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1. Impact of Beta-Lactam Target Attainment on Resistance Development in Patients with Gram-Negative Infections

Author

Nicole F. Maranchick, Jessica Webber, Mohammad H. Alshaer, Timothy W. Felton, and Charles A. Peloquin

Subjects
drug resistance, gram-negative bacteria, beta-lactams, pharmacokinetic/pharmacodynamic, Therapeutics. Pharmacology, RM1-950
Abstract

Background: The objective was to identify associations between beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) targets and Gram-negative bacteria resistance emergence in patients. Methods: Retrospective data were collected between 2016 to 2019 at the University of Florida Health-Shands Hospital in Gainesville, FL. Adult patients with two Gram-negative isolates receiving cefepime, meropenem, or piperacillin-tazobactam and who had plasma beta-lactam concentrations were included. Beta-lactam exposures and time free drug concentrations that exceeded minimum inhibitory concentrations (ƒT > MIC), four multiples of MIC (ƒT > 4× MIC), and free area under the time concentration curve to MIC (ƒAUC/MIC) were generated. Resistance emergence was defined as any increase in MIC or two-fold increase in MIC. Multiple regression analysis assessed the PK/PD parameter impact on resistance emergence. Results: Two hundred fifty-six patients with 628 isolates were included. The median age was 58 years, and 59% were males. Cefepime was the most common beta-lactam (65%) and Pseudomonas aeruginosa the most common isolate (43%). The mean daily ƒAUC/MIC ≥ 494 was associated with any increase in MIC (p = 0.002) and two-fold increase in MIC (p = 0.004). The daily ƒAUC/MIC ≥ 494 was associated with decreased time on antibiotics (p = 0.008). P. aeruginosa was associated with any increase in MIC (OR: 6.41, 95% CI [3.34–12.28]) or 2× increase in MIC (7.08, 95% CI [3.56–14.07]). Conclusions: ƒAUC/MIC ≥ 494 may be associated with decreased Gram-negative resistance emergence.

Published
2023
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2. The Use of Different Sepsis Risk Stratification Tools on the Wards and in Emergency Departments Uncovers Different Mortality Risks: Results of the Three Welsh National Multicenter Point-Prevalence Studies

