephan N. Müller, Masahiro Tanaka, Stephan G. Müller, Andrew J. Carpenter, Cheol-Min Park, Yolanda Martin-Cantalejo, Shiozaki Makoto, Carsten Siedenbiedel, Donald J. Skalitzky, Patrick G. Harran, Paul A. Wender, Juan Miguel Jimenez, and Blaise Lippa
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Stereochemistry ,General Chemical Engineering ,Enantioselective synthesis ,Total synthesis ,Biological activity ,General Chemistry ,Combinatorial chemistry ,chemistry.chemical_compound ,chemistry ,Phorbol ,Pharmacophore ,Bryostatin ,Protein kinase C ,Binding domain - Abstract
This lecture provides an overview of investigations directed towards understanding the molecular mechanism of protein kinase C (PKC) activation and function. Central to this effort are studies on the total synthesis of phorbol, the first asymmetric synthesis of phorbol, and the first synthesis of resiniferatoxin, all involving highly effective applications of (5+2) oxidopyrylium-alkene cycloadditions. The synthesis and affinities of the phorbol ester binding domain of PKC are also presented. In addition, a pharmacophore model for agonist binding to PKC is presented in connection with the design of novel PKC activators. Finally, the computer modeling, NMR structure, synthesis, and biological activity of the first fully synthetic bryostatin analogs are described.
- Published
- 1998
25. Effect of counterion structure on rates and diastereoselectivities in α,β-unsaturated iminium-ion Diels-Alder reactions
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David Marcoux, Pascal Bindschädler, David A. Evans, George Borg, Joseph E. Pero, Anna Chiu, and Alexander W. H. Speed
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Stereochemistry ,Stereoisomerism ,Biochemistry ,Medicinal chemistry ,Catalysis ,Article ,Ion ,Lactones ,Alkaloids ,Diels alder ,Molecule ,Combinatorial Chemistry Techniques ,Reactivity (chemistry) ,Spiro Compounds ,Physical and Theoretical Chemistry ,chemistry.chemical_classification ,Aza Compounds ,Molecular Structure ,Organic Chemistry ,Iminium ,Alkadienes ,chemistry ,Cyclization ,Imines ,Counterion - Abstract
The use of cyclic α,β-unsaturated iminium-ion dienophiles is documented in two highly diastereoselective Diels–Alder (DA) reactions. The dienophilic counterion was found to have a significant effect on reactivity.
- Published
- 2011
26. Public involvement in big data projects: an ethnographically-informed study.
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Elisa Jones, Lucy Frith, Anna Chiumento, Sarah Rodgers, Alan Clarke, Sarah Markham, and Iain Buchan
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Public involvement and engagement ,participation ,citizen jury ,public panel ,case studies ,qualitative research ,Demography. Population. Vital events ,HB848-3697 - Abstract
Objectives Public involvement and engagement (PIE) is playing an increasingly important role in big data initiatives and projects. It is therefore important to gain a deeper understanding of the different approaches used. Approach This study explores PIE using ethnographically-informed qualitative case studies. The case studies include: three citizen juries, each one carried out over eight days and that asked jurors to consider different real-world health data initiatives; and a public panel set up by a regional databank that carries out data linking. Data collection is ongoing and I will be continuing to carry out close observations of activities, and conducting semi-structured 1:1 interviews with those that organise and have taken part in the activities. Results Data collection so far comprises completed observations at the citizen juries (~96 hours), ongoing observations of the public panel meetings (~15 hours), and thirty semi-structured 1:1 interviews with public contributors and other stakeholders about their experiences of the activities they were involved in. Early data analysis indicates key themes of: jurors feeling heard, but unsure whether anybody was listening; stakeholders being impressed by informed jurors, but raising concerns over contributors becoming too ‘expert’; how who is at the table and what information is presented impacts what is discussed; differences between online and in-person participation; and public involvement not being a substitute for informing the public about how their data is used. Conclusion ‘Who’ is involved, and ‘how’ PPIE activities are designed and run can facilitate or constrain discussion, enhancing or limiting public contributions. If public involvement is to achieve its aims, including increasing trustworthiness, deeper consideration of these factors by those who seek the public’s views in their data projects is recommended.
