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AnteayerPLOS ONE Medicine&Health

Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in the Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD): Trial protocol and rationale of an open-label pragmatic, prospective randomized controlled

by Sonal Singh, Noelle M. Cocoros, Xiaojuan Li, Kathleen M. Mazor, Mary T. Antonelli, Lauren Parlett, Mark Paullin, Thomas P. Harkins, Yunping Zhou, Paula A. Rochon, Richard Platt, Inna Dashevsky, Carly Massino, Cassandra Saphirak, Sybil L. Crawford, Jerry H. Gurwitz

Context

Potentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, “light touch”, approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia.

Objectives

The objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics.

Methods

The D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes.

Conclusion

This large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia.ClinicalTrials.gov Identifier: NCT05147428.

Hepatitis E virus infections among patients with acute febrile jaundice in two regions of Cameroon: First molecular characterization of hepatitis E virus genotype 4

by Abdou Fatawou Modiyinji, Lange Tchamba Amorgathe Tankeu, Chavely Gwladys Monamele, Moise Henri Yifomnjou Moumbeket, Paul Alain Tagnouokam Ngoupo, Huguette Tchetgna Simo, Abanda Njei Ngu, Kazanji Mirdad, Richard Njouom

Background

Febrile jaundice is a common indicator of certain infectious diseases, including hepatitis E. In Cameroon, the yellow fever virus is the only pathogen that is monitored in patients who present with this symptom. However, more than 90% of the samples received as part of this surveillance are negative for yellow fever. This study aimed to describe the prevalence and hepatitis E virus (HEV) genotype among yellow fever-negative patients in the Far North and West regions of Cameroon.

Methods

In a cross-sectional study, yellow fever surveillance-negative samples collected between January 2021 and January 2023 were retrospectively analyzed. Anti-HEV IgM and IgG antibodies were tested using commercially available ELISA kits. Anti-HEV IgM and/or IgG positive samples were tested for HEV RNA by real-time RT-PCR, followed by nested RT-PCR, sequencing and phylogenetic analysis.

Results

Overall, 121 of the 543 samples (22.3%, 95% CI: 19.0% - 26.0%) were positive for at least one anti-HEV marker. Amongst these, 8.1% (44/543) were positive for anti-HEV IgM, 5.9% (32/543) for anti-HEV IgG, and 8.3% (45/544) for both markers. A total of 15.2% (12/79) samples were positive for HEV RNA real-time RT-PCR and 8 samples were positive for HEV RNA by nested RT-PCR. Phylogenetic analysis showed that the retrieved sequences clustered within HEV genotypes/subtypes 1/1e, 3/3f and 4/4b.

Conclusion

Our results showed that HEV is one of the causes of acute febrile jaundice in patients enrolled in the yellow fever surveillance program in two regions of Cameroon. We described the circulation of three HEV genotypes, including two zoonotic genotypes. Further studies will be important to elucidate the transmission routes of these zoonotic HEV genotypes to humans in Cameroon.

Allogeneic limbo-deep anterior lamellar keratoplasty (Limbo-DALK)—A novel surgical technique in corneal stromal disease and limbal stem cell deficiency

by Verena Schöneberger, Volkan Tahmaz, Mario Matthaei, Sigrid Roters, Simona L. Schlereth, Friederike Schaub, Claus Cursiefen, Björn O. Bachmann

Purpose

To describe a novel corneal surgical technique combining Deep Anterior Lamellar Keratoplasty (DALK) with grafting of allogeneic limbus (Limbo-DALK) for the treatment of eyes with corneal stromal pathology and limbal stem cell deficiency (LSCD).

Methods

Clinical records of six Limbo-DALKs performed in five patients diagnosed with LSCD and corneal stromal pathology requiring keratoplasty were retrospectively reviewed. All patients were diagnosed with LSCD due to various pathologies including thermal and chemical burns, congenital aniridia or chronic inflammatory ocular surface disease. Parameters analysed included demographics, diagnoses, clinical history, thickness measurements using anterior segment OCT, visual acuity, and epithelial status. Regular follow-up visits were scheduled at 6 weeks as well as 3, 6, 9, and 12 and 18 months postoperatively. Main outcome measures were time to graft epithelialisation and the occurrence of corneal endothelial decompensation.