Author

Harry J. A. Unwin, MBBCh, BSc, Maja Kopczynska, MBBCh, BSc, Richard Pugh, FRCA, Laura J. P. Tan, MBBS, BSc, Christian P. Subbe, MD, Gemma Ellis, MSc, Paul Morgan, FRCA, Peter Havalda, MD, Ben Sharif, MBBCh, John Burke, MSc, Tamas Szakmany, MD, PhD, FCCM, on behalf of Welsh Digital Data Collection Platform (WDDCP) Collaborators, Maria Hobrok, Moriah Thomas, Annie Burden, Nadia Youssef, Katherine Carnegie, Helena Colling-Sylvester, Natasha Logier, Meshari Alsaeed, Hannah Williams, Arfa Ayob, Nor Farzana, Sweta Parida, David Lawson, Emily Evans, Laura Jane Davis, Billie Atkins, Llywela Wyn Davies, Lee Sanders-Crook, Steffan Treharne Seal, Alice Cains, Richard Pugh, Katy Crisp, Sarah Venning, Ella Sykes, Stephanie Narine, Georgia Parry, Emily Angela Dillon, Qi Zhuang Siah, Ting Yang, Tyler Jones, Parvathi Thara, Emma Wood, Lara Wirt, Georgina St Pier, Richard Betts, Kyriaki Mitsaki, Mari Tachweed Pierce, Sioned Davies, Yakeen Hafouda, Erin Ifan, Grace Lacey, Francesca Mitchell, John Lynch, Michal Mazur, Lezia D’Souza, Bethan Ponting, Terrance Lau, Ruairidh Kerrigan, Lucy Morgan, Roshan Vindla, Claudia Zeicu, Becky James, Amirah Amin Ariff, Wan Binti Wan Azzlan, Charlotte Collins, Elizabeth Wickens, Alisa Norbee, Aliya Zulkefli, Thomas Haddock, Megan Thomas, Matthew Lee, Miriam Cynan, Nik-Syakirah Nik Azis, Imogen Hay, Catherine Russell, Margriet Vreugdenhil, Mustafa Abdimalik, Joseph Davies, Peter Havalda, Angharad Evans, Kate Robertson, Grace Gitau, Mei-yin Gruber, Thomas Telford, Anas Qarout, Naomi Nandra, Hannah Garrard, James Cutler, Rhiannon Tammy Jones, Amy Prideaux, Timothy Spence, Sarah Hardie, Harriet Seymour, Sam Willis, Matthew Warlow, Shanali Thanthilla, Thomas Downs, Nina Foley, Chad McKeown, Akshita Dandawate, Holleh Shayan-Arani, Ellie Taylor, Oliver Kyriakides, Rachel Price, Ffion Haf Mackey, Emily Haines, Samuel Chun, Nilarnti Vignarajah, Tessa Chamberlain, Dongying Zhao, Nayanatara Nadeesha T Tantirige, Naomi Dennehey, Georgina Evans, John Watts, Ceri Battle, Ryan Jones, Selina Jones, Charlotte James, James O’Hanlon, Isabella Bridges, Bethany Hughes, Leo Polchar, Elise Bisson, Charlotte Mykura, Lara Money, Joshua McKenna, Sarah Kinsman, Demiana Hanna, Emily Baker, Harrison Sprague, Liam Sharma, Tom Pontin, Emma Shore, Tamara Hughes, Sam Nightingale, Philby Baby, Matthew Shield, Alice Cross, Jenna Boss, Olivia Ross, George Ashton, Kimaya Pandit, Daniel Davies, Cameron Garbutt, Charlotte Johnston, Marcus Cox, Chantal Roberts, Alessia Waller, Laura Heekin, Kathy Wang, Rhianna Church, Shrina Patel, Marianne Broderick, Hannah Whillis, Daniel Craig Hathaway, Emel Yildirim, Caitlin Atkins, Elin Walters, Carys Durie, Robert James Hamilton Sinnerton, Benjamin Tanner, Julimar Abreu, Kiran Bashir, Vincent Hamlyn, Amelia Tee, Zoe Ann Hinchcliffe, Rita Otto, Georgie Covell, Megan Stone, Victoria Maidman, Katherine Godfray, Rhidian Caradine, Hannah Beetham, Adanna Nicole Anomneze-Collins, Jeanette Tan, Yasmina Abdelrazik, Azizah Khan, Nabihah Malik, Aidan Clack, Lewis Oliva, Tyler Thomas, Adam George Mounce, Anoopama Ramjeeawon, Ndaba Mtunzi, Duncan Soppitt, Jay Hale, Jack Wellington, Robert