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- 2022
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27. ChemInform Abstract: A Novel and Facile One-Pot Method for the Synthesis of N-Substituted Sulfamates
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Hallena Rogers, Tao Pei, Guy R. Humphrey, and Anna Chiu
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Chemistry ,Organic chemistry ,General Medicine ,Combinatorial chemistry - Published
- 2008
28. Task-Sharing Psychosocial Support with Refugees and Asylum Seekers: Reflections and Recommendations for Practice from the PROSPER Study
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Anna Chiumento, Leah Billows, Annette Mackinnon, Rachel McCluskey, Ross G White, Naila Khan, Atif Rahman, Grahame Smith, and Christopher Dowrick
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asylum seekers ,mental health and psychosocial support ,problem management plus (pm+) ,refugee ,task-sharing ,Psychology ,BF1-990 ,Mental healing ,RZ400-408 - Abstract
To address the unmet need for accessible mental health services for refugees and asylum seekers in high-income countries, the PROSPER study is testing implementation of the World Health Organization Problem Management Plus (PM+) intervention. Incorporating task-sharing strategies, the intervention is delivered by Peer Lay Therapists with lived experience of seeking asylum or migration. The PM+ training adopts a cascade apprenticeship model, where Master Trainers train and supervise Wellbeing Mentors; who subsequently train and supervise the Peer Lay Therapists. We describe application of this training and supervision approach in PROSPER, drawing on Master Trainer and Wellbeing Mentor perspectives. We then reflect on our experiences, highlighting logistical challenges when working with refugee and asylum-seeking Peer Lay Therapists, the strategies to promote their ongoing engagement and the opportunities for team and personal growth. A core learning point has been the role of straddling the intervention and research components of the PROSPER study. Based on our experiences, we make recommendations for others adopting a task-sharing approach by training refugees and asylum seekers as Peer Lay Therapists in high-income countries, so that this might inform service programming and/or associated research activity.
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- 2021
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29. Asymmetric syntheses of pectenotoxins-4 and -8, part II: synthesis of the C20-C30 and C31-C40 subunits and fragment assembly
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David A, Evans, Hemaka A, Rajapakse, Anna, Chiu, and Dirk, Stenkamp
- Subjects
Alkylation ,Molecular Conformation ,Epoxy Compounds ,Marine Toxins ,Macrolides ,Pyrans - Published
- 2002
30. Exploring the mental health and psychosocial problems of Congolese refugees living in refugee settings in Rwanda and Uganda: a rapid qualitative study
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Anna Chiumento, Theoneste Rutayisire, Emmanuel Sarabwe, M. Tasdik Hasan, Rosco Kasujja, Rachel Nabirinde, Joseph Mugarura, Daniel M. Kagabo, Paul Bangirana, Stefan Jansen, Peter Ventevogel, Jude Robinson, and Ross G. White
- Subjects
Mental health and psychosocial support ,Qualitative ,Refugees ,Community-based support ,Humanitarian settings ,Post-conflict ,Special situations and conditions ,RC952-1245 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Background Refugees fleeing conflict often experience poor mental health due to experiences in their country of origin, during displacement, and in new host environments. Conditions in refugee camps and settlements, and the wider socio-political and economic context of refugees’ lives, create structural conditions that compound the effects of previous adversity. Mental health and psychosocial support services must address the daily stressors and adversities refugees face by being grounded in the lived reality of refugee’s lives and addressing issues relevant to them. Methods We undertook a rapid qualitative study between March and May 2019 to understand the local prioritisation of problems facing Congolese refugees living in two refugee settings in Uganda and Rwanda. Thirty free list interviews were conducted in each setting, followed by 11 key informant interviews in Uganda and 12 in Rwanda. Results Results from all interviews were thematically analysed following a deductive process by the in-country research teams. Free list interview findings highlight priority problems of basic needs such as food, shelter, and healthcare access; alongside contextual social problems including discrimination/inequity and a lack of gender equality. Priority problems relating to mental and psychosocial health explored in key informant interviews include discrimination and inequity; alcohol and substance abuse; and violence and gender-based violence. Conclusions Our findings strongly resonate with models of mental health and psychosocial wellbeing that emphasise their socially determined and contextually embedded nature. Specifically, findings foreground the structural conditions of refugees’ lives such as the physical organisation of camp spaces or refugee policies that are stigmatising through restricting the right to work or pursue education. This structural environment can lead to disruptions in social relationships at the familial and community levels, giving rise to discrimination/inequity and gender-based violence. Therefore, our findings foreground that one consequence of living in situations of pervasive adversity caused by experiences of discrimination, inequity, and violence is poor mental health and psychosocial wellbeing. This understanding reinforces the relevance of feasible and acceptable intervention approaches that aim to strengthening familial and community-level social relationships, building upon existing community resources to promote positive mental health and psychosocial wellbeing among Congolese refugees in these settings.