Results

Two grafts showed complete epithelial closure at 2 days, two at 14 days. In one eye, complete epithelial closure was not achieved after the first Limbo-DALK, but was achieved one month after the second Limbo-DALK. No endothelial decompensation occurred except in one patient with silicone oil associated keratopathy. Endothelial graft rejection was not observed in any of the grafts.

Conclusion

Based on the data from this pilot series, limbo-DALK appears to be a viable surgical approach for eyes with severe LSCD and corneal stromal pathology, suitable for emergency situations (e.g. corneal ulceration with impending corneal perforation), while minimising the risk of corneal endothelial decompensation.

Ceragenin-mediated disruption of <i>Pseudomonas aeruginosa</i> biofilms

by Urszula Wnorowska, Dawid Łysik, Ewelina Piktel, Magdalena Zakrzewska, Sławomir Okła, Agata Lesiak, Jakub Spałek, Joanna Mystkowska, Paul B. Savage, Paul Janmey, Krzysztof Fiedoruk, Robert Bucki

Background

Microbial biofilms, as a hallmark of cystic fibrosis (CF) lung disease and other chronic infections, remain a desirable target for antimicrobial therapy. These biopolymer-based viscoelastic structures protect pathogenic organisms from immune responses and antibiotics. Consequently, treatments directed at disrupting biofilms represent a promising strategy for combating biofilm-associated infections. In CF patients, the viscoelasticity of biofilms is determined mainly by their polymicrobial nature and species-specific traits, such as Pseudomonas aeruginosa filamentous (Pf) bacteriophages. Therefore, we examined the impact of microbicidal ceragenins (CSAs) supported by mucolytic agents–DNase I and poly-aspartic acid (pASP), on the viability and viscoelasticity of mono- and bispecies biofilms formed by Pf-positive and Pf-negative P. aeruginosa strains co-cultured with Staphylococcus aureus or Candida albicans.

Methods

The in vitro antimicrobial activity of ceragenins against P. aeruginosa in mono- and dual-species cultures was assessed by determining minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). Inhibition of P. aeruginosa mono- and dual-species biofilms formation by ceragenins alone and in combination with DNase I or poly-aspartic acid (pASP) was estimated by the crystal violet assay. Additionally, the viability of the biofilms was measured by colony-forming unit (CFU) counting. Finally, the biofilms’ viscoelastic properties characterized by shear storage (G’) and loss moduli (G”), were analyzed with a rotational rheometer.

Results

Our results demonstrated that ceragenin CSA-13 inhibits biofilm formation and increases its fluidity regardless of the Pf-profile and species composition; however, the Pf-positive biofilms are characterized by elevated viscosity and elasticity parameters.

Conclusion

Due to its microbicidal and viscoelasticity-modifying properties, CSA-13 displays therapeutic potential in biofilm-associated infections, especially when combined with mucolytic agents.

Therapeutic interventions on human breast cancer xenografts promote systemic dissemination of oncogenes

by Gorantla V. Raghuram, Kavita Pal, Gaurav Sriram, Afzal Khan, Ruchi Joshi, Vishalkumar Jadhav, Sushma Shinde, Alfina Shaikh, Bhagyeshri Rane, Harshada Kangne, Indraneel Mittra

Metastatic dissemination following successful treatment of the primary tumour remains a common cause of death. There is mounting evidence that therapeutic interventions themselves may promote development of metastatic disease. We earlier reported that cell-free chromatin particles (cfChPs) released from dying cancer cells are potentially oncogenic. Based on this observation we hypothesized that therapeutic interventions may lead to the release of cfChPs from therapy induced dying cancer cells which could be carried via the blood stream to distant organs to transform healthy cells into new cancers that would masquerade as metastasis. To test this hypothesis, we generated xenografts of MDA-MB-231 human breast cancer cells in severe combined immune-deficient mice, and using immuno-fluorescence and FISH analysis looked for cfChPs in their brain cells. We detected multiple human DNA signals representing cfChPs in nuclei of brain cells of mice which co-localized with eight human onco-proteins. No intact MDA-MB-231 cells were detected. The number of co-localizing human DNA and human c-Myc signals increased dramatically following treatment with chemotherapy, localized radiotherapy or surgery, which could be prevented by concurrent treatment with three different cfChPs deactivating agents. These results suggest that therapeutic interventions lead to the release cfChPs from therapy induced dying cancer cells carrying oncogenes and are transported via the blood stream to brain cells to potentially transform them to generate new cancers that would appear as metastases. cfChPs induced metastatic spread of cancer is preventable by concurrent treatment with agents that deactivate cfChPs.