Buchanan Ross, Danielle Lis, Rebecca Parsonson, Jude Joseph-Gubra, Ajitha Arunthavarajah, Jessica Nicholas, Aaron Harris, Henry Atkinson, Jessica Webster, Tim Burnett, Josephine Raffan Gowar, Sam DeFriend, Jasmine Whitaker, Elizabeth Beasant, Luis Macchiavello, Danyal Usman, Abdullah Mahdi, Tiffany Ye Tze Shan, Nick Savill, Jennifer Gee, Lizzie Hodges, Ami Desai, Hannah Rossiter, Matthew Taylor, Kevin Pinto, Eleanor Hartley, Oscar Emanuel, Rhiannon Long, Megan Selby, Elilis Wardle, Alexandra Urquhart, Jack Barrington, Matthew Ashman, Elizabeth Adcock, Amelia Dickinson, Rebecca Jordache, Rym Chafai El Alaoui, Sophie Stovold, Sam Vickery, Nia Jones, Alice O’Donnell, Monty Cuthbert, Osa Eghosa, Muhammad Karim, Lowri Williams, Louise Tucker, Tom Downs, Rebecca Walford, Annabelle Hook, Adam Mounce, Emily Eccles, Ross Edwards, Kirtika Ramesh, Charlie Hall, Maria Lazarou, Rhidian Jones, Katy McGillian, Hari Singh Bhachoo, Zoe The, Vithusha Inpahas, Ruchi Desai, Yusuf Cheema, Andrew Hughes, Olivia Cranage, Felicity Bee, Khalid Osman, Humza Khan, Jennifer Pitt, Charlotte Pickwick, Jorge Carter, Fiona Andrew, Naseera Seedat, Roshni Patel, Megan Walker, Alicia Boam, Jessica Randall, Beth Bowyer, Josh Edwards, Natasha Jones, Emma Walker, Ailsa MacNaught, Swagath Balachandran, Abbie Shipley, Jennifer Louise Kent, Samuel Tilley, Bethany Davies, Emma Withers, Krishna Parmar, Lucie Webber, Angelica Sharma, Amy Handley, Alexandra Gordon, Lucy Allen, Rebecca Paddock, Harriet Penney, Lopa Banerjee, Chloe Victoria Vanderpump, Kate Harding, John Burke, Orsolya Minik, Nia Jarrett, Ellie Rowe, Adanna Anomneze-Collins, Harry Griffiths, Sarah Pengelly, Ffion Bennett, Ahmed Bilal, Abdullah El-badawey, Bethan Ellis, Luke Cook, Harriet Elizabeth Valentine Maine, Kiri Armstrong, Hannah Beresford, Timia Raven-Gregg, Tom Liddell-Lowe, Caitlin Ong, Harriet Reed, Frederika Alice St John, Weronika Julia Kozuch, Isabelle Ray, Irukshi Anuprabha Silva, Sin Ting Natalie Cheng, Umme-Laila Ali, Noreena Syed, Luke Murphy, Thomas Grother, Harry Smith, Rachel Watson, Omar Marei, Emma Kirby, Anna Gilfedder, Lydia Maw, Sarah O’Connor, Charlotte Maden, Helena Jones, Hazel Preston, Nur Amirah Binti Maliki, Mark Zimmerman, Jessica Webber, Llewelyn Jones, Rebecca Phillips, Lauren McCarthy, Emily Hubbard, Leo Duffy, Abigail Guerrier Sadler, Tamas Szakmany, Owen Richards, Charles King, Charlotte Killick, Yusuf Chema, Kavita Shergill, Yi Huen, Lillian Lau, Hannah Mustafa Ali, Lucas Wilcock, Molly Timlin, Ayeesha Rela, Daniel Smith, Sarah Ireland, Jennifer Evans, Nayanatara Poobalan, Jessica Pearce, Thivya V Vadiveloo, Zoe Black, Daniel Elis Samuel, Humaira Hussain, Joanna Hawkins, Zeid Atiyah, Rebecca Creamer, Maham Zafar, Ahmad Almazeedi, Hannah Brunnock, Zain Nasser, Mekha Jeyanthi, Poorya Moghbel, Katie Kwan, Isobel Sutherland, Frank Davis, Abigail Rogers, Zhao Xuan Tan, Clare Chantrill, Amal Robertson, Jonathan Foulkes, Rahana Khanam, Jomcy John, Sarah Hannah Meehan, Huria Metezai, Hannah Dawson, Navrhinaa Vadivale, Camilla Lee, Amrit Dhadda, Sian Cleaver, Genna Logue, Joy Inns, Isabel Jones, Robyn Howcroft, Carys Gilbert, Matthew Bradley, Louise