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- 2020
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31. Lay-therapist-delivered, low-intensity, psychosocial intervention for refugees and asylum seekers (PROSPER): protocol for a pilot randomised controlled trial
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Rebecca Rawlinson, Rabeea’h W. Aslam, Girvan Burnside, Anna Chiumento, Malena Eriksson-Lee, Amy Humphreys, Naila Khan, Daniel Lawrence, Rachel McCluskey, Annette Mackinnon, Lois Orton, Atif Rahman, Ewan Roberts, Anna Rosala-Hallas, Rhiannon Tudor Edwards, Philomene Uwamaliya, Ross G. White, Eira Winrow, and Christopher Dowrick
- Subjects
Asylum seekers ,Refugees ,Mental health ,Psychosocial intervention ,Problem management ,Lay therapists ,Medicine (General) ,R5-920 - Abstract
Abstract Background Asylum seekers and refugees (AS&Rs) experience impaired mental health and wellbeing, related to stresses in their country of origin, experiences in transit and reception on arrival, including significant barriers to accessing mainstream services. Their contact with health care is often crisis-driven and mediated through non-governmental organisations (NGOs). Problem Management Plus (PM+) is a psychosocial intervention recommended by the World Health Organisation to address distress experienced by adults affected by humanitarian crises. We are investigating its application for the first time in a high-income country. Methods In a pilot randomised controlled trial (RCT), PM+ will be delivered to AS&Rs in contact with NGOs in Liverpool City Region, UK by lay therapists who have lived experience of forced migration. Following systematic review and stakeholder engagement, PM+ has been adapted to the local context, and lay therapists have been trained in its delivery. We will assess the feasibility of conducting a three-arm RCT of five 90-min sessions of PM+, delivered individually or in groups by lay therapists to AS&Rs experiencing emotional distress and functional impairment, compared with each other and with usual support offered by local NGOs. Distress and impairment at baseline will be measured by the Hospital Anxiety and Depression Scale (HADS) and the WHO Disability Assessment Schedule (WHO-DAS). We aim to recruit 105 participants, 35 per arm. Primary health outcomes are anxiety and depressive symptoms at 3 months, measured by HADS. Secondary outcomes include subjective wellbeing, functional status, progress on identified problems, presence of post-traumatic stress disorder and depressive disorder and service usage. Longer-term impact will be assessed at 6 months post baseline, on the same parameters. We will assess the feasibility of conducting a full RCT in relation to the following elements: recruitment and retention of lay therapists and study participants; fidelity of delivery of PM+; and suitability of the study measures, including any linguistic or cultural barriers. Discussion We will use these findings to specify the parameters for a full RCT to test the effectiveness and cost-effectiveness of PM+ in reducing emotional distress and health inequalities, and improving functional ability and wellbeing, amongst asylum seekers and refugees. Trial registration ISRCTN, ID: ISRCTN15214107 . Registered on 10 September 2019.