Cost-effectiveness analysis of olaparib maintenance therapy for BRCA mutation ovarian cancer in the public sector in Malaysia

by Chee Meng Yong, Prathepamalar A. P. Yehgambaram, Shaun Wen Huey Lee

Introduction

Ovarian cancer is one of the most common cancer among women in Malaysia. Patients with ovarian cancer are often diagnosed at an advanced stage. Despite initial response to surgery and chemotherapy, most patients will experience a relapse. Olaparib has been reported have promising effects among BRCA mutated ovarian cancer patients. This study aimed to evaluate the cost–effectiveness of olaparib as a maintenance therapy for BRCA ovarian cancer in Malaysia.

Methods

We developed a four-state partitioned survival model which compared treatment with olaparib versus routine surveillance (RS) from a Malaysian healthcare perspective. Mature overall survival (OS) data from the SOLO-1 study were used and extrapolated using parametric models. Medication costs and healthcare resource usage costs were derived from local inputs and publications. Deterministic and probabilistic sensitivity analyses (PSA) were performed to explore uncertainties.

Results

In Malaysia, treating patients with olaparib was found to be more costly compared to RS, with an incremental cost of RM149,858 (USD 33,213). Patients treated with olaparib increased life years by 3.05 years and increased quality adjusted life years (QALY) by 2.76 (9.45 years vs 6.40 years; 7.62 vs 4.86 QALY). This translated to an incremental cost-effectiveness ratio (ICER) of RM 49,159 (USD10,895) per life year gained and RM54,357 (USD 12,047) per QALY gained, respectively. ICERs were most sensitive to time horizon of treatment, discount rate for outcomes, cost of treatment and health state costs, but was above the RM53,770/QALY threshold.

Conclusion

The use of olaparib is currently not a cost-effective strategy compared to routine surveillance based upon the current price in Malaysia for people with ovarian cancer with BRCA mutation, despite the improvement in overall survival.

Creating a psychosocial intervention combining growth mindset and implementation intentions (GMII) to reduce alcohol consumption: A mixed method approach

by Sacha Parada, Bérengère Rubio, Elsa Taschini, Xavier Laqueille, Malika El Youbi, Pierre Paris, Bernard Angerville, Alain Dervaux, Jean-François Verlhiac, Eve Legrand

This work aimed at creating a psychosocial intervention based on growth mindset theory and implementation intention strategies, in order to reduce alcohol consumption among users in the general population, and the clinical population of individuals with alcohol use disorder. A mixed method approach was used, combining qualitative and quantitative research methods among both populations. Four focus groups were first conducted to extract arguments in favor of a malleable view of alcohol consumption (study 1A), situations that trigger the desire to drink alcohol, as well as strategies used by people to counteract this need (study 1B). Data were analyzed using reflective thematic analysis in line with the scientific literature on alcohol consumption. The results were used to create a questionnaire scoring the relevance of each argument, situation and strategy (study 2). The 20 best scored arguments, situations and strategies were selected to create the intervention. The created intervention consisted in a popularized scientific article describing alcohol consumption as malleable, including the selected arguments and followed by two internalization exercises. Then, a volitional help sheet included the selected situations and solutions was presented, allowing forming up to three plans. The discussion focused on the added value of the created material compared to pre-existing tools in the literature, and presents plans to test the intervention in a future study.

Assessing the basic knowledge and awareness of dengue fever prevention among migrant workers in Klang Valley, Malaysia

by Maryam N. Chaudhary, Voon-Ching Lim, Erwin Martinez Faller, Pramod Regmi, Nirmal Aryal, Siti Nursheena Mohd Zain, Adzzie Shazleen Azman, Norhidayu Sahimin

Background

Globally, 390 million dengue virus infections occur per year. In Malaysia, migrant workers are particularly vulnerable to dengue fever (DF) due to mosquito breeding sites exposure and poor health literacy. Therefore, this study aimed to (i) assess the current DF knowledge, attitudes and practices (KAP), and (ii) identify strategies to promote DF awareness, among migrant workers in Klang Valley.

Method

A survey was conducted with 403 Nepali, Filipino and Indonesian migrant workers through phone interviews and online self-administered questionnaires. Piecewise structural equation modelling was applied to identify predictor variables for DF KAP.

