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The impacts of pandemics are recognized to go beyond infection, physical suffering, and socio-economic disruptions. Other consequences include psychological responses. Using a mental wellbeing lens, we analyzed COVID-19-related stressors in healthcare workers (HCWs) and community members who provided and regularly accessed health services in South Africa, respectively. From February to September 2021, during the second COVID-19 wave we conducted a qualitative study in one urban and one rural district. In-depth interviews and focus group discussions were used to collect data among 43 HCWs and 51 community members purposely and conveniently selected. Most participants experienced mental health challenges regarding multiple aspects of the COVID-19 pandemic and its resulting lockdown, with a few reporting positive adjustments to change. COVID-19 impacts on mental health were consistent among both HCWs and community members in urban and rural alike. Participants' COVID-19-induced psychological responses included anxiety and fear of the unknown, perceived risk of infection, fear of hospitalization, and fear of dying. Physical effects of the pandemic on participants included COVID-19 infection and associated symptoms, possibilities of severe illness and discomfort of using personal protective equipment. These distresses were exacerbated by social repercussions related to concerns for family wellbeing and infection stigma. Lockdown regulations also intensified anxieties about financial insecurities and social isolation. At times when common coping mechanisms such as family support were inaccessible, cultural consequences related to lack of spiritual gatherings and limited funeral rites posed additional stress on participants. In preparation for future public health emergencies, recognition needs to be given to mental health support and treatment.

Background: Live oral rotavirus vaccines (LORVs) have significantly reduced rotavirus hospitalizations and deaths worldwide. However, LORVs are less effective in low- and middle-income countries (LMICs). Next-generation rotavirus vaccines (NGRVs) may be more effective but require administration by injection or a neonatal oral dose, adding operational complexity. Healthcare providers (HPs) were interviewed to assess rotavirus vaccine preferences and identify delivery issues as part of an NGRV value proposition., Objective: Determine HP vaccine preferences about delivering LORVs compared to injectable (iNGRV) and neonatal oral (oNGRV) NGRVs., Methods: 64 HPs from Ghana, Kenya, Malawi, Peru, and Senegal were interviewed following a mixed-method guide centered on three vaccine comparisons: LORV vs. iNGRV; LORV vs. oNGRV; oNGRV vs. iNGRV. HPs reviewed attributes for each vaccine in the comparisons, then indicated and explained their preference. Additional questions elicited views about co-administering iNGRV+LORV for greater public health impact, a possible iNGRV-DTP-containing combination vaccine, and delivering neonatal doses., Results: Almost all HPs preferred oral vaccine options over iNGRV, with many emphasizing an aversion to additional injections. Despite this strong preference, HPs described challenges delivering oral doses. Preferences for LORV vs. oNGRV were split, marked by disparate views on rotavirus disease epidemiology and the safety, need, and feasibility of delivering neonatal vaccines. Although overwhelmingly enthusiastic about an iNGRV-DTP-containing combination option, several HPs had concerns. HP views were divided on the feasibility of co-administering iNGRV+LORV, citing challenges around logistics and caregiver sensitization., Conclusion: Our findings provide valuable insights on delivering NGRVs in routine immunization. Despite opposition to injectables, openness to co-administering LORV+iNGRV to improve efficacy suggests future HP support of iNGRV if adequately informed of its advantages. Rationales for LORV vs. oNGRV underscore needs for training on rotavirus epidemiology and stronger service integration. Expressed challenges delivering existing LORVs merit further examination and indicate need for improved delivery., Competing Interests: The authors have declared that no competing interests exist.

