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Background and MethodsProfessionals in Liverpool have designed the IMPaCT (Integrated Mersey Palliative Care Team) model of care to improve access for patients, their families and other professionals. The COVID-19 pandemic enabled implementation of this much more quickly than envisaged. The IMPaCT service in North Liverpool was piloted over July to September 2020 and went ‘live’ in October. The ‘Hub’ accepts calls and referrals from anyone and comprises coordinators from hospice outpatient, hospital and community palliative care specialist nursing teams. This single point of access allows for sharing of information, elimination of duplication, and reduces delays in care. Patients are no longer discharged when they move between settings; once they are referred to the IMPaCT service, they remain on the locality caseload until their death.ResultsIn North Liverpool 136 patients have been regularly reviewed under the newly formed nurse-led surveillance clinic in place of the old medical outpatient system. Where medical input was required, advice could be sought from the hub doctor and patients could be seen in the new ambulatory clinic or at home as needed. Of 21 patients were referred for hospice inpatient admission, 18 were admitted within 1 day, an improvement on the 2019–2020 average time from referral to admission of 3 working days. Of 26 patients triaged for medical outpatient review 23 were reviewed within 24 hours (8 same day) ‒ the previous average was 15 working days from referral to appointment.ConclusionsThe switch to a daily ambulatory clinic has improved timeliness of medical assessment and domiciliary visits have been completed in a more timely manner due to freeing up medical availability. Co-location of team members has enhanced information sharing and transfer of care between settings. Patients, carers and staff have reported the benefits of reduced waiting times for specialist input across the services.

Prior to the start of the COVID-19 pandemic, Woodlands Hospice Wellbeing and Support Centre ran several regular groups plus nurse-led clinics for patients well enough to attend the hospice. When the pandemic started it was clear that this would no longer be an option as most of the patients were in the shielding category.Clearly the needs of these patients would not go away but the community palliative care and district nursing services could not be expected to take on the role that the hospice had previously played, as they also faced increased demand due to the pandemic.Out of necessity and working towards a new city-wide integrated palliative care model, a decision was made to move to a system of triage coordinators and regular nurse led telephone clinics to monitor these patients. The nursing team underwent an education programme to enhance their triage and symptom management skills and they had ready access to the medical team for support if there were problems.Consultations are carried out by telephone or video consultation as well as face-to-face where needed. The nursing team gradually took over the surveillance role of the medical clinics to free capacity for urgent medical appointments so patients could be assessed by the doctors when problems arise or when symptoms are more complex. The triage coordinator now looks at all referrals coming into the hospice and assesses the patient’s needs to ensure the patient is linked into the most appropriate services. All this integrated working has reduced the time from referral to comprehensive specialist nursing assessment in the hospice from two weeks to within five working days. The working relationships with all teams has become closer and more effective, and patients are still able to access services despite the restrictions that the pandemic has brought.

Existing quantitative evidence for the benefits of Hospice Day Services is limited. Clinical Commissioning Group funding decisions are often based on numbers of attendees, rather than overall impact on individuals engaging with those services.At Woodlands Hospice, an outcome measures questionnaire, the Integrated Palliative Care Outcome Scale (iPOS), was implemented on the inpatient unit several years ago, and, in addition to being clinically useful for individual patients, audit data showed an overall improvement in average iPOS score during patients’ admission.The use of iPOS was piloted for new patients to our Day Services at their initial assessment from December 2018. This tool was used to assist in transforming our individual patient care plan, with a change in our practice being to repeat iPOS for each patient every four weeks to update the care plan. A baseline audit showed a mean overall improvement in patients’ iPOS score when repeated after four weeks. Interventions during the four-week intervening period varied according to the patient’s own personalised plan of care. The interventions ranged from solely medical outpatient review, to multidisciplinary assessment and management, with some patients attending individual outpatient sessions only, and others attending group therapy sessions.This audit looks at the breakdown in improvement of physical symptoms and psychological wellbeing, and compares the reduction in iPOS score to changes in other outcome measures, namely the OACC Phase of illness and the Palliative Performance Scale. The use of these outcome measures will enable the hospice to monitor the effect of the care and interventions it provides to each individual patient and ensure their personal care plan is continually adapted in accordance with their specific needs as their condition changes.

Palliative and end-of-life care services across Liverpool and South Sefton have been transformed over the last year to ensure that patients and their families have access to the right care from the right people when needed via a single phone number.Patients and their families struggled to navigate previously complex health care systems in Liverpool. There were many different teams providing care across the hospitals, hospices, and community, usually requiring a referral for each new encounter resulting in duplication of work, multiple handoffs between services, and confusion amongst referrers. This meant that there was inequity in the level of service patients received and some patients were unable to get the care they needed.The IMPaCT (Integrated Mersey Palliative Care Team) model is a consultant-led service to support patients nearing the end-of-life which was developed by reorganising existing services with key stakeholder involvement in the design. The essence of its success is collaborative working between services to prevent crises and timely response to problems as they arise. There are regular multidisciplinary meetings to ensure that services are directed to the areas of most need and ensuring that patients do not ‘slip through the net,’ especially on discharge from hospital.There were 1320 patients supported by IMPaCT in April 2021. Referrals and calls for help come from any healthcare professional or patients and families themselves. Each call or referral is handled by a nurse specialist from the hospital, hospice or community specialist palliative care teams based in one of the two hospice hubs who assesses the patient’s needs and arranges intervention by the most appropriate person, removing the need for the patient to contact multiple agencies and reducing stress. The patient stays on the IMPaCT register unless they die, move away, or their illness is cured.