- Published
- 2020
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32. Remote Desymmetrization at Near-Nanometer Group Separation Catalyzed by a Miniaturized Enzyme Mimic
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Karl Hansen, Robert A. Reamer, David Pollard, Scott J. Miller, Jaume Balsells, Chad A. Lewis, Craig K. Esser, Anna Chiu, Michele Kubryk, and Jerry A. Murry
- Subjects
inorganic chemicals ,Magnetic Resonance Spectroscopy ,Chemistry ,Stereochemistry ,organic chemicals ,Biphenyl Compounds ,Molecular Conformation ,Enantioselective synthesis ,Substrate (chemistry) ,Stereoisomerism ,General Chemistry ,Sensitivity and Specificity ,Biochemistry ,Desymmetrization ,Catalysis ,Enzymes ,Colloid and Surface Chemistry ,Enzyme mimic ,heterocyclic compounds ,Enantiomer ,Peptides ,Chirality (chemistry) ,Macromolecule - Abstract
The chirality of biological receptors often requires syntheses of therapeutic compounds in single enantiomer form. The field of asymmetric catalysis addresses enantioselective synthesis with chiral catalysts. Chemical differentiation of sites within molecules that are separated in space by long distances presents special challenges to chiral catalysts. As the distance between enantiotopic sites increases within a substrate, so too may the requirements for size and complexity for the catalyst. The extreme of catalyst complexity could be defined by macromolecular enzymes and their amazing capacity to effect stereospecific reactions over long distances between reactive sites and enzyme-substrate contacts. We report here a synthetic, miniaturized enzyme mimic that catalyzes a desymmetrization reaction over a very long distance.
- Published
- 2006
33. A haven of green space: learning from a pilot pre-post evaluation of a school-based social and therapeutic horticulture intervention with children
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Anna Chiumento, Ipshita Mukherjee, Jaya Chandna, Carl Dutton, Atif Rahman, and Katie Bristow
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Children and young people ,Greenspace ,Behavioural, emotional and social problems ,Mental health and psychosocial wellbeing ,Schools ,Community-based ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Research suggests outdoor activity in green spaces is important for children’s mental, emotional and social wellbeing. A recognised green space intervention is “Social and Therapeutic Horticulture” (STH). We discuss findings from a pilot STH intervention, “A Haven of Green Space” conducted in North West England. The target group were school children aged 9–15 years experiencing behavioural, emotional and social difficulties. This exploratory study aims to assess the mental wellbeing of the children pre- and post-intervention, and assess the value of the evaluation methods and “Five Ways to Wellbeing” evaluation framework. Methods The intervention involved 6 monthly sessions with two horticulturists and a psychotherapist. Sessions were participatory with the development of selected greenspaces at each school directed by the children. Evaluation was situated in the “Five Ways to Wellbeing” framework, using a mixed-methods pre- post-evaluation design. Existing public mental health evaluation methodologies were adapted for use with school children: Mental Well Being Impact Assessment (MWIA) and Wellbeing Check Cards. The MWIA was analysed qualitatively identifying over-arching themes. The quantitative wellbeing check cards were analysed by mean score comparison. Results Results were collected from 36 children across the three participating schools, and suggest that the Haven Green Space intervention was associated with improved mental wellbeing. MWIA factors relating to mental wellbeing (“emotional wellbeing” and “self-help”) were positively impacted in all three schools. However, findings from the wellbeing check cards challenge this, with worsening scores across many domains. Conclusions A key study limitation is the pilot nature of the intervention and challenges in adapting evaluation methods to context and age-range. However, results indicate that group based socially interactive horticulture activities facilitated by trained therapists are associated with positive impacts upon the mental and emotional wellbeing of children experiencing behavioural, emotional and social difficulties. Further research is needed to verify this, and to support using the “Five Ways” in intervention development and evaluation. Finally, we recommend continued efforts to develop age-appropriate evaluation methods.