Pike, Rachel Keeling, Charldré Banks, Eleanor Cochrane, James McFadyen, Matthew Mo, Emily Ireland, Esme Brittain, Ihssen Laid, Charlotte Green, Adriel Mcforrester, Xuong Michelle Ly, Mariana Nalbanti, Raven Joseph, Jack Tagg, David Purchase, Pan Myat, Ayako Niina, Tyler Joshua Jones, Lowri Hughes Thomas, Natalie Hoyle, Patrick Benc, Ellen Davies, Meng-Chieh Wu, David Fellows, Sam Tilley, Eloise Baxendale, Karishma Khan, Andrew Forrester, Oliver Moore, Hse Juinn Lim, Aimee Owen, Faris Hussain, Nima-banu Allybocus, Maneha Sethi, Harry Waring, Adeel Khan, Claire Smith, Nicholas Doyle, Mohammad Yahya Amjad, Luke Galloway, Paul Morgan, Gemma Ellis, Robert Lundin, Haamed Al Hassan, Bethan Markall, Namratha Kaur, Emmanuel Onyango, Heather Beard, Elliot Field, Ellen Nelson-Rowe, Lizzie Adcock, Amelia Stoddart, Frederika St John, Mathoorika Sivananthan, Rhys Jones, Sung Yeon Kwak, Lily Farakish, Holly Rhys-Ellis, Kate Moss, Tallulah Ray, Tessa David, Talea Roberts, Annie Quy, Aniket Paranjape, Nutchanun Poolworaluk, Mary Keast, Si Liang Yao, Dion Manning, Isobel Irwin, Umair Asim, Emelia Boggon, Ibrahim Alkurd, Genevieve Lawerece, Jade Brown, Emily Murphy, Evie Lambert, Jeremy Guilford, Beth Payne, Mariam Almulaifi, Arwel Poacher, Sashiananthan Ganesananthan, Berenice Cunningham-Walker, Chloe Spooner, Akanksha Kiran, Nabeegh Nadeem, Vidhi Unadkat, Esme Sparey, David Li, Jessica Smith, India Corrin, Amit Kurani, Paul McNulty, Ceri Brown, Wojciech Groblewski, Szilvia Szoke, Amelia Redman, Esther McKeag, Anastasia Donnir, Gaautham Ravishangar, Emanuela Howard, Charlotte Salmon, Sara Tanatova, Jasmine Kew, Megan Eilis Clark, Ellen Hannay, Olesya Godsafe, Christina Houghton, Francesca Lavric, Rachel Mallinson, Chris Littler, Harsha Reddy, Andrew Campbell, Benedict Soo, Rachel Evans, Georgina Donowho, Alexandra Cawthra, Maddison Davies, Matthew Lawrence Ashman, Jamie Scriven, James Vautrey, Shannon Seet, Imogen Britton, Abigail Hodgson, Emma Twohey, Joseph Robbins, Vanessa Yeo Yung Ling, Kimiya Asjadi, Carven Chin Yee Shean, Zoe McCarroll, Oritseweyimi Amatotsero, Hei Man Priscilla Chan, John Ng Cho Hui, Antonia Ashaye, Josephine Acheampong, Ayowade Adeleye, Saber Ahmed, Alexandra Chrysostomou, Harry Unwin, Eshen Ang, Niamh McSwiney, Yin Yin Lim, Zong Xuan Lee, Svetlana Kulikouskaya, Nur Zulkifili, Sheryl Lim, Lim Xin, Adiya Urazbayeva, Nur Haslina Ahmad Hanif, Yau Ke Ying, Alice Coleclough, Eilis Higgins, Naomi Spencer, Tze Gee Ng, Sam Booth, Stephanie Wai Yee Ng, Christian P Subbe, Isabella Patterson, Wen Li Chia, Abdullah Mukit, Hei Yi Vivian Pak, Felicity Lock, Mariana Nalmpanti, Shôn Alun Thomas, Tanisha Burgher, Alfred Wei Zhen Yeo, Siwan Powell Jones, Charlie Miles, Millicent Perry, Holly Burton, Katharine Powell, Luthfun Nessa, Aalaa Fadlalla, Rhian Morgan, Elizabeth Hodges, Amelia Heal, Chloe Scott, Alice Tayler, Thomas Chandy, Abduahad Taufik, James Cochrane, Samuel Willis, Sieh Yen Heng, Alex Cooper, Henrik Graf von der Pahlen, Isabella Talbot, Robin Gwyn Roberts, Jessica Sharma Smith, Aisling Sweeney, Cerian Roberts, Laura Bausor, Chania, Daniah Thomas, Elen Wyn Puw, Ronan A Lyons, and Judith E Hall

