HIV outcomes during the COVID-19 pandemic in people of Black ethnicities living with HIV in England.

OBJECTIVES: To describe HIV care outcomes in people of Black ethnicities living in England during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) pandemic. METHODS: This was an observational cohort study of people of self-reported Black ethnicities attending for HIV care at nine HIV clinics across England. The primary outcome was a composite of antiretroviral therapy (ART) interruption and HIV viraemia (HIV RNA ≥200 copies/mL) ascertained via self-completed questionnaires and review of medical records. We used multivariable logistic regression to explore associations between ART interruption/HIV viraemia and demographic factors, pre-pandemic HIV immunovirological control, comorbidity status, and COVID-19 disease and vaccination status. RESULTS: We included 2290 people (median age 49.3 years; 56% female; median CD4 cell count 555 cells/mm3; 92% pre-pandemic HIV RNA <200 copies/mL), of whom 302 (13%) reported one or more ART interruption, 312 (14%) had documented HIV viraemia ≥200 copies/mL, and 401 (18%) experienced the composite endpoint of ART interruption/HIV viraemia. In multivariable analysis, a pre-pandemic HIV RNA <200 copies/mL (odds ratio [OR] 0.21; 95% confidence interval [CI] 0.15-0.30) and being vaccinated against SARS-CoV-2 (OR 0.41; 95% CI 0.30-0.55) were associated with reduced odds of ART interruption/HIV viraemia; pandemic-related disruptions to HIV care were common self-reported additional factors. CONCLUSIONS: During the COVID-19 pandemic, one in six people of Black ethnicities in this HIV cohort experienced an ART interruption/HIV viraemia. Some of these episodes resulted from pandemic-related healthcare disruptions. Associations with suboptimal engagement in HIV care pre-pandemic and not being vaccinated against SARS-CoV-2 suggest that wider health beliefs and/or poor healthcare access may have been contributory factors.

Clinical epidemiology of COVID-19 in people of black ethnicity living with HIV in the UK.

OBJECTIVES: To describe the clinical epidemiology of COVID-19 in people of black ethnicity living with HIV in the UK. METHODS: We investigated the incidence and factors associated with COVID-19 in a previously established and well-characterized cohort of black people with HIV. Primary outcomes were COVID-19 acquisition and severe COVID-19 disease (requiring hospitalization and/or resulting in death). Cumulative incidence was analysed using Nelson-Aalen methods, and associations between demographic, pre-pandemic immune-virological parameters, comorbidity status and (severe) COVID-19 were identified using Cox regression analysis. RESULTS: COVID-19 status was available for 1847 (74%) of 2495 COVID-AFRICA participants (median age 49.6 years; 56% female; median CD4 cell count = 555 cells/µL; 93% HIV RNA <200 copies/mL), 573 (31%) of whom reported at least one episode of COVID-19. The cumulative incidence rates of COVID-19 and severe COVID-19 were 31.0% and 3.4%, respectively. Region of ancestry (East/Southern/Central vs. West Africa), nadir CD4 count and kidney disease were associated with COVID-19 acquisition. Diabetes mellitus [adjusted hazard ratio (aHR) = 2.39, 95% confidence interval (CI): 1.26-4.53] and kidney disease (aHR = 2.53, 95% CI: 1.26-4.53) were associated with an increased risk, and recent CD4 count >500 cells/µL (aHR = 0.49, 95% CI: 0.25-0.93) with a lower risk of severe COVID-19. CONCLUSIONS: Region of ancestry was associated with COVID-19 acquisition, and immune and comorbidity statuses were associated with COVID-19 disease severity in people of black ethnicity living with HIV in the UK.

Reduced risk for Omicron SARS-CoV-2 infection observed in older adults with hybrid immunity.

