Implementation of novel and conventional outbreak control measures in managing COVID-19 outbreaks in a large UK prison.

BACKGROUND: Outbreak control measures during COVID-19 outbreaks in a large UK prison consisted of standard (e.g., self-isolation) and novel measures, including establishment of: (i) reverse cohorting units for accommodating new prison admissions; (ii) protective isolation unit for isolating symptomatic prisoners, and (iii) a shielding unit to protect medically vulnerable prisoners. METHODS: Single-centre prospective longitudinal study (outbreak control study), implementing novel and traditional outbreak control measures to prevent a SARS-COV-2 outbreak. The prison held 977 prisoners and employed 910 staff at that start of the outbreak. RESULTS: 120 probable and 25 confirmed cases among prisoners and staff were recorded between March and June 2020 during the first outbreak. Over 50% of initial cases among prisoners were on the two wings associated with the index case. During the second outbreak, 182 confirmed cases were recorded after probable reintroduction from a staff member. Widespread testing identified 145 asymptomatic prisoners, 16.9% of the total prisoner cases. The cohorting units prevented re-infection from new prison admissions and the shielding unit had no COVID-19 infections linked to either outbreak. CONCLUSIONS: Identifying and isolating infected prisoners, cohorting new admissions and shielding vulnerable individuals helped prevent uncontrollable spread of SARS-COV-2. These novel and cost-effective approaches can be implemented in correctional facilities globally.

Extending the 30-minute rule for red cell units - investigation of the bacterial risk of 60-minute exposures to ambient temperature.

BACKGROUND AND OBJECTIVES: In the UK, a significant proportion of red cell units is discarded due to the 30-min rule governing out of temperature control. Studies have shown that repeated warming to ambient temperature has little impact on red cell quality or bacterial growth. We aimed to validate extension of the rule to 60 minutes by investigation of repeated same, and different, day exposures on bacterial growth. MATERIALS AND METHODS: Red cell units were seeded individually at 100-1000 cfu/ml with Yersinia enterocolitica, Serratia liquefaciens, Pseudomonas putida, Staphylococcus epidermidis, Enterobacter cloacae and Bacillus cereus. Test units were exposed to 30°C for 30 or 60 min on a single occasion at days 15, 17 and 21, or thrice on day 15 of a 35-day storage period. A 10-fold increase in bacterial counts in tests versus controls maintained in cold storage was considered indicative of significant bacterial proliferation. RESULTS: Exposure of units to 30°C for up to 60 min had no substantial impact on the growth of bacteria and all mesophiles declined steadily in tests and controls. Only P. putida showed a near significant elevation in count on exposure for 60 min at day 35. CONCLUSIONS: Extension of the out of temperature rule for red cells to 60 min will potentially not compromise patient safety, although exposures to ambient temperatures should be minimized. Units returned to storage must not be reissued for at least 6 hours and not be exposed to ambient temperatures on more than three occasions.

Respiratory symptoms in people living with HIV and the effect of antiretroviral therapy: a systematic review and meta-analysis.

BACKGROUND: Antiretroviral therapy (ART) has significantly altered the pattern of acute and chronic HIV-related disease. However, it is not clear what this means in terms of respiratory symptoms. We sought to investigate the association between HIV status and respiratory symptoms and how these have changed with the availability of ART. METHODS: We searched Cochrane, Medline and Embase databases for studies published between 1946 and August 2015 comparing the prevalence of respiratory symptoms in populations with and without HIV infection. We undertook random effects meta-analysis of the main symptoms reported. We studied heterogeneity and completed sensitivity analyses and funnel plots. RESULTS: From 5788 unique references identified, 24 papers provided relevant data: 18 documented the prevalence of cough and 11 examined the prevalence of breathlessness among other symptoms reported. Compared with the HIV negative, people living with HIV (PLWH) were more likely to have respiratory symptoms with pooled ORs for the prevalence of cough of 3.05 (95% CI 2.24 to 4.16) in resource-limited populations without access to ART; 2.18 (1.56 to 3.18) in resource-rich populations without access to ART and 1.11 (0.99 to 1.24) in resource-rich populations with access to ART. In resource-rich settings, although the availability of ART was associated with a reduction in the difference between HIV-positive and HIV-negative individuals, PLWH were more likely to report breathlessness, OR 1.39 (95% CI 1.11 to 1.73). CONCLUSIONS: Respiratory symptoms are more common in PLWH than controls. This association persists although at a reduced level in populations with access to ART.