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments. DESIGN:. Secondary analysis of three annual 24-hour point-prevalence study periods. SETTING:. The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019. PATIENTS:. We screened all patients presenting to the emergency department and on the general wards. MEASUREMENTS AND MAIN RESULTS:. We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the “High risk” category in comparison with 665 (52.3%) in “Moderate to High risk” and 156 (12.3%) in “Low risk” category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points. CONCLUSIONS:. Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis.

Published
2021
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3. 'Nobody knows, or seems to know how rheumatology and breastfeeding works': Women's experiences of breastfeeding whilst managing a long-term limiting condition - A qualitative visual methods study

Author

Denitza, Williams, Jessica, Webber, Bethan, Pell, Aimee, Grant, Julia, Sanders, Ernest, Choy, Adrian, Edwards, Ann, Taylor, Meng-Chieh, Wu, and Rhiannon, Phillips

Subjects
Adult, Disability, Breastfeeding, Mothers, Social Support, Timeline-facilitated interview, Long-term illness, Visual methods, Focus Groups, United Kingdom, Article, Time-lining, Breast Feeding, Rheumatology, Autoimmune rheumatic disease, Humans, Female, Qualitative, Qualitative Research, Shared decision-making
Abstract

Background Only around 1% of babies in the UK are breastfed exclusively until six months of age as recommended by the World Health Organisation. One in ten women who have recently given birth in the UK have a long-term illness and they are at increased risk of stopping breastfeeding early. We considered women with autoimmune rheumatic diseases as an exemplar group of long term illnesses, to explore the barriers and enablers to breastfeeding Aim To understand the experiences of infant feeding among women with autoimmune rheumatic diseases and to identify potential barriers and enablers. Design Qualitative visual timeline-facilitated interviews. Participants and setting 128 women with autoimmune rheumatic diseases who were considering pregnancy, pregnant, or had young children took part in an online survey as part of the STAR Family Study. Of these, 13 women who had children were purposefully sampled to be interviewed. Interviews took place in person or on the telephone. Timeline-facilitated interviews were used to focus on lived experiences and topics important to the women, including early parenting. We conducted a focused thematic analysis of women's lived experiences of infant feeding. Results Three main themes were identified in relation to breastfeeding: lack of information about medication safety, lack of support in decision-making and maintaining breastfeeding, and maternal guilt. Conclusions Women with autoimmune rheumatic diseases found it difficult to access the information they needed about medications to make informed decisions about breastfeeding. They often also felt pressurised into breastfeeding and experienced feelings of guilt if they were unable, or did not wish to breastfeed. Tailored interventions are required that adopt a non-judgmental and person-centred approach to support decision-making in regard to infant feeding, providing women with information that can best enable them to make infant feeding choices.

Published
2019

4. Macrophage Class A Scavenger Receptors Bind Tumor‐Associated Carbohydrate Antigens and Promote Breast Cancer Growth and Metastases in Mice

Author

Behjatolah Monzavi-Karbassi, Christy M. Simecka, Jessica Webber, Eric R. Siegel, Beixiang He, Taylor Wadley, Steven R. Post, Thomas Kelly, Asangi Kumarapeli, Trevor Meece, and Fariba Jousheghany

Subjects
Tumor-Associated Carbohydrate Antigens, Breast cancer, Chemistry, Genetics, medicine, Cancer research, Macrophage, Scavenger receptor, medicine.disease, Molecular Biology, Biochemistry, Biotechnology
Published
2020
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5. Abstract 092: Novel Mechanism of Salt-sensitive Hypertension: CD8 + T Cells Stimulate Sodium Chloride Co-transporter NCC in Kidney

Author

Shengyu Mu, Beixiang He, Jessica Webber, Sung Rhee, Tonya M. Rafferty, and Yunmeng Liu