BACKGROUND: Hybrid SARS-CoV-2 immunity may provide longer duration protection against severe SARS-CoV-2 infection and hospitalisation than purely vaccine-derived immunity. Older adults represent a high-risk group for severe disease, yet available data is skewed towards younger adults. METHODS: A prospective longitudinal study at a large London long-term care facility (LTCF) was conducted from March 2020 to April 2022 to assess the effect of hybrid versus vaccine-only immunity on SARS-CoV-2 infection in older adults during Omicron variant dominance. Hybrid immunity was assessed by a combination of SARS-CoV-2 polymerase chain reaction testing weekly (asymptomatic screening) and as required (symptomatic testing), as well as serial SARS-CoV-2 serology. RESULTS: 280 participants (median age 82 yrs, IQR 76-88 yrs; 95.4% male) were followed up. 168/280 (60%) had evidence of hybrid immunity prior to the Omicron variant wave. Participants with hybrid immunity had substantially lower odds of acquiring COVID-19 infection during the Omicron wave compared to those with vaccine-only immunity (unadjusted odds ratio 0.26, 95% CI 0.14-0.47, chi-squared P < .0001). Participants with hybrid immunity had an odds ratio of 0.40 (0.19-0.79) for asymptomatic infection and 0.15 (0.06-0.34) for symptomatic infection (Likelihood ratio test, P < .0001). DISCUSSION: Our data highlight potential opportunities to target ongoing booster vaccination campaigns for those most at risk of severe infection. Reporting of data in older adults will be of particular value to examine the effect of hybrid immunity as new variants continue to emerge and vaccination strategies evolve.

Research gaps and priorities for quantitative microbial risk assessment (QMRA).

The coronavirus disease 2019 pandemic highlighted the need for more rapid and routine application of modeling approaches such as quantitative microbial risk assessment (QMRA) for protecting public health. QMRA is a transdisciplinary science dedicated to understanding, predicting, and mitigating infectious disease risks. To better equip QMRA researchers to inform policy and public health management, an Advances in Research for QMRA workshop was held to synthesize a path forward for QMRA research. We summarize insights from 41 QMRA researchers and experts to clarify the role of QMRA in risk analysis by (1) identifying key research needs, (2) highlighting emerging applications of QMRA; and (3) describing data needs and key scientific efforts to improve the science of QMRA. Key identified research priorities included using molecular tools in QMRA, advancing dose-response methodology, addressing needed exposure assessments, harmonizing environmental monitoring for QMRA, unifying a divide between disease transmission and QMRA models, calibrating and/or validating QMRA models, modeling co-exposures and mixtures, and standardizing practices for incorporating variability and uncertainty throughout the source-to-outcome continuum. Cross-cutting needs identified were to: develop a community of research and practice, integrate QMRA with other scientific approaches, increase QMRA translation and impacts, build communication strategies, and encourage sustainable funding mechanisms. Ultimately, a vision for advancing the science of QMRA is outlined for informing national to global health assessments, controls, and policies.

Interfacing Motor Units in Non-Human Primates Identifies a Principal Neural Component for Force Control Constrained by the Size Principle.

Motor units convert the last neural code of movement into muscle forces. The classic view of motor unit control is that the central nervous system sends common synaptic inputs to motoneuron pools and that motoneurons respond in an orderly fashion dictated by the size principle. This view however is in contrast with the large number of dimensions observed in motor cortex which may allow individual and flexible control of motor units. Evidence for flexible control of motor units may be obtained by tracking motor units longitudinally during tasks with some level of behavioural variability. Here we identified and tracked populations of motor units in the brachioradialis muscle of two macaque monkeys during ten sessions spanning over one month with a broad range of rate of force development (1.8 - 38.6 N·m·s-1). We found a very stable recruitment order and discharge characteristics of the motor units over sessions and contraction trials. The small deviations from orderly recruitment were fully predicted by the motor unit recruitment intervals, so that small shifts in recruitment thresholds happened only during contractions at high rate of force development. Moreover, we also found that one component explained more than ∼50% of the motor unit discharge rate variance, and that the remaining components represented a time-shifted version of the first. In conclusion, our results show that motoneurons recruitment is determined by the interplay of the size principle and common input and that this recruitment scheme is not violated over time nor by the speed of the contractions.SIGNIFICANCE STATEMENT:With a new non-invasive high-density electromyographic framework we show the activity of motor unit ensembles in macaques during voluntary contractions. The discharge characteristics of brachioradialis motor units revealed a relatively fixed recruitment order and discharge characteristics across days and rate of force developments. These results were further confirmed through invasive axonal stimulation and recordings of intramuscular electromyographic activity from 16 arm muscles. The study shows for the first time the feasibility of longitudinal non-invasive motor unit interfacing and tracking of the same motor units in non-human primates.