Bacterial screening of platelet components by National Health Service Blood and Transplant, an effective risk reduction measure.

BACKGROUND: Bacterial contamination of blood components remains a major cause of sepsis in transfusion medicine. Between 2006 and 2010 in the 5 years before the introduction of bacterial screening of platelet (PLT) components by National Health Service Blood and Transplant (NHSBT), seven cases of PLT component-associated transmission of bacterial infection were recorded for 10 patients, three of which were fatal. STUDY DESIGN AND METHODS: Sampling of individual PLT components was undertaken at 36 to 48 hours after donation and tested in the BacT/ALERT system with 8 mL inoculated into each of aerobic and anaerobic culture bottles. Bottles were incubated until the end of the 7-day shelf life and initial reactive bottles were examined for contamination. Bacterial screened time-expired PLTs were tested as in the screen method. RESULTS: From February 2011 to September 2015, a total of 1,239,029 PLT components were screened. Initial-reactive, confirmed-positive, and false-positive rates were 0.37, 0.03, and 0.19%, respectively. False-negative cultures, all with Staphylococcus aureus, occurred on four occasions; three were visually detected before transfusion and one confirmed transmission resulted in patient morbidity. The NHSBT screening protocol effectively reduced the number of clinically adverse transfusion transmissions by 90% in this reporting period, compared to a similar time period before implementation. Delayed testing of 4515 time-expired PLT units after screening revealed no positives. CONCLUSION: The implementation of bacterial screening of PLT components with the NHSBT BacT/ALERT protocol was an effective risk reduction measure and increased the safety of the blood supply.

Short-term nutrition education reduces low birthweight and improves pregnancy outcomes among urban poor women in Bangladesh.

BACKGROUND: Maternal malnutrition and poor gestational weight gain are the most important causes of low birthweight and infant mortality in Bangladesh. OBJECTIVE: To assess the effect of short-term nutrition education on weight gain in the third trimester of pregnancy, birth outcomes, and breastfeeding. METHODS: Three hundred pregnant women participated in this randomized, controlled trial during a 3-month intervention period. The study was conducted in two antenatal clinics in urban Dhaka. One group of women was given monthly education sessions during the third trimester of pregnancy to promote consumption of khichuri, while the control group received only routine services from the health facilities. Birthweight was recorded within 24 hours after delivery. Breastfeeding practices were observed for 1 month after delivery. RESULTS: In the intervention group, maternal weight gain in the third trimester was 60% higher (8.60 vs. 5.38 kg, p = .011), mean birthweight was 20% higher (2.98 vs. 2.49 kg, p < .001), the rate of low birthweight was 94% lower (2.7% vs. 44.7%; p < .001), and the rate of initiation of breastfeeding within 1 hour after birth was 52% higher (86.0% vs. 56.7%, p < .001), in comparison with the control group. Birthweight was associated with frequency of intake of khichuri (p < 0.001). CONCLUSIONS: Nutrition education with a focus on promoting consumption of khichuri during the third trimester of pregnancy significantly reduced the rate of low birthweight and increased maternal weight gain.

Interventions to improve latent and active tuberculosis treatment completion rates in underserved groups in low incidence countries: a scoping review.