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- 2018
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34. Addressing culture and context in humanitarian response: preparing desk reviews to inform mental health and psychosocial support
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M. Claire Greene, Mark J. D. Jordans, Brandon A. Kohrt, Peter Ventevogel, Laurence J. Kirmayer, Ghayda Hassan, Anna Chiumento, Mark van Ommeren, and Wietse A. Tol
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Mental health ,Psychosocial ,Humanitarian ,Emergency ,Culture ,Context ,Special situations and conditions ,RC952-1245 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Delivery of effective mental health and psychosocial support programs requires knowledge of existing health systems and socio-cultural context. To respond rapidly to humanitarian emergencies, international organizations often seek to design programs according to international guidelines and mobilize external human resources to manage and deliver programs. Familiarizing international humanitarian practitioners with local culture and contextualizing programs is essential to minimize risk of harm, maximize benefit, and optimize efficient use of resources. Timely literature reviews on traditional health practices, cultural beliefs and attitudes toward mental health and illness, local health care systems and previous experiences with humanitarian interventions can provide international practitioners with crucial background information to improve their capacity to work efficiently and with maximum benefit. In this paper, we draw on experience implementing desk review guidance from the World Health Organization (WHO) and UNHCR, the United Nations Refugee Agency (2012) in four diverse humanitarian crises (earthquakes in Haiti and Nepal; forced displacement among Syrians and Congolese). We discuss critical parameters for the design and implementation of desk reviews, and discuss current challenges and future directions to improve mental health care and psychosocial support in humanitarian emergencies.
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- 2017
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35. Evaluating effectiveness and cost-effectiveness of a group psychological intervention using cognitive behavioural strategies for women with common mental disorders in conflict-affected rural Pakistan: study protocol for a randomised controlled trial
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Anna Chiumento, Syed Usman Hamdani, Muhammad Naseem Khan, Katie Dawson, Richard A. Bryant, Marit Sijbrandij, Huma Nazir, Parveen Akhtar, Aqsa Masood, Duolao Wang, Mark van Ommeren, and Atif Rahman
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Mental health and psychosocial support ,Cluster randomised controlled trial ,Effectiveness ,Nonspecialist health worker ,Humanitarian ,Group intervention ,Medicine (General) ,R5-920 - Abstract
Abstract Background The impact of humanitarian disasters upon mental health is well recognised. The evidence for psychological interventions for mental health is mounting, but few interventions have been rigorously tested in humanitarian settings. To be sustainable in humanitarian settings interventions need to be short, simple, deliverable by nonspecialists under supervision, and adopt a transdiagnostic approach where an array of mental health outcomes are addressed simultaneously. These elements have been incorporated into the newly developed WHO Problem Management Plus (PM+) Group intervention. The aim of this trial is to evaluate the locally adapted PM+ Group intervention for women in Swat, Pakistan. Methods This PM+ Group trial is a two-arm, single-blind, cluster randomised controlled trial conducted in a community-based setting with women in rural Pakistan. PM+ is delivered in partnership with the Lady Health Worker (LHW) Programme which provides community-based health care to women in Pakistan. Thirty-four LHW clusters will be randomised in a 1:1 allocation ratio using a permuted-block randomisation method. Participants screened and found to meet the inclusion criteria will be allocated to either the PM+ intervention group (n = 306), or the control arm (n = 306). The manualised PM+ intervention involves five sessions, each lasting 3 h, and introduces four strategies applied by participants to problems that they are facing. It is delivered by local female facilitators with a minimum of 16 years of education who are provided with targeted training and supervision. The primary outcome is individual psychological distress, measured by levels of anxiety and depression on the Hospital Anxiety and Depression Scale at 20 weeks after baseline. Secondary outcomes include major depression, post-traumatic stress disorder, levels of social support, levels of functioning, and economic effectiveness. Intervention acceptability will be explored through an embedded qualitative study. Discussion The PM+ Group trial will provide important evidence on the effectiveness of an empirically supported psychological treatment delivered by nonspecialists in a humanitarian setting. If proven effective, the qualitative component will inform strategies for PM+ Group scale-up in health systems in other humanitarian settings. Trial registration Australian New Zealand Clinical Trials Registry, identifier: ACTRN12616000037404. Registered on 19 January 2016; WHO Protocol ID RPC705, v.4, 2 November 2015.