Novel use of oral chloramphenicol for treatment-resistant Mycoplasma genitalium.

We describe the novel use of oral chloramphenicol for treatment-resistant Mycoplasma genitalium (M. genitalium) infection in a 20-year-old heterosexual cisgender male presenting with recurrent symptomatic non-gonococcal urethritis. M. genitalium urethritis is an increasingly common clinical conundrum in sexual health clinics and in cases of second-line treatment failure (such as moxifloxacin), UK and international guidelines struggle to make recommendations for third-line treatments. As shown in our case, the evidence base for third-line treatments is lacking, with poor success rates, and may be poorly tolerated. Here we demonstrate the novel use of a well-tolerated oral antimicrobial, chloramphenicol, resulting in rapid microbiological and clinical cure in treatment-resistant M. genitalium urethritis.

Surveillance of Mpox Cases Attending Sexual Health Services in England (SOMASS): design, implementation and initial findings from the SOMASS data collection tool, 2022.

OBJECTIVES: We aimed to design and implement a data collection tool to support the 2022 mpox (monkeypox) outbreak, and to describe clinical and epidemiological data from individuals with mpox attending sexual health services (SHSs) in England. METHODS: The UK Health Security Agency and the British Association for Sexual Health and HIV established the Surveillance of Mpox Cases Attending Sexual Health Services in England (SOMASS) system.Descriptive data were collected via a secure web-based data collection tool, completed by SHS clinicians following consultation with individuals with suspected mpox. Data were collected on patient demographics, clinical presentation and severity, exposures and behavioural characteristics. RESULTS: As of 17 November 2022, 276 SOMASS responses were submitted from 31 SHSs in England.Where recorded, most (245 of 261; 94%) individuals identified as gay, bisexual or men who have sex with men (GBMSM), of whom two-thirds were HIV negative (170 of 257; 66%) and taking HIV pre-exposure prophylaxis (87 of 140; 62%), with a median age of 37 years (IQR: 30-43). Where known, thirty-nine per cent (63 of 161) had a concurrent sexually transmitted infection (STI) at the time of their mpox diagnosis.For 46% of individuals (127 of 276), dermatological lesions were the initial symptom. Lesions were mostly asymmetrical and polymorphic, predominately affecting the genital area and perianal areas.Nine per cent (24 of 276) of individuals were hospitalised. We report an association between receptive anal intercourse among GBMSM and proctitis (27 of 115; 24% vs 7 of 130; 5%; p<0.0001), and the presence of perianal lesions as the primary lesion site (46 of 115; 40% vs 25 of 130; 19%; p=0.0003). CONCLUSIONS: We demonstrate multidisciplinary and responsive working to develop a robust data collection tool, which improved surveillance and strengthened the knowledge base. The SOMASS tool will allow data collection if mpox resurges in England. The model for developing the tool can be adapted to facilitate the preparedness and response to future STI outbreaks.

Aerosol containment device design considerations and performance evaluation metrics.