BACKGROUND: People in underserved groups have higher rates of tuberculosis (TB) and poorer treatment outcomes compared with people with no social risk factors. OBJECTIVES: This scoping review aimed to identify interventions that improve TB treatment adherence or completion rates. ELIGIBILITY CRITERIA: Studies of any design focusing on interventions to improve adherence or completion of TB treatment in underserved populations in low incidence countries. SOURCES OF EVIDENCE: MEDLINE, Embase and Cochrane CENTRAL were searched (January 2015 to December 2023). CHARTING METHODS: Piloted data extraction forms were used. Findings were tabulated and reported narratively. Formal risk of bias assessment or synthesis was not undertaken. RESULTS: 47 studies were identified. There was substantial heterogeneity in study design, population, intervention components, usual care and definition of completion rates. Most studies were in migrants or refugees, with fewer in populations with other risk factors (eg, homelessness, imprisonment or substance abuse). Based on controlled studies, there was limited evidence to suggest that shorter treatment regimens, video-observed therapy (compared with directly observed therapy), directly observed therapy (compared with self-administered treatment) and approaches that include tailored health or social support beyond TB treatment may lead to improved outcomes. This evidence is mostly observational and subject to confounding. There were no studies in Gypsy, Roma and Traveller populations, or individuals with mental health disorders and only one in sex workers. Barriers to treatment adherence included a lack of knowledge around TB, lack of general health or social support and side effects. Facilitators included health education, trusted relationships between patients and healthcare staff, social support and reduced treatment duration. CONCLUSIONS: The evidence base is limited, and few controlled studies exist. Further high-quality research in well-defined underserved populations is needed to confirm the limited findings and inform policy and practice in TB management. Further qualitative research should include more people from underserved groups.

Universal HIV testing in London tuberculosis clinics: a cluster randomised controlled trial.

We assessed whether implementation of a combination of interventions in London tuberculosis clinics raised the levels of HIV test offers, acceptance and coverage. A stepped-wedge cluster randomised controlled trial was conducted across 24 clinics. Interventions were training of clinical staff and provision of tailor-made information resources with or without a change in clinic policy from selective to universal HIV testing. The primary outcome was HIV test acceptance amongst those offered a test, before and after the intervention; the secondary outcome was an offer of HIV testing. Additionally, the number and proportion of HIV tests among all clinic attendees (coverage) was assessed. 1,315 patients were seen in 24 clinics. The offer and coverage of testing rose significantly in clinics without (p = 0.002 and p = 0.004, respectively) and with an existing policy of universal testing (p = 0.02 and p = 0.04, respectively). However, the level of HIV test acceptance did not increase in 18 clinics without routine universal testing (p = 0.76) or the six clinics with existing universal testing (p = 0.40). The intervention significantly increased the number of HIV tests offered and proportion of participants tested, although acceptance did not change significantly. However, the magnitude of increase is modest due to the high baseline coverage.

Scoping review of mental health in prisons through the COVID-19 pandemic.

OBJECTIVE: To examine the extent, nature and quality of literature on the impact of the COVID-19 pandemic on the mental health of imprisoned people and prison staff. DESIGN: Scoping review. DATA SOURCES: PubMed, Embase, CINAHL, Global Health, Cochrane, PsycINFO, PsychExtra, Web of Science and Scopus were searched for any paper from 2019 onwards that focused on the mental health impact of COVID-19 on imprisoned people and prison staff. A grey literature search focused on international and government sources and professional bodies representing healthcare, public health and prison staff was also performed. We also performed hand searching of the reference lists of included studies. ELIGIBILITY CRITERIA FOR SELECTION OF STUDIES: All papers, regardless of study design, were included if they examined the mental health of imprisoned people or prison staff specifically during the COVID-19 pandemic. Imprisoned people could be of any age and from any countries. All languages were included. Two independent reviewers quality assessed appropriate papers. RESULTS: Of 647 articles found, 83 were eligible for inclusion, the majority (58%) of which were opinion pieces. The articles focused on the challenges to prisoner mental health. Fear of COVID-19, the impact of isolation, discontinuation of prison visits and reduced mental health services were all likely to have an adverse effect on the mental well-being of imprisoned people. The limited research and poor quality of articles included mean that the findings are not conclusive. However, they suggest a significant adverse impact on the mental health and well-being of those who live and work in prisons. CONCLUSIONS: It is key to address the mental health impacts of the pandemic on people who live and work in prisons. These findings are discussed in terms of implications for getting the balance between infection control imperatives and the fundamental human rights of prison populations.

A novel rapid and effective donor arm disinfection method.