Results

Most respondents were male, working in the services industry, had completed high school, aged between 30–39 years and with less than ten years work experience in Malaysia. Overall, respondents’ knowledge was positively correlated with attitude but negatively with practices. Older respondents, who had completed higher education, obtained higher knowledge scores. Similarly, those with working experience of >20 years in Malaysia obtained higher attitude scores. Respondents with a previous history of DF strongly considered the removal of mosquito breeding sites as their own responsibility, hence tended to frequently practise DF preventive measures. Respondents’ knowledge was also positively correlated to their understanding of DF information sourced from social media platforms.

Conclusion

These findings highlighted: (i) the need for targeted DF educational intervention among younger and newly arrived workers with lower levels of education and (ii) maximising the usage of social media platforms to improve DF public awareness.

Factors associated with pressure ulcer and dehydration in long-term care settings in Ontario, Canada

by Mary Crea-Arsenio, Andrea Baumann, Valentina Antonipillai, Noori Akhtar-Danesh

Pressure ulcers and dehydration are common conditions among residents of long-term care facilities that result in negative health effects. They have been associated with signs of neglect and increased 30-day mortality among LTC residents. However, they are both preventable and with proper care can be effectively managed and treated. We conducted a retrospective cohort study to examine factors associated with pressure ulcers and dehydration among long-term care residents in the province of Ontario, Canada. Results indicated that close to one-fifth of residents were dehydrated (17.3%) or had a pressure ulcer (18.9%) during the study period. Advanced age was significantly associated with the presence of pressure ulcers and dehydration for both men and women. However, men were more likely to present with a pressure ulcer while women were more likely to exhibit symptoms of dehydration. Study findings also demonstrate the presence of both conditions being higher in municipal and not-for-profit homes compared to for-profit homes. The significant differences observed in relation to home ownership which require further investigation to identify the most relevant factors in explaining these differences. Overall, pressure ulcers and dehydration are preventable conditions that warrant attention from policymakers to ensure quality of care and resident safety are prioritized.

Non-invasive cumulus cell analysis can be applied for oocyte ranking and is useful for countries with legal restrictions on embryo generation or freezing

by Tom Adriaenssens, Inge Van Vaerenbergh, Lisbet Van Landuyt, Greta Verheyen, Michaël De Brucker, Michel Camus, Peter Platteau, Michel De Vos, Maria Reis, Elien Van Hecke, André Rosenthal, Johan Smitz

Research question

Can a strategy for scoring oocyte quality, based on cumulus cell (CC) gene expression, prioritize oocytes with the highest implantation potential, while limiting the number of embryos to be processed in culture and the number of supernumerary embryos to be vitrified?

Design

An interventional, blinded, prospective cohort study was retrospectively analyzed. In the original study, patients underwent a fresh Day3 single embryo transfer with embryos ranked based on morphology and CC gene expression (Aurora Test). The additional ranking of the embryos with the Aurora Test resulted in significant higher clinical pregnancy and live birth rates. Now it is investigated if the Aurora Test ranking could be applied to select oocytes. The effect of an Aurora Test based restriction to 2 and 3 2PN or MII oocytes on clinical pregnancy and other outcomes, was analyzed in two subsets of patients with all 2PN (n = 83) or all MII oocytes (n = 45) ranked.

Results

Considering only the top three ranked 2PN oocytes, 95% of the patients would have received a fresh SET on Day3 resulting in 65% clinical pregnancies. This was not different from the pregnancy rate obtained in a strategy using all oocytes but significantly reduced the need for vitrification of supernumerary embryos by 3-fold. Considering only top-ranked MII oocytes gave similar results.

Conclusions

In countries with legal restrictions on freezing of embryos, gene expression of CC can be used for the selective processing of oocytes and would thus decrease the twin pregnancy rate and workload, especially for embryo morphology scoring and transfers as the handling and processing of lower competence oocytes is prevented, while improving the ART outcome.

Characterization and comparison of human and mouse milk cells

by Rose Doerfler, Saigopalakrishna Yerneni, Alexandra Newby, Namit Chaudhary, Ashley Shu, Katherine Fein, Juliana Hofstatter Azambuja, Kathryn A. Whitehead

Recent data has characterized human milk cells with unprecedented detail and provided insight into cell populations. While such analysis of freshly expressed human milk has been possible, studies of cell functionality within the infant have been limited to animal models. One commonly used animal model for milk research is the mouse; however, limited data are available describing the composition of mouse milk. In particular, the maternal cells of mouse milk have not been previously characterized in detail, in part due to the difficulty in collecting sufficient volumes of mouse milk. In this study, we have established a method to collect high volumes of mouse milk, isolate cells, and compare the cell counts and types to human milk. Surprisingly, we found that mouse milk cell density is three orders of magnitude higher than human milk. The cell types present in the milk of mice and humans are similar, broadly consisting of mammary epithelial cells and immune cells. These results provide a basis of comparison for mouse and human milk cells and will inform the most appropriate uses of mouse models for the study of human phenomena.