Exposure to fungi is inevitable, yet only a small number of patients with significant clinical risk develop invasive aspergillosis (IA). While timing of exposure in relation to immune status, environmental and occupational factors will influence the probability of developing IA, factors specific to the individual will likely play a role and variation in the host's genetic code associated with the immunological response to fungi have been linked to increased risk of developing IA. Screening for SNPs in genes significantly associated with IA (e.g. Pentraxin-3, Toll-like receptor 4, Dectin-1, DC-SIGN) could form part of the clinical work-up on admission or post allogeneic stem cell transplantation, to complement fungal biomarker screening. Through the combination of clinical and genetic risk with mycological evidence, we are approaching a time when we should be able to accurately predict the risk of IA in the haematology patient, using predictive modelling to stratifying each individual's management. Understanding the host and their immune responses to infection through genomics, transcriptomics and metabolomics/proteomics is critical to achieving how we manage the individual's risk of IA, underpinning personalized medicine. This review will investigate what is known about the genetic risk associated with developing IA, primarily in haematology patients and whether these strategies are ready to be incorporated into routine clinical practice, and if not what are the remaining hurdles to implementation., Competing Interests: PW: performed diagnostic evaluations and received meeting sponsorship from Bruker, Dynamiker, and Launch Diagnostics; received speaker fees, expert advice fees, and meeting sponsorship from Gilead; received speaker and expert advice fees from F2G and speaker fees MSD and Pfizer; and is a founding member of the European Aspergillus PCR Initiative. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 White and Price.)

Background/purpose: As survival rates for patients with congenital diaphragmatic hernia (CDH) increase, long-term sequelae become increasingly prevalent. We present the outcomes of patients who underwent CDH repair at our institution and discuss standardization of follow-up care in our long-term multidisciplinary follow-up clinic., Methods: A retrospective review of patients followed in multidisciplinary clinic after CDH repair at our institution from January 1, 2005 to December 1, 2020., Results: A total of 193 patients met inclusion criteria, 73 females (37.8%) and 120 males (62.2%). Left-sided defects were most common (75.7%), followed by right-sided defects (20.7%). Median age at repair was 4 days (IQR 3-6) and 59.6% of all defects required patch repair. Median length of stay was 29 days (IQR 16.8-50.0). Median length of follow up was 49 months (IQR 17.8-95.3) with 25 patients followed for more than 12 years. Long-term outcomes included gastroesophageal reflux disease (42.0%), diaphragmatic hernia recurrence (10.9%), asthma (23.6%), neurodevelopmental delay (28.6%), attention deficit hyperactivity disorder (7.3%), autism (1.6%), chest wall deformity (15.5%), scoliosis (11.4%), and inguinal hernia (6.7%)., Conclusion: As survival of patients with CDH improves, long-term care must be continuously studied and fine-tuned to ensure appropriate surveillance and optimization of long-term outcomes., (Copyright © 2021. Published by Elsevier Inc.)

Background: Currently available live, oral rotavirus vaccines (LORVs) have significantly reduced severe rotavirus hospitalizations and deaths worldwide. However, LORVs are not as effective in low- and middle-income countries (LMIC) where rotavirus disease burden is highest. Next-generation rotavirus vaccine (NGRV) candidates in development may have a greater public health impact where they are needed most. The feasibility and acceptability of possible new rotavirus vaccines were explored as part of a larger public health value proposition for injectable NGRVs in LMICs., Objective: To assess national stakeholder preferences for currently available LORVs and hypothetical NGRVs and understand rationales and drivers for stated preferences., Methods: Interviews were conducted with 71 national stakeholders who influence vaccine policy and national programming. Stakeholders from Ghana, Kenya, Malawi, Peru, Senegal, and Sri Lanka were interviewed using a mixed-method guide. Vaccine preferences were elicited on seven vaccine comparisons involving LORVs and hypothetical NGRVs based on information presented comparing the vaccines' attributes. Reasons for vaccine preference were elicited in open-ended questions, and the qualitative data were analyzed on key preference drivers., Results: Nearly half of the national stakeholders