BACKGROUND: The aim of the study was to derive a donor arm disinfection technique that was rapid, but with a disinfection efficacy equivalent to a previous "best-practice" technique. This method consisted of a two-stage procedure with an initial application of 70% isopropyl alcohol and then 2% tincture of iodine (IATI). The total time for the IATI method was 2 minutes in duration. A rapid technique (1 min in duration) was needed to obviate potential problems due to increased donor waiting time, had the IATI method been implemented at blood donation sessions. STUDY DESIGN AND METHODS: A direct swabbing and plating technique was used to enumerate bacteria present before and after disinfection. In total, seven methods were evaluated. RESULTS: The chlorhexidine/alcohol applicator (CAA) disinfection device containing 1.5 mL of 2% chlorhexidine gluconate and 70% isopropyl alcohol (99.91% reduction; confidence limits, 99.55%, 99.98%) was shown to have equivalent disinfection efficacy as the IATI method (99.89% reduction; confidence limits, 99.36%, 99.98%; p = 0.86). Procedural time for the 1.5-mL CAA method was 1 minute thereby avoiding potential problems of increased donor waiting time, inherent in the IATI 2-minute procedure at blood donation sessions. CONCLUSIONS: The 1.5-mL CAA disinfection method offers blood services a rapid and effective donor arm disinfection procedure. In 2006, the 1.5-mL CAA procedure was implemented throughout the entire English blood service for all donations.

Non-enzymatic glycation induces structural modifications of myoglobin.

Increased glucose concentration in diabetes mellitus causes glycation of several proteins, leading to changes in their properties. Although glycation-induced functional modification of myoglobin is known, structural modification of the protein has not yet been reported. Here, we have studied glucose-modified structural changes of the heme protein. After in vitro glycation of metmyoglobin (Mb) by glucose at 25 degrees C for 6 days, glycated myoglobin (GMb) and unchanged Mb have been separated by ion exchange (BioRex 70) chromatography, and their properties have been compared. Compared to Mb, GMb exhibits increased absorbance around 280 nm and enhanced fluorescence emission with excitation at 285 nm. Fluorescence quenching experiments of the proteins by acrylamide and KI indicate that more surface accessible tryptophan residues are exposed in GMb. CD spectroscopic study reveals a change in the secondary structure of GMb with decreased alpha-helix content. 1-anilino-naphthaline-8-sulfonate (ANS) binding with Mb and GMb indicates that glycation increases hydrophobicity of the heme protein. GMb appears to be less stable with respect to thermal denaturation and differential calorimetry experiments. Heme-globin linkage becomes weaker in GMb, as shown by spectroscopic and gel electrophoresis experiments. A correlation between glycation-induced structural and functional modifications of the heme protein has been suggested.

Evaluating knowledge gain from TB leaflets for prison and homeless sector staff: the National Knowledge Service TB pilot.

BACKGROUND: The National Knowledge Service (NKS) is a National Health Service initiative to make patient and public information available to patients and healthcare professionals. The current study was carried out with a view to determine whether the resources developed by the NKS Tuberculosis Pilot have improved knowledge about tuberculosis among the target group in the short term. METHODS: Information resources specifically targeted and developed for homeless sector staff, managers and prison officials were used for this study. Questionnaires were designed to assess a change in the level of knowledge by completing a 'before' and 'after 'questionnaire. A total of 51 participants took part in the evaluation. McNemar's test for matched pairs was used to determine observed change in knowledge. RESULTS: Staff knowledge on symptoms of tuberculosis (TB) increased significantly after reading the targeted information resources. Knowledge gain for symptoms ranged from 17% (P = 0.007) for weight loss to 45% (P = 0.00001) for persistent fever. Knowledge about general guidelines that are available to this target group also improved, as did knowledge about the potential role of staff in supporting directly observed treatment (by 68% P = 0.00001) and the usual length of TB treatment (by 32% P = 0.0001). Pre-existing knowledge about the infectiousness of TB, risks for transmission and the likely period of hospitalization of patients with TB was high. CONCLUSIONS: This study demonstrates that purposefully designed and targeted information leaflets can be used successfully to translate complex information into a simple understandable format and impart knowledge of TB.

Cultured interstitial cells from human heart valves express both specific skeletal muscle and non-muscle markers.