Marital/Partner support is associated with lower mortality and morbidity following acute myocardial infarction (AMI) and stroke. Despite an increasing focus on the effect of patient-centered factors on health outcomes, little is known about the impact of marital/partner status on patient-reported outcome measures (PROMs). To synthesize evidence of the association between marital/partner status and PROMs after AMI and stroke and to determine whether associations differ by sex. We will search MEDLINE (via Ovid), Web of Science Core Collection (as licensed by Yale University), Scopus, EMBASE (via Ovid), and PsycINFO (via Ovid) from inception to July 15, 2022. Two authors will independently screen titles, abstracts, and then full texts as appropriate, extract data, and assess risk of bias. Conflicts will be resolved by discussion with a third reviewer. The primary outcomes will be the associations between marital/partner status and PROMs. An outcome framework was designed to classify PROMs into four domains (health-related quality of life, functional status, symptoms, and personal recovery). Meta-analysis will be conducted if appropriate. Subgroup analysis by sex and meta-regression with a covariate for the proportion of male participants will be performed to explore differences by sex. This research is exempt from ethics approval because the study will be conducted using published data. We will disseminate the results of the analysis in a related peer-reviewed journal. PROSPERO registration number: CRD42022295975.

Candida auris was first detected at a university-affiliated hospital in Johannesburg, South Africa, in 2009. We used whole-genome sequencing to describe the molecular epidemiology of C. auris in the same hospital during 2016–2020; the neonatal unit had a persistent outbreak beginning in June 2019. Of 287 cases with culture-confirmed C. auris infection identified through laboratory surveillance, 207 (72%) had viable isolates and 188 (66%) were processed for whole-genome sequencing. Clade III (118/188, 63%) and IV (70/188, 37%) isolates co-circulated in the hospital. All 181/188 isolates that had a fluconazole MIC >32 µg/mL had ERG11 mutations; clade III isolates had VF125AL substitutions, and clade IV isolates had K177R/N335S/E343D substitutions. Dominated by clade III, the neonatal unit outbreak accounted for 32% (91/287) of all cases during the study period. The outbreak may have originated through transmission from infected or colonized patients, colonized healthcare workers, or contaminated equipment/environment.

Although flucytosine is a key component of WHO-recommended induction treatment for HIV-associated cryptococcal meningitis, this antifungal agent is not widely available in low-income and middle-income countries due to limited production and cost. In 2018, a national flucytosine access programme was initiated in South Africa. We aimed to determine the effectiveness of flucytosine-containing induction regimens in routine care to motivate for the urgent registration of flucytosine and its inclusion in treatment guidelines. In this cross-sectional study, we compared outcomes of adults aged 18 years and older with incident laboratory-confirmed cryptococcal meningitis treated with or without flucytosine-containing regimens at 19 sentinel hospitals in South Africa. A case of cryptococcosis was defined as illness in an adult with: (1) positive cerebrospinal fluid (CSF) India ink microscopy; (2) a positive CSF cryptococcal antigen test; or (3) culture of Cryptococcus neoformans or Cryptococcus gattii from CSF or any other specimen. We excluded patients without a case report form, those with an unknown or negative HIV serology result, those with a recurrent episode, and those who did not receive antifungal treatment in hospital. We assessed cumulative in-hospital mortality at 14 days and 30 days and calculated the overall crude in-hospital case-fatality ratio. We used random-effects logistic regression to examine the association between treatment group and in-hospital mortality. From July 1, 2018, to March 31, 2020, 10 668 individuals were diagnosed with laboratory-confirmed cryptococcal meningitis, 7787 cases diagnosed at non-enhanced surveillance sites and 567 cases from eight enhanced surveillance sites with no access to flucytosine were excluded. Of 2314 adults with a first episode of cryptococcosis diagnosed at 19 facilities with access to flucytosine, 1996 had a case report form and of these, 1539 received induction antifungal treatment and were confirmed HIV-seropositive first-episode cases. Of 1539 patients who received antifungal therapy, 596 (38·7%) individuals received a flucytosine-containing regimen and 943 (61·3%) received another regimen. The median age was 36 years (IQR 32–43) and 906 (58·9%) participants were male and 633 (41·1%) were female. The crude in-hospital case-fatality ratio was 23·9% (95% CI 20·0–27·0; 143 of 596) in those treated with flucytosine-containing regimens and 37·2% (95% CI 34·0–40·0; 351 of 943) in those treated with other regimens. Patients admitted to non-academic hospitals (adjusted odds ratio [aOR] 1·95 [95% CI 1·53–2·48]; p<0·0001) and those who were antiretroviral treatment-experienced (aOR 1·30 [1·02–1·67]; p=0·033) were more likely to receive flucytosine. After adjusting for relevant confounders, flucytosine treatment was associated with a 53% reduction in mortality (aOR 0·47 [95% CI 0·35–0·64]; p<0·0001). Among survivors, the median length of hospital admission in the flucytosine group was 11 days (IQR 8–15) versus 17 days (13–21) in the comparison group (p=0·0010). In-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit. National Institute for Communicable Diseases, a Division of the National Health Laboratory Service. For the Zulu translation of the abstract see Supplementary Materials section.