BACKGROUND: Spurred by the Coronavirus infectious disease 2019 pandemic, aerosol containment devices (ACDs) were developed to capture infectious respiratory aerosols generated by patients at their source. Prior reviews indicated that such devices had low evidence of effectiveness, but did not address how ACDs should be evaluated, how well they should perform, nor have clearly defined performance standards. Towards developing design criteria for ACDs, two questions were posed: 1) What characteristics have guided the design of ACDs? 2) How have these characteristics been evaluated? METHODS: A scoping review was performed consistent with PRISMA guidelines. Data were extracted with respect to general study information, intended use of the device, device design characteristics and evaluation. RESULTS: Fifty-four articles were included. Evaluation was most commonly performed with respect to device aerosol containment (n = 31, 61%), with only 5 (9%), 3 (6%) and 8 (15%) formally assessing providing experience, patient experience and procedure impact, respectively. Nearly all of the studies that explored provider experience and procedure impact studied intubation. Few studies provided a priori performance criteria for any evaluation metric, or referenced any external guidelines by which to bench mark performance. CONCLUSION: With respect to aerosol containment, ACDs should reduce exposure among HCP with the device compared with the absence of the device, and provide ≥90% reduction in respirable aerosols, equivalent in performance to N95 filtering facepiece respirators, if the goal is to reduce reliance on personal protective equipment. The ACD should not increase awkward or uncomfortable postures, or adversely impact biomechanics of the procedure itself as this could have implications for procedure outcomes. A variety of standardized instruments exist to assess the experience of patients and healthcare personnel. Integration of ACDs into routine clinical practice requires rigorous studies of aerosol containment and the user experience.

Impact of respiratory aerosol size and number distribution on the relative importance of different routes in SARS-CoV-2 transmission.

Exploring the relative importance of different routes in SARS-CoV-2 transmission is crucial in infection prevention. However, even in the same environmental setting, the relative importance of different routes has varied in different studies. We hypothesize that respiratory aerosol size and number distribution might play a key role. In this study, size and number distribution of respiratory droplets emitted from breathing, talking, and coughing were identified from PubMed and Web of Science. The infection risk of SARS-CoV-2 via airborne, droplet, and fomite transmission routes was modeled in a household and a healthcare setting. The relative importance of three routes varied with different size distributions in both settings. Generally, the contribution of the airborne route increased with the volume percentage of respirable droplets emitted. And the increase of the total number of emitted droplets leads to an increase in the contribution of tdroplet route. In the healthcare setting, as the total number of emitted droplets increased from 110 to 4,973, the contribution of droplet route increased from 62.24% to 98.11%. Next, by considering the combination of breathing, coughing, and talking when the infected person was asymptomatic, the airborne route predominated over the droplet and contact routes. When the infected person had developed symptoms, that is, cough, the droplet route played a dominant role in SARS-CoV-2 transmission. In conclusion, risk analyses will be improved with improved sampling methods that enable characterization of viruses within respiratory droplets of different sizes.

Exposure frequency, intensity, and duration: What we know about work-related asthma risks for healthcare workers from cleaning and disinfection.

The objective of this review was to scope the current evidence base related to three exposure assessment concepts: frequency, intensity, and duration (latency) for cleaning and disinfection exposures in healthcare and subsequent work-related asthma risks. A search strategy was developed addressing intersections of four main concepts: (1) work-related asthma; (2) occupation (healthcare workers/nurses); (3) cleaning and disinfection; and (4) exposure. Three databases were searched: Embase, PubMed, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) database. Data were extracted related to three main components of risk assessment: (1) exposure frequency, (2) exposure intensity, and (3) exposure duration. Latency data were analyzed using an exponential distribution fit, and extracted concentration data were compared to occupational exposure limits. The final number of included sources from which data were extracted was 133. Latency periods for occupational asthma were exponentially distributed, with a mean waiting time (1/λ) of 4.55 years. No extracted concentration data were above OELs except for some formaldehyde and glutaraldehyde concentrations. Data from included sources also indicated some evidence for a dose-response relationship regarding increased frequency yielding increased risk, but this relationship is unclear due to potential confounders (differences in role/task and associated exposure) and the healthy worker effect. Data priority needs to include linking concentration data to health outcomes, as most current literature does not include both types of measurements in a single study, leading to uncertainty in dose-response relationships.

Transmission of Respiratory Viral Diseases to Health Care Workers: COVID-19 as an Example.