Preference of cesarean delivery and its associated factors among pregnant women attending ante natal care at public health facilities of Debrebrehan City, Ethiopia: Cross-sectional study

by Lemlem Zewudu, Fetene Keshaun, Mulualem Silesh, Mitiku Tefera, Eyob Ketema Bogale, Aberham Demis, Zewedie Yeshaw Tekle

Background

A Caesarean section is a surgical procedure used to prevent or treat life-threatening maternal or fetal complications. Women’s delivery preferences have become a global issue of interest to many researchers and clinicians, especially given the ever-increasing rate of cesarean sections. There is limited data on the preference for cesarean delivery and its associated factors for Ethiopian women, particularly in the study area. The aim of the study is to assess the preference for cesarean delivery and its associated factors among pregnant women attending antenatal care at public health facilities in Debre Berhan, Ethiopia, in 2023.

Methods

An institution-based cross-sectional study design was done from May 5–20, 2023, among 512 participants, and a multi-stage sampling technique was used. The data were collected by using interviewer-administered semi-structured questionnaires. The data were entered by Epi Data version 4.6 and then transferred to SPSS version 25 for analysis. With logistic regression, those variables with a p-value Result

The preference for a cesarean section was 26%, with a CI of 22.3% to 29.9%. Pregnant mothers who were not satisfied with their previous intrapartum care (AOR; 6.3 CI = (3.5–11), P = 0.01), had no knowledge about cesarean delivery (AOR; 2.9; 95% CI = 1.6–5.3), P = 0.01), had a previous history of spontaneous abortion (AOR; 3.1; 95% CI = (1.5–6.3), P = 0.001), lived in an urban area (AOR; 1.9; 95% CI = (1.0–3.5), P = 0.038), and had a current pregnancy-related problem (AOR; 4.8; 95% CI = 1.9–10), P = 0.001) were significantly associated with the preference for cesarean delivery.

Conclusion

In this study, the preference for cesarean delivery was high as compared to the World Health Organization recommendation. Pregnant mothers who were not satisfied with their previous intrapartum care, had no knowledge about cesarean delivery, had a previous history of spontaneous abortion, had an urban residence, and had a current pregnancy-related problem were significantly associated with a preference for caesarean delivery. Clinicians who are working in the delivery room should improve their service provision by using patient-centered care to increase patient satisfaction.

Supporting regional pandemic management by enabling self-service reporting—A case report

by Richard Gebler, Martin Lehmann, Maik Löwe, Mirko Gruhl, Markus Wolfien, Miriam Goldammer, Franziska Bathelt, Jens Karschau, Andreas Hasselberg, Veronika Bierbaum, Toni Lange, Katja Polotzek, Hanns-Christoph Held, Michael Albrecht, Jochen Schmitt, Martin Sedlmayr

Background

The COVID-19 pandemic revealed a need for better collaboration among research, care, and management in Germany as well as globally. Initially, there was a high demand for broad data collection across Germany, but as the pandemic evolved, localized data became increasingly necessary. Customized dashboards and tools were rapidly developed to provide timely and accurate information. In Saxony, the DISPENSE project was created to predict short-term hospital bed capacity demands, and while it was successful, continuous adjustments and the initial monolithic system architecture of the application made it difficult to customize and scale.

Methods

To analyze the current state of the DISPENSE tool, we conducted an in-depth analysis of the data processing steps and identified data flows underlying users’ metrics and dashboards. We also conducted a workshop to understand the different views and constraints of specific user groups, and brought together and clustered the information according to content-related service areas to determine functionality-related service groups. Based on this analysis, we developed a concept for the system architecture, modularized the main services by assigning specialized applications and integrated them into the existing system, allowing for self-service reporting and evaluation of the expert groups’ needs.

Results

We analyzed the applications’ dataflow and identified specific user groups. The functionalities of the monolithic application were divided into specific service groups for data processing, data storage, predictions, content visualization, and user management. After composition and implementation, we evaluated the new system architecture against the initial requirements by enabling self-service reporting to the users.