Cardiac valve interstitial cells are a phenotypically diverse and dynamic population, comprising myofibroblasts, fibroblasts and smooth muscle cells. To understand how these contribute to valve function and to optimize the choice of cells for seeding tissue-engineered valves, we are fingerprinting interstitial cells from all four human heart valves for useful phenotypic markers. We have begun by selecting markers indicated as of interest from previous work on myofibroblast-like cell lines. We show that interstitial cells express a variety of skeletal muscle contractile proteins and the skeletal muscle transcription factor myogenin, but not the related factors MyoD, myf-5 and MRF4, suggesting partial activation of the muscle programme in these cells. Expression of non-muscle isoforms of creatine kinase (CK-B) and AMP deaminase (AMPD2 and AMPD3) was found in contrast to muscle-restricted isoforms. Non-muscle isoforms of alpha- and beta-tropomyosins were detected specifically in contrast to skeletal muscle-specific isoforms. Several members of the Frizzled (FZD) family of Wnt receptors were also detected. In addition, intact cusps of all four valves from pig were capable of contacting to non-receptor and receptor-mediated stimulation in vitro. We conclude that interstitial cells from human heart valves express various sarcomeric proteins, and suggest that these cells have contractile potential due to a unique pattern of expression of both muscle-specific and non-muscle isoforms of metabolic and structural proteins. This may be under the control of myogenin, activated through specific Wnt/FZD signaling. Identifying such molecular markers could prove useful for engineering allogenic non-valve cell sources for seeding the synthetic valve.

Effect of glycation of hemoglobin on its interaction with trifluoperazine.

Trifluoperazine (TFZ), a phenothiazine drug, penetrates into human erythrocytes and releases oxygen by interaction with hemoglobin. TFZ-induced oxygen release from hyperglycemic erythrocytes isolated from diabetic patients is considerably less compared to that from the cells of normoglycemic individuals. In diabetes mellitus, hemoglobin is significantly glycated by glucose. Non-glycated hemoglobin, HbA0 and its major glycated analog, HbA1c have been separated from the blood samples of diabetic patients. TFZ releases considerable amount of oxygen from HbA0, but very little from HbA1c. Spectrofluorimetric studies reveal that TFZ forms excited state complexes with both HbA0 and HbAlc. Titration of HbA0 with TFZ in a spectrophotometric study exhibits two isosbestic points. Similar experiment with HbAlc causes gradual loss of the Soret peak without appearance of any isosbestic point indicating a possibility of heme loss during interaction, which is also supported by gel filtration experiment and SDS-PAGE experiment followed by heme staining. The results suggest that drug action on hemoglobin is influenced by glycation-induced structural modification of the protein.

Web-based provision of information on infectious diseases: a systems study.

The National electronic Library for Health (NeLH) is an Internet medical information resources portal, principally for healthcare professionals, within which the National electronic Library of Infection (NeLI) is one of NeLH Specialist Libraries providing evidence on infectious diseases. In this article, we describe a systems-based evaluation of NeLI based on a soft systems methodology. User feedback and other data for the analysis were obtained using online questionnaires. This evaluation, which is a pilot study aimed at demonstrating proof of concept, provided evidence for improving three systems that are crucial to effective NeLI provision. These are navigation of the site, quality and tagging of information provided by NeLI, and information regarding users and their usage of the system. On the basis of a soft systems analysis, an action plan was formulated identifying areas where improvement is needed. Actions for consideration included simplifying terminologies to improve the navigation, enhancing the provision of research assessments, quality tagging NeLI documents, provided by experts in the field, and attracting a broader cross-section of healthcare professional user.

Lessons learned from evaluation of the use of the National electronic Library of Infection.

The National electronic Library of Infection (NeLI: http://www.neli.org.uk) in the UK is a freely available portal to key evidence and guidelines in the infectious disease field. This paper discusses 5 years of evaluation of the pilot library and how this evaluation informed design of the new library website. The importance of combining qualitative and quantitative evaluation is highlighted and the results of web access logs analysis, free text search query analysis and an online user survey are compared. The paper concludes with a discussion of lessons learned for future development and evaluation of this Internet digital library.

Effect of nonenzymatic glycation on functional and structural properties of hemoglobin.

HbA(1c), the major glycated hemoglobin increases proportionately with blood glucose concentration in diabetes mellitus. H(2)O(2) promotes more iron release from HbA(1c) than that from nonglycated hemoglobin, HbA(0). This free iron, acting as a Fenton reagent, might produce free radicals and degrade cell constituents. Here we demonstrate that in the presence of H(2)O(2), HbA(1c) degrades DNA and protein more efficiently than HbA(0). Formation of carbonyl content, an index of oxidative stress, is higher by HbA(1c). Compared to HbA(0), HbA(1c) is more rapidly autooxidized. Besides these functional changes, glycation also causes structural modifications of hemoglobin. This is demonstrated by reduced alpha-helix content, more surface accessible hydrophobic tryptophan residues, increased thermolability and weaker heme-globin linkage in HbA(1c) than in its nonglycated analog. The glycation-induced structural modification of hemoglobin may be associated with its functional modification leading to oxidative stress in diabetic patients.