Health care workers (HCWs) can acquire infectious diseases, including coronavirus disease 2019 (COVID-19), from patients. Herein, COVID-19 is used with the source-pathway-receptor framework as an example to assess evidence for the roles of aerosol transmission and indirect contact transmission in viral respiratory infectious diseases. Evidence for both routes is strong for COVID-19 and other respiratory viruses, but aerosol transmission is likely dominant for COVID-19. Key knowledge gaps about transmission processes and control strategies include the distribution of viable virus among respiratory aerosols of different sizes, the mechanisms and efficiency by which virus deposited on the facial mucous membrane moves to infection sites inside the body, and the performance of source controls such as face coverings and aerosol containment devices. To ensure that HCWs are adequately protected from infection, guidelines and regulations must be updated to reflect the evidence that respiratory viruses are transmitted via aerosols.

Efficacy of EPA-registered disinfectants against two human norovirus surrogates and Clostridioides difficile endospores.

AIMS: To determine the efficacy of a panel of nine EPA-registered disinfectants against two human norovirus (HuNoV) surrogates (feline calicivirus [FCV] and Tulane virus [TuV]) and Clostridioides difficile endospores. METHODS AND RESULTS: Nine EPA-registered products, five of which contained H2 O2 as active ingredient, were tested against infectious FCV, TuV and C. difficile endospores using two ASTM methods, a suspension and carrier test. Efficacy claims against FCV were confirmed for 8 of 9 products. The most efficacious product containing H2 O2 as ingredient achieved a >5.1 log reduction of FCV and >3.1 log reduction of TuV after 5 min, and >6.0 log reduction of C. difficile endospores after 10 min. Of the five products containing H2 O2 , no strong correlation (R2  = 0.25, p = 0.03) was observed between disinfection efficacy and H2 O2 concentration. Addition of 0.025% ferrous sulphate to 1% H2 O2 solution improved efficacy against FCV, TuV and C. difficile. CONCLUSION: Disinfectants containing H2 O2 are the most efficacious disinfection products against FCV, TuV and C. difficile endospores. Product formulation, rather than the concentration of H2 O2 in a product, impacts the efficacy of a disinfection product. SIGNIFICANCE AND IMPACT OF STUDY: H2 O2 -based disinfectants are efficacious against surrogate viruses for HuNoV and C. difficile endospores.

The Dyadic Health Influence Model.

Relationship partners affect one another's health outcomes through their health behaviors, yet how this occurs is not well understood. To fill this gap, we present the Dyadic Health Influence Model (DHIM). The DHIM identifies three routes through which a person (the agent) can impact the health beliefs and behavior of their partner (the target). An agent may (a) model health behaviors and shape the shared environment, (b) enact behaviors that promote their relationship, and/or (c) employ strategies to intentionally influence the target's health behavior. A central premise of the DHIM is that agents act based on their beliefs about their partner's health and their relationship. In turn, their actions have consequences not only for targets' health behavior but also for their relationship. We review theoretical and empirical research that provides initial support for the routes and offer testable predictions at the intersection of health behavior change research and relationship science.

Variability in detection of SARS-CoV-2-specific antibody responses following mild infection: a prospective multicentre cross-sectional study, London, United Kingdom, 17 April to 17 July 2020.