Discussion

By modularizing the monolithic application and creating a more flexible system, the challenges of rapidly changing requirements, growing need for information, and high administrative efforts were addressed.

Conclusion

We demonstrated an improved adaptation towards the needs of various user groups, increased efficiency, and reduced burden on administrators, while also enabling self-service functionalities and specialization of single applications on individual service groups.

Intimate partner violence and excess fertility among women of reproductive age in Malawi

by Sufia Dadabhai, Laura Quaynor, Antonio Bandala-Jacques, Linly Seyama, Md Hafizur Rahman, Richard Phiri, Michele R. Decker, Taha E. Taha

Purpose

Gender inequity and adverse health outcomes continue to be of concern among women in sub-Saharan Africa. We determined prevalence of intimate partner violence and excess fertility (having more children than desired) in reproductive age women in Malawi. We also explored factors associated with these outcomes and with spousal fertility intentions.

Patients and methods

In a cross-sectional study, a total of 360 women and 410 men were recruited using multi-stage sampling from communities in a peri-urban setting in Blantyre District, Southern Malawi in 2021. Women and men were separately interviewed by trained study workers using a structured questionnaire. In addition to descriptive analyses, we used univariate and multivariate logistic regression models to assess associations of risk factors with the outcomes of intimate partner violence and excess fertility.

Results

Among women, lifetime prevalence of intimate partner violence was 23.1%, and excess fertility was experienced by 25.6%. Intimate partner violence was associated with male partners alcohol consumption (adjusted odds ratio 2.13; P = 0.019). Women were more likely to report excess fertility if they were older (adjusted odds ratio 2.0, P Conclusions

Intimate partner violence, excess fertility, and social and health inequities continue to be prevalent in Malawi. These data suggest the underlying proximal and distal factors associated with these adverse outcomes such as alcohol consumption may be addressed through education, couple interactive communication, and community dialogue. To ensure sustainability and effectiveness, strong leadership involvement, both governmental and non-governmental, is needed.

Incidence, pathogens and antimicrobial resistance of blood and cerebrospinal fluid isolates from a tertiary neonatal unit in South Africa: A 10 year retrospective review

by Reenu Thomas, Claude Ondongo-Ezhet, Nini Motsoaledi, Mike Sharland, Michelle Clements, Sithembiso Velaphi

Objective

To determine trends in incidence, etiology and antimicrobial susceptibility of blood and cerebrospinal fluid (CSF) culture confirmed infections in hospitalized infants in a large tertiary neonatal unit in South Africa.

Methods

Single-center, retrospective review of laboratory records of bacteria and fungi, and their susceptibility profiles, isolated from blood and CSF of infants hospitalized in the neonatal unit at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from 1st January 2010 to 31st December 2019. Laboratory data on isolates and their antimicrobial susceptibilities were collected. Coagulase-negative Staphylococcus, Corynebacteria and Bacillus spp. were excluded. Patient-level clinical and laboratory data were not available.

Results

There were 8,319 significant isolates, giving an infection rate of 14.3/1000 patient-days. Infection rates increased from 12.0 to 15.7/1000 patient-days (estimated average yearly change 0.6[95%CI, 0.5–0.7];p = Acinetobacter baumannii (44%) and Klebsiella pneumoniae (39%). Carbapenem resistance was seen in 31% of all Gram-negatives and increased over time (estimated average yearly change 4.8%[95%CI,4.2%-5.3%];pStaphylococcus aureus was the most common Gram-positive isolated. Rates of methicillin-resistant Staphylococcus aureus decreased from 91% to 55%(estimated average yearly change -2.8%[95%CI,-3.5%–2%],pCandida parapsilosis (52%) and Candida albicans (35%) were the most common fungi isolated.

Conclusions

There has been a marked overall increase in rates of blood and/or CSF infections, with an absolute increase in Gram-negative infections observed, replacing Gram-positive and fungal pathogens. Extended spectrum beta-lactamase Gram-negative isolates are being replaced by carbapenem resistance, with around one third of all significant Gram-negative isolates now carbapenem resistant. Research into hospital based novel treatment and prevention interventions for neonatal sepsis should be urgently prioritized.