interviewed preferred a highly effective standalone, injectable NGRV over current LORVs. When presented as having similar efficacy to the LORV, however, very few stakeholders preferred the injectable NGRV, even at substantially lower cost. Similarly, a highly effective standalone injectable NGRV was generally not favored over an equally effective oral NGRV following a neonatal-infant schedule, despite higher cost of the neonatal option. An NGRV-DTP-containing combination vaccine was strongly preferred over all other options, whether delivered alone with efficacy similar to current LORVs or co-administered alongside an LORV (LORV + NGRV-DTP) to increase efficacy., Conclusion: Results from these national stakeholder interviews provide valuable insights to inform ongoing and future NGRV research and development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This multicenter study evaluated the IMMY Aspergillus Galactomannan Lateral Flow Assay (LFA) with automated reader for diagnosis of pulmonary aspergillosis in patients with COVID-19-associated acute respiratory failure (ARF) requiring intensive care unit (ICU) admission between 03/2020 and 04/2021. A total of 196 respiratory samples and 148 serum samples ( n  = 344) from 238 patients were retrospectively included, with a maximum of one of each sample type per patient. Cases were retrospectively classified for COVID-19-associated pulmonary aspergillosis (CAPA) status following the 2020 consensus criteria, with the exclusion of LFA results as a mycological criterion. At the 1.0 cutoff, sensitivity of LFA for CAPA (proven/probable/possible) was 52%, 80% and 81%, and specificity was 98%, 88% and 67%, for bronchoalveolar lavage fluid (BALF), nondirected bronchoalveolar lavage (NBL), and tracheal aspiration (TA), respectively. At the 0.5 manufacturer's cutoff, sensitivity was 72%, 90% and 100%, and specificity was 79%, 83% and 44%, for BALF, NBL and TA, respectively. When combining all respiratory samples, the receiver operating characteristic (ROC) area under the curve (AUC) was 0.823, versus 0.754, 0.890 and 0.814 for BALF, NBL and TA, respectively. Sensitivity and specificity of serum LFA were 20% and 93%, respectively, at the 0.5 ODI cutoff. Overall, the Aspergillus Galactomannan LFA showed good performances for CAPA diagnosis, when used from respiratory samples at the 1.0 cutoff, while sensitivity from serum was limited, linked to weak invasiveness during CAPA. As some false-positive results can occur, isolated results slightly above the recommended cutoff should lead to further mycological investigations.

Background: Recognising that the causes of over half the world's deaths pass unrecorded, the World Health Organization (WHO) leads development of Verbal Autopsy (VA): a method to understand causes of death in otherwise unregistered populations. Recently, VA has been developed for use outside research environments, supporting countries and communities to recognise and act on their own health priorities. We developed the Circumstances of Mortality Categories (COMCATs) system within VA to provide complementary circumstantial categorisations of deaths., Objectives: Refine the COMCAT system to (a) support large-scale population assessment and (b) inform public health decision-making., Methods: We analysed VA data for 7,980 deaths from two South African Health and Socio-Demographic Surveillance Systems (HDSS) from 2012 to 2019: the Agincourt HDSS in Mpumalanga and the Africa Health Research Institute HDSS in KwaZulu-Natal. We assessed the COMCAT system's reliability (consistency over time and similar conditions), validity (the extent to which COMCATs capture a sufficient range of key circumstances and events at and around time of death) and relevance (for public health decision-making)., Results: Plausible results were reliably produced, with 'emergencies', 'recognition, 'accessing care' and 'perceived quality' characterising the majority of avoidable deaths. We identified gaps and developed an additional COMCAT 'referral', which accounted for a significant proportion of deaths in sub-group analysis. To support decision-making, data that establish an impetus for action, that can be operationalised into interventions and that capture deaths outside facilities are important., Conclusions: COMCAT is a pragmatic, scalable approach enhancing functionality of VA providing basic information, not available from other sources, on care seeking and utilisation at and around time of death. Continued development with stakeholders in health systems, civil registration, community and research environments will further strengthen the tool to capture social and health systems drivers of avoidable deaths and promote use in practice settings.