IntroductionImmunoassays targeting different SARS-CoV-2-specific antibodies are employed for seroprevalence studies. The degree of variability between immunoassays targeting anti-nucleocapsid (anti-NP; the majority) vs the potentially neutralising anti-spike antibodies (including anti-receptor-binding domain; anti-RBD), particularly in mild or asymptomatic disease, remains unclear.AimsWe aimed to explore variability in anti-NP and anti-RBD antibody detectability following mild symptomatic or asymptomatic SARS-CoV-2 infection and analyse antibody response for correlation with symptomatology.MethodsA multicentre prospective cross-sectional study was undertaken (April-July 2020). Paired serum samples were tested for anti-NP and anti-RBD IgG antibodies and reactivity expressed as binding ratios (BR). Multivariate linear regression was performed analysing age, sex, time since onset, symptomatology, anti-NP and anti-RBD antibody BR.ResultsWe included 906 adults. Antibody results (793/906; 87.5%; 95% confidence interval: 85.2-89.6) and BR strongly correlated (ρ = 0.75). PCR-confirmed cases were more frequently identified by anti-RBD (129/130) than anti-NP (123/130). Anti-RBD testing identified 83 of 325 (25.5%) cases otherwise reported as negative for anti-NP. Anti-NP presence (+1.75/unit increase; p < 0.001), fever (≥ 38°C; +1.81; p < 0.001) or anosmia (+1.91; p < 0.001) were significantly associated with increased anti-RBD BR. Age (p = 0.85), sex (p = 0.28) and cough (p = 0.35) were not. When time since symptom onset was considered, we did not observe a significant change in anti-RBD BR (p = 0.95) but did note decreasing anti-NP BR (p < 0.001).ConclusionSARS-CoV-2 anti-RBD IgG showed significant correlation with anti-NP IgG for absolute seroconversion and BR. Higher BR were seen in symptomatic individuals, particularly those with fever. Inter-assay variability (12.5%) was evident and raises considerations for optimising seroprevalence testing strategies/studies.

Influence of face shields on exposures to respirable aerosol.

The objective of this study was to determine the influence of face shields on the concentration of respirable aerosols in the breathing zone of the wearer. The experimental approach involved the generation of poly-dispersed respirable test dust aerosol in a low-speed wind tunnel over 15 min, with a downstream breathing mannequin. Aerosol concentrations were measured in the breathing zone of the mannequin and at an upstream location using two laser spectrophotometers that measured particle number concentration over the range 0.25-31 µm. Three face shield designs were tested (A, B, and C) and were positioned on the mannequin operated at a high and low breathing rate. Efficiency-the reduction in aerosol concentration in the breathing zone-was calculated as a function of particle size and overall, for each face shield. Face shield A, a bucket hat with flexible shield, had the highest efficiency, approximately 95%, while more traditional face shield designs had efficiency 53-78%, depending on face shield and breathing rate. Efficiency varied by particle size, but the pattern differed among face shield designs. Face shields decreased the concentration of respirable aerosols in the breathing zone when aerosols were carried perpendicular to the face. Additional research is needed to understand the impact of face shield position relative to the source.

Chronic itch induced by thalamic deep brain stimulation: a case for a central itch centre.

BACKGROUND: Central itch syndrome has been previously described in conditions such as stroke. The neurophysiology of central itch syndrome has been investigated in non-human primates but remains incompletely understood. METHODS: We report an observational study of a rare case of severe central itch following thalamic deep brain stimulation and postulate the location of the central itch centre in humans. RESULTS: The patient was a 47-year-old female, with congenital spinal malformations, multiple previous corrective spinal surgeries and a 30-year history of refractory neuropathic pain in her back and inferior limbs. Following multidisciplinary pain assessment and recommendation, she was referred for spinal cord stimulation, but the procedure failed technically due to scarring related to her multiple previous spinal surgeries. She was therefore referred to our centre and underwent bilateral deep brain stimulation (DBS) of the ventral posterolateral nucleus of the thalamus for management of her chronic pain. Four weeks after switching on the stimulation, the patient reported significant improvement in her pain but developed a full body progressive itch which was then complicated with a rash. Common causes of skin eczema were ruled out by multiple formal dermatological evaluation. A trial of unilateral "off stimulation" was performed showing improvement of the itchy rash. Standard and normalized brain atlases were used to localize the active stimulating contact within the thalamus at a location we postulate as the central itch centre. CONCLUSIONS: Precise stereotactic imaging points to the lateral portion of the ventral posterolateral and posteroinferior nuclei of the thalamus as critical in the neurophysiology of itch in humans.

Menopausal status, age and management among women living with HIV in the UK.