Implementation of antimicrobial stewardship programs: A study of prescribers’ perspective of facilitators and barriers

by Emelda E. Chukwu, Dennis Abuh, Ifeoma E. Idigbe, Kazeem A. Osuolale, Vivian Chuka-Ebene, Oluwatoyin Awoderu, Rosemary A. Audu, Folasade T. Ogunsola

Background

Despite promising signs of the benefits associated with Antimicrobial Stewardship Programs (ASPs), there remains limited knowledge on how to implement ASPs in peculiar settings for a more elaborate impact. This study explored prescriber experiences and perceptions of the usefulness, and feasibility of strategies employed for the implementation of antimicrobial stewardship (AMS) interventions as well as challenges encountered.

Methods

This is a cross-sectional mixed-method survey of prescribers’ perspective of the facilitators and barriers of implementing ASP. The quantitative approach comprised of a semi-structured questionnaire and data collected were analyzed using SPSS version 26 while the qualitative approach used focus group discussions followed by content analysis.

Results

Out of the thirty people that participated in the workshop, twenty-five completed the questionnaires which were analyzed. The respondents included 15 (60.0%) medical doctors and 10 (40.0%) pharmacists. The mean age of the respondents was 36.39±7.23 years with mean year of practice of 9.48±6.01 years. Majority of them (84.0%) were in a position to provide input on the implementation of AMS in their facilities, although their managements had the final decision. The pharmacists (100%) were more likely to agree that antibiotic resistance was a problem for their practice than the medical doctors (78.6%) while equal number (80.0%) of respondents (pharmacists and medical doctors) believed that inappropriate prescribing was a problem. Having a specialized and dedicated team with effective monitoring was recognized as crucial for effective ASP while inadequate personnel was identified as a major barrier. We identified stakeholder’s engagement, policies and regulation, as well as education as themes for improving AMS in the country.

Conclusion

The results gave insight into the prescribers’ perspective on the facilitators and barriers to antimicrobial stewardship; challenges and possible solutions to implementing ASPs in health facilities in Lagos State. We further identified pertinent contextual factors that need to be addressed when developing ASPs in healthcare facilities in a resource-poor setting.

Primary care quality for older adults: Practice-based quality measures derived from a RAND/UCLA appropriateness method study

by Rebecca H. Correia, Darly Dash, Aaron Jones, Meredith Vanstone, Komal Aryal, Henry Yu-Hin Siu, Aquila Gopaul, Andrew P. Costa

We established consensus on practice-based metrics that characterize quality of care for older primary care patients and can be examined using secondary health administrative data. We conducted a two-round RAND/UCLA Appropriateness Method (RAM) study and recruited 10 Canadian clinicians and researchers with expertise relevant to the primary care of elderly patients. Informed by a literature review, the first RAM round evaluated the appropriateness and importance of candidate quality measures in an online questionnaire. Technical definitions were developed for each endorsed indicator to specify how the indicator could be operationalized using health administrative data. In a virtual synchronous meeting, the expert panel offered feedback on the technical specifications for the endorsed indicators. Panelists then completed a second (final) questionnaire to rate each indicator and corresponding technical definition on the same criteria (appropriateness and importance). We used statistical integration to combine technical expert panelists’ judgements and content analysis of open-ended survey responses. Our literature search and internal screening resulted in 61 practice-based quality indicators for rating. We developed technical definitions for indicators endorsed in the first questionnaire (n = 55). Following the virtual synchronous meeting and second questionnaire, we achieved consensus on 12 practice-based quality measures across four Priority Topics in Care of the Elderly. The endorsed indicators provide a framework to characterize practice- and population-level encounters of family physicians delivering care to older patients and will offer insights into the outcomes of their care provision. This study presented a case of soliciting expert feedback to develop measurable practice-based quality indicators that can be examined using administrative data to understand quality of care within population-based data holdings. Future work will refine and operationalize the technical definitions established through this process to examine primary care provision for older adults in a particular context (Ontario, Canada).