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- 2017
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36. A qualitative evaluation of a brief multicomponent intervention provided by lay health workers for women affected by adversity in urban Kenya
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Edith van't Hof, Katie S. Dawson, Alison Schafer, Anna Chiumento, Melissa Harper Shehadeh, Marit Sijbrandij, Richard A. Bryant, Dorothy Anjuri, Phiona Koyiet, Lincoln Ndogoni, Jeannette Ulate, and Mark van Ommeren
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Adversity ,intervention ,mental health ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Background: Problem Management Plus (PM+) is a brief multicomponent intervention incorporating behavioral strategies delivered by lay health workers. The effectiveness of PM+ has been evaluated in randomized controlled trials in Kenya and Pakistan. When developing interventions for large-scale implementation it is considered essential to evaluate their feasibility and acceptability in addition to their efficacy. This paper discusses a qualitative evaluation of PM+ for women affected by adversity in Kenya. Methods: Qualitative interviews were conducted with 27 key informants from peri-urban Nairobi, Kenya, where PM+ was tested. Interview participants included six women who completed PM+, six community health volunteers (CHVs) who delivered the intervention, seven people with local decision making power, and eight project staff involved in the PM+ trial. Results: Key informants generally noted positive experiences with PM+. Participants and CHVs reported the positive impact PM+ had made on their lives. Nonetheless, potential structural and psychological barriers to scale up were identified. The sustainability of CHVs as unsalaried, volunteer providers was mentioned by most interviewees as the main barrier to scaling up the intervention. Conclusions: The findings across diverse stakeholders show that PM+ is largely acceptable in this Kenyan setting. The results indicated that when further implemented, PM+ could be of great value to people in communities exposed to adversities such as interpersonal violence and chronic poverty. Barriers to large-scale implementation were identified, of which the sustainability of the non-specialist health workforce was the most important one.
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- 2018
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37. Online interviewing with interpreters in humanitarian contexts
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Anna Chiumento, Laura Machin, Atif Rahman, and Lucy Frith
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qualitative interviews ,online interviews ,internet communication ,research methods ,cross-cultural ,humanitarian emergencies ,post-conflict ,research ethics ,Medicine (General) ,R5-920 - Abstract
Purpose: Recognising that one way to address the logistical and safety considerations of research conducted in humanitarian emergencies is to use internet communication technologies to facilitate interviews online, this article explores some practical and methodological considerations inherent to qualitative online interviewing. Method: Reflections from a case study of a multi-site research project conducted in post-conflict countries are presented. Synchronous online cross-language qualitative interviews were conducted in one country. Although only a small proportion of interviews were conducted online (six out of 35), it remains important to critically consider the impact upon data produced in this way. Results: A range of practical and methodological considerations are discussed, illustrated with examples. Results suggest that whilst online interviewing has methodological and ethical potential and versatility, there are inherent practical challenges in settings with poor internet and electricity infrastructure. Notable methodological limitations include barriers to building rapport due to partial visual and non-visual cues, and difficulties interpreting pauses or silences. Conclusions: Drawing upon experiences in this case study, strategies for managing the practical and methodological limitations of online interviewing are suggested, alongside recommendations for supporting future research practice. These are intended to act as a springboard for further reflection, and operate alongside other conceptual frameworks for online interviewing.
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- 2018
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38. Erratum to: Ethical standards for mental health and psychosocial support research in emergencies: review of literature and current debates
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Anna Chiumento, Atif Rahman, Lucy Frith, Leslie Snider, and Wietse A. Tol
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Public aspects of medicine ,RA1-1270 - Published
- 2017
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39. Correction to: Problem management plus (PM+) for common mental disorders in a humanitarian setting in Pakistan; study protocol for a randomised controlled trial (RCT)
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Marit Sijbrandij, Saeed Farooq, Richard A Bryant, Katie Dawson, Syed Usman Hamdani, Anna Chiumento, Fareed Minhas, Khalid Saeed, Atif Rahman, and Mark van Ommeren
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Psychiatry ,RC435-571 - Abstract
Following publication of the original article [1], the first author reported an error in referring his paper.