Logistic, ethical, and political dimensions of stepped wedge trials: critical review and case studies.

BACKGROUND: Three arguments are usually invoked in favour of stepped wedge cluster randomised controlled trials: the logistic convenience of implementing an intervention in phases, the ethical benefit of providing the intervention to all clusters, and the potential to enhance the social acceptability of cluster randomised controlled trials. Are these alleged benefits real? We explored the logistic, ethical, and political dimensions of stepped wedge trials using case studies of six recent evaluations. METHODS: We identified completed or ongoing stepped wedge evaluations using two systematic reviews. We then purposively selected six with a focus on public health in high, middle, and low-income settings. We interviewed their authors about the logistic, ethical, and social issues faced by their teams. Two authors reviewed interview transcripts, identified emerging issues through qualitative thematic analysis, reflected upon them in the context of the literature, and invited all participants to co-author the manuscript. RESULTS: Our analysis raises three main points. First, the phased implementation of interventions can alleviate problems linked to simultaneous roll-out, but also brings new challenges. Issues to consider include the feasibility of organising intervention activities according to a randomised sequence, estimating time lags in implementation and effects, and accommodating policy changes during the trial period. Second, stepped wedge trials, like parallel cluster trials, require equipoise: without it, randomising participants to a control condition, even for a short time, remains problematic. In stepped wedge trials, equipoise is likely to lie in the degree of effect, effectiveness in a specific operational milieu, and the balance of benefit and harm, including the social value of better evaluation. Third, the strongest arguments for a stepped wedge design are logistic and political rather than ethical. The design is advantageous when simultaneous roll-out is impractical and when it increases the acceptability of using counterfactuals. CONCLUSIONS: The logistic convenience of phased implementation is context-dependent, and may be vitiated by the additional requirements of phasing. The potential for stepped wedge trials to enhance the social acceptability of cluster randomised trials is real, but their ethical legitimacy still rests on demonstrating equipoise and its configuration for each research question and setting.

In vitro nonenzymatic glycation enhances the role of myoglobin as a source of oxidative stress.

Metmyoglobin (Mb) was glycated by glucose in a non-enzymatic in vitro reaction. Amount of iron release from the heme pocket of myoglobin was found to be directly related with the extent of glycation. After in vitro glycation, the unchanged Mb and glycated myoglobin (GMb) were separated by ion exchange (BioRex 70) chromatography, which eliminated free iron from the protein fractions. Separated fractions of Mb and GMb were converted to their oxy forms -MbO2 and GMbO2, respectively. H2O2-induced iron release was significantly higher from GMbO2 than that from MbO2. This free iron, acting as a Fenton reagent, might produce free radicals and degrade different cell constituents. To verify this possibility, degradation of different cell constituents catalyzed by these fractions in the presence of H2O2 was studied. GMbO2 degraded arachidonic acid, deoxyribose and plasmid DNA more efficiently than MbO2. Arachidonic acid peroxidation and deoxyribose degradation were significantly inhibited by desferrioxamine (DFO), mannitol and catalase. However, besides free iron-mediated free radical reactions, role of iron of higher oxidation states, formed during interaction of H2O2 with myoglobin might also be involved in oxidative degradation processes. Formation of carbonyl content, an index of oxidative stress, was higher by GMbO2. Compared to MbO2, GMbO2 was rapidly autooxidized and co-oxidized with nitroblue tetrazolium, indicating increased rate of Mb and superoxide radical formation in GMbO2. GMb exhibited more peroxidase activity than Mb, which was positively correlated with ferrylmyoglobin formation in the presence of H2O2. These findings correlate glycation-induced modification of myoglobin and a mechanism of increased formation of free radicals. Although myoglobin glycation is not significant within muscle cells, free myoglobin in circulation, if becomes glycated, may pose a serious threat by eliciting oxidative stress, particularly in diabetic patients.