Clinical evaluation of a fully electronic microfluidic white blood cell analyzer

by Jianye Sui, Zhongtian Lin, Shahriar Azizpour, Fei Chen, Sunanda Gaur, Kelly Keene, Farzad Soleimani, Tanaya Bhowmick, Zubaid Rafique, Mehdi Javanmard

The White Blood Cell (WBC) count is one of the key parameters signaling the health of the immune system. Abnormal WBC counts often signal a systemic insult to the body such as an underlying infection or an adverse side effect to medication. Typically, the blood collected is sent to a central lab for testing, and results come back within hours, which is often inconvenient and may delay time-sensitive diagnosis or treatment. Here, we present the CytoTracker, a fully electronic, microfluidic based instant WBC analyzer with the potential to be used at point-of-care. The CytoTracker is a lightweight, portable, affordable platform capable of quantifying WBCs within minutes using only 50 μl of blood (approximately one drop of blood). In this study, we clinically evaluated the accuracy and performance of CytoTracker in measuring WBC and granulocyte counts. A total of 210 adult patients were recruited in the study. We validated the CytoTracker against a standard benchtop analyzer (Horiba Point of Care Hematology Analyzer, ABX Micros 60). Linear dynamic ranges of 2.5 k/μl– 35 k/μl and 0.6 k/μl– 26 k/μl were achieved for total WBC count and granulocyte count with correlation coefficients of 0.97 and 0.98. In addition, we verified CytoTracker’s capability of identifying abnormal blood counts with above 90% sensitivity and specificity. The promising results of this clinical validation study demonstrate the potential for the use of the CytoTracker as a reliable and accurate point-of-care WBC analyzer.

Sleep and cognition in South African patients with non-functioning pituitary adenomas

by Olivia de Villiers, Claudia Elliot-Wilson, Kevin G. F. Thomas, Patrick L. Semple, Thurandrie Naiker, Michelle Henry, Ian L. Ross

Strong lines of evidence in the neuroscience literature indicate that (a) healthy sleep facilitates cognitive processing, and (b) sleep disruption is associated with cognitive dysfunction. Despite the fact that patients with pituitary disease often display both disrupted sleep and cognitive dysfunction, few previous studies investigate whether these clinical characteristics in these patients might be related. Hence, we explored whether sleep disruption in patients with pituitary disease mediates their cognitive dysfunction. We recruited 18 patients with non-functioning pituitary adenomas (NFPA) and 19 sociodemographically matched healthy controls. They completed the Global Sleep Assessment Questionnaire (thus providing self-report data regarding sleep disruption) and were administered the Brief Test of Adult Cognition by Telephone, which assesses cognitive functioning in the domains of processing speed, working memory, episodic memory, inhibition, and reasoning. We found no significant differences in cognition between patients and controls. Furthermore, spectra of sleep disturbance did not differ significantly between patients and controls. Our data suggest that NFPA patients’ cognition and sleep quality is relatively intact, and that sleep disruption does not mediate cognitive dysfunction. Larger studies should characterize sleep and cognition in patients with NFPA (and other pituitary diseases) to confirm whether disruption of the former mediates impairment in the latter.

<i>Metarhizium</i> spp. isolates effective against Queensland fruit fly juvenile life stages in soil

by Madita Prince, Aimee C. McKinnon, Diana Leemon, Tim Sawbridge, John Paul Cunningham

Queensland fruit fly, Bactrocera tryoni, Froggatt (Diptera: Tephritidae) is Australia’s primary fruit fly pest species. Integrated Pest Management (IPM) has been adopted to sustainably manage this polyphagous species with a reduced reliance on chemical pesticides. At present, control measures are aimed at the adult stages of the fly, with no IPM tools available to target larvae once they exit the fruit and pupate in the soil. The use of entomopathogenic fungi may provide a biologically-based control method for these soil-dwelling life stages. The effectiveness of fungal isolates of Metarhizium and Beauveria species were screened under laboratory conditions against Queensland fruit fly. In bioassays, 16 isolates were screened for pathogenicity following exposure of third-instar larvae to inoculum-treated vermiculite used as a pupation substrate. The best performing Metarhizium sp. isolate achieved an average percentage mortality of 93%, whereas the best performing Beauveria isolate was less efficient, with an average mortality of 36%. Susceptibility to infection during different development stages was investigated using selected fungal isolates, with the aim of assessing all soil-dwelling life stages from third-instar larvae to final pupal stages and emerging adults. Overall, the third larval instar was the most susceptible stage, with average mortalities between 51–98% depending on the isolate tested. Moreover, adult mortality was significantly higher when exposed to inoculum during pupal eclosion, with mortalities between 56–76% observed within the first nine days post-emergence. The effect of temperature and inoculum concentration on insect mortality were assessed independently with candidate isolates to determine the optimum temperature range for fungal biological control activity and the rate required for application in field conditions. Metarhizium spp. are highly efficacious at killing Queensland fruit fly and have potential for use as biopesticides to target soil-dwelling and other life stages of B. tryoni.
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