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40. Antibody dependent cellular cytotoxicity: cytotoxicity mediated by non t-lymphocytes
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Robert C. Ossorio, Ben Bonavida, Jacob Zighelboim, Robert Peter Gale, Anna Chiu, and John L. Fahey
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Protein Denaturation ,Erythrocytes ,T-Lymphocytes ,Immunology ,chemical and pharmacologic phenomena ,Thymus Gland ,Antibodies ,Pathology and Forensic Medicine ,HUMAN THYMUS ,Immunology and Allergy ,Cytotoxic T cell ,Animals ,Humans ,Lymphocytes ,Receptor ,Cytotoxicity ,Antibody-dependent cell-mediated cytotoxicity ,Immunity, Cellular ,Leukemia, Experimental ,Sheep ,biology ,Chemistry ,Immune Sera ,Cytotoxicity Tests, Immunologic ,Molecular biology ,Peripheral blood ,Chromium Radioisotopes ,Immune Adherence Reaction ,Immunoglobulin G ,biology.protein ,Chromatography, Gel ,Rabbits ,Antibody ,Function (biology) - Abstract
The cytotoxic capacity of human lymphocytes in antibody dependent cellular cytotoxicity (ADCC) is mediated by non T-lymphocytes. Evidence is presented that purified peripheral blood T-lymphocytes as well as human thymus cells are inefective in ADCC. By contrast, lymphocytes bearing a receptor for immunoglobulin (Ig) effectively mediated this function.
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41. Usefulness of previous methicillin-resistant Staphylococcus aureus screening results in guiding empirical therapy for S aureus bacteremia
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Lisa Burry, Daniel R. Ricciuto, Sumit Raybardhan, Tania Fernandes, Chaim M. Bell, Anna Chiu, Andrew Morris, Adrienne Showler, George Tomlinson, Marilyn Steinberg, and Anthony D. Bai
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Microbiology (medical) ,Meticillin ,medicine.drug_class ,Antibiotics ,Infectious and parasitic diseases ,RC109-216 ,Drug resistance ,Antimicrobial stewardship ,medicine.disease_cause ,Microbiology ,Sensitivity ,Pharmacotherapy ,Medicine ,Infection control ,MRSA screening ,business.industry ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,medicine.disease ,Methicillin-resistant Staphylococcus aureus ,QR1-502 ,3. Good health ,Infectious Diseases ,Empirical antimicrobial therapy ,Bacteremia ,Specificity ,Original Article ,Staphylococcus aureus bacteremia ,business ,medicine.drug - Abstract
Staphylococcus aureus bacteremia (SAB), which may be caused by methicillin-resistant S aureus (MRSA), is a leading cause of bloodstream infections. SAB and MRSA can cause an increase in mortality, result in longer hospital stays and increase medical costs. However, it is possible that MRSA colonization may predict infection. Using a retrospective cohort investigation, this study evaluated the clinical utility of past MRSA screening swabs for predicting methicillin resistance and its use in guiding empirical antibiotic therapy for SAB., BACKGROUND: Staphylococcus aureus bacteremia (SAB) is an important infection. Methicillin-resistant S aureus (MRSA) screening is performed on hospitalized patients for infection control purposes. OBJECTIVE: To assess the usefulness of past MRSA screening for guiding empirical antibiotic therapy for SAB. METHODS: A retrospective cohort study examined consecutive patients with confirmed SAB and previous MRSA screening swab from six academic and community hospitals between 2007 and 2010. Diagnostic test properties were calculated for MRSA screening swab for predicting methicillin resistance of SAB. RESULTS: A total of 799 patients underwent MRSA screening swabs before SAB. Of the 799 patients, 95 (12%) had a positive and 704 (88%) had a negative previous MRSA screening swab. There were 150 (19%) patients with MRSA bacteremia. Overall, previous MRSA screening swabs had a positive likelihood ratio of 33 (95% CI 18 to 60) and a negative likelihood ratio of 0.45 (95% CI 0.37 to 0.54). Diagnostic accuracy differed depending on mode of acquisition (ie, community-acquired, nosocomial or health care-associated infection) (P
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