BACKGROUND: There is currently little evidence exploring menopausal status, age at last menstrual period (LMP) and management of menopause among women living with HIV aged 45-60 years in England. METHODS: Socio-demographic, lifestyle and clinical data were collected through a self-completed cross-sectional survey. Longitudinal CD4 count and viral load data were available from linkage to clinical records, if consent was provided. Women were categorised as pre-, peri- or post-menopausal. Factors associated with menopausal stage were examined using ordinal logistic regression adjusting for age. Age at LMP was estimated using Kaplan-Meier survival analysis. RESULTS: The 847 women had a median age of 49 [interquartile range (IQR): 47-52] years. Most were of black ethnicity (81.3%), were born outside the UK (85.0%) and had completed secondary education (88.7%); 177 (20.4%), 373 (43.0%) and 297 (34.2%) were pre-, peri- or post-menopausal, respectively. After adjusting for age, associations of menopausal status with non-cohabiting relationship [adjusted odds ratio = 0.63 (95% confidence interval: 0.43-0.91)], baseline viral load ≥ 100 000 copies/mL [2.67 (1.20-5.94)] and unemployment [1.34 (0.97-1.84)] remained significant. Median (IQR) age at LMP was 54 (51-55) years in the group. In total, 27.9% (233/836) of women reported severe menopausal symptoms; 45.6% of those with somatic symptoms had heard of hormone replacement therapy and 8.7% had used it. Only 5.6% of women with urogenital symptoms had used topical oestrogen. CONCLUSIONS: Our findings highlight the importance of educating both women and their healthcare providers about menopausal symptoms and management options.

The incidence and prevalence of patients with paroxysmal nocturnal haemoglobinuria and aplastic anaemia PNH syndrome: A retrospective analysis of the UK's population-based haematological malignancy research network 2004-2018.

OBJECTIVES: A retrospective population-based study to determine the incidence and prevalence of patients with the rare blood disease paroxysmal nocturnal haemoglobinuria (PNH). METHODS: All patients were identified by flow cytometric detection of blood cells deficient in glycosylphosphatidylinositol (GPI) linked proteins at a single diagnostic reference laboratory that serves the Yorkshire based, Haematological Malignancy Research Network (HMRN) with a population of 3.8 million. RESULTS: One hundred and ninety-seven patients with detectable PNH clones at a level of >0.01% in at least two lineages of cells (neutrophils, monocytes and/or red cells) were identified over a 15-year period (2004-2018). Of these, 88% had aplastic anaemia (AA), 8% classical PNH and 3% myelodysplastic syndrome. The overall incidence rate was estimated at 0.35 cases per 100 000 people per year. This equates to 220 cases newly diagnosed in the United Kingdom each year. The overall prevalence rate was 3.81 per 100 000, this equates to an estimated 2400 prevalent cases in the UK. The overall and relative 5-year survival rates were 72% and 82.7%, respectively. CONCLUSIONS: This study showed that classical haemolytic PNH is a rare disease and represents only a small proportion overall of patients with detectable PNH cells, the majority of which have aplastic anaemia.

The association between severe menopausal symptoms and engagement with HIV care and treatment in women living with HIV.

Using data from the PRIME Study, an observational study of the menopause in women living with HIV in England, we explored the association between menopausal symptoms and: (i) antiretroviral therapy (ART) adherence and (ii) HIV clinic attendance. We measured menopausal symptom severity with the Menopause Rating Scale (MRS, score ≥17 indicating severe symptoms), adherence with the CPCRA Antiretroviral Medication Adherence Self-Report Form, and ascertained HIV clinic attendance via self-report. Odds ratios were obtained using logistic regression. Women who reported severe menopausal symptoms had greater odds of suboptimal ART adherence (adjusted odds ratio (AOR) 2.22; 95% CI 1.13, 4.35) and suboptimal clinic attendance (AOR 1.52; 95% CI 1.01, 2.29). When psychological, somatic and urogenital domains of the MRS were analysed individually there was no association between adherence and severe symptoms (all p > 0.1), however there was an association between suboptimal HIV clinic attendance and severe somatic (AOR 1.98; 95% CI 1.24, 3.16) and psychological (AOR 1.76; 95% CI 1.17, 2.65) symptoms. Severe menopausal symptoms were significantly associated with sub-optimal ART adherence and HIV clinic attendance, however we cannot infer causality, highlighting the need for longitudinal data.