Background: While the serological detection of (1→3)-β-D-glucan (BDG) can indicate invasive fungal disease (IFD), false positivity occurs. Nevertheless, the presence of BDG can still be recognized by the host's innate immune system and persistent BDG antigenemia, in the absence of IFD, can result in deleterious proinflammatory immune responses., Methods: During the XXX (INTENSE) study into the preemptive use of micafungin to prevent invasive candidiasis (IC) after abdominal surgery, the serum burden of BDG was determined to aid diagnosis of IC. Data from the INTENSE study were analyzed to determine whether BDG was associated with organ failure and patient mortality, while accounting for the influences of IC and antifungal therapy., Results: A BDG concentration >100 pg/mL was associated with a significantly increased Sequential Organ Failure Assessment score (≤100 pg/mL: 2 vs >100 pg/mL: 5; P < .0001) and increased rates of mortality (≤100 pg/mL: 13.7% vs >100 pg/mL: 39.0%; P = .0002). Multiple (≥2) positive results >100 pg/mL or a BDG concentration increasing >100 pg/mL increased mortality (48.1%). The mortality rate in patients with IC and a BDG concentration >100 pg/mL and ≤100 pg/mL was 42.3% and 25.0%, respectively. The mortality rate in patients without IC but a BDG concentration >100 pg/mL was 37.3%. The use of micafungin did not affect the findings., Conclusions: The presence of persistent or increasing BDG in the patient's circulation is associated with significant morbidity and mortality after abdominal surgery, irrespective of IC. The potential lack of a specific therapeutic focus has consequences when trying to manage these patients, and when designing clinical trials involving patients where host-associated BDG concentrations may be elevated., Clinical Trials Registration: NCT01122368., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Pregnancy-related health services, an important mediator of global health priorities, require robust health infrastructure. We described pregnancy-related healthcare utilisation among rural South African women from 1993 to 2018, a period of social, political and economic transition., Methods: We included participants enrolled in the Agincourt Health and Socio-Demographic Surveillance System in Mpumalanga Province, South Africa, a population-based longitudinal cohort, who reported pregnancy between 1993 and 2018. We assessed age, antenatal visits, years of education, pregnancy intention, nationality, residency status, previous pregnancies, prepregnancy and postpregnancy contraceptive use, and student status over the study period and modelled predictors of antenatal care utilisation (ordinal), skilled birth attendant presence (logistic) and delivery at a health facility (logistic)., Results: Between 1993 and 2018, 51 355 pregnancies occurred. Median antenatal visits, skilled birth attendant presence and healthcare facility deliveries increased over time. Delivery in 2018 vs 2004 was associated with an increased likelihood of ≥1 additional antenatal visits (adjusted OR (aOR) 10.81, 95% CI 9.99 to 11.71), skilled birth attendant presence (aOR 4.58, 95% CI 3.70 to 5.67) and delivery at a health facility (aOR 3.78, 95% CI 3.15 to 4.54). Women of Mozambican origin were less likely to deliver with a skilled birth attendant (aOR 0.42, 95% CI 0.39 to 0.45) or at a health facility (aOR 0.43, 95% CI 0.41 to 0.46) versus South Africans. Temporary migrants reported fewer antenatal visits (aOR 0.35, 95% CI 0.33 to 0.38) but were more likely to deliver with a skilled birth attendant (aOR 1.91, 95% CI 1.66 to 2.2) or at a health facility (aOR 1.4, 95% CI 1.24 to 1.58) versus permanent residents., Conclusion: Pregnancy-related healthcare utilisation and skilled birth attendant presence at delivery have increased steadily since 1993 in rural northeastern South Africa, aligning with health policy changes enacted during this time. However, mothers of Mozambican descent are still less likely to use free care, which requires further study and policy interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: This study aimed to better understand reasons why children in South Africa die at home, including caregivers' care-seeking experiences, decision-making, choice of treatment provider and barriers to accessing care during a child's final illness., Design: This qualitative study included semi-structured in-depth interviews and focus group discussions with caregivers of children who died below the age of 5 years. Data were thematically analysed, and key findings compared with the Pathways to Survival Framework-a model frequently used in the study of child mortality. An adapted model was developed., Setting: Two rural health and demographic surveillance system (HDSS) sites in South Africa-the Agincourt HDSS and the Africa Health Research Institute., Participants: Thirty-eight caregivers of deceased children (29 participated in in-depth interviews and 9 were participants in two focus group discussions). Caregivers were purposively sampled to ensure maximum variation across place of death, child age at death, household socioeconomic status, maternal migration status and maternal HIV status., Findings: Although caregivers faced barriers in providing care to children (including insufficient knowledge and poor transport), almost all did seek care from the formal health system. Negative experiences in health facilities did not deter care-seeking, but most respondents still received poor quality care and were not given adequate