Abstract Aims Little is known about the relationship between marital/partner status and patient-reported outcome measures (PROMs) following myocardial infarction (MI). We conducted a systematic review/meta-analysis and explored potential sex differences. Methods and results We searched five databases (Medline, Web of Science, Scopus, EMBASE, and PsycINFO) from inception to 27 July 2022. Peer-reviewed studies of MI patients that evaluated marital/partner status as an independent variable and reported its associations with defined PROMs were eligible for inclusion. Results for eligible studies were classified into four pre-specified outcome domains [health-related quality of life (HRQoL), functional status, symptoms, and personal recovery (i.e. self-efficacy, adherence, and purpose/hope)]. Study quality was appraised using Newcastle–Ottawa Scale, and data were synthesized by outcome domains. We conducted subgroup analysis by sex. We included 34 studies (n = 16 712), of which 11 were included in meta-analyses. Being married/partnered was significantly associated with higher HRQoL {six studies [n = 2734]; pooled standardized mean difference, 0.37 [95% confidence interval (CI), 0.12–0.63], I2 = 51%} but not depression [three studies (n = 2005); pooled odds ratio, 0.72 (95% CI, 0.32–1.64); I2 = 65%] or self-efficacy [two studies (n = 356); pooled β, 0.03 (95% CI, −0.09 to 0.14); I2 = 0%]. The associations of marital/partner status with functional status, personal recovery outcomes, and symptoms of anxiety and fatigue were mixed. Sex differences were not evident due to mixed results from the available studies. Conclusions Married/partnered MI patients had higher HRQoL than unpartnered patients, but the associations with functional, symptom, and personal recovery outcomes and sex differences were less clear. Our findings inform better methodological approaches and standardized reporting to facilitate future research on these relationships. Graphical Abstract Graphical abstract CI, confidence interval; HRQoL, health-related quality of life; MI, myocardial infarction; OR, odds ratio; SMD, standardized mean difference; β, regression coefficient.

Genetic programs can direct living systems to perform diverse, pre-specified functions. As the library of parts available for building such programs continues to expand, computation-guided design is increasingly helpful and necessary. Predictive models aid the challenging design process, but iterative simulation and experimentation are intractable for complex functions. Computer-aided design accelerates this process, but existing tools do not yet capture the behavior of mammalian-specific parts and population-level effects needed for mammalian synthetic biologists. To address these needs, we developed a framework for mammalian genetic program computer-aided design. Starting with a user-defined design specification to quantify circuit performance, the framework uses a genetic algorithm to search through possible designs. Circuit space is defined by a library of experimentally characterized parts and dynamical systems models for gene expression in a heterogeneous cell population. We developed this genetic algorithm using a directed graph-based formulation with biologically constrained rules to explore regulatory connections and parts. We evaluated the framework for design problems of varying complexity, including programs we describe as an amplifier, signal conditioner, and pulse generator, demonstrating that the algorithm can successfully find optimal circuit designs. Finally, we experimentally evaluated selected circuits, demonstrating the path from a predicted circuit design to experimental testing and highlighting the importance of characterization for enabling predictive design. Overall, this framework establishes general approaches that can be refined and expanded, accelerating the design and implementation of mammalian genetic programs.

Recent years have seen intense interest in the development of point-of-care nucleic acid diagnostic technologies to address the scaling limitations of laboratory-based approaches. Chief among these are combinations of isothermal amplification approaches with CRISPR-based detection and readouts of target products. Here, we contribute to the growing body of rapid, programmable point-of-care pathogen tests by developing and optimizing a one-pot NASBA-Cas13a nucleic acid detection assay. This test uses the isothermal amplification technique NASBA to amplify target viral nucleic acids, followed by Cas13a-based detection of amplified sequences. We first demonstrate an in-house formulation of NASBA that enables optimization of individual NASBA components. We then present design rules for NASBA primer sets and LbuCas13a guide RNAs for fast and sensitive detection of SARS-CoV-2 viral RNA fragments, resulting in 20 - 200 aM sensitivity without any specialized equipment. Finally, we explore the combination of high-throughput assay condition screening with mechanistic ordinary differential equation modeling of the reaction scheme to gain a deeper understanding of the NASBA-Cas13a system. This work presents a framework for developing a mechanistic understanding of reaction performance and optimization that uses both experiments and modeling, which we anticipate will be useful in developing future nucleic acid detection technologies.