Subjects
medicine.medical_specialty, Kidney, urogenital system, Chemistry, Sodium, chemistry.chemical_element, Immune system, medicine.anatomical_structure, Endocrinology, Internal medicine, Internal Medicine, medicine, Chloride channel, Cytotoxic T cell, Distal convoluted tubule, Intracellular, CD8
Abstract

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention is an important question, which if answered, could reveal a critical relationship between adaptive immunity and pathogenesis of salt-sensitive hypertension. In the present study, we propose a novel mechanism of salt-sensitive hypertension via the distal nephron: that in salt-sensitive hypertension, renal infiltrating T cells interact with distal convoluted tubule cells (mDCTs), which leads to up-regulation of the sodium-chloride-co-transporter (NCC), and thus enhancement of sodium retention. In vivo tests used DOCA-salt mice (SBP~190mmHg on a high salt diet) and T cell-adoptive transferred mice (SBP~170mmHg on a high salt diet). Results confirmed enhanced NCC & p-NCC expression (>2.5X) in the kidneys of both mouse models. We found significantly more T cells infiltrating the kidneys of DOCA-salt & T cell-transferred mice compared to their controls. It is noteworthy that in both models a great number of CD8 + T cells (CD8Ts) in the renal tubulointerstitium surround DCT segments which have higher levels of NCC expression. Direct contact between these two cell types was confirmed by super-resolution structured illumination microscopy. In vitro, we co-cultured mDCTs with T cells, and found that CD8Ts, but not CD4Ts, significantly increased NCC expression (>3X) in mDCTs via “direct cell-cell contact”. An intracellular sodium-indicator detected higher NCC-mediated sodium uptake (>1.5X) in mDCTs treated with CD8Ts compared to untreated controls. Moreover, these effects were mediated by increased (>2.2X) functional chloride channel Clc-k in the cell membrane. Clc-k knockdown by siRNA blunted chloride efflux and abolished CD8T-induced NCC activation and sodium retention in mDCTs. Taken together, our findings suggest a novel role for CD8 + T cells in enhancement of salt retention contributing to salt-sensitive hypertension: that CD8 + T cells directly contact mDCTs, stimulate NCC by upregulating the chloride channel Clc-k on the mDCT plasma membrane, thereby increasing chloride efflux, which leads to compensatory chloride influx via NCC activation at the cost of increasing sodium influx.

Published
2016
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6. Emergency contraceptive pill (ECP) and sexual risk behaviour

Author

Susan Thornton, Kavita Dass, Jessica Webber, and Simon Dupont

Subjects
Adult, medicine.medical_specialty, Pediatrics, Unprotected Sexual Intercourse, Sexual Behavior, education, Sexually Transmitted Diseases, HIV Infections, Dermatology, law.invention, Condoms, fluids and secretions, Risk-Taking, Condom, law, Surveys and Questionnaires, Epidemiology, Medicine, Humans, Pharmacology (medical), Risk factor, Contraception Behavior, Sexual risk, Contraceptives, Postcoital, Reproductive health, Pregnancy, business.industry, Public Health, Environmental and Occupational Health, medicine.disease, Infectious Diseases, Attitude, Family medicine, Pill, Female, business
Abstract

The study describes a cross-section of women using the emergency contraceptive pill (ECP), with regard to demographics, ECP use, sexual health, sexually transmitted infection (STI)/HIV risk perception and attitudes to condom use. All women attending a London hospital for the ECP over a four-month period were invited to complete a 30-item questionnaire anonymously. Of the 150 women attending, 88 (59%) took part. Over 60% needed the ECP because of unprotected sexual intercourse (UPSI). A third had had UPSI in the previous three months, 70% had used ECP previously. The vast majority (>95%) did not think they were at high risk of STIs or HIV infection, and though the most likely explanations for UPSI were that it is more enjoyable and that people get 'carried away'. There are concerns that women are using the ECP as a form of contraception and are putting themselves at risk of STIs and HIV infection. Information regarding risk behaviour needs to be routinely given with the ECP in order to avoid further large increases in infection.

Published
2002

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