safety-netting advice. Traditional healers were only consulted as a last resort when other approaches had failed., Conclusion: Barriers to accessing healthcare disrupt the workings of previously accepted care-seeking models. The adapted model presented in this paper more realistically reflects care-seeking experiences and decision-making during severe childhood illness in rural South Africa and helps explain both the persistence of home deaths despite seeking healthcare, and the impact of a child's death on care-seeking in future childhood illness. This model can be used as the basis for developing interventions to reduce under-5 mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: The use of molecular tests to aid the diagnosis of invasive yeast infection, in particular invasive candidosis, has been described for over two decades, yet widespread application is limited, and diagnosis remains heavily dependent on classical microbiology. This article will review developments from the past decade in attempt to build on existing knowledge. It will highlight clinical performance and limitations while reviewing developments on recognized procedures; it will also provide insight into novel approaches incorporated in response to clinical demand (e.g. C. auris and antifungal resistance) or technological advances (e.g. next-generation sequencing)., Recent Findings: Limited methodological standardization and, until recently, unavailability of commercial options have hindered the integration of molecular diagnostics for yeasts. The development of certain, novel commercial methods has received considerable evaluation allowing a greater understanding of individual assay performance, but widespread multicentre evaluation of most commercial kits is lacking. The detection of emerging pathogens (e.g. C. auris ) has been enhanced by the development of molecular tests. Molecular methods are providing a better understanding of the mycobiome, mechanisms of resistance and epidemiology/phylogeny., Summary: Despite over two decades of use, the incorporation of molecular methods to enhance the diagnosis of yeast infections remains limited to certain specialist centres. While the development of commercial tests will provide stimulus for broader application, further validation and reduced costs are required. Over the same period of time, Aspergillus PCR has become more widely accepted driven by international efforts to standardize methodology; it is critical that yeast PCR follows suit. Next-generation sequencing will provide significant information on the mycobiome, antifungal resistance mechanism and even broad-range detection directly from the specimen, which may be critical for the molecular detection of yeasts other than Candida species, which is currently limited., Competing Interests: Conflict of InterestP. Lewis White: Performed diagnostic evaluations and received meeting sponsorship from Associates of Cape Cod, Bruker, Dynamiker and Launch Diagnostics; speakers’ fees, expert advice fees and meeting sponsorship from Gilead; and speaker and expert advice fees from F2G and speaker fees from IMMY, MSD and Pfizer. Is a founding member of the European Aspergillus PCR Initiative.Matthijs Backx: Speakers’ fees, expert advice fees and meeting sponsorship from Gilead. Meeting sponsorship from AbbVie. Jessica S. Price and Alan Cordey declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

An estimated 2.1% of Americans have psoriasis and approximately 30% of them have moderate to severe psoriasis. Although the disease is not associated with mortality, it has a significant impact on health-related quality of life among patients. Several therapies are available for psoriasis including topical agents, phototherapy, and systemic medications. Recently, effective yet expensive biologic agents have been added as treatments for moderate to severe psoriasis. Biologics are recommended in patients for whom all other available treatment options have failed. This extensive review provides important information on the clinical and patient-related outcomes associated with the biologic agents used in psoriasis.

Background: Although patients suffer the effects of medical errors and iatrogenic injuries, little is known about their ability to recognize these events in ambulatory specialty care., Methods: At a Boston cancer center in 2004, 193 adult oncology patients treated on a chemotherapy infusion unit were interviewed by four patient safety liaisons--volunteers recruited from the organization's Adult Patient and Family Advisory Council., Results: Among 193 patients, 83 reported 121 incidents. Investigators classified 2 (1%) adverse events, 4 (2%) close calls, 14 (7%) errors without risk of harm, and 101 (52%) service quality incidents. Respondents reported high staff compliance with safe practices such as identity checking (95%). Examining the most serious described by each of 42 (22%) respondents who reported a recent unsafe experience, investigators classified only one adverse event, 3 close calls, 9 harmless errors, and 27 service quality incidents., Discussion: Patients' perception of unsafe care was surprising, given the same patients' recognition of consistent application of safe practices, such as the use of two forms of identification before performing tests and administering treatments. Many ambulatory oncology patients also reported poor service quality. The relationship between patient perception of safe care, medical injury, and service quality merits further study.